Mark S. Gold, MD

The Centers for Disease Control and Prevention reported recently that opioid overdose deaths will increase to a new U.S. record, and more are expected as pandemic-related overdose deaths are yet to be counted.¹

Specifically, according to the CDC, 70,980 people died from fatal overdoses in 2019,² which is record high. Experts such as Bruce A. Goldberger, PhD, fear that the 2020 numbers could rise even higher, exacerbated by the coronavirus pandemic.

Deaths from drug overdoses remain higher than the peak yearly death totals ever recorded for car accidents, guns, or AIDS. Overdose deaths have accelerated further – pushing down overall life expectancy in the United States.³ Headlines purporting to identify good news in drug death figures don’t always get below top-level data. Deaths and despair tied to drug dependence are indeed accelerating. I am concerned about these alarmingly dangerous trends.

Synthetic opioids such as fentanyl accounted for about 3,000 deaths in 2013. By 2019, they accounted for more than 37,137.⁴ In addition, 16,539 deaths involved stimulants such as methamphetamine, and 16,196 deaths involved cocaine, the most recent CDC reporting shows. Opioids continue to play a role in U.S. “deaths of despair,” or rising fatalities from drugs, suicides, and alcohol among Americans without employment, hope of job opportunities, or college degrees.⁵ As the American Medical Association has warned,⁶ more people are dying from overdoses amid the COVID-19 pandemic. Clinicians need to be aware of trends so that we can help our patients navigate these challenges.
 

Fentanyl presents dangers

Experts had predicted that the pandemic, by limiting access to treatment, rescue, or overdose services, and increasing time at home and in the neighborhood, would result in more tragedy. In addition, the shift from prescription opioids to heroin and now to fentanyl has made deaths more common.

Fentanyls – synthetic opioids – are involved in more than half of overdose deaths, and in many of the cocaine and methamphetamine-related deaths, which also are on the rise. Fentanyl is about 100 times more potent than morphine and 50 times more potent than heroin. Breathing can stop after use of just 2 mg of fentanyl, which is about as much as trace amounts of table salt. Fentanyl has replaced heroin in many cities as the pandemic changed the relative ease of importing raw drugs such as heroin.

Another important trend is that fentanyl production and distribution throughout the United States have expanded. The ease of manufacture in unregulated sectors of the Chinese and Mexican economies is difficult for U.S. authorities to curb or eliminate. The Internet promotes novel strategies for synthesizing the substance, spreading its production across many labs; suppliers use the U.S. Postal Service for distribution, and e-commerce helps to get the drug from manufacturers to U.S. consumers for fentanyl transactions.

A recent RAND report observes that, for only $10 through the postal service, suppliers can ship a 1-kg parcel from China to the United States, and private shipments cost about $100.⁷ And with large volumes of legal trade between the two countries making rigorous scrutiny of products difficult, especially given the light weight of fentanyl, suppliers find it relatively easy to hide illicit substances in licit shipments. Opioid users have made the switch to fentanyl, and have seen fentanyl added to cocaine and methamphetamine they buy on the streets.
 

OUD and buprenorphine

Fentanyl is one part of the overdose crisis. Opioid use disorder (OUD) is the other. Both need to be addressed if we are to make any progress in this epidemic of death and dependency.

The OUD crisis continues amid the pandemic – and isn’t going away.⁸ Slips, relapses, and overdoses are all too common. Medication-assisted treatment (MAT) and OUD treatment programs are essential parts of our response to overdose initiatives. After naloxone rescue, the best anti-overdose response is to get the OUD patient into treatment with MATs. Patients with OUD have continuously high risks of overdose. The best outcomes appear to be related to treatment duration of greater than 2 years. But it is common to see patients with OUDs who have been in treatment multiple times, taking MATs, dropping out, overdosing, and dying. Some have been described as treatment resistant.⁹ It is clear that treatment can work, but also that even evidence-based treatments often fail.¹⁰

A recent study compared OUD patients who continued treatment for 6-9 months to those patients who had continued MAT treatment for 15-18 months. The longer the treatment, the fewer emergencies, prescriptions, or hospitalizations.¹¹

But this study reminds us that all OUD patients, whether they are currently buprenorphine treated or not, experience overdoses and emergency department interventions. Short and longer treatment groups have a similar nonfatal overdose rate, about 6%, and went to the emergency department at a high rate, above 40%. Discontinuation of buprenorphine treatment is a major risk factor in opioid relapse, emergency department visits, and overdose. Cures are not common. Whether an OUD patient is being treated or has been treated in the past, carrying naloxone (brand name Narcan), makes sense and can save lives.
 

Methadone still considered most effective

Methadone is a synthetic opioid first studied as a treatment for OUD at Rockefeller University in New York City in the 1960s. Methadone may be the most effective treatment for OUD in promoting treatment retention for years, decreasing intravenous drug use, and decreasing deaths.¹² It has been studied and safely used in treatment programs for decades. Methadone is typically administered in a clinic, daily, and with observation. In addition, methadone patients periodically take urine drug tests, which can distinguish methadone from substances of abuse. They also receive counseling. But methadone can be prescribed and administered only in methadone clinics in the United States. It is available for prescription in primary care clinics in Great Britain, Canada, and Australia.¹³ Numerous experts have suggested passing new legislation aimed at changing how methadone can be prescribed. Allowing primary care to administer methadone, just like buprenorphine, can improve access and benefit OUD patients.¹²

Availability of Narcan is critical

A comprehensive treatment model for OUDs includes prescribing naloxone, encouraging those patients with an OUD and their loved ones to have naloxone with them, and providing MATs and appropriate therapies, such as counseling.

As described by Allison L. Pitt and colleagues at Stanford (Calif.) University,¹⁴ the United States might be on track to have up to 500,000 deaths tied to opioid overdoses that might occur over the next 5 years. They modeled the effect on overdose of a long list of interventions, but only a few had an impact. At the top of the list was naloxone availability. We need to focus on saving lives by increasing naloxone availability, improving initiation, and expanding access to MAT, and increasing psychosocial treatment to improve outcomes, increase life-years and quality-adjusted life-years, and reduce opioid-related deaths. When Ms. Pitt and colleagues looked at what would make the most impact in reducing OUD deaths, it was naloxone. Pain patients on higher doses of opioids, nonprescription opioid users, OUD patients should be given naloxone prescriptions. While many can give a Heimlich to a choking person or CPR, few have naloxone to rescue a person who has overdosed on opioids. If an overdose is suspected, it should be administered by anyone who has it, as soon as possible. Then, the person who is intervening should call 911.
 

What we can do today

At this moment, clinicians can follow the Surgeon General’s advice,¹⁵ and prescribe naloxone.

We should give naloxone to OUD patients and their families, to pain patients at dosages of greater than or equal to 50 MME. Our top priorities should be patients with comorbid pain syndromes, those being treated with benzodiazepines and sleeping medications, and patients with alcohol use disorders. This is also an important intervention for those who binge drink, and have sleep apnea, and heart and respiratory diseases.

Naloxone is available without a prescription in at least 43 states. Naloxone is available in harm reduction programs and in hospitals, and is carried by emergency medical staff, law enforcement, and EMTs. It also is available on the streets, though it does not appear to have a dollar value like opioids or even buprenorphine. Also, the availability of naloxone in pharmacies has made it easier for family members and caregivers of pain patients or those with OUD to have it to administer in an emergency.

An excellent place for MDs to start is to do more to encourage all patients with OUD to carry naloxone, for their loved ones to carry naloxone, and for their homes to have naloxone nearby in the bedroom or bathroom. It is not logical to expect a person with an OUD to rescue themselves. Current and past OUD patients, as well as their loved ones, are at high risk – and should have naloxone nearby at all times.

Naloxone reverses an opioid overdose, but it should be thought about like cardioversion or CPR rather than a treatment for an underlying disease. Increasing access to buprenorphine, buprenorphine + naloxone, and naltrexone treatment for OUDs is an important organizing principle. Initiation of MAT treatment in the emergency setting or most anywhere and any place a patient with an OUD can begin treatment is necessary. Treatment with buprenorphine or methadone reduces opioid overdose and opioid-related acute care use.¹⁶

Reducing racial disparities in OUD treatment is necessary, because buprenorphine treatment is concentrated among White patients who either use private insurance or are self-pay.¹⁷ Reducing barriers to methadone program licenses, expanding sites for distribution,¹⁸ prescribing methadone in an office setting might help. Clinicians can do a better job of explaining the risks associated with opioid prescriptions, including diversion and overdose, and the benefits of OUD treatment. So, while naloxone saves lives and is a wonder drug, it does not replace an intervention such as MAT, a counselor, a good treatment program, and a treatment plan. To reduce opioid overdoses, we must increase physician competencies in addiction medicine.
 

Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He disclosed financial ties with ADAPT Pharma and Magstim Ltd.

References

1. Kamp J. Overdose deaths rise, may reach record level, federal data show. Wall Street Journal. 2020 Jul 15.

2. 12 month–ending provisional number of drug overdose drugs. Centers for Disease Control and Prevention. 2020 Jul 5.

3. Katz J et al. In shadow of pandemic, U.S. drug overdose deaths resurge to record. New York Times. 2020 Jul 15.

4. Gold MS. The fentanyl crisis is only getting worse. Addiction Policy Forum. Updated 2020 Mar 12.

5. Gold MS. Mo Med. 2020-Mar-Apr;117(2):99-101.

6. Reports of increases in opioid-related overdoses and other concerns during the COVID-19 pandemic. American Medical Association. Issue brief. Updated 2020 Jul 20.

7. Pardo B et al. The future of fentanyl and other synthetic opioids. RAND report.

8. Gold MS. New challenges in the opioid epidemic. Addiction Policy Forum. 2020 Jun 4.

9. Patterson Silver Wolf DA and Gold MS. J Neurol Sci. 2020;411:116718.

10. Oesterle TS et al. Mayo Clin Proc. 2019;94(10):2072-86.

11. Connery HS and Weiss RD. Am J Psychiatry. 2020;177(2):104-6.

12. Kleber HD. JAMA. 2008;300(19):2303-5.

13. Samet JH et al. N Engl J Med. 2018;379(1):7-8.

14. Pitt AL et al. Am J Public Health. 2018;108(10):1394-1400.

15. U.S. Surgeon General’s Advisory on Naloxone and Opioid Overdose. hhs.gov.

16. Wakeman SE et al. JAMA Netw Open. 2020;3(2):e1920622.

17. Lagisetty PA et al. JAMA Psychiatry. 2019;76(9):979-81.

18. Kleinman RA. JAMA Psychiatry. 2020 Jul 15. doi: 10.1001/jamapsychiatry.2020.1624.

The Centers for Disease Control and Prevention reported recently that opioid overdose deaths will increase to a new U.S. record, and more are expected as pandemic-related overdose deaths are yet to be counted.¹

Specifically, according to the CDC, 70,980 people died from fatal overdoses in 2019,² which is record high. Experts such as Bruce A. Goldberger, PhD, fear that the 2020 numbers could rise even higher, exacerbated by the coronavirus pandemic.

Deaths from drug overdoses remain higher than the peak yearly death totals ever recorded for car accidents, guns, or AIDS. Overdose deaths have accelerated further – pushing down overall life expectancy in the United States.³ Headlines purporting to identify good news in drug death figures don’t always get below top-level data. Deaths and despair tied to drug dependence are indeed accelerating. I am concerned about these alarmingly dangerous trends.

Synthetic opioids such as fentanyl accounted for about 3,000 deaths in 2013. By 2019, they accounted for more than 37,137.⁴ In addition, 16,539 deaths involved stimulants such as methamphetamine, and 16,196 deaths involved cocaine, the most recent CDC reporting shows. Opioids continue to play a role in U.S. “deaths of despair,” or rising fatalities from drugs, suicides, and alcohol among Americans without employment, hope of job opportunities, or college degrees.⁵ As the American Medical Association has warned,⁶ more people are dying from overdoses amid the COVID-19 pandemic. Clinicians need to be aware of trends so that we can help our patients navigate these challenges.
 

Fentanyl presents dangers

Experts had predicted that the pandemic, by limiting access to treatment, rescue, or overdose services, and increasing time at home and in the neighborhood, would result in more tragedy. In addition, the shift from prescription opioids to heroin and now to fentanyl has made deaths more common.

Fentanyls – synthetic opioids – are involved in more than half of overdose deaths, and in many of the cocaine and methamphetamine-related deaths, which also are on the rise. Fentanyl is about 100 times more potent than morphine and 50 times more potent than heroin. Breathing can stop after use of just 2 mg of fentanyl, which is about as much as trace amounts of table salt. Fentanyl has replaced heroin in many cities as the pandemic changed the relative ease of importing raw drugs such as heroin.

Another important trend is that fentanyl production and distribution throughout the United States have expanded. The ease of manufacture in unregulated sectors of the Chinese and Mexican economies is difficult for U.S. authorities to curb or eliminate. The Internet promotes novel strategies for synthesizing the substance, spreading its production across many labs; suppliers use the U.S. Postal Service for distribution, and e-commerce helps to get the drug from manufacturers to U.S. consumers for fentanyl transactions.

A recent RAND report observes that, for only $10 through the postal service, suppliers can ship a 1-kg parcel from China to the United States, and private shipments cost about $100.⁷ And with large volumes of legal trade between the two countries making rigorous scrutiny of products difficult, especially given the light weight of fentanyl, suppliers find it relatively easy to hide illicit substances in licit shipments. Opioid users have made the switch to fentanyl, and have seen fentanyl added to cocaine and methamphetamine they buy on the streets.
 

OUD and buprenorphine

Fentanyl is one part of the overdose crisis. Opioid use disorder (OUD) is the other. Both need to be addressed if we are to make any progress in this epidemic of death and dependency.

The OUD crisis continues amid the pandemic – and isn’t going away.⁸ Slips, relapses, and overdoses are all too common. Medication-assisted treatment (MAT) and OUD treatment programs are essential parts of our response to overdose initiatives. After naloxone rescue, the best anti-overdose response is to get the OUD patient into treatment with MATs. Patients with OUD have continuously high risks of overdose. The best outcomes appear to be related to treatment duration of greater than 2 years. But it is common to see patients with OUDs who have been in treatment multiple times, taking MATs, dropping out, overdosing, and dying. Some have been described as treatment resistant.⁹ It is clear that treatment can work, but also that even evidence-based treatments often fail.¹⁰

A recent study compared OUD patients who continued treatment for 6-9 months to those patients who had continued MAT treatment for 15-18 months. The longer the treatment, the fewer emergencies, prescriptions, or hospitalizations.¹¹

But this study reminds us that all OUD patients, whether they are currently buprenorphine treated or not, experience overdoses and emergency department interventions. Short and longer treatment groups have a similar nonfatal overdose rate, about 6%, and went to the emergency department at a high rate, above 40%. Discontinuation of buprenorphine treatment is a major risk factor in opioid relapse, emergency department visits, and overdose. Cures are not common. Whether an OUD patient is being treated or has been treated in the past, carrying naloxone (brand name Narcan), makes sense and can save lives.
 

Methadone still considered most effective

Methadone is a synthetic opioid first studied as a treatment for OUD at Rockefeller University in New York City in the 1960s. Methadone may be the most effective treatment for OUD in promoting treatment retention for years, decreasing intravenous drug use, and decreasing deaths.¹² It has been studied and safely used in treatment programs for decades. Methadone is typically administered in a clinic, daily, and with observation. In addition, methadone patients periodically take urine drug tests, which can distinguish methadone from substances of abuse. They also receive counseling. But methadone can be prescribed and administered only in methadone clinics in the United States. It is available for prescription in primary care clinics in Great Britain, Canada, and Australia.¹³ Numerous experts have suggested passing new legislation aimed at changing how methadone can be prescribed. Allowing primary care to administer methadone, just like buprenorphine, can improve access and benefit OUD patients.¹²

Availability of Narcan is critical

A comprehensive treatment model for OUDs includes prescribing naloxone, encouraging those patients with an OUD and their loved ones to have naloxone with them, and providing MATs and appropriate therapies, such as counseling.

As described by Allison L. Pitt and colleagues at Stanford (Calif.) University,¹⁴ the United States might be on track to have up to 500,000 deaths tied to opioid overdoses that might occur over the next 5 years. They modeled the effect on overdose of a long list of interventions, but only a few had an impact. At the top of the list was naloxone availability. We need to focus on saving lives by increasing naloxone availability, improving initiation, and expanding access to MAT, and increasing psychosocial treatment to improve outcomes, increase life-years and quality-adjusted life-years, and reduce opioid-related deaths. When Ms. Pitt and colleagues looked at what would make the most impact in reducing OUD deaths, it was naloxone. Pain patients on higher doses of opioids, nonprescription opioid users, OUD patients should be given naloxone prescriptions. While many can give a Heimlich to a choking person or CPR, few have naloxone to rescue a person who has overdosed on opioids. If an overdose is suspected, it should be administered by anyone who has it, as soon as possible. Then, the person who is intervening should call 911.
 

What we can do today

At this moment, clinicians can follow the Surgeon General’s advice,¹⁵ and prescribe naloxone.

We should give naloxone to OUD patients and their families, to pain patients at dosages of greater than or equal to 50 MME. Our top priorities should be patients with comorbid pain syndromes, those being treated with benzodiazepines and sleeping medications, and patients with alcohol use disorders. This is also an important intervention for those who binge drink, and have sleep apnea, and heart and respiratory diseases.

Naloxone is available without a prescription in at least 43 states. Naloxone is available in harm reduction programs and in hospitals, and is carried by emergency medical staff, law enforcement, and EMTs. It also is available on the streets, though it does not appear to have a dollar value like opioids or even buprenorphine. Also, the availability of naloxone in pharmacies has made it easier for family members and caregivers of pain patients or those with OUD to have it to administer in an emergency.

An excellent place for MDs to start is to do more to encourage all patients with OUD to carry naloxone, for their loved ones to carry naloxone, and for their homes to have naloxone nearby in the bedroom or bathroom. It is not logical to expect a person with an OUD to rescue themselves. Current and past OUD patients, as well as their loved ones, are at high risk – and should have naloxone nearby at all times.

Naloxone reverses an opioid overdose, but it should be thought about like cardioversion or CPR rather than a treatment for an underlying disease. Increasing access to buprenorphine, buprenorphine + naloxone, and naltrexone treatment for OUDs is an important organizing principle. Initiation of MAT treatment in the emergency setting or most anywhere and any place a patient with an OUD can begin treatment is necessary. Treatment with buprenorphine or methadone reduces opioid overdose and opioid-related acute care use.¹⁶

Reducing racial disparities in OUD treatment is necessary, because buprenorphine treatment is concentrated among White patients who either use private insurance or are self-pay.¹⁷ Reducing barriers to methadone program licenses, expanding sites for distribution,¹⁸ prescribing methadone in an office setting might help. Clinicians can do a better job of explaining the risks associated with opioid prescriptions, including diversion and overdose, and the benefits of OUD treatment. So, while naloxone saves lives and is a wonder drug, it does not replace an intervention such as MAT, a counselor, a good treatment program, and a treatment plan. To reduce opioid overdoses, we must increase physician competencies in addiction medicine.
 

Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He disclosed financial ties with ADAPT Pharma and Magstim Ltd.

References

1. Kamp J. Overdose deaths rise, may reach record level, federal data show. Wall Street Journal. 2020 Jul 15.

2. 12 month–ending provisional number of drug overdose drugs. Centers for Disease Control and Prevention. 2020 Jul 5.

3. Katz J et al. In shadow of pandemic, U.S. drug overdose deaths resurge to record. New York Times. 2020 Jul 15.

4. Gold MS. The fentanyl crisis is only getting worse. Addiction Policy Forum. Updated 2020 Mar 12.

5. Gold MS. Mo Med. 2020-Mar-Apr;117(2):99-101.

6. Reports of increases in opioid-related overdoses and other concerns during the COVID-19 pandemic. American Medical Association. Issue brief. Updated 2020 Jul 20.

7. Pardo B et al. The future of fentanyl and other synthetic opioids. RAND report.

8. Gold MS. New challenges in the opioid epidemic. Addiction Policy Forum. 2020 Jun 4.

9. Patterson Silver Wolf DA and Gold MS. J Neurol Sci. 2020;411:116718.

10. Oesterle TS et al. Mayo Clin Proc. 2019;94(10):2072-86.

11. Connery HS and Weiss RD. Am J Psychiatry. 2020;177(2):104-6.

12. Kleber HD. JAMA. 2008;300(19):2303-5.

13. Samet JH et al. N Engl J Med. 2018;379(1):7-8.

14. Pitt AL et al. Am J Public Health. 2018;108(10):1394-1400.

15. U.S. Surgeon General’s Advisory on Naloxone and Opioid Overdose. hhs.gov.

16. Wakeman SE et al. JAMA Netw Open. 2020;3(2):e1920622.

17. Lagisetty PA et al. JAMA Psychiatry. 2019;76(9):979-81.

18. Kleinman RA. JAMA Psychiatry. 2020 Jul 15. doi: 10.1001/jamapsychiatry.2020.1624.

The Centers for Disease Control and Prevention reported recently that opioid overdose deaths will increase to a new U.S. record, and more are expected as pandemic-related overdose deaths are yet to be counted.¹

Specifically, according to the CDC, 70,980 people died from fatal overdoses in 2019,² which is record high. Experts such as Bruce A. Goldberger, PhD, fear that the 2020 numbers could rise even higher, exacerbated by the coronavirus pandemic.

Deaths from drug overdoses remain higher than the peak yearly death totals ever recorded for car accidents, guns, or AIDS. Overdose deaths have accelerated further – pushing down overall life expectancy in the United States.³ Headlines purporting to identify good news in drug death figures don’t always get below top-level data. Deaths and despair tied to drug dependence are indeed accelerating. I am concerned about these alarmingly dangerous trends.

Synthetic opioids such as fentanyl accounted for about 3,000 deaths in 2013. By 2019, they accounted for more than 37,137.⁴ In addition, 16,539 deaths involved stimulants such as methamphetamine, and 16,196 deaths involved cocaine, the most recent CDC reporting shows. Opioids continue to play a role in U.S. “deaths of despair,” or rising fatalities from drugs, suicides, and alcohol among Americans without employment, hope of job opportunities, or college degrees.⁵ As the American Medical Association has warned,⁶ more people are dying from overdoses amid the COVID-19 pandemic. Clinicians need to be aware of trends so that we can help our patients navigate these challenges.
 

Fentanyl presents dangers

Experts had predicted that the pandemic, by limiting access to treatment, rescue, or overdose services, and increasing time at home and in the neighborhood, would result in more tragedy. In addition, the shift from prescription opioids to heroin and now to fentanyl has made deaths more common.

Fentanyls – synthetic opioids – are involved in more than half of overdose deaths, and in many of the cocaine and methamphetamine-related deaths, which also are on the rise. Fentanyl is about 100 times more potent than morphine and 50 times more potent than heroin. Breathing can stop after use of just 2 mg of fentanyl, which is about as much as trace amounts of table salt. Fentanyl has replaced heroin in many cities as the pandemic changed the relative ease of importing raw drugs such as heroin.

Another important trend is that fentanyl production and distribution throughout the United States have expanded. The ease of manufacture in unregulated sectors of the Chinese and Mexican economies is difficult for U.S. authorities to curb or eliminate. The Internet promotes novel strategies for synthesizing the substance, spreading its production across many labs; suppliers use the U.S. Postal Service for distribution, and e-commerce helps to get the drug from manufacturers to U.S. consumers for fentanyl transactions.

A recent RAND report observes that, for only $10 through the postal service, suppliers can ship a 1-kg parcel from China to the United States, and private shipments cost about $100.⁷ And with large volumes of legal trade between the two countries making rigorous scrutiny of products difficult, especially given the light weight of fentanyl, suppliers find it relatively easy to hide illicit substances in licit shipments. Opioid users have made the switch to fentanyl, and have seen fentanyl added to cocaine and methamphetamine they buy on the streets.
 

OUD and buprenorphine

Fentanyl is one part of the overdose crisis. Opioid use disorder (OUD) is the other. Both need to be addressed if we are to make any progress in this epidemic of death and dependency.

The OUD crisis continues amid the pandemic – and isn’t going away.⁸ Slips, relapses, and overdoses are all too common. Medication-assisted treatment (MAT) and OUD treatment programs are essential parts of our response to overdose initiatives. After naloxone rescue, the best anti-overdose response is to get the OUD patient into treatment with MATs. Patients with OUD have continuously high risks of overdose. The best outcomes appear to be related to treatment duration of greater than 2 years. But it is common to see patients with OUDs who have been in treatment multiple times, taking MATs, dropping out, overdosing, and dying. Some have been described as treatment resistant.⁹ It is clear that treatment can work, but also that even evidence-based treatments often fail.¹⁰

A recent study compared OUD patients who continued treatment for 6-9 months to those patients who had continued MAT treatment for 15-18 months. The longer the treatment, the fewer emergencies, prescriptions, or hospitalizations.¹¹

But this study reminds us that all OUD patients, whether they are currently buprenorphine treated or not, experience overdoses and emergency department interventions. Short and longer treatment groups have a similar nonfatal overdose rate, about 6%, and went to the emergency department at a high rate, above 40%. Discontinuation of buprenorphine treatment is a major risk factor in opioid relapse, emergency department visits, and overdose. Cures are not common. Whether an OUD patient is being treated or has been treated in the past, carrying naloxone (brand name Narcan), makes sense and can save lives.
 

Methadone still considered most effective

Methadone is a synthetic opioid first studied as a treatment for OUD at Rockefeller University in New York City in the 1960s. Methadone may be the most effective treatment for OUD in promoting treatment retention for years, decreasing intravenous drug use, and decreasing deaths.¹² It has been studied and safely used in treatment programs for decades. Methadone is typically administered in a clinic, daily, and with observation. In addition, methadone patients periodically take urine drug tests, which can distinguish methadone from substances of abuse. They also receive counseling. But methadone can be prescribed and administered only in methadone clinics in the United States. It is available for prescription in primary care clinics in Great Britain, Canada, and Australia.¹³ Numerous experts have suggested passing new legislation aimed at changing how methadone can be prescribed. Allowing primary care to administer methadone, just like buprenorphine, can improve access and benefit OUD patients.¹²

Availability of Narcan is critical

A comprehensive treatment model for OUDs includes prescribing naloxone, encouraging those patients with an OUD and their loved ones to have naloxone with them, and providing MATs and appropriate therapies, such as counseling.

As described by Allison L. Pitt and colleagues at Stanford (Calif.) University,¹⁴ the United States might be on track to have up to 500,000 deaths tied to opioid overdoses that might occur over the next 5 years. They modeled the effect on overdose of a long list of interventions, but only a few had an impact. At the top of the list was naloxone availability. We need to focus on saving lives by increasing naloxone availability, improving initiation, and expanding access to MAT, and increasing psychosocial treatment to improve outcomes, increase life-years and quality-adjusted life-years, and reduce opioid-related deaths. When Ms. Pitt and colleagues looked at what would make the most impact in reducing OUD deaths, it was naloxone. Pain patients on higher doses of opioids, nonprescription opioid users, OUD patients should be given naloxone prescriptions. While many can give a Heimlich to a choking person or CPR, few have naloxone to rescue a person who has overdosed on opioids. If an overdose is suspected, it should be administered by anyone who has it, as soon as possible. Then, the person who is intervening should call 911.
 

What we can do today

At this moment, clinicians can follow the Surgeon General’s advice,¹⁵ and prescribe naloxone.

We should give naloxone to OUD patients and their families, to pain patients at dosages of greater than or equal to 50 MME. Our top priorities should be patients with comorbid pain syndromes, those being treated with benzodiazepines and sleeping medications, and patients with alcohol use disorders. This is also an important intervention for those who binge drink, and have sleep apnea, and heart and respiratory diseases.

Naloxone is available without a prescription in at least 43 states. Naloxone is available in harm reduction programs and in hospitals, and is carried by emergency medical staff, law enforcement, and EMTs. It also is available on the streets, though it does not appear to have a dollar value like opioids or even buprenorphine. Also, the availability of naloxone in pharmacies has made it easier for family members and caregivers of pain patients or those with OUD to have it to administer in an emergency.

An excellent place for MDs to start is to do more to encourage all patients with OUD to carry naloxone, for their loved ones to carry naloxone, and for their homes to have naloxone nearby in the bedroom or bathroom. It is not logical to expect a person with an OUD to rescue themselves. Current and past OUD patients, as well as their loved ones, are at high risk – and should have naloxone nearby at all times.

Naloxone reverses an opioid overdose, but it should be thought about like cardioversion or CPR rather than a treatment for an underlying disease. Increasing access to buprenorphine, buprenorphine + naloxone, and naltrexone treatment for OUDs is an important organizing principle. Initiation of MAT treatment in the emergency setting or most anywhere and any place a patient with an OUD can begin treatment is necessary. Treatment with buprenorphine or methadone reduces opioid overdose and opioid-related acute care use.¹⁶

Reducing racial disparities in OUD treatment is necessary, because buprenorphine treatment is concentrated among White patients who either use private insurance or are self-pay.¹⁷ Reducing barriers to methadone program licenses, expanding sites for distribution,¹⁸ prescribing methadone in an office setting might help. Clinicians can do a better job of explaining the risks associated with opioid prescriptions, including diversion and overdose, and the benefits of OUD treatment. So, while naloxone saves lives and is a wonder drug, it does not replace an intervention such as MAT, a counselor, a good treatment program, and a treatment plan. To reduce opioid overdoses, we must increase physician competencies in addiction medicine.
 

Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He disclosed financial ties with ADAPT Pharma and Magstim Ltd.

References

1. Kamp J. Overdose deaths rise, may reach record level, federal data show. Wall Street Journal. 2020 Jul 15.

2. 12 month–ending provisional number of drug overdose drugs. Centers for Disease Control and Prevention. 2020 Jul 5.

3. Katz J et al. In shadow of pandemic, U.S. drug overdose deaths resurge to record. New York Times. 2020 Jul 15.

4. Gold MS. The fentanyl crisis is only getting worse. Addiction Policy Forum. Updated 2020 Mar 12.

5. Gold MS. Mo Med. 2020-Mar-Apr;117(2):99-101.

6. Reports of increases in opioid-related overdoses and other concerns during the COVID-19 pandemic. American Medical Association. Issue brief. Updated 2020 Jul 20.

7. Pardo B et al. The future of fentanyl and other synthetic opioids. RAND report.

8. Gold MS. New challenges in the opioid epidemic. Addiction Policy Forum. 2020 Jun 4.

9. Patterson Silver Wolf DA and Gold MS. J Neurol Sci. 2020;411:116718.

10. Oesterle TS et al. Mayo Clin Proc. 2019;94(10):2072-86.

11. Connery HS and Weiss RD. Am J Psychiatry. 2020;177(2):104-6.

12. Kleber HD. JAMA. 2008;300(19):2303-5.

13. Samet JH et al. N Engl J Med. 2018;379(1):7-8.

14. Pitt AL et al. Am J Public Health. 2018;108(10):1394-1400.

15. U.S. Surgeon General’s Advisory on Naloxone and Opioid Overdose. hhs.gov.

16. Wakeman SE et al. JAMA Netw Open. 2020;3(2):e1920622.

17. Lagisetty PA et al. JAMA Psychiatry. 2019;76(9):979-81.

18. Kleinman RA. JAMA Psychiatry. 2020 Jul 15. doi: 10.1001/jamapsychiatry.2020.1624.

A new article in the Journal of the Neurological Sciences provides an impressive review of research on the complex impairments produced by a wide range of drugs of abuse with a close look at physicians and other health care professionals.¹

This review breaks new ground in outlining fitness for duty as an important outcome of the state physician health programs (PHPs). In addition, the review and case report by Alexandria G. Polles, MD, and colleagues are a response to the growing call for the state PHP system of care management to explicitly endorse the use of medication-assisted treatment, specifically the use of buprenorphine and methadone, in the treatment of physicians diagnosed with opioid use disorder (OUD). The article usefully situates the controversy in the context of other safety-sensitive jobs, including commercial pilots, truck drivers, and police, because of the elevated rate of substance use disorders among physicians and the safety-sensitive nature of the practice of medicine.

Medication-assisted treatment (MAT)² for opioid use disorders now dominates the field of treatment in terms of prescribing and also funding to address the opioid overdose crisis. MAT generally includes naltrexone and injectable naltrexone, though those antagonist medications have been used successfully for many decades by PHPs.³ However, to understand the controversy over the use of MAT in the care management of physicians first requires an understanding of state PHPs and how those programs oversee the care of physicians diagnosed with substance use disorders (SUDs), including OUDs.

A national blueprint study of PHPs showed that care begins with a formal diagnostic evaluation.⁴ Only when a diagnosis of an SUD is established is a physician referred to the attention of a state PHP, and a monitoring contract is signed. PHPs typically do not offer any direct treatment; instead, they manage the care of physician participants in programs in which the PHPs have confidence. Formal addiction treatment most often is 30 days of residential treatment, but many physicians receive intensive outpatient treatment.

After completing an episode of formal treatment, physicians are closely monitored, usually for 5 years, through random drug and alcohol tests, and work site monitors. They are required to engage in intensive recovery support, typically 12-step fellowships but also other alternative recovery support programs. Comorbid conditions, including mental health disorders, are also treated. Managing PHPs have no sanctions for noncompliance; however, importantly, they do offer a safe haven from state medical licensing boards for physicians who are compliant with their recommendations and who remain abstinent from any use of alcohol, marijuana, illicit drugs, or other nonmedical drug use.

The national blueprint study included 16 state PHPs and reviewed single episodes of PHP care for 908 physicians. Complete abstinence from any use of alcohol, marijuana, or other drugs was required of all physicians for monitoring periods of at least 5 years. During the extended period, 78% of the physicians did not have a single positive or missed test. Two-thirds of physicians who had one positive or missed test did not have a second. About a dozen publications have resulted from this national study, including an analysis of the roughly one-third of the physicians who were diagnosed with OUD.⁵

A sample of 702 PHP participants was grouped based on primary drug at intake: alcohol only, any opioid with or without alcohol, and nonopioid drugs. No significant differences were found among these groups in the percentage who completed PHP contracts, failed to complete their contract, or extended their contract and continued to be monitored. Only one physician received methadone to treat chronic pain. None received opioid agonists to treat their opioid use disorder. Opioid antagonist medication (naltrexone) was used for 40 physicians, or 5.7% of the total sample: 2 physicians (1%) from the alcohol-only group; 35 physicians (10.3%) from the any opioid group, and 3 physicians (1.9%) from nonopioid group.

The second fact that needs to be understood is that medical practice in relationship to SUDs is treated by state licensing boards as a safety-sensitive job, analogous to commercial airline pilots who have the Human Intervention Motivation Study (HIMS),⁶ which is their own care management program analogous to that of PHPs. A similar program exists for attorneys known as Commission on Lawyer Assistance Programs (CoLAP).⁷ Fitness for duty and prevention of harm are major concerns in occupations such as those of physicians, commercial truck drivers, and people working in the nuclear power industry, all of whom have similar safety protections requiring no drug use.

A third fact that deserves special attention is that the unique system of care management for physicians began in the early 1970s. It grew out of employee assistance programs, led then and often now by physicians who are themselves in recovery from SUDs. Many of the successful addiction treatment tools used today come from extensive research of their use in PHPs. Contingency management, 12 steps, caduceus recovery, cognitive-behavioral therapy, and treatment outcomes defined in years are examples in which PHP research helped change treatment and long-term management of SUDs in non-PHP populations.

Dr. Polles and colleagues provide an impressive and comprehensive summary of the issues involved in the new interest in providing the physicians with OUD under PHP care management the option of using buprenorphine or methadone. Such a model within an abstinence-based framework is now being pioneered by a variety of programs, from COAT⁸ at West Virginia University, Morgantown, to the Hazelden Betty Ford Foundation.⁹ In those programs, patients with OUD are offered the option of using buprenorphine, methadone, or naltrexone as well as the option of using none of those medications in an extended abstinence-based intensive treatment. The authors impressively and fairly summarize the evidence on whether there are cognitive or behavioral deficits associated with the therapeutic use of either buprenorphine or methadone, which might make them unacceptable for physicians. The strongest evidence that these medicines are not necessary in the treatment of OUDs in PHPs is the outstanding outcomes PHPs produce without use of these two medications. If skeptical of the use of medications for OUD treatment in PHP care management, Dr. Polles and colleagues are open to experiments to test the effects of this option just as Florida PHP programs pioneered contracts that included mandatory naltrexone.¹⁰ West Virginia University, the Hazelden Betty Ford Foundation, and other programs should be tested to evaluate just how safe, effective, and attractive such an option would be to physicians.

Many, if not most, SUD treatment programs that use MAT are not associated with the intensive psychological treatment or extended participation in recovery support, such as the 12-step fellowships. MAT is viewed as a harm reduction strategy rather than conceptualized as an abstinence-oriented treatment. For example, there is seldom a “sobriety date” among individuals in MAT, i.e., the last day the individual used any substance of abuse, including alcohol and marijuana. These are, however, central features of PHP care, and they are features of the Hazelden Betty Ford Foundation’s definition of recovery¹¹ and use of MAT.

Dr. Polles and colleagues call attention to the unique care management of the PHP for all SUDs, not just for OUDs, because the PHPs set the standard for returning physicians to work who have the fitness and cognitive skills to first do no harm. They emphasize the importance of making sustained recovery the expected outcome of SUD treatment. There is a robust literature on the ways in which this distinctive system of care management shows the path forward for addiction treatment generally to regularly achieve 5-year recovery.¹² The current controversy over the potential use of buprenorphine and buprenorphine plus naloxone in PHPs is a useful entry into this far larger issue of the potential for PHPs to show the path forward for the addiction treatment field.
 

Dr. DuPont, the first director of the National Institute on Drug Abuse (NIDA), is president of the Institute for Behavior and Health Inc., a nonprofit drug-policy research organization in Rockville, Md. He has no disclosures. Dr. Gold is professor of psychiatry (adjunct) at Washington University in St. Louis. He is also the 17th Distinguished Alumni Professor at the University of Florida Gainesville. He has no disclosures.

References

1. Polles AG et al. J Neurol Sci. 2020 Jan 30;411:116714.

2. Oesterle TS et al. Mayo Clin Proc. 2019 Oct;94(10):2072-86.

3. Srivastava AB and Gold MS. Cerebrum. 2018 Sep-Oct; cer-13-8.

4. DuPont RL et al. J Subst Abuse Treat. 2009 Mar 1;36(2):159-71.

5. Merlo LJ et al. J Subst Abuse Treat. 2016 May 1;64:47-54.

6. Human Intervention Motivation Study (HIMS): An Occupational Substance Abuse Treatment Program.

7. Commission on Lawyer Assistance Programs (CoLAP).

8. Lander LR et al. J Neurol Sci. 2020;411:116712-8.

9. Klein AA et al. J Subst Abuse Treat. 2019;104:51-63.

10. Merlo LJ et al. J Addict Med. 2012;5(4):279-83.

11. Betty Ford Consensus Panel. J Subst Abuse Treat. 2007 Oct;33(3):221-8.

12. Carr GD et al. “Physician health programs: The U.S. model.” In KJ Brower and MB Riba, (eds.) Physician Mental Health and Well-Being (pp. 265-94). Cham, Switzerland: Springer International Publishing, 2017.

A new article in the Journal of the Neurological Sciences provides an impressive review of research on the complex impairments produced by a wide range of drugs of abuse with a close look at physicians and other health care professionals.¹

This review breaks new ground in outlining fitness for duty as an important outcome of the state physician health programs (PHPs). In addition, the review and case report by Alexandria G. Polles, MD, and colleagues are a response to the growing call for the state PHP system of care management to explicitly endorse the use of medication-assisted treatment, specifically the use of buprenorphine and methadone, in the treatment of physicians diagnosed with opioid use disorder (OUD). The article usefully situates the controversy in the context of other safety-sensitive jobs, including commercial pilots, truck drivers, and police, because of the elevated rate of substance use disorders among physicians and the safety-sensitive nature of the practice of medicine.

Medication-assisted treatment (MAT)² for opioid use disorders now dominates the field of treatment in terms of prescribing and also funding to address the opioid overdose crisis. MAT generally includes naltrexone and injectable naltrexone, though those antagonist medications have been used successfully for many decades by PHPs.³ However, to understand the controversy over the use of MAT in the care management of physicians first requires an understanding of state PHPs and how those programs oversee the care of physicians diagnosed with substance use disorders (SUDs), including OUDs.

A national blueprint study of PHPs showed that care begins with a formal diagnostic evaluation.⁴ Only when a diagnosis of an SUD is established is a physician referred to the attention of a state PHP, and a monitoring contract is signed. PHPs typically do not offer any direct treatment; instead, they manage the care of physician participants in programs in which the PHPs have confidence. Formal addiction treatment most often is 30 days of residential treatment, but many physicians receive intensive outpatient treatment.

After completing an episode of formal treatment, physicians are closely monitored, usually for 5 years, through random drug and alcohol tests, and work site monitors. They are required to engage in intensive recovery support, typically 12-step fellowships but also other alternative recovery support programs. Comorbid conditions, including mental health disorders, are also treated. Managing PHPs have no sanctions for noncompliance; however, importantly, they do offer a safe haven from state medical licensing boards for physicians who are compliant with their recommendations and who remain abstinent from any use of alcohol, marijuana, illicit drugs, or other nonmedical drug use.

The national blueprint study included 16 state PHPs and reviewed single episodes of PHP care for 908 physicians. Complete abstinence from any use of alcohol, marijuana, or other drugs was required of all physicians for monitoring periods of at least 5 years. During the extended period, 78% of the physicians did not have a single positive or missed test. Two-thirds of physicians who had one positive or missed test did not have a second. About a dozen publications have resulted from this national study, including an analysis of the roughly one-third of the physicians who were diagnosed with OUD.⁵

A sample of 702 PHP participants was grouped based on primary drug at intake: alcohol only, any opioid with or without alcohol, and nonopioid drugs. No significant differences were found among these groups in the percentage who completed PHP contracts, failed to complete their contract, or extended their contract and continued to be monitored. Only one physician received methadone to treat chronic pain. None received opioid agonists to treat their opioid use disorder. Opioid antagonist medication (naltrexone) was used for 40 physicians, or 5.7% of the total sample: 2 physicians (1%) from the alcohol-only group; 35 physicians (10.3%) from the any opioid group, and 3 physicians (1.9%) from nonopioid group.

The second fact that needs to be understood is that medical practice in relationship to SUDs is treated by state licensing boards as a safety-sensitive job, analogous to commercial airline pilots who have the Human Intervention Motivation Study (HIMS),⁶ which is their own care management program analogous to that of PHPs. A similar program exists for attorneys known as Commission on Lawyer Assistance Programs (CoLAP).⁷ Fitness for duty and prevention of harm are major concerns in occupations such as those of physicians, commercial truck drivers, and people working in the nuclear power industry, all of whom have similar safety protections requiring no drug use.

A third fact that deserves special attention is that the unique system of care management for physicians began in the early 1970s. It grew out of employee assistance programs, led then and often now by physicians who are themselves in recovery from SUDs. Many of the successful addiction treatment tools used today come from extensive research of their use in PHPs. Contingency management, 12 steps, caduceus recovery, cognitive-behavioral therapy, and treatment outcomes defined in years are examples in which PHP research helped change treatment and long-term management of SUDs in non-PHP populations.

Dr. Polles and colleagues provide an impressive and comprehensive summary of the issues involved in the new interest in providing the physicians with OUD under PHP care management the option of using buprenorphine or methadone. Such a model within an abstinence-based framework is now being pioneered by a variety of programs, from COAT⁸ at West Virginia University, Morgantown, to the Hazelden Betty Ford Foundation.⁹ In those programs, patients with OUD are offered the option of using buprenorphine, methadone, or naltrexone as well as the option of using none of those medications in an extended abstinence-based intensive treatment. The authors impressively and fairly summarize the evidence on whether there are cognitive or behavioral deficits associated with the therapeutic use of either buprenorphine or methadone, which might make them unacceptable for physicians. The strongest evidence that these medicines are not necessary in the treatment of OUDs in PHPs is the outstanding outcomes PHPs produce without use of these two medications. If skeptical of the use of medications for OUD treatment in PHP care management, Dr. Polles and colleagues are open to experiments to test the effects of this option just as Florida PHP programs pioneered contracts that included mandatory naltrexone.¹⁰ West Virginia University, the Hazelden Betty Ford Foundation, and other programs should be tested to evaluate just how safe, effective, and attractive such an option would be to physicians.

Many, if not most, SUD treatment programs that use MAT are not associated with the intensive psychological treatment or extended participation in recovery support, such as the 12-step fellowships. MAT is viewed as a harm reduction strategy rather than conceptualized as an abstinence-oriented treatment. For example, there is seldom a “sobriety date” among individuals in MAT, i.e., the last day the individual used any substance of abuse, including alcohol and marijuana. These are, however, central features of PHP care, and they are features of the Hazelden Betty Ford Foundation’s definition of recovery¹¹ and use of MAT.

Dr. Polles and colleagues call attention to the unique care management of the PHP for all SUDs, not just for OUDs, because the PHPs set the standard for returning physicians to work who have the fitness and cognitive skills to first do no harm. They emphasize the importance of making sustained recovery the expected outcome of SUD treatment. There is a robust literature on the ways in which this distinctive system of care management shows the path forward for addiction treatment generally to regularly achieve 5-year recovery.¹² The current controversy over the potential use of buprenorphine and buprenorphine plus naloxone in PHPs is a useful entry into this far larger issue of the potential for PHPs to show the path forward for the addiction treatment field.
 

Dr. DuPont, the first director of the National Institute on Drug Abuse (NIDA), is president of the Institute for Behavior and Health Inc., a nonprofit drug-policy research organization in Rockville, Md. He has no disclosures. Dr. Gold is professor of psychiatry (adjunct) at Washington University in St. Louis. He is also the 17th Distinguished Alumni Professor at the University of Florida Gainesville. He has no disclosures.

References

1. Polles AG et al. J Neurol Sci. 2020 Jan 30;411:116714.

2. Oesterle TS et al. Mayo Clin Proc. 2019 Oct;94(10):2072-86.

3. Srivastava AB and Gold MS. Cerebrum. 2018 Sep-Oct; cer-13-8.

4. DuPont RL et al. J Subst Abuse Treat. 2009 Mar 1;36(2):159-71.

5. Merlo LJ et al. J Subst Abuse Treat. 2016 May 1;64:47-54.

6. Human Intervention Motivation Study (HIMS): An Occupational Substance Abuse Treatment Program.

7. Commission on Lawyer Assistance Programs (CoLAP).

8. Lander LR et al. J Neurol Sci. 2020;411:116712-8.

9. Klein AA et al. J Subst Abuse Treat. 2019;104:51-63.

10. Merlo LJ et al. J Addict Med. 2012;5(4):279-83.

11. Betty Ford Consensus Panel. J Subst Abuse Treat. 2007 Oct;33(3):221-8.

12. Carr GD et al. “Physician health programs: The U.S. model.” In KJ Brower and MB Riba, (eds.) Physician Mental Health and Well-Being (pp. 265-94). Cham, Switzerland: Springer International Publishing, 2017.

A new article in the Journal of the Neurological Sciences provides an impressive review of research on the complex impairments produced by a wide range of drugs of abuse with a close look at physicians and other health care professionals.¹

This review breaks new ground in outlining fitness for duty as an important outcome of the state physician health programs (PHPs). In addition, the review and case report by Alexandria G. Polles, MD, and colleagues are a response to the growing call for the state PHP system of care management to explicitly endorse the use of medication-assisted treatment, specifically the use of buprenorphine and methadone, in the treatment of physicians diagnosed with opioid use disorder (OUD). The article usefully situates the controversy in the context of other safety-sensitive jobs, including commercial pilots, truck drivers, and police, because of the elevated rate of substance use disorders among physicians and the safety-sensitive nature of the practice of medicine.

Medication-assisted treatment (MAT)² for opioid use disorders now dominates the field of treatment in terms of prescribing and also funding to address the opioid overdose crisis. MAT generally includes naltrexone and injectable naltrexone, though those antagonist medications have been used successfully for many decades by PHPs.³ However, to understand the controversy over the use of MAT in the care management of physicians first requires an understanding of state PHPs and how those programs oversee the care of physicians diagnosed with substance use disorders (SUDs), including OUDs.

A national blueprint study of PHPs showed that care begins with a formal diagnostic evaluation.⁴ Only when a diagnosis of an SUD is established is a physician referred to the attention of a state PHP, and a monitoring contract is signed. PHPs typically do not offer any direct treatment; instead, they manage the care of physician participants in programs in which the PHPs have confidence. Formal addiction treatment most often is 30 days of residential treatment, but many physicians receive intensive outpatient treatment.

After completing an episode of formal treatment, physicians are closely monitored, usually for 5 years, through random drug and alcohol tests, and work site monitors. They are required to engage in intensive recovery support, typically 12-step fellowships but also other alternative recovery support programs. Comorbid conditions, including mental health disorders, are also treated. Managing PHPs have no sanctions for noncompliance; however, importantly, they do offer a safe haven from state medical licensing boards for physicians who are compliant with their recommendations and who remain abstinent from any use of alcohol, marijuana, illicit drugs, or other nonmedical drug use.

The national blueprint study included 16 state PHPs and reviewed single episodes of PHP care for 908 physicians. Complete abstinence from any use of alcohol, marijuana, or other drugs was required of all physicians for monitoring periods of at least 5 years. During the extended period, 78% of the physicians did not have a single positive or missed test. Two-thirds of physicians who had one positive or missed test did not have a second. About a dozen publications have resulted from this national study, including an analysis of the roughly one-third of the physicians who were diagnosed with OUD.⁵

A sample of 702 PHP participants was grouped based on primary drug at intake: alcohol only, any opioid with or without alcohol, and nonopioid drugs. No significant differences were found among these groups in the percentage who completed PHP contracts, failed to complete their contract, or extended their contract and continued to be monitored. Only one physician received methadone to treat chronic pain. None received opioid agonists to treat their opioid use disorder. Opioid antagonist medication (naltrexone) was used for 40 physicians, or 5.7% of the total sample: 2 physicians (1%) from the alcohol-only group; 35 physicians (10.3%) from the any opioid group, and 3 physicians (1.9%) from nonopioid group.

The second fact that needs to be understood is that medical practice in relationship to SUDs is treated by state licensing boards as a safety-sensitive job, analogous to commercial airline pilots who have the Human Intervention Motivation Study (HIMS),⁶ which is their own care management program analogous to that of PHPs. A similar program exists for attorneys known as Commission on Lawyer Assistance Programs (CoLAP).⁷ Fitness for duty and prevention of harm are major concerns in occupations such as those of physicians, commercial truck drivers, and people working in the nuclear power industry, all of whom have similar safety protections requiring no drug use.

A third fact that deserves special attention is that the unique system of care management for physicians began in the early 1970s. It grew out of employee assistance programs, led then and often now by physicians who are themselves in recovery from SUDs. Many of the successful addiction treatment tools used today come from extensive research of their use in PHPs. Contingency management, 12 steps, caduceus recovery, cognitive-behavioral therapy, and treatment outcomes defined in years are examples in which PHP research helped change treatment and long-term management of SUDs in non-PHP populations.

Dr. Polles and colleagues provide an impressive and comprehensive summary of the issues involved in the new interest in providing the physicians with OUD under PHP care management the option of using buprenorphine or methadone. Such a model within an abstinence-based framework is now being pioneered by a variety of programs, from COAT⁸ at West Virginia University, Morgantown, to the Hazelden Betty Ford Foundation.⁹ In those programs, patients with OUD are offered the option of using buprenorphine, methadone, or naltrexone as well as the option of using none of those medications in an extended abstinence-based intensive treatment. The authors impressively and fairly summarize the evidence on whether there are cognitive or behavioral deficits associated with the therapeutic use of either buprenorphine or methadone, which might make them unacceptable for physicians. The strongest evidence that these medicines are not necessary in the treatment of OUDs in PHPs is the outstanding outcomes PHPs produce without use of these two medications. If skeptical of the use of medications for OUD treatment in PHP care management, Dr. Polles and colleagues are open to experiments to test the effects of this option just as Florida PHP programs pioneered contracts that included mandatory naltrexone.¹⁰ West Virginia University, the Hazelden Betty Ford Foundation, and other programs should be tested to evaluate just how safe, effective, and attractive such an option would be to physicians.

Many, if not most, SUD treatment programs that use MAT are not associated with the intensive psychological treatment or extended participation in recovery support, such as the 12-step fellowships. MAT is viewed as a harm reduction strategy rather than conceptualized as an abstinence-oriented treatment. For example, there is seldom a “sobriety date” among individuals in MAT, i.e., the last day the individual used any substance of abuse, including alcohol and marijuana. These are, however, central features of PHP care, and they are features of the Hazelden Betty Ford Foundation’s definition of recovery¹¹ and use of MAT.

Dr. Polles and colleagues call attention to the unique care management of the PHP for all SUDs, not just for OUDs, because the PHPs set the standard for returning physicians to work who have the fitness and cognitive skills to first do no harm. They emphasize the importance of making sustained recovery the expected outcome of SUD treatment. There is a robust literature on the ways in which this distinctive system of care management shows the path forward for addiction treatment generally to regularly achieve 5-year recovery.¹² The current controversy over the potential use of buprenorphine and buprenorphine plus naloxone in PHPs is a useful entry into this far larger issue of the potential for PHPs to show the path forward for the addiction treatment field.
 

Dr. DuPont, the first director of the National Institute on Drug Abuse (NIDA), is president of the Institute for Behavior and Health Inc., a nonprofit drug-policy research organization in Rockville, Md. He has no disclosures. Dr. Gold is professor of psychiatry (adjunct) at Washington University in St. Louis. He is also the 17th Distinguished Alumni Professor at the University of Florida Gainesville. He has no disclosures.

References

1. Polles AG et al. J Neurol Sci. 2020 Jan 30;411:116714.

2. Oesterle TS et al. Mayo Clin Proc. 2019 Oct;94(10):2072-86.

3. Srivastava AB and Gold MS. Cerebrum. 2018 Sep-Oct; cer-13-8.

4. DuPont RL et al. J Subst Abuse Treat. 2009 Mar 1;36(2):159-71.

5. Merlo LJ et al. J Subst Abuse Treat. 2016 May 1;64:47-54.

6. Human Intervention Motivation Study (HIMS): An Occupational Substance Abuse Treatment Program.

7. Commission on Lawyer Assistance Programs (CoLAP).

8. Lander LR et al. J Neurol Sci. 2020;411:116712-8.

9. Klein AA et al. J Subst Abuse Treat. 2019;104:51-63.

10. Merlo LJ et al. J Addict Med. 2012;5(4):279-83.

11. Betty Ford Consensus Panel. J Subst Abuse Treat. 2007 Oct;33(3):221-8.

12. Carr GD et al. “Physician health programs: The U.S. model.” In KJ Brower and MB Riba, (eds.) Physician Mental Health and Well-Being (pp. 265-94). Cham, Switzerland: Springer International Publishing, 2017.

A significant proportion of patients with major depressive disorder (MDD) either do not respond or have partial responses to the currently available Food and Drug Administration–approved antidepressants.

In controlled clinical trials, there is about a 40%-60% symptom remission rate with a 20%-40% remission rate in community-based treatment settings. Not only do those medications lack efficacy in treating MDD, but there are currently no cures for this debilitating illness. As a result, many patients with MDD continue to suffer.

In response to those poor outcomes, researchers and clinicians have developed algorithms aimed at diagnosing the condition of treatment-resistant depression (TRD),¹ which enable opportunities for various treatment methods.² Several studies underway across the United States are testing what some might consider medically invasive procedures, such as electroconvulsive therapy (ECT), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT often is considered the gold standard of treatment response, but it requires anesthesia, induces a convulsion, and needs a willing patient and clinician. DBS has been used more widely in neurological treatment of movement disorders. Pioneering neurosurgical treatment for TRD reported recently in the American Journal of Psychiatry found that DBS of an area in the brain called the subcallosal cingulate produces clear and apparently sustained antidepressant effects.³ VNS⁴ remains an experimental treatment for MDD. TMS is safe, noninvasive, and approved by the FDA for depression, but responses appear similar to those with usual antidepressants.

It is not surprising, given those outcomes, that ketamine was fast-tracked in 2016. The enthusiasm related to ketamine’s effect on MDD and TRD has grown over time as more research findings reach the public. While it is unknown how ketamine affects the biological neural network, a single intravenous dose of ketamine (0.5 mg/kg) in patients diagnosed with TRD can lead to improved depression symptoms outcomes within a few hours – and those effects were sustained in 65%-70% of patients at 24 hours. Antidepressants take many weeks to show effects. Ketamine’s exciting findings also offered hope to clinicians and patients trying to manage suicidal thoughts and plans. Ketamine was quickly approved by the FDA as a nasal spray medication.

Now, in another encouraging development, the FDA has granted the Usona Institute Breakthrough Therapy designation for psilocybin for the treatment of MDD. The medical benefits of psilocybin, or “magic mushrooms,” has a long empirical history in our literature. Most recently, psilocybin was featured on “60 Minutes,”⁵ and in his book, “How to Change Your Mind,”⁶Michael Pollan details how psychedelic drugs where used to investigate and treat psychiatric disorders until the 1960s, when street use and unsupervised administration led to restrictions on their research and clinical use.

We are now in a renaissance period⁷ where psychedelic drugs are being reestablished as a new approach to very important public health problems. With protocol-driven specific trials, they might become critical medications for a wide range of psychiatric disorders, such as depression, PTSD, anxiety, and addictions. Exciting findings are coming from Roland R. Griffiths, PhD, and his team at Johns Hopkins University’s Center for Psychedelic and Consciousness Research. In a recent study⁸ with cancer patients suffering from depression and anxiety, carefully administered, specific and supervised high doses of psilocybin produced decreases in depression and anxiety, and increases in quality of life and life meaning attitudes. Those improved attitudes, behavior, and responses were sustained by 80% of the sample 6 months post treatment.

Dr. Griffiths’ center is collaborating with Usona, and this collaboration should result in specific guidelines for dose, safety, and protection against abuse and diversion,⁹ as the study and FDA trials for ketamine have as well.¹⁰ It is very encouraging that psychedelic drugs are receiving fast-track designations, and this development reflects a shift in the risk-benefit considerations taking place in our society. Changing attitudes about depression and other psychiatric diseases are encouraging new approaches and new treatments. Psychiatric suffering and pain are being prioritized in research and appreciated by the general public as devastating. Serious, random assignment placebo-controlled and double- blind research studies will define just how valuable these medications might be, what is the safe dose and duration, and for whom they might prove more effective than existing treatments.

The process will take some time. And it is worth remembering that, although research has been promising,¹¹ the number of patients studied, research design, and outcomes are not yet proven for psilosybin.¹² The FDA fast-track makes sense, and the agency should continue supporting these efforts for psychedelics. In fact, we think the FDA also should support the promising trials of nitrous oxide¹³ (laughing gas), and other safe and novel approaches to successfully treat refractory depression. While we wait for personalized psychiatric medicines to be developed and validated through the long process of FDA approval, we will at least have a larger suite of treatment options to match patients with, along with some new algorithms that treat MDD,* TRD, and other disorders just are around the corner.

Dr. Patterson Silver Wolf is an associate professor at Washington University in St. Louis’s Brown School of Social Work. He is a training faculty member for two National Institutes of Health–funded (T32) training programs and serves as the director of the Community Academic Partnership on Addiction (CAPA). He’s chief research officer at the new CAPA Clinic, a teaching addiction treatment facility that is incorporating and testing various performance-based practice technology tools to respond to the opioid crisis and improve addiction treatment outcomes. Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He has written several books and published more than 1,000 peer-reviewed scientific articles, texts, and practice guidelines.

References

1. Sackeim HA et al. J Psychiatr Res. 2019 Jun;113:125-36.

2. Conway CR et al. J Clin Psychiatry. 25 Nov;76(11):1569-70.

3. Crowell AL et al. Am J Psychiatry. 2019 Oct 4. doi: 10.1176.appi.ajp.2019.18121427.

4. Kumar A et al. Neuropsychiatr Dis Treat. 2019 Feb 13;15:457-68.

5. Psilocybin sessions: Psychedelics could help people with addiction and anxiety. “60 Minutes” CBS News. 2019 Oct 13.

6. Pollan M. How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (Penguin Random House, 2018).

7. Nutt D. Dialogues Clin Neurosci. 2019;21(2):139-47.

8. Griffiths RR et al. J Psychopharmacol 2016 Dec;30(12):1181-97.

9. Johnson MW et al. Neuropsychopharmacology. 2018 Nov;142:143-66.

10. Schwenk ES et al. Reg Anesth Pain Med. 2018 Jul;43(5):456-66.

11. Johnson MW et al. Neurotherapeutics. 2017 Jul;14(3):734-40.

12. Mutonni S et al. J Affect Disord. 2019 Nov.1;258:11-24.

13. Nagele P et al. J Clin Psychopharmacol. 2018 Apr;38(2):144-8.

*Correction, 1/9/2020: An earlier version of this story misidentified the intended disease state.

A significant proportion of patients with major depressive disorder (MDD) either do not respond or have partial responses to the currently available Food and Drug Administration–approved antidepressants.

In controlled clinical trials, there is about a 40%-60% symptom remission rate with a 20%-40% remission rate in community-based treatment settings. Not only do those medications lack efficacy in treating MDD, but there are currently no cures for this debilitating illness. As a result, many patients with MDD continue to suffer.

In response to those poor outcomes, researchers and clinicians have developed algorithms aimed at diagnosing the condition of treatment-resistant depression (TRD),¹ which enable opportunities for various treatment methods.² Several studies underway across the United States are testing what some might consider medically invasive procedures, such as electroconvulsive therapy (ECT), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT often is considered the gold standard of treatment response, but it requires anesthesia, induces a convulsion, and needs a willing patient and clinician. DBS has been used more widely in neurological treatment of movement disorders. Pioneering neurosurgical treatment for TRD reported recently in the American Journal of Psychiatry found that DBS of an area in the brain called the subcallosal cingulate produces clear and apparently sustained antidepressant effects.³ VNS⁴ remains an experimental treatment for MDD. TMS is safe, noninvasive, and approved by the FDA for depression, but responses appear similar to those with usual antidepressants.

It is not surprising, given those outcomes, that ketamine was fast-tracked in 2016. The enthusiasm related to ketamine’s effect on MDD and TRD has grown over time as more research findings reach the public. While it is unknown how ketamine affects the biological neural network, a single intravenous dose of ketamine (0.5 mg/kg) in patients diagnosed with TRD can lead to improved depression symptoms outcomes within a few hours – and those effects were sustained in 65%-70% of patients at 24 hours. Antidepressants take many weeks to show effects. Ketamine’s exciting findings also offered hope to clinicians and patients trying to manage suicidal thoughts and plans. Ketamine was quickly approved by the FDA as a nasal spray medication.

Now, in another encouraging development, the FDA has granted the Usona Institute Breakthrough Therapy designation for psilocybin for the treatment of MDD. The medical benefits of psilocybin, or “magic mushrooms,” has a long empirical history in our literature. Most recently, psilocybin was featured on “60 Minutes,”⁵ and in his book, “How to Change Your Mind,”⁶Michael Pollan details how psychedelic drugs where used to investigate and treat psychiatric disorders until the 1960s, when street use and unsupervised administration led to restrictions on their research and clinical use.

We are now in a renaissance period⁷ where psychedelic drugs are being reestablished as a new approach to very important public health problems. With protocol-driven specific trials, they might become critical medications for a wide range of psychiatric disorders, such as depression, PTSD, anxiety, and addictions. Exciting findings are coming from Roland R. Griffiths, PhD, and his team at Johns Hopkins University’s Center for Psychedelic and Consciousness Research. In a recent study⁸ with cancer patients suffering from depression and anxiety, carefully administered, specific and supervised high doses of psilocybin produced decreases in depression and anxiety, and increases in quality of life and life meaning attitudes. Those improved attitudes, behavior, and responses were sustained by 80% of the sample 6 months post treatment.

Dr. Griffiths’ center is collaborating with Usona, and this collaboration should result in specific guidelines for dose, safety, and protection against abuse and diversion,⁹ as the study and FDA trials for ketamine have as well.¹⁰ It is very encouraging that psychedelic drugs are receiving fast-track designations, and this development reflects a shift in the risk-benefit considerations taking place in our society. Changing attitudes about depression and other psychiatric diseases are encouraging new approaches and new treatments. Psychiatric suffering and pain are being prioritized in research and appreciated by the general public as devastating. Serious, random assignment placebo-controlled and double- blind research studies will define just how valuable these medications might be, what is the safe dose and duration, and for whom they might prove more effective than existing treatments.

The process will take some time. And it is worth remembering that, although research has been promising,¹¹ the number of patients studied, research design, and outcomes are not yet proven for psilosybin.¹² The FDA fast-track makes sense, and the agency should continue supporting these efforts for psychedelics. In fact, we think the FDA also should support the promising trials of nitrous oxide¹³ (laughing gas), and other safe and novel approaches to successfully treat refractory depression. While we wait for personalized psychiatric medicines to be developed and validated through the long process of FDA approval, we will at least have a larger suite of treatment options to match patients with, along with some new algorithms that treat MDD,* TRD, and other disorders just are around the corner.

Dr. Patterson Silver Wolf is an associate professor at Washington University in St. Louis’s Brown School of Social Work. He is a training faculty member for two National Institutes of Health–funded (T32) training programs and serves as the director of the Community Academic Partnership on Addiction (CAPA). He’s chief research officer at the new CAPA Clinic, a teaching addiction treatment facility that is incorporating and testing various performance-based practice technology tools to respond to the opioid crisis and improve addiction treatment outcomes. Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He has written several books and published more than 1,000 peer-reviewed scientific articles, texts, and practice guidelines.

References

1. Sackeim HA et al. J Psychiatr Res. 2019 Jun;113:125-36.

2. Conway CR et al. J Clin Psychiatry. 25 Nov;76(11):1569-70.

3. Crowell AL et al. Am J Psychiatry. 2019 Oct 4. doi: 10.1176.appi.ajp.2019.18121427.

4. Kumar A et al. Neuropsychiatr Dis Treat. 2019 Feb 13;15:457-68.

5. Psilocybin sessions: Psychedelics could help people with addiction and anxiety. “60 Minutes” CBS News. 2019 Oct 13.

6. Pollan M. How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (Penguin Random House, 2018).

7. Nutt D. Dialogues Clin Neurosci. 2019;21(2):139-47.

8. Griffiths RR et al. J Psychopharmacol 2016 Dec;30(12):1181-97.

9. Johnson MW et al. Neuropsychopharmacology. 2018 Nov;142:143-66.

10. Schwenk ES et al. Reg Anesth Pain Med. 2018 Jul;43(5):456-66.

11. Johnson MW et al. Neurotherapeutics. 2017 Jul;14(3):734-40.

12. Mutonni S et al. J Affect Disord. 2019 Nov.1;258:11-24.

13. Nagele P et al. J Clin Psychopharmacol. 2018 Apr;38(2):144-8.

*Correction, 1/9/2020: An earlier version of this story misidentified the intended disease state.

A significant proportion of patients with major depressive disorder (MDD) either do not respond or have partial responses to the currently available Food and Drug Administration–approved antidepressants.

In controlled clinical trials, there is about a 40%-60% symptom remission rate with a 20%-40% remission rate in community-based treatment settings. Not only do those medications lack efficacy in treating MDD, but there are currently no cures for this debilitating illness. As a result, many patients with MDD continue to suffer.

In response to those poor outcomes, researchers and clinicians have developed algorithms aimed at diagnosing the condition of treatment-resistant depression (TRD),¹ which enable opportunities for various treatment methods.² Several studies underway across the United States are testing what some might consider medically invasive procedures, such as electroconvulsive therapy (ECT), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT often is considered the gold standard of treatment response, but it requires anesthesia, induces a convulsion, and needs a willing patient and clinician. DBS has been used more widely in neurological treatment of movement disorders. Pioneering neurosurgical treatment for TRD reported recently in the American Journal of Psychiatry found that DBS of an area in the brain called the subcallosal cingulate produces clear and apparently sustained antidepressant effects.³ VNS⁴ remains an experimental treatment for MDD. TMS is safe, noninvasive, and approved by the FDA for depression, but responses appear similar to those with usual antidepressants.

It is not surprising, given those outcomes, that ketamine was fast-tracked in 2016. The enthusiasm related to ketamine’s effect on MDD and TRD has grown over time as more research findings reach the public. While it is unknown how ketamine affects the biological neural network, a single intravenous dose of ketamine (0.5 mg/kg) in patients diagnosed with TRD can lead to improved depression symptoms outcomes within a few hours – and those effects were sustained in 65%-70% of patients at 24 hours. Antidepressants take many weeks to show effects. Ketamine’s exciting findings also offered hope to clinicians and patients trying to manage suicidal thoughts and plans. Ketamine was quickly approved by the FDA as a nasal spray medication.

Now, in another encouraging development, the FDA has granted the Usona Institute Breakthrough Therapy designation for psilocybin for the treatment of MDD. The medical benefits of psilocybin, or “magic mushrooms,” has a long empirical history in our literature. Most recently, psilocybin was featured on “60 Minutes,”⁵ and in his book, “How to Change Your Mind,”⁶Michael Pollan details how psychedelic drugs where used to investigate and treat psychiatric disorders until the 1960s, when street use and unsupervised administration led to restrictions on their research and clinical use.

We are now in a renaissance period⁷ where psychedelic drugs are being reestablished as a new approach to very important public health problems. With protocol-driven specific trials, they might become critical medications for a wide range of psychiatric disorders, such as depression, PTSD, anxiety, and addictions. Exciting findings are coming from Roland R. Griffiths, PhD, and his team at Johns Hopkins University’s Center for Psychedelic and Consciousness Research. In a recent study⁸ with cancer patients suffering from depression and anxiety, carefully administered, specific and supervised high doses of psilocybin produced decreases in depression and anxiety, and increases in quality of life and life meaning attitudes. Those improved attitudes, behavior, and responses were sustained by 80% of the sample 6 months post treatment.

Dr. Griffiths’ center is collaborating with Usona, and this collaboration should result in specific guidelines for dose, safety, and protection against abuse and diversion,⁹ as the study and FDA trials for ketamine have as well.¹⁰ It is very encouraging that psychedelic drugs are receiving fast-track designations, and this development reflects a shift in the risk-benefit considerations taking place in our society. Changing attitudes about depression and other psychiatric diseases are encouraging new approaches and new treatments. Psychiatric suffering and pain are being prioritized in research and appreciated by the general public as devastating. Serious, random assignment placebo-controlled and double- blind research studies will define just how valuable these medications might be, what is the safe dose and duration, and for whom they might prove more effective than existing treatments.

The process will take some time. And it is worth remembering that, although research has been promising,¹¹ the number of patients studied, research design, and outcomes are not yet proven for psilosybin.¹² The FDA fast-track makes sense, and the agency should continue supporting these efforts for psychedelics. In fact, we think the FDA also should support the promising trials of nitrous oxide¹³ (laughing gas), and other safe and novel approaches to successfully treat refractory depression. While we wait for personalized psychiatric medicines to be developed and validated through the long process of FDA approval, we will at least have a larger suite of treatment options to match patients with, along with some new algorithms that treat MDD,* TRD, and other disorders just are around the corner.

Dr. Patterson Silver Wolf is an associate professor at Washington University in St. Louis’s Brown School of Social Work. He is a training faculty member for two National Institutes of Health–funded (T32) training programs and serves as the director of the Community Academic Partnership on Addiction (CAPA). He’s chief research officer at the new CAPA Clinic, a teaching addiction treatment facility that is incorporating and testing various performance-based practice technology tools to respond to the opioid crisis and improve addiction treatment outcomes. Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He has written several books and published more than 1,000 peer-reviewed scientific articles, texts, and practice guidelines.

References

1. Sackeim HA et al. J Psychiatr Res. 2019 Jun;113:125-36.

2. Conway CR et al. J Clin Psychiatry. 25 Nov;76(11):1569-70.

3. Crowell AL et al. Am J Psychiatry. 2019 Oct 4. doi: 10.1176.appi.ajp.2019.18121427.

4. Kumar A et al. Neuropsychiatr Dis Treat. 2019 Feb 13;15:457-68.

5. Psilocybin sessions: Psychedelics could help people with addiction and anxiety. “60 Minutes” CBS News. 2019 Oct 13.

6. Pollan M. How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (Penguin Random House, 2018).

7. Nutt D. Dialogues Clin Neurosci. 2019;21(2):139-47.

8. Griffiths RR et al. J Psychopharmacol 2016 Dec;30(12):1181-97.

9. Johnson MW et al. Neuropsychopharmacology. 2018 Nov;142:143-66.

10. Schwenk ES et al. Reg Anesth Pain Med. 2018 Jul;43(5):456-66.

11. Johnson MW et al. Neurotherapeutics. 2017 Jul;14(3):734-40.

12. Mutonni S et al. J Affect Disord. 2019 Nov.1;258:11-24.

13. Nagele P et al. J Clin Psychopharmacol. 2018 Apr;38(2):144-8.

*Correction, 1/9/2020: An earlier version of this story misidentified the intended disease state.

What do Queen Silvia of Sweden, Pope Francis, and the first director of the National Institute on Drug Abuse (NIDA) have in common? They all share a deep and sobering commitment to fighting the global disease of addiction.

Robert L. DuPont, MD, has written a beautiful and surprisingly spiritual guide into the American addiction epidemic. He is the author of “The Selfish Brain: Learning From Addiction” (Center City, Minn.: Hazelden, 2000) and with his newest publication, “Chemical Slavery: Understanding Addiction and Stopping the Drug Epidemic” (Institute for Behavior and Health, 2018), he writes a clear-eyed tome detailing the history of drug and alcohol use within the United States and the current state of America’s drug epidemic.

Dr. DuPont is well known within the American addiction community as NIDA’s first director and as the second drug czar, under two presidents, Richard M. Nixon and Gerald R. Ford. His breadth of experience, spanning 50-plus years, dates from his early career with the District of Columbia Department of Corrections, into his work in public policy on drugs and alcohol. This experience infuses his book with the hard science of addiction and the common-sense compassion required to shepherd people into recovery. One of us has worked with and been influenced by him since the 1970s. The other, also an addiction psychiatrist, finished this book both invigorated and compelled to say thank you to Dr. DuPont and his life’s work! He remains relevant, insightful, and always optimistic about the future of addiction treatment.
 

Harm reduction explored

The book begins with a cogent history of drug and alcohol use in America. Dr. DuPont details this as well as the public policies that have evolved to address them. He weaves into our national history reasoning behind why, as a “mass consumer” culture, we are more prone to addiction than ever before. The loss of cultural and societal pressures has a role to play in the rise along with genetics and environmental stress. The adolescent brain is prominently discussed throughout this first section as a highly vulnerable organ that can lead to lifelong addiction if primed early by addictive chemicals.

Dr. DuPont addresses the biology of addiction, delving into both the biological mechanisms within the brain, making those details accessible and understandable – to a practicing physician as well as a family member or patient struggling with addiction.

He also addresses harm reduction, a fairly new concept within the field. Harm reduction has taken on more prominence with localities across the country providing people with addictions with safe places and clean needles to continue their substance use without risks of serious or life-threatening diseases and crime. He challenges the idea that harm reduction is active recovery from substance addiction. Instead, he opines that harm reduction must be tethered to and must lead to real recovery work or it risks becoming an organizational enabling of the addict’s behavior.

Dr. DuPont pulls no punches with his language. He uses words such as “fatal,” “addict,” and “alcoholic.” He addresses the concerns by some in the field that those kinds of words are harsh, derogatory, and prejudicial by calling out addiction as a disease hallmarked primarily by loss of control and by dishonesty. To shun those words is to perpetuate the disease, delaying life-saving treatment.

Compassion is a theme throughout. He says we must stigmatize the addiction but not the addict. He advocates for real consequences to addictive behaviors as a key to getting addicted physicians and others with this disease into recovery. Treatment works, but we also have studied specific approaches that work and why.¹ His writing conveys a genuine empathy for his patients and argues that treatment is delayed when serious and negative consequences for patients are removed.
 

Focus on prevention

A clear passion for prevention is evident within his chapters on youth addiction. For adolescents, Dr. DuPont presents a “One Choice approach,” which requires complete abstinence from alcohol, tobacco, and marijuana. He also presents science showing that patients younger than age 21 will have a greater risk of developing lifelong and debilitating addictions if they use these chemicals prior to this age. His emphasis for the One Choice approach carries ramifications throughout the primary care, pediatric, and family practice communities.

Dr. DuPont is nothing if not an optimist. Though he clearly defines addiction as an often-fatal disease, he remains positive about the future of addiction treatment, both with changes in public policy and with advancements in the medicine of addiction. He makes a compelling argument regarding Sweden’s approach to the drug problem, citing Queen Silvia’s lifelong commitment to prevent, control, and treat drug and alcohol addiction. Sweden’s model is, indeed, intriguing, and that country’s outcomes present a strong argument for the marriage of the criminal justice system with medical intervention – an approach that the United States has adopted only in a patchwork fashion.

Courtesy Dr. Jorandby

The book describes controversies throughout, such as Dr. DuPont’s furtherance of our work on how best to treat dual disorders.² He is not impressed with the self-medication hypothesis as well as the dive into the U.S. national medical marijuana experiment. We had looked at college students having new-onset memory or attention-deficit/hyperactivity problems, only to find that it was likely psychostimulant seeking to reverse marijuana effects.³ Physicians, families, and patients would be well served to review his arguments on the clear definition of “medicine” with regard to marijuana and the risks taken when we medicalize a known addictive chemical. He tackles the push for legalization as well, and the risks of increased societal acceptance and commercialization power that comes with this. He has led the field in thinking about the role of early drug exposure, brain training, and hijacking in the addictive process. This gateway hypothesis can occur whether the first teen drugs are cannabis or tobacco⁴ or alcohol.

Dr. DuPont finishes his work with a detailed biography, in which he addresses his family history of addiction, and his own overuse of alcohol in his late teens and early 20s as well as a confession of onetime use of marijuana during medical school. He always has led the field in trying to explain the disease of addiction, intervention, treatment, and recovery. But this self-reflection and brutal honesty is refreshing and in step with themes in his book, which promote the idea of recovery as an embrace of honesty, in mind, body, and spirit.
 

Dr. Jorandby trained in addiction psychiatry at Yale University, New Haven, Conn., and works as an addiction psychiatrist with Amen Clinics in Washington. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis.

References

1. J Subst Abuse Treat. 2009 Mar;36(2):159-71.

2. J Addict Dis. 2007;26 Suppl 1:13-23.

3. Am J Psychiatry. 2007 Jun;164(6):973.

4. J Addict Dis. 2003;22(3):51-62.

What do Queen Silvia of Sweden, Pope Francis, and the first director of the National Institute on Drug Abuse (NIDA) have in common? They all share a deep and sobering commitment to fighting the global disease of addiction.

Robert L. DuPont, MD, has written a beautiful and surprisingly spiritual guide into the American addiction epidemic. He is the author of “The Selfish Brain: Learning From Addiction” (Center City, Minn.: Hazelden, 2000) and with his newest publication, “Chemical Slavery: Understanding Addiction and Stopping the Drug Epidemic” (Institute for Behavior and Health, 2018), he writes a clear-eyed tome detailing the history of drug and alcohol use within the United States and the current state of America’s drug epidemic.

Dr. DuPont is well known within the American addiction community as NIDA’s first director and as the second drug czar, under two presidents, Richard M. Nixon and Gerald R. Ford. His breadth of experience, spanning 50-plus years, dates from his early career with the District of Columbia Department of Corrections, into his work in public policy on drugs and alcohol. This experience infuses his book with the hard science of addiction and the common-sense compassion required to shepherd people into recovery. One of us has worked with and been influenced by him since the 1970s. The other, also an addiction psychiatrist, finished this book both invigorated and compelled to say thank you to Dr. DuPont and his life’s work! He remains relevant, insightful, and always optimistic about the future of addiction treatment.
 

Harm reduction explored

The book begins with a cogent history of drug and alcohol use in America. Dr. DuPont details this as well as the public policies that have evolved to address them. He weaves into our national history reasoning behind why, as a “mass consumer” culture, we are more prone to addiction than ever before. The loss of cultural and societal pressures has a role to play in the rise along with genetics and environmental stress. The adolescent brain is prominently discussed throughout this first section as a highly vulnerable organ that can lead to lifelong addiction if primed early by addictive chemicals.

Dr. DuPont addresses the biology of addiction, delving into both the biological mechanisms within the brain, making those details accessible and understandable – to a practicing physician as well as a family member or patient struggling with addiction.

He also addresses harm reduction, a fairly new concept within the field. Harm reduction has taken on more prominence with localities across the country providing people with addictions with safe places and clean needles to continue their substance use without risks of serious or life-threatening diseases and crime. He challenges the idea that harm reduction is active recovery from substance addiction. Instead, he opines that harm reduction must be tethered to and must lead to real recovery work or it risks becoming an organizational enabling of the addict’s behavior.

Dr. DuPont pulls no punches with his language. He uses words such as “fatal,” “addict,” and “alcoholic.” He addresses the concerns by some in the field that those kinds of words are harsh, derogatory, and prejudicial by calling out addiction as a disease hallmarked primarily by loss of control and by dishonesty. To shun those words is to perpetuate the disease, delaying life-saving treatment.

Compassion is a theme throughout. He says we must stigmatize the addiction but not the addict. He advocates for real consequences to addictive behaviors as a key to getting addicted physicians and others with this disease into recovery. Treatment works, but we also have studied specific approaches that work and why.¹ His writing conveys a genuine empathy for his patients and argues that treatment is delayed when serious and negative consequences for patients are removed.
 

Focus on prevention

A clear passion for prevention is evident within his chapters on youth addiction. For adolescents, Dr. DuPont presents a “One Choice approach,” which requires complete abstinence from alcohol, tobacco, and marijuana. He also presents science showing that patients younger than age 21 will have a greater risk of developing lifelong and debilitating addictions if they use these chemicals prior to this age. His emphasis for the One Choice approach carries ramifications throughout the primary care, pediatric, and family practice communities.

Dr. DuPont is nothing if not an optimist. Though he clearly defines addiction as an often-fatal disease, he remains positive about the future of addiction treatment, both with changes in public policy and with advancements in the medicine of addiction. He makes a compelling argument regarding Sweden’s approach to the drug problem, citing Queen Silvia’s lifelong commitment to prevent, control, and treat drug and alcohol addiction. Sweden’s model is, indeed, intriguing, and that country’s outcomes present a strong argument for the marriage of the criminal justice system with medical intervention – an approach that the United States has adopted only in a patchwork fashion.

Courtesy Dr. Jorandby

The book describes controversies throughout, such as Dr. DuPont’s furtherance of our work on how best to treat dual disorders.² He is not impressed with the self-medication hypothesis as well as the dive into the U.S. national medical marijuana experiment. We had looked at college students having new-onset memory or attention-deficit/hyperactivity problems, only to find that it was likely psychostimulant seeking to reverse marijuana effects.³ Physicians, families, and patients would be well served to review his arguments on the clear definition of “medicine” with regard to marijuana and the risks taken when we medicalize a known addictive chemical. He tackles the push for legalization as well, and the risks of increased societal acceptance and commercialization power that comes with this. He has led the field in thinking about the role of early drug exposure, brain training, and hijacking in the addictive process. This gateway hypothesis can occur whether the first teen drugs are cannabis or tobacco⁴ or alcohol.

Dr. DuPont finishes his work with a detailed biography, in which he addresses his family history of addiction, and his own overuse of alcohol in his late teens and early 20s as well as a confession of onetime use of marijuana during medical school. He always has led the field in trying to explain the disease of addiction, intervention, treatment, and recovery. But this self-reflection and brutal honesty is refreshing and in step with themes in his book, which promote the idea of recovery as an embrace of honesty, in mind, body, and spirit.
 

Dr. Jorandby trained in addiction psychiatry at Yale University, New Haven, Conn., and works as an addiction psychiatrist with Amen Clinics in Washington. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis.

References

1. J Subst Abuse Treat. 2009 Mar;36(2):159-71.

2. J Addict Dis. 2007;26 Suppl 1:13-23.

3. Am J Psychiatry. 2007 Jun;164(6):973.

4. J Addict Dis. 2003;22(3):51-62.

What do Queen Silvia of Sweden, Pope Francis, and the first director of the National Institute on Drug Abuse (NIDA) have in common? They all share a deep and sobering commitment to fighting the global disease of addiction.

Robert L. DuPont, MD, has written a beautiful and surprisingly spiritual guide into the American addiction epidemic. He is the author of “The Selfish Brain: Learning From Addiction” (Center City, Minn.: Hazelden, 2000) and with his newest publication, “Chemical Slavery: Understanding Addiction and Stopping the Drug Epidemic” (Institute for Behavior and Health, 2018), he writes a clear-eyed tome detailing the history of drug and alcohol use within the United States and the current state of America’s drug epidemic.

Dr. DuPont is well known within the American addiction community as NIDA’s first director and as the second drug czar, under two presidents, Richard M. Nixon and Gerald R. Ford. His breadth of experience, spanning 50-plus years, dates from his early career with the District of Columbia Department of Corrections, into his work in public policy on drugs and alcohol. This experience infuses his book with the hard science of addiction and the common-sense compassion required to shepherd people into recovery. One of us has worked with and been influenced by him since the 1970s. The other, also an addiction psychiatrist, finished this book both invigorated and compelled to say thank you to Dr. DuPont and his life’s work! He remains relevant, insightful, and always optimistic about the future of addiction treatment.
 

Harm reduction explored

The book begins with a cogent history of drug and alcohol use in America. Dr. DuPont details this as well as the public policies that have evolved to address them. He weaves into our national history reasoning behind why, as a “mass consumer” culture, we are more prone to addiction than ever before. The loss of cultural and societal pressures has a role to play in the rise along with genetics and environmental stress. The adolescent brain is prominently discussed throughout this first section as a highly vulnerable organ that can lead to lifelong addiction if primed early by addictive chemicals.

Dr. DuPont addresses the biology of addiction, delving into both the biological mechanisms within the brain, making those details accessible and understandable – to a practicing physician as well as a family member or patient struggling with addiction.

He also addresses harm reduction, a fairly new concept within the field. Harm reduction has taken on more prominence with localities across the country providing people with addictions with safe places and clean needles to continue their substance use without risks of serious or life-threatening diseases and crime. He challenges the idea that harm reduction is active recovery from substance addiction. Instead, he opines that harm reduction must be tethered to and must lead to real recovery work or it risks becoming an organizational enabling of the addict’s behavior.

Dr. DuPont pulls no punches with his language. He uses words such as “fatal,” “addict,” and “alcoholic.” He addresses the concerns by some in the field that those kinds of words are harsh, derogatory, and prejudicial by calling out addiction as a disease hallmarked primarily by loss of control and by dishonesty. To shun those words is to perpetuate the disease, delaying life-saving treatment.

Compassion is a theme throughout. He says we must stigmatize the addiction but not the addict. He advocates for real consequences to addictive behaviors as a key to getting addicted physicians and others with this disease into recovery. Treatment works, but we also have studied specific approaches that work and why.¹ His writing conveys a genuine empathy for his patients and argues that treatment is delayed when serious and negative consequences for patients are removed.
 

Focus on prevention

A clear passion for prevention is evident within his chapters on youth addiction. For adolescents, Dr. DuPont presents a “One Choice approach,” which requires complete abstinence from alcohol, tobacco, and marijuana. He also presents science showing that patients younger than age 21 will have a greater risk of developing lifelong and debilitating addictions if they use these chemicals prior to this age. His emphasis for the One Choice approach carries ramifications throughout the primary care, pediatric, and family practice communities.

Dr. DuPont is nothing if not an optimist. Though he clearly defines addiction as an often-fatal disease, he remains positive about the future of addiction treatment, both with changes in public policy and with advancements in the medicine of addiction. He makes a compelling argument regarding Sweden’s approach to the drug problem, citing Queen Silvia’s lifelong commitment to prevent, control, and treat drug and alcohol addiction. Sweden’s model is, indeed, intriguing, and that country’s outcomes present a strong argument for the marriage of the criminal justice system with medical intervention – an approach that the United States has adopted only in a patchwork fashion.

Courtesy Dr. Jorandby

The book describes controversies throughout, such as Dr. DuPont’s furtherance of our work on how best to treat dual disorders.² He is not impressed with the self-medication hypothesis as well as the dive into the U.S. national medical marijuana experiment. We had looked at college students having new-onset memory or attention-deficit/hyperactivity problems, only to find that it was likely psychostimulant seeking to reverse marijuana effects.³ Physicians, families, and patients would be well served to review his arguments on the clear definition of “medicine” with regard to marijuana and the risks taken when we medicalize a known addictive chemical. He tackles the push for legalization as well, and the risks of increased societal acceptance and commercialization power that comes with this. He has led the field in thinking about the role of early drug exposure, brain training, and hijacking in the addictive process. This gateway hypothesis can occur whether the first teen drugs are cannabis or tobacco⁴ or alcohol.

Dr. DuPont finishes his work with a detailed biography, in which he addresses his family history of addiction, and his own overuse of alcohol in his late teens and early 20s as well as a confession of onetime use of marijuana during medical school. He always has led the field in trying to explain the disease of addiction, intervention, treatment, and recovery. But this self-reflection and brutal honesty is refreshing and in step with themes in his book, which promote the idea of recovery as an embrace of honesty, in mind, body, and spirit.
 

Dr. Jorandby trained in addiction psychiatry at Yale University, New Haven, Conn., and works as an addiction psychiatrist with Amen Clinics in Washington. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis.

References

1. J Subst Abuse Treat. 2009 Mar;36(2):159-71.

2. J Addict Dis. 2007;26 Suppl 1:13-23.

3. Am J Psychiatry. 2007 Jun;164(6):973.

4. J Addict Dis. 2003;22(3):51-62.

The national opioid epidemic is one of the most important public health challenges facing the United States today. This crisis has resulted in death, disability, and increased infectious and other comorbid diseases.

sdominick/iStock/Getty Images

Public attention has been focused on the medical management of pain, patterns of opioid prescriptions, and use of heroin and fentanyl. But the opioid crisis is, in fact, part of a far larger drug epidemic. The foundation on which the opioid epidemic is built is recreational pharmacology – the widespread use of aggressively marketed chemicals that seductively superstimulate brain-reward producing alterations in consciousness and pleasure, often mislabeled “self-medication.”

Drugs of abuse are unique chemicals that stimulate their own taking by producing an intense reinforcement in the human brain, which tells users that they have done something monumentally good. Instead of preserving the species, this chemical stimulation of brain reward begins the process of retraining the brain and reward system to respond quickly to drugs of abuse and drug-promoting cues. Drugs of abuse do not come from one class or chemical structure, but, rather, from disparate chemical classes that have in common the stimulation of brain reward. This bad learning is accelerated to addiction when drugs of abuse are smoked, snorted, vaped, or injected, as these routes of administration produce rapidly rising and falling blood levels.

Thanks to the science of animal models, we understand drug self-administration and abstinence. However, in animals, we cannot approximate addiction beyond the mechanical because of the cultural complexity of human behavior. Most animal models are good at predicting what treatments will work for drug addiction in animals. They are less predictive when it comes to humans. Animal models are good for understanding withdrawal reversal and identifying self-administration reductions and even changes in place preference. Animal models have consistently shown that drugs of abuse raise the brain’s reward threshold and cause epigenetic changes, and that many of these changes are persistent, if not permanent. In animal models, clonidine or opioid detoxification followed by naltrexone is a cure for opioid use disorder. Again, in animal models, this protocol is tied to no relapses – just a cure. We know that this is not the case for humans suffering from opioid addiction, where relapses define the disorder.

A closer look at opioid overdoses

Opioid overdose deaths are skyrocketing in the United States. The number of deaths tied to opioid overdoses quadrupled between 1999 and 2015 (in this 15-year period, that is more than 500,000 deaths). Then, between 2015 and 2016, they further increased dramatically to more than 60,000 and in 2017 topped 72,000. This increase was driven partly by a sevenfold increase in overdose deaths involving synthetic opioids (excluding methadone): from 3,105 in 2013 to about 20,000 in 2016.

Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase. In addition, fentanyl analogs such as acetyl fentanyl, furanyl fentanyl, and carfentanil are being detected increasingly in overdose deaths and the illicit opioid drug supply. Drug overdose is the leading cause of accidental death in the United States, with opioids implicated in more than half of these deaths. Moreover, drug overdose is now the leading cause of death of all Americans under age 50. As if these data were not bad enough, recent analyses suggest that the number of opioid overdose deaths might be significantly undercounted. Without intervention, we would expect 235,000 opioid-related deaths (85,000 from prescription opioids and 150,000 from heroin) from 2016 to 2020; and 510,000 opioid-related deaths (170,000 from prescription opioids and 340,000 from heroin) from 2016 to 2025.¹ In these opioid overdose deaths, rarely is the opioid the only drug present. Data from the Florida Drug-Related Outcomes Surveillance & Tracking System show that, in that state, more than 90% of opioid overdose deaths in 2016 showed other drugs of abuse present at death, an average of 2 to 4 – but as many as 11.²

It is well-accepted that medicine – in particular the overprescribing of opioids for pain and downplaying the risks of prescription opioid use – has played a fundamental role in the exponential rise in addiction and overdose death. The prescribing of other controlled substances, especially stimulants and benzodiazepines, also is a factor in overdose deaths.

To say that the country has an opioid problem would be a simplistic understatement. It has been too easy to zero in on opioids while ignoring the ubiquity of polysubstance use by almost all individuals suffering from opioid and other substance use disorders and related drug problems, including overdose. Drug sellers are innovative, consistently adding new chemicals to the menu of available drugs. The user market keeps adding potential customers who already have trained their brains and dopamine systems to respond vigorously to drug-promoting cues and drugs. We are a nation of polydrug users without drug or brand loyalty, engaging in “recreational pharmacology.” Framing the national drug problem around opioids misses the bigger target. The future of the national drug problem is more drugs used by more drug users – not simply prescription misuse or even opioids but instead globally produced illegal synthetic drugs as is now common in Hong Kong and Southeast Asia. A focus exclusively on opioid use disorders might yield great progress in new treatment developments that are specific to opioids. But few people addicted to opioids do not also use many other drugs in other drug classes. The opioid treatments (for example, buprenorphine, methadone, naltrexone) are irrelevant to these other addictive and problem-generating drugs.

Finally, as a very recent report found, the national opioid epidemic has had profound second- and third-hand effects on those with opioid use disorders, their families, and communities, costing about $80 billion yearly in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.¹ Worse yet, missing from current discussion is the simple fact that drug users in the United States spend $100 billion on drugs each year. The entire annual cost of all treatment – both public and private – for alcohol and other substance use disorders is $34 billion a year. Drug users could pay for all of the treatment in the country with one-third of the money they now spend on drugs.

How much do drug users themselves spend on addiction treatment? Close to zero. The costs of both treatment and prevention are almost all carried by nondrug users. While many drug policy discussions call for “more treatment,” as important as that objective is, overlooked is the fact that 95% of people with substance use disorders do not think they have a drug problem and do not want treatment. What actions are needed now?

Control drug supply

Illicit drug supply used to be centrally controlled and reasonably well understood by law enforcement. Today, the illegal supply of addicting chemicals is global, innovative, massive, and decentralized. More drugs, including opioids, are now manufactured and delivered to users in higher potency, at lower prices, and with greater convenience than ever before. At the same time, illegal drug suppliers are moving away from agriculturally produced drugs such as marijuana, cocaine, and heroin to purely synthetic drugs such as synthetic cannabis, methamphetamine, and fentanyl. These synthetics do not require growing fields that are difficult to conceal, nor do they require farmers, or complex, clandestine, and vulnerable modes of transportation.

Instead, these new drugs can be synthesized in small and mobile laboratories located in any part of the globe and delivered anonymously, often by mail, to the users’ addresses. In addition, there remains ample illegal access to the older addicting agricultural chemicals and access to the many addicting legal chemicals that are widely used in the practice of medicine (for example, prescription drugs, including opioids). These abundant and varied sources make addicting drugs widely available to millions of Americans. Strong supply reduction efforts are needed. We must use the Drug Enforcement Administration to increase the cost of doing business in the illegal drug supply chain, and decrease access to drugs by bolstering interdiction and reducing precursor access. We can work to screen packages for drugs sent by U.S. mail or other express services.

It is gratifying to see so many of the missing pieces identified in the classic report³ published in 2012 by Columbia University in New York. Health care providers and professionals-in-training are being taught addiction medicine principles and practices. The Surgeon General has helped mobilize the public response to this crisis, and rightly suggested⁴ that everyone learn how to use and carry naloxone. Researchers are refocused on more than supply reduction.⁵ In addition, the Substance Abuse and Mental Health Services Administration and the National Institute on Drug Abuse (NIDA) are working on delivery service improvements, developing nonopioid pain medications, and new treatments for addiction.

Increase access to naloxone

Increasing access to the opioid reversal medication is critical. Because of the surge in opioid overdose–related mortality, considerable resources have been devoted to emergency response and the widespread dissemination of the mu-opioid receptor antagonist naloxone.⁶

Naloxone should be readily available without prescription and at a price that makes access practical for emergency technicians and any concerned citizen. Administering naloxone should be analogous to CPR or cardioversion. They are similar, in that they are life-saving actions, but the target within the patient is the brain, rather than the heart. CPR education and cardioversion training efforts and access have been promoted well across the United States and can be done for naloxone.

Another comparison has been made between naloxone and giving an EpiPen to an allergic person in an anaphylaxis emergency or crisis. We need and want to rescue, resuscitate, and revive the overdosed patient and give the person another chance to make a change. We want to administer naloxone and get the patient evaluated and into long-term treatment. Now, rapid return to drug use is common after overdose reversal. We need to use overdose reversal as a path to treatment and see that it is sustained to long-term abstinence from drug use. The most recent report on the high cost of drug use correctly points out that none of the current treatment and policy proposals can reduce substantially the number of overdose deaths.¹ Among 11 interventions analyzed by those researchers, making naloxone more available resulted in the greatest number of addiction deaths prevented.


 

Learn from physician health model of care

An assessment is needed of the 5-year recovery outcomes of all interventions for substance use disorder, including treatments that use and do not use medications, and harm-reduction interventions such as naloxone, needle exchange, and safe injection sites. A few years ago, researchers reported on a sample of 904 physicians consecutively admitted to 16 state Physician Health Programs (PHPs) that was monitored for 5 years or longer.⁷

This study characterized the outcomes of this episode of care and explored the elements of those programs that could improve the care routinely given to physicians but not to other addicted populations. PHPs were abstinence based and required physicians to abstain from any use of alcohol or other drugs of abuse as assessed by frequent random tests typically lasting for 5 years. Random tests rapidly identified any return to substance use, leading to swift and significant consequences.

Remarkably, 78% of participants had no positive test for either alcohol or drugs over the 5-year period of intensive monitoring. At posttreatment follow-up, 72% of the physicians were continuing to practice medicine. A key to the PHPs’ success is the 5 years of close monitoring with immediate consequences for any use and rapid, vigorous intervention upon any relapse to alcohol or drugs.

The unique PHP care management included close links to the 12-step fellowships of Alcoholics Anonymous (AA), Narcotics Anonymous, and other intensive recovery support for the entire 5 years of care management. The PHPs used relatively brief residential and outpatient treatment programs. Given the remarkable long-term outcomes of the PHPs, this model of care management should inspire new approaches to integrated and sustained care management of addiction in health care generally. The 5-year recovery standard should be applied to all addiction treatments to judge their value.⁸

Re-energize prevention efforts

The country must integrate addiction care into all of health care in the model of other chronic disease management: from prevention to intervention, treatment, monitoring, and intervention for any relapse. For prevention, we must retarget the health goal for youth under age 21 of no use of alcohol, nicotine, marijuana, or other drugs. Substance use disorders, including opioid use disorders, can be traced to adolescent use of alcohol and other drugs. The younger the age of a person initiating the use of any addicting substance – and the more chronic that use – the greater the likelihood of subsequent substance use problems persisting, or reigniting, later in life.

This later addiction risk resulting from adolescent drug use is no surprise, given the unique vulnerability of the adolescent brain, a brain that is especially vulnerable to addicting chemicals and that is not fully developed until about age 25. Effective addiction prevention – for example, helping youth grow up drug free – can improve dramatically public health by reducing the lifetime prevalence of substance use disorders, including opioid addiction.

Youth prevention efforts today vary tremendously in message and scope. Often, prevention messages for youth are limited to specific drugs (for example, nonmedical use of prescription drugs or tobacco) to specific situations (e.g., drunk driving), or to specific amounts of drug use (for example, binge drinking) when all substance use among youth is linked and all drug use poses health risks during adolescence and beyond. Among youth aged 12-17, the use of any one of the three most widely used and available drugs – alcohol, nicotine, and marijuana – increases the likelihood of using the other two drugs, as well as other illicit drugs.⁹ Similarly, no use of alcohol, nicotine, or marijuana decreases the likelihood of using the others, or of using other illicit drugs.

A recent clinical report and policy statement issued by the American Academy of Pediatrics affirms that it is in the best interests of young patients to not use any substances.¹⁰ The screening recommendations issued by the AAP further encourage pediatricians and adolescent medicine physicians to help guide their patients to this fundamental and easily-understood health goal.

A new and better vision for addiction prevention must focus on the single, clear goal of no use of alcohol, nicotine, marijuana, or other drugs for health by youth under age 21.¹¹ Some good news for prevention is that, for the past 3 decades, there has been a slow but steadily increasing percentage of American high school seniors reporting abstinence from any use of alcohol, cigarettes, marijuana, and other illicit drugs.¹² In 2014, 25.5% of high school seniors reported lifetime abstinence, and fully 50% reported past-month abstinence from all substances. Those figures are dramatic, compared with abstinence rates during the nation’s peak years of youth drug use. In 1978, among high school seniors, 4.4% reported lifetime abstinence from any use of alcohol, cigarettes, marijuana, and other illicit drugs and 21% reported past-month abstinence. Notably, similar increasing rates of abstinence have been recorded among eighth- and 10th-graders. This encouraging and largely overlooked reality demonstrates that the no-use prevention goal for youth is both realistic and attainable.
 

Expand drug and alcohol courts

We need to rehabilitate the role of the criminal justice system in a public health–oriented policy to achieve two essential goals: 1) to improve supply reduction as described above, and 2) to reshape the criminal justice system as an engine of recovery as it is now for alcohol addiction.

The landmark report, “Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs and Health,” called for a continuum of health care extending from prevention to early identification and treatment of substance use disorders and long-term health care management with the goal of sustained recovery.¹³ A growing number of pioneering programs within the criminal justice system (for example, Hawaii’s HOPE Probation, South Dakota’s 24/7 Sobriety Project, and drug courts) are using innovative monitoring strategies for individuals with substance use problems, including providing substance use disorder treatment, with results showing reduced substance use, reduced recidivism, and reduced incarceration.¹⁴

In HOPE, drug-involved offenders are subject to frequent random drug testing, rather than the typical drug testing done on standard probation, only at the time of scheduled meetings with probation officers. Failure to abstain from drugs or failure to show up for random drug testing always results in a brief jail sanction, usually 2-15 days, depending on the nature and severity of the offense. Upon placement in HOPE at a warning hearing, probationers are encouraged to succeed, and are fully informed of the length of the jail sanctions that will be imposed for each type of violation. They are assured of the certainty and speed with which the sanctions will be applied.

Sanctions are applied consistently and impartially to ensure fairness for all. Substance abuse treatment is available to all offenders who want it and to those who demonstrate a need for treatment through “behavioral triage.” Offenders who test positive for drugs two or more times in short order with jail sanctions are referred for a substance abuse assessment and instructed to follow any recommended treatment. For this reason, offenders in HOPE succeed in treatment – because they are the offenders in most need and are supported by the leverage provided by the court to help them complete treatment.

A randomized, controlled trial compared offenders assigned to HOPE Probation and a control group assigned to probation as usual. Compared with offenders on probation as usual, at 1-year follow-up, HOPE offenders were:

• 55% less likely to be arrested for a new crime.

• 72% less likely to test positive for illegal drugs.

• 61% less likely to skip appointments with their supervisory officer.

• 53% less likely to have their probation revoked.

There also is a growing potential to harness the latent but enormous strength of the families who have confronted and are continuing to confront addiction in a family member. Families and those with addictions can be engaged in alcohol or drug courts, which can act like the PHP for addicted individuals in the criminal justice system.
 

Implications for treatment

The diversion of medications that are prescribed and intended for patients in pain is just one part of the far larger drug use and overdose problem. An addicted person with a hijacked brain is not the same as a nonaddicted pain patient. Taking medication as prescribed for pain can produce physical dependence, but importantly, this is not addiction. The person who is using drugs – whether or not prescribed – to produce euphoria is a different person from the person in that same body who is abstinent and not using. Talking with a person in active addiction often is frustrating and futile. That addicted user’s brain wants to use drugs.

The PHP system of care management demonstrates that individuals with substance use disorders can refrain from any substance use for extended periods of time with a carrot and stick approach; permitting a physician to earn a livelihood as a physician is the carrot. In medication-assisted treatment (MAT), the carrot is provided by agonist drugs and the comfort-fit they provide in the brain. They protect the patient from anxiety, and reduce stress and craving responsivity. The stick is an environment that is intolerant of continued nonmedical or addicting drug use. This can be the family, an employer, the criminal justice system, or others in a position to insist on abstinence.

PHP care management shows the way to improve all treatment outcomes; however, an even larger lesson can be learned from the millions of Americans now in recovery from addiction to opioids and other drugs. The “evidence” of what recovery is and how it is achieved and sustained is available to everyone who knows or comes into contact with people in recovery. How did that near-miraculous transformation happen? Even more importantly, how is it sustained when relapse is so common in addiction? The millions of Americans in recovery are the inspiration for a new generation of improved addiction treatment.

Addiction reprioritizes the brain toward continued drug use first, rather than family, friends, health, job, or another important remnant of the addicted person’s past having any meaningful standing. It is often a question like that raised by the AA axiom that it is easy to change a cucumber (naive or new drug user) into a pickle (an addict), but turning a pickle into a cucumber is very difficult. Risk-benefit research has shown that drugs change the ability to accurately assess risks and benefits by prioritizing drug use over virtually everything else, including the interests of the drug users themselves.

Along with judgment deficits comes dishonesty – a hallmark of addiction. The person with addictions lies, minimizes, and denies drug use, thus keeping the addictive run going. That often is the heart of addiction. The point is that once the disease is in control of the addicted brain, those around that hijacked brain must intervene – and the goal of cutting down drug use or limiting it to exclude one or another drug is not useful. Rather, it perpetuates the addiction. Freedom from addiction, that modern chemical slavery, requires no use of alcohol and other drugs, including marijuana, and a return to healthy relationships, sleep, eating, exercise, etc.

Recovery is more than abstinence from all drug use; it includes character development and citizenship. The data supporting the essential goal of recovery are found in the people who are in recovery not in today’s scientific research, which generally is off-target on recovery. Just because recovering people are anonymous does not mean that they do not exist. They prove that recovery happens all the time. They show what recovery is, and how it is achieved and maintained. Current arguments over which MAT is the best in a 3-month study is too short-term for a lifetime disorder and it ignores the concept of recovery despite the millions of people who are living it. Their stories are the bedrock of our message.

Our core evidence, our inspiration, comes from asking the people in recovery from the deadly, chronic disease of addiction three questions: 1) What was your life like when using drugs? 2) What happened to get you to stop using drugs? and 3) What is your life like when not using any drugs?” Every American who knows someone in recovery can do this research for themselves. We have been doing that research for decades.

People in recovery all have sobriety dates. Few in MAT have sobriety dates. Recovery from addiction is not just not taking Vicodin but living the life of a drug-free, recovering person. How do they hold onto recovery, and prevent and deal with relapses and slips? MAT is a major achievement in addiction treatment, including agonist maintenance with buprenorphine and methadone, but it needs to build in the goal of sustained recovery and strong recovery support. That means building into MAT the 12-step fellowships and related recovery support, as is done every day by James H. Berry, DO, of the Chestnut Ridge Center at West Virginia University’s Comprehensive Opioid Addiction Treatment, or COAT, program.¹⁵

MAT is good. It needs to be targeted on recovery, which can include continued use of the medicines now widely used: methadone, buprenorphine, and naltrexone. But recovery cannot include continued nonmedical drug use, and it also must include character development – with honesty replacing the dishonesty that is at the heart of addiction.

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, professor of psychiatry (adjunct) at Washington University in St. Louis. Dr. DuPont is the first director of the National Institute on Drug Abuse and the second White House drug chief, founding president of the Institute for Behavior and Health in Rockville, Md., and author of “Chemical Slavery: Understanding Addiction and Stopping the Drug Epidemic” (Create Space Independent Publishing Platform), 2018.

References

1. Am J Public Health. 2018 Oct 108(10):1394-1400.

2. Florida Drug-Related Outcomes Surveillance & Tracking system (FROST)

3. Center on Addiction. Addiction Medicine: Closing the Gap Between Science and Practice. 2012 Jun.

4. Surgeon General’s Advisory on Naloxone and Opioid Overdose.

5. Mayo Clin Proc. 2018 Mar;93(3):269-72.

6. Ther Adv Drug Saf. 2015 Feb;6(1):20-31.

7. J Subst Abuse Treat. 2009 Mar;36(2):159-71.

8. J Subst Abuse Treat. 2015 Nov;58:1-5.

9. Prev Med. 2018 Aug;113:68-73.

10. Pediatrics. 2016 Jun;138(1). doi: 10.1542/peds.2016-1211.

11. Institute for Behavior and Health. (updated) 2018 Aug 29.

12. Pediatrics. 2018 Aug;142(2). doi: 10.1542/peds.2017-3498.

13. Office of the Surgeon General. 2016.

14. The ASAM Principles of Addiction Medicine. (6th ed.) (in press) Wolters Kluwer, 2018.

15. West Virginia Clinical and Translational Science Institute. 2017 Aug 21.

The national opioid epidemic is one of the most important public health challenges facing the United States today. This crisis has resulted in death, disability, and increased infectious and other comorbid diseases.

sdominick/iStock/Getty Images

Public attention has been focused on the medical management of pain, patterns of opioid prescriptions, and use of heroin and fentanyl. But the opioid crisis is, in fact, part of a far larger drug epidemic. The foundation on which the opioid epidemic is built is recreational pharmacology – the widespread use of aggressively marketed chemicals that seductively superstimulate brain-reward producing alterations in consciousness and pleasure, often mislabeled “self-medication.”

Drugs of abuse are unique chemicals that stimulate their own taking by producing an intense reinforcement in the human brain, which tells users that they have done something monumentally good. Instead of preserving the species, this chemical stimulation of brain reward begins the process of retraining the brain and reward system to respond quickly to drugs of abuse and drug-promoting cues. Drugs of abuse do not come from one class or chemical structure, but, rather, from disparate chemical classes that have in common the stimulation of brain reward. This bad learning is accelerated to addiction when drugs of abuse are smoked, snorted, vaped, or injected, as these routes of administration produce rapidly rising and falling blood levels.

Thanks to the science of animal models, we understand drug self-administration and abstinence. However, in animals, we cannot approximate addiction beyond the mechanical because of the cultural complexity of human behavior. Most animal models are good at predicting what treatments will work for drug addiction in animals. They are less predictive when it comes to humans. Animal models are good for understanding withdrawal reversal and identifying self-administration reductions and even changes in place preference. Animal models have consistently shown that drugs of abuse raise the brain’s reward threshold and cause epigenetic changes, and that many of these changes are persistent, if not permanent. In animal models, clonidine or opioid detoxification followed by naltrexone is a cure for opioid use disorder. Again, in animal models, this protocol is tied to no relapses – just a cure. We know that this is not the case for humans suffering from opioid addiction, where relapses define the disorder.

A closer look at opioid overdoses

Opioid overdose deaths are skyrocketing in the United States. The number of deaths tied to opioid overdoses quadrupled between 1999 and 2015 (in this 15-year period, that is more than 500,000 deaths). Then, between 2015 and 2016, they further increased dramatically to more than 60,000 and in 2017 topped 72,000. This increase was driven partly by a sevenfold increase in overdose deaths involving synthetic opioids (excluding methadone): from 3,105 in 2013 to about 20,000 in 2016.

Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase. In addition, fentanyl analogs such as acetyl fentanyl, furanyl fentanyl, and carfentanil are being detected increasingly in overdose deaths and the illicit opioid drug supply. Drug overdose is the leading cause of accidental death in the United States, with opioids implicated in more than half of these deaths. Moreover, drug overdose is now the leading cause of death of all Americans under age 50. As if these data were not bad enough, recent analyses suggest that the number of opioid overdose deaths might be significantly undercounted. Without intervention, we would expect 235,000 opioid-related deaths (85,000 from prescription opioids and 150,000 from heroin) from 2016 to 2020; and 510,000 opioid-related deaths (170,000 from prescription opioids and 340,000 from heroin) from 2016 to 2025.¹ In these opioid overdose deaths, rarely is the opioid the only drug present. Data from the Florida Drug-Related Outcomes Surveillance & Tracking System show that, in that state, more than 90% of opioid overdose deaths in 2016 showed other drugs of abuse present at death, an average of 2 to 4 – but as many as 11.²

It is well-accepted that medicine – in particular the overprescribing of opioids for pain and downplaying the risks of prescription opioid use – has played a fundamental role in the exponential rise in addiction and overdose death. The prescribing of other controlled substances, especially stimulants and benzodiazepines, also is a factor in overdose deaths.

To say that the country has an opioid problem would be a simplistic understatement. It has been too easy to zero in on opioids while ignoring the ubiquity of polysubstance use by almost all individuals suffering from opioid and other substance use disorders and related drug problems, including overdose. Drug sellers are innovative, consistently adding new chemicals to the menu of available drugs. The user market keeps adding potential customers who already have trained their brains and dopamine systems to respond vigorously to drug-promoting cues and drugs. We are a nation of polydrug users without drug or brand loyalty, engaging in “recreational pharmacology.” Framing the national drug problem around opioids misses the bigger target. The future of the national drug problem is more drugs used by more drug users – not simply prescription misuse or even opioids but instead globally produced illegal synthetic drugs as is now common in Hong Kong and Southeast Asia. A focus exclusively on opioid use disorders might yield great progress in new treatment developments that are specific to opioids. But few people addicted to opioids do not also use many other drugs in other drug classes. The opioid treatments (for example, buprenorphine, methadone, naltrexone) are irrelevant to these other addictive and problem-generating drugs.

Finally, as a very recent report found, the national opioid epidemic has had profound second- and third-hand effects on those with opioid use disorders, their families, and communities, costing about $80 billion yearly in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.¹ Worse yet, missing from current discussion is the simple fact that drug users in the United States spend $100 billion on drugs each year. The entire annual cost of all treatment – both public and private – for alcohol and other substance use disorders is $34 billion a year. Drug users could pay for all of the treatment in the country with one-third of the money they now spend on drugs.

How much do drug users themselves spend on addiction treatment? Close to zero. The costs of both treatment and prevention are almost all carried by nondrug users. While many drug policy discussions call for “more treatment,” as important as that objective is, overlooked is the fact that 95% of people with substance use disorders do not think they have a drug problem and do not want treatment. What actions are needed now?

Control drug supply

Illicit drug supply used to be centrally controlled and reasonably well understood by law enforcement. Today, the illegal supply of addicting chemicals is global, innovative, massive, and decentralized. More drugs, including opioids, are now manufactured and delivered to users in higher potency, at lower prices, and with greater convenience than ever before. At the same time, illegal drug suppliers are moving away from agriculturally produced drugs such as marijuana, cocaine, and heroin to purely synthetic drugs such as synthetic cannabis, methamphetamine, and fentanyl. These synthetics do not require growing fields that are difficult to conceal, nor do they require farmers, or complex, clandestine, and vulnerable modes of transportation.

Instead, these new drugs can be synthesized in small and mobile laboratories located in any part of the globe and delivered anonymously, often by mail, to the users’ addresses. In addition, there remains ample illegal access to the older addicting agricultural chemicals and access to the many addicting legal chemicals that are widely used in the practice of medicine (for example, prescription drugs, including opioids). These abundant and varied sources make addicting drugs widely available to millions of Americans. Strong supply reduction efforts are needed. We must use the Drug Enforcement Administration to increase the cost of doing business in the illegal drug supply chain, and decrease access to drugs by bolstering interdiction and reducing precursor access. We can work to screen packages for drugs sent by U.S. mail or other express services.

It is gratifying to see so many of the missing pieces identified in the classic report³ published in 2012 by Columbia University in New York. Health care providers and professionals-in-training are being taught addiction medicine principles and practices. The Surgeon General has helped mobilize the public response to this crisis, and rightly suggested⁴ that everyone learn how to use and carry naloxone. Researchers are refocused on more than supply reduction.⁵ In addition, the Substance Abuse and Mental Health Services Administration and the National Institute on Drug Abuse (NIDA) are working on delivery service improvements, developing nonopioid pain medications, and new treatments for addiction.

Increase access to naloxone

Increasing access to the opioid reversal medication is critical. Because of the surge in opioid overdose–related mortality, considerable resources have been devoted to emergency response and the widespread dissemination of the mu-opioid receptor antagonist naloxone.⁶

Naloxone should be readily available without prescription and at a price that makes access practical for emergency technicians and any concerned citizen. Administering naloxone should be analogous to CPR or cardioversion. They are similar, in that they are life-saving actions, but the target within the patient is the brain, rather than the heart. CPR education and cardioversion training efforts and access have been promoted well across the United States and can be done for naloxone.

Another comparison has been made between naloxone and giving an EpiPen to an allergic person in an anaphylaxis emergency or crisis. We need and want to rescue, resuscitate, and revive the overdosed patient and give the person another chance to make a change. We want to administer naloxone and get the patient evaluated and into long-term treatment. Now, rapid return to drug use is common after overdose reversal. We need to use overdose reversal as a path to treatment and see that it is sustained to long-term abstinence from drug use. The most recent report on the high cost of drug use correctly points out that none of the current treatment and policy proposals can reduce substantially the number of overdose deaths.¹ Among 11 interventions analyzed by those researchers, making naloxone more available resulted in the greatest number of addiction deaths prevented.


 

Learn from physician health model of care

An assessment is needed of the 5-year recovery outcomes of all interventions for substance use disorder, including treatments that use and do not use medications, and harm-reduction interventions such as naloxone, needle exchange, and safe injection sites. A few years ago, researchers reported on a sample of 904 physicians consecutively admitted to 16 state Physician Health Programs (PHPs) that was monitored for 5 years or longer.⁷

This study characterized the outcomes of this episode of care and explored the elements of those programs that could improve the care routinely given to physicians but not to other addicted populations. PHPs were abstinence based and required physicians to abstain from any use of alcohol or other drugs of abuse as assessed by frequent random tests typically lasting for 5 years. Random tests rapidly identified any return to substance use, leading to swift and significant consequences.

Remarkably, 78% of participants had no positive test for either alcohol or drugs over the 5-year period of intensive monitoring. At posttreatment follow-up, 72% of the physicians were continuing to practice medicine. A key to the PHPs’ success is the 5 years of close monitoring with immediate consequences for any use and rapid, vigorous intervention upon any relapse to alcohol or drugs.

The unique PHP care management included close links to the 12-step fellowships of Alcoholics Anonymous (AA), Narcotics Anonymous, and other intensive recovery support for the entire 5 years of care management. The PHPs used relatively brief residential and outpatient treatment programs. Given the remarkable long-term outcomes of the PHPs, this model of care management should inspire new approaches to integrated and sustained care management of addiction in health care generally. The 5-year recovery standard should be applied to all addiction treatments to judge their value.⁸

Re-energize prevention efforts

The country must integrate addiction care into all of health care in the model of other chronic disease management: from prevention to intervention, treatment, monitoring, and intervention for any relapse. For prevention, we must retarget the health goal for youth under age 21 of no use of alcohol, nicotine, marijuana, or other drugs. Substance use disorders, including opioid use disorders, can be traced to adolescent use of alcohol and other drugs. The younger the age of a person initiating the use of any addicting substance – and the more chronic that use – the greater the likelihood of subsequent substance use problems persisting, or reigniting, later in life.

This later addiction risk resulting from adolescent drug use is no surprise, given the unique vulnerability of the adolescent brain, a brain that is especially vulnerable to addicting chemicals and that is not fully developed until about age 25. Effective addiction prevention – for example, helping youth grow up drug free – can improve dramatically public health by reducing the lifetime prevalence of substance use disorders, including opioid addiction.

Youth prevention efforts today vary tremendously in message and scope. Often, prevention messages for youth are limited to specific drugs (for example, nonmedical use of prescription drugs or tobacco) to specific situations (e.g., drunk driving), or to specific amounts of drug use (for example, binge drinking) when all substance use among youth is linked and all drug use poses health risks during adolescence and beyond. Among youth aged 12-17, the use of any one of the three most widely used and available drugs – alcohol, nicotine, and marijuana – increases the likelihood of using the other two drugs, as well as other illicit drugs.⁹ Similarly, no use of alcohol, nicotine, or marijuana decreases the likelihood of using the others, or of using other illicit drugs.

A recent clinical report and policy statement issued by the American Academy of Pediatrics affirms that it is in the best interests of young patients to not use any substances.¹⁰ The screening recommendations issued by the AAP further encourage pediatricians and adolescent medicine physicians to help guide their patients to this fundamental and easily-understood health goal.

A new and better vision for addiction prevention must focus on the single, clear goal of no use of alcohol, nicotine, marijuana, or other drugs for health by youth under age 21.¹¹ Some good news for prevention is that, for the past 3 decades, there has been a slow but steadily increasing percentage of American high school seniors reporting abstinence from any use of alcohol, cigarettes, marijuana, and other illicit drugs.¹² In 2014, 25.5% of high school seniors reported lifetime abstinence, and fully 50% reported past-month abstinence from all substances. Those figures are dramatic, compared with abstinence rates during the nation’s peak years of youth drug use. In 1978, among high school seniors, 4.4% reported lifetime abstinence from any use of alcohol, cigarettes, marijuana, and other illicit drugs and 21% reported past-month abstinence. Notably, similar increasing rates of abstinence have been recorded among eighth- and 10th-graders. This encouraging and largely overlooked reality demonstrates that the no-use prevention goal for youth is both realistic and attainable.
 

Expand drug and alcohol courts

We need to rehabilitate the role of the criminal justice system in a public health–oriented policy to achieve two essential goals: 1) to improve supply reduction as described above, and 2) to reshape the criminal justice system as an engine of recovery as it is now for alcohol addiction.

The landmark report, “Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs and Health,” called for a continuum of health care extending from prevention to early identification and treatment of substance use disorders and long-term health care management with the goal of sustained recovery.¹³ A growing number of pioneering programs within the criminal justice system (for example, Hawaii’s HOPE Probation, South Dakota’s 24/7 Sobriety Project, and drug courts) are using innovative monitoring strategies for individuals with substance use problems, including providing substance use disorder treatment, with results showing reduced substance use, reduced recidivism, and reduced incarceration.¹⁴

In HOPE, drug-involved offenders are subject to frequent random drug testing, rather than the typical drug testing done on standard probation, only at the time of scheduled meetings with probation officers. Failure to abstain from drugs or failure to show up for random drug testing always results in a brief jail sanction, usually 2-15 days, depending on the nature and severity of the offense. Upon placement in HOPE at a warning hearing, probationers are encouraged to succeed, and are fully informed of the length of the jail sanctions that will be imposed for each type of violation. They are assured of the certainty and speed with which the sanctions will be applied.

Sanctions are applied consistently and impartially to ensure fairness for all. Substance abuse treatment is available to all offenders who want it and to those who demonstrate a need for treatment through “behavioral triage.” Offenders who test positive for drugs two or more times in short order with jail sanctions are referred for a substance abuse assessment and instructed to follow any recommended treatment. For this reason, offenders in HOPE succeed in treatment – because they are the offenders in most need and are supported by the leverage provided by the court to help them complete treatment.

A randomized, controlled trial compared offenders assigned to HOPE Probation and a control group assigned to probation as usual. Compared with offenders on probation as usual, at 1-year follow-up, HOPE offenders were:

• 55% less likely to be arrested for a new crime.

• 72% less likely to test positive for illegal drugs.

• 61% less likely to skip appointments with their supervisory officer.

• 53% less likely to have their probation revoked.

There also is a growing potential to harness the latent but enormous strength of the families who have confronted and are continuing to confront addiction in a family member. Families and those with addictions can be engaged in alcohol or drug courts, which can act like the PHP for addicted individuals in the criminal justice system.
 

Implications for treatment

The diversion of medications that are prescribed and intended for patients in pain is just one part of the far larger drug use and overdose problem. An addicted person with a hijacked brain is not the same as a nonaddicted pain patient. Taking medication as prescribed for pain can produce physical dependence, but importantly, this is not addiction. The person who is using drugs – whether or not prescribed – to produce euphoria is a different person from the person in that same body who is abstinent and not using. Talking with a person in active addiction often is frustrating and futile. That addicted user’s brain wants to use drugs.

The PHP system of care management demonstrates that individuals with substance use disorders can refrain from any substance use for extended periods of time with a carrot and stick approach; permitting a physician to earn a livelihood as a physician is the carrot. In medication-assisted treatment (MAT), the carrot is provided by agonist drugs and the comfort-fit they provide in the brain. They protect the patient from anxiety, and reduce stress and craving responsivity. The stick is an environment that is intolerant of continued nonmedical or addicting drug use. This can be the family, an employer, the criminal justice system, or others in a position to insist on abstinence.

PHP care management shows the way to improve all treatment outcomes; however, an even larger lesson can be learned from the millions of Americans now in recovery from addiction to opioids and other drugs. The “evidence” of what recovery is and how it is achieved and sustained is available to everyone who knows or comes into contact with people in recovery. How did that near-miraculous transformation happen? Even more importantly, how is it sustained when relapse is so common in addiction? The millions of Americans in recovery are the inspiration for a new generation of improved addiction treatment.

Addiction reprioritizes the brain toward continued drug use first, rather than family, friends, health, job, or another important remnant of the addicted person’s past having any meaningful standing. It is often a question like that raised by the AA axiom that it is easy to change a cucumber (naive or new drug user) into a pickle (an addict), but turning a pickle into a cucumber is very difficult. Risk-benefit research has shown that drugs change the ability to accurately assess risks and benefits by prioritizing drug use over virtually everything else, including the interests of the drug users themselves.

Along with judgment deficits comes dishonesty – a hallmark of addiction. The person with addictions lies, minimizes, and denies drug use, thus keeping the addictive run going. That often is the heart of addiction. The point is that once the disease is in control of the addicted brain, those around that hijacked brain must intervene – and the goal of cutting down drug use or limiting it to exclude one or another drug is not useful. Rather, it perpetuates the addiction. Freedom from addiction, that modern chemical slavery, requires no use of alcohol and other drugs, including marijuana, and a return to healthy relationships, sleep, eating, exercise, etc.

Recovery is more than abstinence from all drug use; it includes character development and citizenship. The data supporting the essential goal of recovery are found in the people who are in recovery not in today’s scientific research, which generally is off-target on recovery. Just because recovering people are anonymous does not mean that they do not exist. They prove that recovery happens all the time. They show what recovery is, and how it is achieved and maintained. Current arguments over which MAT is the best in a 3-month study is too short-term for a lifetime disorder and it ignores the concept of recovery despite the millions of people who are living it. Their stories are the bedrock of our message.

Our core evidence, our inspiration, comes from asking the people in recovery from the deadly, chronic disease of addiction three questions: 1) What was your life like when using drugs? 2) What happened to get you to stop using drugs? and 3) What is your life like when not using any drugs?” Every American who knows someone in recovery can do this research for themselves. We have been doing that research for decades.

People in recovery all have sobriety dates. Few in MAT have sobriety dates. Recovery from addiction is not just not taking Vicodin but living the life of a drug-free, recovering person. How do they hold onto recovery, and prevent and deal with relapses and slips? MAT is a major achievement in addiction treatment, including agonist maintenance with buprenorphine and methadone, but it needs to build in the goal of sustained recovery and strong recovery support. That means building into MAT the 12-step fellowships and related recovery support, as is done every day by James H. Berry, DO, of the Chestnut Ridge Center at West Virginia University’s Comprehensive Opioid Addiction Treatment, or COAT, program.¹⁵

MAT is good. It needs to be targeted on recovery, which can include continued use of the medicines now widely used: methadone, buprenorphine, and naltrexone. But recovery cannot include continued nonmedical drug use, and it also must include character development – with honesty replacing the dishonesty that is at the heart of addiction.

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, professor of psychiatry (adjunct) at Washington University in St. Louis. Dr. DuPont is the first director of the National Institute on Drug Abuse and the second White House drug chief, founding president of the Institute for Behavior and Health in Rockville, Md., and author of “Chemical Slavery: Understanding Addiction and Stopping the Drug Epidemic” (Create Space Independent Publishing Platform), 2018.

References

1. Am J Public Health. 2018 Oct 108(10):1394-1400.

2. Florida Drug-Related Outcomes Surveillance & Tracking system (FROST)

3. Center on Addiction. Addiction Medicine: Closing the Gap Between Science and Practice. 2012 Jun.

4. Surgeon General’s Advisory on Naloxone and Opioid Overdose.

5. Mayo Clin Proc. 2018 Mar;93(3):269-72.

6. Ther Adv Drug Saf. 2015 Feb;6(1):20-31.

7. J Subst Abuse Treat. 2009 Mar;36(2):159-71.

8. J Subst Abuse Treat. 2015 Nov;58:1-5.

9. Prev Med. 2018 Aug;113:68-73.

10. Pediatrics. 2016 Jun;138(1). doi: 10.1542/peds.2016-1211.

11. Institute for Behavior and Health. (updated) 2018 Aug 29.

12. Pediatrics. 2018 Aug;142(2). doi: 10.1542/peds.2017-3498.

13. Office of the Surgeon General. 2016.

14. The ASAM Principles of Addiction Medicine. (6th ed.) (in press) Wolters Kluwer, 2018.

15. West Virginia Clinical and Translational Science Institute. 2017 Aug 21.

The national opioid epidemic is one of the most important public health challenges facing the United States today. This crisis has resulted in death, disability, and increased infectious and other comorbid diseases.

sdominick/iStock/Getty Images

Public attention has been focused on the medical management of pain, patterns of opioid prescriptions, and use of heroin and fentanyl. But the opioid crisis is, in fact, part of a far larger drug epidemic. The foundation on which the opioid epidemic is built is recreational pharmacology – the widespread use of aggressively marketed chemicals that seductively superstimulate brain-reward producing alterations in consciousness and pleasure, often mislabeled “self-medication.”

Drugs of abuse are unique chemicals that stimulate their own taking by producing an intense reinforcement in the human brain, which tells users that they have done something monumentally good. Instead of preserving the species, this chemical stimulation of brain reward begins the process of retraining the brain and reward system to respond quickly to drugs of abuse and drug-promoting cues. Drugs of abuse do not come from one class or chemical structure, but, rather, from disparate chemical classes that have in common the stimulation of brain reward. This bad learning is accelerated to addiction when drugs of abuse are smoked, snorted, vaped, or injected, as these routes of administration produce rapidly rising and falling blood levels.

Thanks to the science of animal models, we understand drug self-administration and abstinence. However, in animals, we cannot approximate addiction beyond the mechanical because of the cultural complexity of human behavior. Most animal models are good at predicting what treatments will work for drug addiction in animals. They are less predictive when it comes to humans. Animal models are good for understanding withdrawal reversal and identifying self-administration reductions and even changes in place preference. Animal models have consistently shown that drugs of abuse raise the brain’s reward threshold and cause epigenetic changes, and that many of these changes are persistent, if not permanent. In animal models, clonidine or opioid detoxification followed by naltrexone is a cure for opioid use disorder. Again, in animal models, this protocol is tied to no relapses – just a cure. We know that this is not the case for humans suffering from opioid addiction, where relapses define the disorder.

A closer look at opioid overdoses

Opioid overdose deaths are skyrocketing in the United States. The number of deaths tied to opioid overdoses quadrupled between 1999 and 2015 (in this 15-year period, that is more than 500,000 deaths). Then, between 2015 and 2016, they further increased dramatically to more than 60,000 and in 2017 topped 72,000. This increase was driven partly by a sevenfold increase in overdose deaths involving synthetic opioids (excluding methadone): from 3,105 in 2013 to about 20,000 in 2016.

Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase. In addition, fentanyl analogs such as acetyl fentanyl, furanyl fentanyl, and carfentanil are being detected increasingly in overdose deaths and the illicit opioid drug supply. Drug overdose is the leading cause of accidental death in the United States, with opioids implicated in more than half of these deaths. Moreover, drug overdose is now the leading cause of death of all Americans under age 50. As if these data were not bad enough, recent analyses suggest that the number of opioid overdose deaths might be significantly undercounted. Without intervention, we would expect 235,000 opioid-related deaths (85,000 from prescription opioids and 150,000 from heroin) from 2016 to 2020; and 510,000 opioid-related deaths (170,000 from prescription opioids and 340,000 from heroin) from 2016 to 2025.¹ In these opioid overdose deaths, rarely is the opioid the only drug present. Data from the Florida Drug-Related Outcomes Surveillance & Tracking System show that, in that state, more than 90% of opioid overdose deaths in 2016 showed other drugs of abuse present at death, an average of 2 to 4 – but as many as 11.²

It is well-accepted that medicine – in particular the overprescribing of opioids for pain and downplaying the risks of prescription opioid use – has played a fundamental role in the exponential rise in addiction and overdose death. The prescribing of other controlled substances, especially stimulants and benzodiazepines, also is a factor in overdose deaths.

To say that the country has an opioid problem would be a simplistic understatement. It has been too easy to zero in on opioids while ignoring the ubiquity of polysubstance use by almost all individuals suffering from opioid and other substance use disorders and related drug problems, including overdose. Drug sellers are innovative, consistently adding new chemicals to the menu of available drugs. The user market keeps adding potential customers who already have trained their brains and dopamine systems to respond vigorously to drug-promoting cues and drugs. We are a nation of polydrug users without drug or brand loyalty, engaging in “recreational pharmacology.” Framing the national drug problem around opioids misses the bigger target. The future of the national drug problem is more drugs used by more drug users – not simply prescription misuse or even opioids but instead globally produced illegal synthetic drugs as is now common in Hong Kong and Southeast Asia. A focus exclusively on opioid use disorders might yield great progress in new treatment developments that are specific to opioids. But few people addicted to opioids do not also use many other drugs in other drug classes. The opioid treatments (for example, buprenorphine, methadone, naltrexone) are irrelevant to these other addictive and problem-generating drugs.

Finally, as a very recent report found, the national opioid epidemic has had profound second- and third-hand effects on those with opioid use disorders, their families, and communities, costing about $80 billion yearly in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.¹ Worse yet, missing from current discussion is the simple fact that drug users in the United States spend $100 billion on drugs each year. The entire annual cost of all treatment – both public and private – for alcohol and other substance use disorders is $34 billion a year. Drug users could pay for all of the treatment in the country with one-third of the money they now spend on drugs.

How much do drug users themselves spend on addiction treatment? Close to zero. The costs of both treatment and prevention are almost all carried by nondrug users. While many drug policy discussions call for “more treatment,” as important as that objective is, overlooked is the fact that 95% of people with substance use disorders do not think they have a drug problem and do not want treatment. What actions are needed now?

Control drug supply

Illicit drug supply used to be centrally controlled and reasonably well understood by law enforcement. Today, the illegal supply of addicting chemicals is global, innovative, massive, and decentralized. More drugs, including opioids, are now manufactured and delivered to users in higher potency, at lower prices, and with greater convenience than ever before. At the same time, illegal drug suppliers are moving away from agriculturally produced drugs such as marijuana, cocaine, and heroin to purely synthetic drugs such as synthetic cannabis, methamphetamine, and fentanyl. These synthetics do not require growing fields that are difficult to conceal, nor do they require farmers, or complex, clandestine, and vulnerable modes of transportation.

Instead, these new drugs can be synthesized in small and mobile laboratories located in any part of the globe and delivered anonymously, often by mail, to the users’ addresses. In addition, there remains ample illegal access to the older addicting agricultural chemicals and access to the many addicting legal chemicals that are widely used in the practice of medicine (for example, prescription drugs, including opioids). These abundant and varied sources make addicting drugs widely available to millions of Americans. Strong supply reduction efforts are needed. We must use the Drug Enforcement Administration to increase the cost of doing business in the illegal drug supply chain, and decrease access to drugs by bolstering interdiction and reducing precursor access. We can work to screen packages for drugs sent by U.S. mail or other express services.

It is gratifying to see so many of the missing pieces identified in the classic report³ published in 2012 by Columbia University in New York. Health care providers and professionals-in-training are being taught addiction medicine principles and practices. The Surgeon General has helped mobilize the public response to this crisis, and rightly suggested⁴ that everyone learn how to use and carry naloxone. Researchers are refocused on more than supply reduction.⁵ In addition, the Substance Abuse and Mental Health Services Administration and the National Institute on Drug Abuse (NIDA) are working on delivery service improvements, developing nonopioid pain medications, and new treatments for addiction.

Increase access to naloxone

Increasing access to the opioid reversal medication is critical. Because of the surge in opioid overdose–related mortality, considerable resources have been devoted to emergency response and the widespread dissemination of the mu-opioid receptor antagonist naloxone.⁶

Naloxone should be readily available without prescription and at a price that makes access practical for emergency technicians and any concerned citizen. Administering naloxone should be analogous to CPR or cardioversion. They are similar, in that they are life-saving actions, but the target within the patient is the brain, rather than the heart. CPR education and cardioversion training efforts and access have been promoted well across the United States and can be done for naloxone.

Another comparison has been made between naloxone and giving an EpiPen to an allergic person in an anaphylaxis emergency or crisis. We need and want to rescue, resuscitate, and revive the overdosed patient and give the person another chance to make a change. We want to administer naloxone and get the patient evaluated and into long-term treatment. Now, rapid return to drug use is common after overdose reversal. We need to use overdose reversal as a path to treatment and see that it is sustained to long-term abstinence from drug use. The most recent report on the high cost of drug use correctly points out that none of the current treatment and policy proposals can reduce substantially the number of overdose deaths.¹ Among 11 interventions analyzed by those researchers, making naloxone more available resulted in the greatest number of addiction deaths prevented.


 

Learn from physician health model of care

An assessment is needed of the 5-year recovery outcomes of all interventions for substance use disorder, including treatments that use and do not use medications, and harm-reduction interventions such as naloxone, needle exchange, and safe injection sites. A few years ago, researchers reported on a sample of 904 physicians consecutively admitted to 16 state Physician Health Programs (PHPs) that was monitored for 5 years or longer.⁷

This study characterized the outcomes of this episode of care and explored the elements of those programs that could improve the care routinely given to physicians but not to other addicted populations. PHPs were abstinence based and required physicians to abstain from any use of alcohol or other drugs of abuse as assessed by frequent random tests typically lasting for 5 years. Random tests rapidly identified any return to substance use, leading to swift and significant consequences.

Remarkably, 78% of participants had no positive test for either alcohol or drugs over the 5-year period of intensive monitoring. At posttreatment follow-up, 72% of the physicians were continuing to practice medicine. A key to the PHPs’ success is the 5 years of close monitoring with immediate consequences for any use and rapid, vigorous intervention upon any relapse to alcohol or drugs.

The unique PHP care management included close links to the 12-step fellowships of Alcoholics Anonymous (AA), Narcotics Anonymous, and other intensive recovery support for the entire 5 years of care management. The PHPs used relatively brief residential and outpatient treatment programs. Given the remarkable long-term outcomes of the PHPs, this model of care management should inspire new approaches to integrated and sustained care management of addiction in health care generally. The 5-year recovery standard should be applied to all addiction treatments to judge their value.⁸

Re-energize prevention efforts

The country must integrate addiction care into all of health care in the model of other chronic disease management: from prevention to intervention, treatment, monitoring, and intervention for any relapse. For prevention, we must retarget the health goal for youth under age 21 of no use of alcohol, nicotine, marijuana, or other drugs. Substance use disorders, including opioid use disorders, can be traced to adolescent use of alcohol and other drugs. The younger the age of a person initiating the use of any addicting substance – and the more chronic that use – the greater the likelihood of subsequent substance use problems persisting, or reigniting, later in life.

This later addiction risk resulting from adolescent drug use is no surprise, given the unique vulnerability of the adolescent brain, a brain that is especially vulnerable to addicting chemicals and that is not fully developed until about age 25. Effective addiction prevention – for example, helping youth grow up drug free – can improve dramatically public health by reducing the lifetime prevalence of substance use disorders, including opioid addiction.

Youth prevention efforts today vary tremendously in message and scope. Often, prevention messages for youth are limited to specific drugs (for example, nonmedical use of prescription drugs or tobacco) to specific situations (e.g., drunk driving), or to specific amounts of drug use (for example, binge drinking) when all substance use among youth is linked and all drug use poses health risks during adolescence and beyond. Among youth aged 12-17, the use of any one of the three most widely used and available drugs – alcohol, nicotine, and marijuana – increases the likelihood of using the other two drugs, as well as other illicit drugs.⁹ Similarly, no use of alcohol, nicotine, or marijuana decreases the likelihood of using the others, or of using other illicit drugs.

A recent clinical report and policy statement issued by the American Academy of Pediatrics affirms that it is in the best interests of young patients to not use any substances.¹⁰ The screening recommendations issued by the AAP further encourage pediatricians and adolescent medicine physicians to help guide their patients to this fundamental and easily-understood health goal.

A new and better vision for addiction prevention must focus on the single, clear goal of no use of alcohol, nicotine, marijuana, or other drugs for health by youth under age 21.¹¹ Some good news for prevention is that, for the past 3 decades, there has been a slow but steadily increasing percentage of American high school seniors reporting abstinence from any use of alcohol, cigarettes, marijuana, and other illicit drugs.¹² In 2014, 25.5% of high school seniors reported lifetime abstinence, and fully 50% reported past-month abstinence from all substances. Those figures are dramatic, compared with abstinence rates during the nation’s peak years of youth drug use. In 1978, among high school seniors, 4.4% reported lifetime abstinence from any use of alcohol, cigarettes, marijuana, and other illicit drugs and 21% reported past-month abstinence. Notably, similar increasing rates of abstinence have been recorded among eighth- and 10th-graders. This encouraging and largely overlooked reality demonstrates that the no-use prevention goal for youth is both realistic and attainable.
 

Expand drug and alcohol courts

We need to rehabilitate the role of the criminal justice system in a public health–oriented policy to achieve two essential goals: 1) to improve supply reduction as described above, and 2) to reshape the criminal justice system as an engine of recovery as it is now for alcohol addiction.

The landmark report, “Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs and Health,” called for a continuum of health care extending from prevention to early identification and treatment of substance use disorders and long-term health care management with the goal of sustained recovery.¹³ A growing number of pioneering programs within the criminal justice system (for example, Hawaii’s HOPE Probation, South Dakota’s 24/7 Sobriety Project, and drug courts) are using innovative monitoring strategies for individuals with substance use problems, including providing substance use disorder treatment, with results showing reduced substance use, reduced recidivism, and reduced incarceration.¹⁴

In HOPE, drug-involved offenders are subject to frequent random drug testing, rather than the typical drug testing done on standard probation, only at the time of scheduled meetings with probation officers. Failure to abstain from drugs or failure to show up for random drug testing always results in a brief jail sanction, usually 2-15 days, depending on the nature and severity of the offense. Upon placement in HOPE at a warning hearing, probationers are encouraged to succeed, and are fully informed of the length of the jail sanctions that will be imposed for each type of violation. They are assured of the certainty and speed with which the sanctions will be applied.

Sanctions are applied consistently and impartially to ensure fairness for all. Substance abuse treatment is available to all offenders who want it and to those who demonstrate a need for treatment through “behavioral triage.” Offenders who test positive for drugs two or more times in short order with jail sanctions are referred for a substance abuse assessment and instructed to follow any recommended treatment. For this reason, offenders in HOPE succeed in treatment – because they are the offenders in most need and are supported by the leverage provided by the court to help them complete treatment.

A randomized, controlled trial compared offenders assigned to HOPE Probation and a control group assigned to probation as usual. Compared with offenders on probation as usual, at 1-year follow-up, HOPE offenders were:

• 55% less likely to be arrested for a new crime.

• 72% less likely to test positive for illegal drugs.

• 61% less likely to skip appointments with their supervisory officer.

• 53% less likely to have their probation revoked.

There also is a growing potential to harness the latent but enormous strength of the families who have confronted and are continuing to confront addiction in a family member. Families and those with addictions can be engaged in alcohol or drug courts, which can act like the PHP for addicted individuals in the criminal justice system.
 

Implications for treatment

The diversion of medications that are prescribed and intended for patients in pain is just one part of the far larger drug use and overdose problem. An addicted person with a hijacked brain is not the same as a nonaddicted pain patient. Taking medication as prescribed for pain can produce physical dependence, but importantly, this is not addiction. The person who is using drugs – whether or not prescribed – to produce euphoria is a different person from the person in that same body who is abstinent and not using. Talking with a person in active addiction often is frustrating and futile. That addicted user’s brain wants to use drugs.

The PHP system of care management demonstrates that individuals with substance use disorders can refrain from any substance use for extended periods of time with a carrot and stick approach; permitting a physician to earn a livelihood as a physician is the carrot. In medication-assisted treatment (MAT), the carrot is provided by agonist drugs and the comfort-fit they provide in the brain. They protect the patient from anxiety, and reduce stress and craving responsivity. The stick is an environment that is intolerant of continued nonmedical or addicting drug use. This can be the family, an employer, the criminal justice system, or others in a position to insist on abstinence.

PHP care management shows the way to improve all treatment outcomes; however, an even larger lesson can be learned from the millions of Americans now in recovery from addiction to opioids and other drugs. The “evidence” of what recovery is and how it is achieved and sustained is available to everyone who knows or comes into contact with people in recovery. How did that near-miraculous transformation happen? Even more importantly, how is it sustained when relapse is so common in addiction? The millions of Americans in recovery are the inspiration for a new generation of improved addiction treatment.

Addiction reprioritizes the brain toward continued drug use first, rather than family, friends, health, job, or another important remnant of the addicted person’s past having any meaningful standing. It is often a question like that raised by the AA axiom that it is easy to change a cucumber (naive or new drug user) into a pickle (an addict), but turning a pickle into a cucumber is very difficult. Risk-benefit research has shown that drugs change the ability to accurately assess risks and benefits by prioritizing drug use over virtually everything else, including the interests of the drug users themselves.

Along with judgment deficits comes dishonesty – a hallmark of addiction. The person with addictions lies, minimizes, and denies drug use, thus keeping the addictive run going. That often is the heart of addiction. The point is that once the disease is in control of the addicted brain, those around that hijacked brain must intervene – and the goal of cutting down drug use or limiting it to exclude one or another drug is not useful. Rather, it perpetuates the addiction. Freedom from addiction, that modern chemical slavery, requires no use of alcohol and other drugs, including marijuana, and a return to healthy relationships, sleep, eating, exercise, etc.

Recovery is more than abstinence from all drug use; it includes character development and citizenship. The data supporting the essential goal of recovery are found in the people who are in recovery not in today’s scientific research, which generally is off-target on recovery. Just because recovering people are anonymous does not mean that they do not exist. They prove that recovery happens all the time. They show what recovery is, and how it is achieved and maintained. Current arguments over which MAT is the best in a 3-month study is too short-term for a lifetime disorder and it ignores the concept of recovery despite the millions of people who are living it. Their stories are the bedrock of our message.

Our core evidence, our inspiration, comes from asking the people in recovery from the deadly, chronic disease of addiction three questions: 1) What was your life like when using drugs? 2) What happened to get you to stop using drugs? and 3) What is your life like when not using any drugs?” Every American who knows someone in recovery can do this research for themselves. We have been doing that research for decades.

People in recovery all have sobriety dates. Few in MAT have sobriety dates. Recovery from addiction is not just not taking Vicodin but living the life of a drug-free, recovering person. How do they hold onto recovery, and prevent and deal with relapses and slips? MAT is a major achievement in addiction treatment, including agonist maintenance with buprenorphine and methadone, but it needs to build in the goal of sustained recovery and strong recovery support. That means building into MAT the 12-step fellowships and related recovery support, as is done every day by James H. Berry, DO, of the Chestnut Ridge Center at West Virginia University’s Comprehensive Opioid Addiction Treatment, or COAT, program.¹⁵

MAT is good. It needs to be targeted on recovery, which can include continued use of the medicines now widely used: methadone, buprenorphine, and naltrexone. But recovery cannot include continued nonmedical drug use, and it also must include character development – with honesty replacing the dishonesty that is at the heart of addiction.

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, professor of psychiatry (adjunct) at Washington University in St. Louis. Dr. DuPont is the first director of the National Institute on Drug Abuse and the second White House drug chief, founding president of the Institute for Behavior and Health in Rockville, Md., and author of “Chemical Slavery: Understanding Addiction and Stopping the Drug Epidemic” (Create Space Independent Publishing Platform), 2018.

References

1. Am J Public Health. 2018 Oct 108(10):1394-1400.

2. Florida Drug-Related Outcomes Surveillance & Tracking system (FROST)

3. Center on Addiction. Addiction Medicine: Closing the Gap Between Science and Practice. 2012 Jun.

4. Surgeon General’s Advisory on Naloxone and Opioid Overdose.

5. Mayo Clin Proc. 2018 Mar;93(3):269-72.

6. Ther Adv Drug Saf. 2015 Feb;6(1):20-31.

7. J Subst Abuse Treat. 2009 Mar;36(2):159-71.

8. J Subst Abuse Treat. 2015 Nov;58:1-5.

9. Prev Med. 2018 Aug;113:68-73.

10. Pediatrics. 2016 Jun;138(1). doi: 10.1542/peds.2016-1211.

11. Institute for Behavior and Health. (updated) 2018 Aug 29.

12. Pediatrics. 2018 Aug;142(2). doi: 10.1542/peds.2017-3498.

13. Office of the Surgeon General. 2016.

14. The ASAM Principles of Addiction Medicine. (6th ed.) (in press) Wolters Kluwer, 2018.

15. West Virginia Clinical and Translational Science Institute. 2017 Aug 21.

Ongoing efforts to understand the impact of cocaine on the brain and on behavior have gained considerable momentum over the past few decades. It was only 30 years ago when cocaine was widely considered both safe and nonaddicting – “the champagne” of drugs.¹ Progress has been steady since the cocaine-dopamine depletion theory was proposed, and ultimately supported by functional and PET imaging.^2,3

Additional discoveries promise further insights into the neuroscience of addiction, pleasure, and mood. While cocaine use, abuse, and dependence might seem relatively quiescent, compared with the scourge of opiate-related deaths and addiction, it remains a public health concern – and now is the second-leading cause of drug deaths. Cocaine cultivation, smuggling, use, and the number of first-time users are all escalating.⁴

These developments suggest that cocaine problems might get much worse and beg an important question: Will new research give us insight into better solutions?

What the neuroscience shows

As discussed, we already know quite a bit about the neuroscience behind cocaine addiction. The positron emission tomography studies conducted by Nora D. Volkow, MD, and her associates have shown long-lasting changes in abstinent cocaine addicts. Specifically, their findings clearly demonstrated that cocaine changes the brain and depletes dopamine-rich areas. Furthermore, dopamine recovery is negligible after months of abstinence.⁵

However, large gaps in our understanding remain. The realm of epigenetic study and protein expression behind abuse will be key in bridging our understanding of phenotype to genotype. A recent article by Eric J. Nestler, MD, PhD, and his research team, published in the Journal of Biological Psychiatry and titled “Cocaine self-administration alters transcriptome-wide responses in the brain’s reward circuitry,” offers exciting new insights (Biol Psychiatry. 2018 Apr. doi: 10.1016/jbiopsych.2018.04.009).

The study, led by Deena M. Walker, PhD, offers perhaps the most complete illumination to date of the genetic and epigenetic changes seen in the brain after cocaine self-administration and application.

Dr. Walker and her associates used a mouse model and sorted them into one of several groups. One group examined self-administered acute cocaine exposure only, with the mice immediately harvested thereafter. Two longer-term groups included one that had cocaine exposure with prolonged (30-day) withdrawal followed by context re-exposure (context re-exposure defined as being placed back in the special chamber and lighting they first received cocaine in) and another that had a cocaine exposure with prolonged withdrawal followed by both context and cocaine re-exposure.

The researchers also ran a parallel set of control groups substituting saline for cocaine with otherwise identical durations of observation and context re-exposure. Reward-related brain regions were harvested from each subject and examined with RNA-sequencing analysis to investigate the full genomic/transcriptomic profile of each. Pairwise comparison of the various experimental groups against the control groups (for example, the theoretical baseline of genetic expression in a non–cocaine-exposed brain) uncovered telling patterns, which the investigators aptly described as a comprehensive picture of transcriptome-wide change cocaine causes within the reward circuit.

The novel and creative approach used by Dr. Walker and her associates allowed them to uncover a wealth of clinically significant findings. Much could be said about their spotlighting of specific gene/protein targets for potential future pharmacological therapies toward cocaine treatment – an area that is indeed in sore need of invention. While we have highly efficacious medications for overdose and chronic treatment of opiate abuse, the landscape of treatment options for cocaine is far bleaker and shrouded in theory. With that in mind, perhaps the most salient take-home point is the evidence that cocaine, even after one exposure/withdrawal event, causes a dramatic rewiring in the very way genes are expressed across the reward circuit. The researchers found large shifts in the patterns of genetic transcription, unique and specific to discrete regions of the examined brain tissue, such as the ventral tegmental area, ventral hippocampus, and basolateral amygdala.

More interestingly, similar patterns of these genetic alternations were observed based on the exact history of the cocaine exposure. Dr. Walker and her associates concluded that the withdrawal phase and context re-exposure appear to be crucial components in the re-sculpting of the transcriptomic profile of the reward circuity.

The brain is unprepared by evolution for the reinforcing and reorganizing effects of cocaine. Clinicians, too, have learned that cocaine is addicting and can quickly replace drives such as food, water, sex, and survival. These new data from Dr. Nestler’s team reinforce the importance of prevention. In addition, they are reminders to physicians that cocaine causes changes in brain and behavior that are persistent and not necessarily reversible. Patterns of transcriptomic change are alarming enough and have only recent begun to be fleshed out, but patterns of global substance use trends suggest that we need to begin cocaine prevention activities.
 

Is another cocaine epidemic inevitable?

The late David F. Musto, MD, who was revered as both expert medical historian and physician at Yale University, New Haven, Conn., offered perhaps the most poignant observation in this regard: He argued that almost every opiate epidemic seems to transition into a psychostimulant epidemic.⁶ Experts have been looking at cocaine and methamphetamine as a way to try to understand the current opioid epidemic. Indeed, the Centers for Disease Control and Prevention’s most recent report on emerging trends in cocaine use shows numerous, concerning upticks in several realms germane to a possible emerging epidemic. One of the more upstream concerns is a gigantic spike in the shear production of coca leaves and cocaine thought to be occurring in Colombia (the principal source of cocaine in the United States). Current U.S. government estimates based on seizure rates from 2016 indicate that Colombia is producing about 910 metric tons of export quality cocaine. That represents a large increase from the 670-ton estimate the year before and the 325-ton estimate the year before that.

Similarly, a sharp rise in cocaine-related deaths, an approximate 52% increase, has been charted from 2015 to 2016. This finding is likely related to the growing presence of adulterants, such as fentanyl and carfentanil, found in seized cocaine samples. However, a rise in first-time cocaine users in the past year, which, according to the National Survey on Drug Use and Health, is up by about 12% (1.1 million people) in the 2015-2016 period, shows that the danger of cocaine-related deaths might not lie solely in adulteration but also increases in use. These signals might herald a grim return of cocaine to the center stage of public health, a development that would be an encore of the crack cocaine epidemic experienced throughout the 1980s and early 1990s.

All the above findings support cocaine as an agent of swift and massive change to our reward systems that might be poised to again surge across the United States at epidemic levels. Given this insight into just how extensively it rewires brains and the unfortunate truth that direct pharmacotherapy treatments remain mostly theoretical, it is evident that the best course of action is simply to keep cocaine from ever reaching the brain in the first place. Prevention does work, and these findings underline the importance of that message. Direct psychoeducation, awareness programs, and deterrence are the best defense we can offer to our patients at this time. In addition to these tried and true techniques, fascinating new models of prevention for cocaine abuse also are in development: vaccines. Synthesized by binding cocaine to inert proteins, these vaccines are designed to prevent addiction by training the immune system to bind cocaine and thus prevent it from crossing the blood brain barrier.⁷ Currently approved for clinical study in humans, these might offer a game-changing new method in the prevention of substance abuse.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

References

1. Yale J Biol Med. 1988 Mar-Apr;61(2):149-55.

2. Neurosci Biobehav Rev. 1985 Fall;9(3):469-77.

3. Am J Psychiatry. 1990;147(6):719-24.

4. DEA Museum. “A New Look at Old and Not So Old Drugs: A 2018 Update on Cocaine.” Drug Enforcement Administration. Retrieved from https://deamuseum.org/lecture-series/new-look-old-not-old-drugs-2018-update-cocaine.

5. J Addict Dis. 1996;15(4):55-71.

6. The American Disease: Origins of Narcotic Control (New York: Oxford University Press, 1999).

7. Br J Clin Pharmacol. 2014 Feb;77(2):368-74.

Ongoing efforts to understand the impact of cocaine on the brain and on behavior have gained considerable momentum over the past few decades. It was only 30 years ago when cocaine was widely considered both safe and nonaddicting – “the champagne” of drugs.¹ Progress has been steady since the cocaine-dopamine depletion theory was proposed, and ultimately supported by functional and PET imaging.^2,3

Additional discoveries promise further insights into the neuroscience of addiction, pleasure, and mood. While cocaine use, abuse, and dependence might seem relatively quiescent, compared with the scourge of opiate-related deaths and addiction, it remains a public health concern – and now is the second-leading cause of drug deaths. Cocaine cultivation, smuggling, use, and the number of first-time users are all escalating.⁴

These developments suggest that cocaine problems might get much worse and beg an important question: Will new research give us insight into better solutions?

What the neuroscience shows

As discussed, we already know quite a bit about the neuroscience behind cocaine addiction. The positron emission tomography studies conducted by Nora D. Volkow, MD, and her associates have shown long-lasting changes in abstinent cocaine addicts. Specifically, their findings clearly demonstrated that cocaine changes the brain and depletes dopamine-rich areas. Furthermore, dopamine recovery is negligible after months of abstinence.⁵

However, large gaps in our understanding remain. The realm of epigenetic study and protein expression behind abuse will be key in bridging our understanding of phenotype to genotype. A recent article by Eric J. Nestler, MD, PhD, and his research team, published in the Journal of Biological Psychiatry and titled “Cocaine self-administration alters transcriptome-wide responses in the brain’s reward circuitry,” offers exciting new insights (Biol Psychiatry. 2018 Apr. doi: 10.1016/jbiopsych.2018.04.009).

The study, led by Deena M. Walker, PhD, offers perhaps the most complete illumination to date of the genetic and epigenetic changes seen in the brain after cocaine self-administration and application.

Dr. Walker and her associates used a mouse model and sorted them into one of several groups. One group examined self-administered acute cocaine exposure only, with the mice immediately harvested thereafter. Two longer-term groups included one that had cocaine exposure with prolonged (30-day) withdrawal followed by context re-exposure (context re-exposure defined as being placed back in the special chamber and lighting they first received cocaine in) and another that had a cocaine exposure with prolonged withdrawal followed by both context and cocaine re-exposure.

The researchers also ran a parallel set of control groups substituting saline for cocaine with otherwise identical durations of observation and context re-exposure. Reward-related brain regions were harvested from each subject and examined with RNA-sequencing analysis to investigate the full genomic/transcriptomic profile of each. Pairwise comparison of the various experimental groups against the control groups (for example, the theoretical baseline of genetic expression in a non–cocaine-exposed brain) uncovered telling patterns, which the investigators aptly described as a comprehensive picture of transcriptome-wide change cocaine causes within the reward circuit.

The novel and creative approach used by Dr. Walker and her associates allowed them to uncover a wealth of clinically significant findings. Much could be said about their spotlighting of specific gene/protein targets for potential future pharmacological therapies toward cocaine treatment – an area that is indeed in sore need of invention. While we have highly efficacious medications for overdose and chronic treatment of opiate abuse, the landscape of treatment options for cocaine is far bleaker and shrouded in theory. With that in mind, perhaps the most salient take-home point is the evidence that cocaine, even after one exposure/withdrawal event, causes a dramatic rewiring in the very way genes are expressed across the reward circuit. The researchers found large shifts in the patterns of genetic transcription, unique and specific to discrete regions of the examined brain tissue, such as the ventral tegmental area, ventral hippocampus, and basolateral amygdala.

More interestingly, similar patterns of these genetic alternations were observed based on the exact history of the cocaine exposure. Dr. Walker and her associates concluded that the withdrawal phase and context re-exposure appear to be crucial components in the re-sculpting of the transcriptomic profile of the reward circuity.

The brain is unprepared by evolution for the reinforcing and reorganizing effects of cocaine. Clinicians, too, have learned that cocaine is addicting and can quickly replace drives such as food, water, sex, and survival. These new data from Dr. Nestler’s team reinforce the importance of prevention. In addition, they are reminders to physicians that cocaine causes changes in brain and behavior that are persistent and not necessarily reversible. Patterns of transcriptomic change are alarming enough and have only recent begun to be fleshed out, but patterns of global substance use trends suggest that we need to begin cocaine prevention activities.
 

Is another cocaine epidemic inevitable?

The late David F. Musto, MD, who was revered as both expert medical historian and physician at Yale University, New Haven, Conn., offered perhaps the most poignant observation in this regard: He argued that almost every opiate epidemic seems to transition into a psychostimulant epidemic.⁶ Experts have been looking at cocaine and methamphetamine as a way to try to understand the current opioid epidemic. Indeed, the Centers for Disease Control and Prevention’s most recent report on emerging trends in cocaine use shows numerous, concerning upticks in several realms germane to a possible emerging epidemic. One of the more upstream concerns is a gigantic spike in the shear production of coca leaves and cocaine thought to be occurring in Colombia (the principal source of cocaine in the United States). Current U.S. government estimates based on seizure rates from 2016 indicate that Colombia is producing about 910 metric tons of export quality cocaine. That represents a large increase from the 670-ton estimate the year before and the 325-ton estimate the year before that.

Similarly, a sharp rise in cocaine-related deaths, an approximate 52% increase, has been charted from 2015 to 2016. This finding is likely related to the growing presence of adulterants, such as fentanyl and carfentanil, found in seized cocaine samples. However, a rise in first-time cocaine users in the past year, which, according to the National Survey on Drug Use and Health, is up by about 12% (1.1 million people) in the 2015-2016 period, shows that the danger of cocaine-related deaths might not lie solely in adulteration but also increases in use. These signals might herald a grim return of cocaine to the center stage of public health, a development that would be an encore of the crack cocaine epidemic experienced throughout the 1980s and early 1990s.

All the above findings support cocaine as an agent of swift and massive change to our reward systems that might be poised to again surge across the United States at epidemic levels. Given this insight into just how extensively it rewires brains and the unfortunate truth that direct pharmacotherapy treatments remain mostly theoretical, it is evident that the best course of action is simply to keep cocaine from ever reaching the brain in the first place. Prevention does work, and these findings underline the importance of that message. Direct psychoeducation, awareness programs, and deterrence are the best defense we can offer to our patients at this time. In addition to these tried and true techniques, fascinating new models of prevention for cocaine abuse also are in development: vaccines. Synthesized by binding cocaine to inert proteins, these vaccines are designed to prevent addiction by training the immune system to bind cocaine and thus prevent it from crossing the blood brain barrier.⁷ Currently approved for clinical study in humans, these might offer a game-changing new method in the prevention of substance abuse.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

References

1. Yale J Biol Med. 1988 Mar-Apr;61(2):149-55.

2. Neurosci Biobehav Rev. 1985 Fall;9(3):469-77.

3. Am J Psychiatry. 1990;147(6):719-24.

4. DEA Museum. “A New Look at Old and Not So Old Drugs: A 2018 Update on Cocaine.” Drug Enforcement Administration. Retrieved from https://deamuseum.org/lecture-series/new-look-old-not-old-drugs-2018-update-cocaine.

5. J Addict Dis. 1996;15(4):55-71.

6. The American Disease: Origins of Narcotic Control (New York: Oxford University Press, 1999).

7. Br J Clin Pharmacol. 2014 Feb;77(2):368-74.

Ongoing efforts to understand the impact of cocaine on the brain and on behavior have gained considerable momentum over the past few decades. It was only 30 years ago when cocaine was widely considered both safe and nonaddicting – “the champagne” of drugs.¹ Progress has been steady since the cocaine-dopamine depletion theory was proposed, and ultimately supported by functional and PET imaging.^2,3

Additional discoveries promise further insights into the neuroscience of addiction, pleasure, and mood. While cocaine use, abuse, and dependence might seem relatively quiescent, compared with the scourge of opiate-related deaths and addiction, it remains a public health concern – and now is the second-leading cause of drug deaths. Cocaine cultivation, smuggling, use, and the number of first-time users are all escalating.⁴

These developments suggest that cocaine problems might get much worse and beg an important question: Will new research give us insight into better solutions?

What the neuroscience shows

As discussed, we already know quite a bit about the neuroscience behind cocaine addiction. The positron emission tomography studies conducted by Nora D. Volkow, MD, and her associates have shown long-lasting changes in abstinent cocaine addicts. Specifically, their findings clearly demonstrated that cocaine changes the brain and depletes dopamine-rich areas. Furthermore, dopamine recovery is negligible after months of abstinence.⁵

However, large gaps in our understanding remain. The realm of epigenetic study and protein expression behind abuse will be key in bridging our understanding of phenotype to genotype. A recent article by Eric J. Nestler, MD, PhD, and his research team, published in the Journal of Biological Psychiatry and titled “Cocaine self-administration alters transcriptome-wide responses in the brain’s reward circuitry,” offers exciting new insights (Biol Psychiatry. 2018 Apr. doi: 10.1016/jbiopsych.2018.04.009).

The study, led by Deena M. Walker, PhD, offers perhaps the most complete illumination to date of the genetic and epigenetic changes seen in the brain after cocaine self-administration and application.

Dr. Walker and her associates used a mouse model and sorted them into one of several groups. One group examined self-administered acute cocaine exposure only, with the mice immediately harvested thereafter. Two longer-term groups included one that had cocaine exposure with prolonged (30-day) withdrawal followed by context re-exposure (context re-exposure defined as being placed back in the special chamber and lighting they first received cocaine in) and another that had a cocaine exposure with prolonged withdrawal followed by both context and cocaine re-exposure.

The researchers also ran a parallel set of control groups substituting saline for cocaine with otherwise identical durations of observation and context re-exposure. Reward-related brain regions were harvested from each subject and examined with RNA-sequencing analysis to investigate the full genomic/transcriptomic profile of each. Pairwise comparison of the various experimental groups against the control groups (for example, the theoretical baseline of genetic expression in a non–cocaine-exposed brain) uncovered telling patterns, which the investigators aptly described as a comprehensive picture of transcriptome-wide change cocaine causes within the reward circuit.

The novel and creative approach used by Dr. Walker and her associates allowed them to uncover a wealth of clinically significant findings. Much could be said about their spotlighting of specific gene/protein targets for potential future pharmacological therapies toward cocaine treatment – an area that is indeed in sore need of invention. While we have highly efficacious medications for overdose and chronic treatment of opiate abuse, the landscape of treatment options for cocaine is far bleaker and shrouded in theory. With that in mind, perhaps the most salient take-home point is the evidence that cocaine, even after one exposure/withdrawal event, causes a dramatic rewiring in the very way genes are expressed across the reward circuit. The researchers found large shifts in the patterns of genetic transcription, unique and specific to discrete regions of the examined brain tissue, such as the ventral tegmental area, ventral hippocampus, and basolateral amygdala.

More interestingly, similar patterns of these genetic alternations were observed based on the exact history of the cocaine exposure. Dr. Walker and her associates concluded that the withdrawal phase and context re-exposure appear to be crucial components in the re-sculpting of the transcriptomic profile of the reward circuity.

The brain is unprepared by evolution for the reinforcing and reorganizing effects of cocaine. Clinicians, too, have learned that cocaine is addicting and can quickly replace drives such as food, water, sex, and survival. These new data from Dr. Nestler’s team reinforce the importance of prevention. In addition, they are reminders to physicians that cocaine causes changes in brain and behavior that are persistent and not necessarily reversible. Patterns of transcriptomic change are alarming enough and have only recent begun to be fleshed out, but patterns of global substance use trends suggest that we need to begin cocaine prevention activities.
 

Is another cocaine epidemic inevitable?

The late David F. Musto, MD, who was revered as both expert medical historian and physician at Yale University, New Haven, Conn., offered perhaps the most poignant observation in this regard: He argued that almost every opiate epidemic seems to transition into a psychostimulant epidemic.⁶ Experts have been looking at cocaine and methamphetamine as a way to try to understand the current opioid epidemic. Indeed, the Centers for Disease Control and Prevention’s most recent report on emerging trends in cocaine use shows numerous, concerning upticks in several realms germane to a possible emerging epidemic. One of the more upstream concerns is a gigantic spike in the shear production of coca leaves and cocaine thought to be occurring in Colombia (the principal source of cocaine in the United States). Current U.S. government estimates based on seizure rates from 2016 indicate that Colombia is producing about 910 metric tons of export quality cocaine. That represents a large increase from the 670-ton estimate the year before and the 325-ton estimate the year before that.

Similarly, a sharp rise in cocaine-related deaths, an approximate 52% increase, has been charted from 2015 to 2016. This finding is likely related to the growing presence of adulterants, such as fentanyl and carfentanil, found in seized cocaine samples. However, a rise in first-time cocaine users in the past year, which, according to the National Survey on Drug Use and Health, is up by about 12% (1.1 million people) in the 2015-2016 period, shows that the danger of cocaine-related deaths might not lie solely in adulteration but also increases in use. These signals might herald a grim return of cocaine to the center stage of public health, a development that would be an encore of the crack cocaine epidemic experienced throughout the 1980s and early 1990s.

All the above findings support cocaine as an agent of swift and massive change to our reward systems that might be poised to again surge across the United States at epidemic levels. Given this insight into just how extensively it rewires brains and the unfortunate truth that direct pharmacotherapy treatments remain mostly theoretical, it is evident that the best course of action is simply to keep cocaine from ever reaching the brain in the first place. Prevention does work, and these findings underline the importance of that message. Direct psychoeducation, awareness programs, and deterrence are the best defense we can offer to our patients at this time. In addition to these tried and true techniques, fascinating new models of prevention for cocaine abuse also are in development: vaccines. Synthesized by binding cocaine to inert proteins, these vaccines are designed to prevent addiction by training the immune system to bind cocaine and thus prevent it from crossing the blood brain barrier.⁷ Currently approved for clinical study in humans, these might offer a game-changing new method in the prevention of substance abuse.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

References

1. Yale J Biol Med. 1988 Mar-Apr;61(2):149-55.

2. Neurosci Biobehav Rev. 1985 Fall;9(3):469-77.

3. Am J Psychiatry. 1990;147(6):719-24.

4. DEA Museum. “A New Look at Old and Not So Old Drugs: A 2018 Update on Cocaine.” Drug Enforcement Administration. Retrieved from https://deamuseum.org/lecture-series/new-look-old-not-old-drugs-2018-update-cocaine.

5. J Addict Dis. 1996;15(4):55-71.

6. The American Disease: Origins of Narcotic Control (New York: Oxford University Press, 1999).

7. Br J Clin Pharmacol. 2014 Feb;77(2):368-74.

The Supreme Court decision to overturn the federal law that prohibited state-sanctioned college and professional sports betting is bad news for clinicians who treat patients with addictions.

On May 14, the high court ruled 7-2 that the 1992 law, called the Professional and Amateur Sports Protection Act (PASPA), was unconstitutional. Now every state is free to operate, sponsor, promote, license, advertise, or authorize gambling for any college or professional sport–based event.

Optimistic outlooks on the death of PASPA include the foreseen opportunity by the states to tax and generate revenue on such gambling. Proponents of the ruling also argue that illegal activity that thrived on sports betting will now end.

But to what extent will either of those scenarios benefit the public?

If passage of various state marijuana laws is any example, assumptions that legal avenues will usurp illegal enterprises are flawed. Also, taxation likely will generate a large sum of revenue for each state. But those revenues might be offset by subsequent changes that will be needed in mental health, addiction, and wellness programs – a difficult proposition given the opioid epidemic already overburdening the country. Remember the tobacco cases and promise of state support for education, treatment, and other noble activities? Addiction medicine specialists worry that taxes collected by the states, and promises to prevent and treat gambling problems – and prevent addiction – will not end up in those coffers.

As clinicians, perhaps our most important contribution to the debates on this ruling lies in raising awareness of pathological gambling as an addiction disorder.
 

Redefining the act of gambling

Breaking down previous barriers to access and increasing convenience to gambling undoubtedly will be associated with increased pathological engagement in gambling. This conclusion is clear, based on past national experiments with substances of addiction (such as alcohol prohibition).

Since the cocaine epidemic of the 1980s, and our increased understanding that addictions need not have prominent withdrawal syndromes, we have focused on addiction as a fatal attraction. Psychiatrists and other clinicians made the case – in some quarters, at least – for sugar, sex, and Internet compulsivity as addictions. Compared with those addictions, the evidence was clearest and most compelling for pathological gambling as an addiction disorder. Indeed, gambling disorder was introduced in 2013 to the DSM-5 as the very first non–substance-based addictive disorder. This was a decisive change, as it recognizes that gambling is more than an environmental hazard for those suffering from dopamine-driven obsessive-compulsive-like dysfunction (the DSM section where it had lived previously). Instead, gambling acts as an agent that can initiate a usurpation of the brain’s reward circuitry. (In addition, this change has reopened the door for other increasingly recognized non–substance-based disorder categories such as video game and pornography addiction, and others.)

Gambling disorder certainly fits well into what many experts view as the essential phenotype of any addiction: Continued use despite harm, waning self-control over engagement, a craving state, and compulsive use. Current research is expanding rapidly and filling in the theoretical framework, strongly supporting gambling disorder based on biological evidence. Much of what we now know about the biology of addiction has been through the efforts of the Yale University–based research group, led by psychiatrist Marc N. Potenza. Dr. Potenza and his colleagues have been investigating gambling disorder in a thorough manner (Harv Rev Psychiatry. 2015 Mar-Apr;23[2]:134-46) and (Curr Treat Options Psychiatry. 2014 Jun 1;1[2]:189-203). Indeed, gambling disorder is much like the other substance-use disorders in which it is grouped, in that it has been found to share some similarities/pathways common to all addictions while also carrying its own specific nuances.

Twin studies have unearthed a wealth of information, such as knowledge that environmental factors seem to be the predominant source of the comorbid development of gambling disorder with the more socially acceptable substances as associated use disorders (alcohol, tobacco, and marijuana) through mechanisms such as peer association and place preference conditioning. Similarly, genetic influences also might be meaningful to treatment. For example, one finding showed that patients with gambling disorder and a family history of alcoholism were found to more preferentially respond to opioid-receptor antagonists as treatment for gambling disorder, compared with individuals without such family history (Psychopharmacology [Berl]. 2008;200[4]:521-7).

Explorations of neurotransmitter involvement and brain connectivity also have been conducted for gambling behaviors. Dopaminergic underpinnings of addiction have been particularly indicated in imaging studies focused on the ventral striatum and other components of reward circuitry. In addition, functional MRI studies have identified both overlapping and discordant brain imaging findings between gambling and many other substance use disorders such as cocaine. All these indicate that gambling seems, like its use-disorder counterparts, to follow a similar but distinct course of hijacking reward systems and priming the brain to seek out further gambling in a pathological manner.
 

Vulnerable populations

Another key finding of recent research exploring the biological foundations of gambling disorder is gender dimorphism. In numerous studies, women have been found to experience a “telescoping effect” from gambling, compared with their male counterparts, where they seem to more quickly advance from first exposure to problematic use. This phenomenon also is seen in women who use cocaine. Also, functional MRI studies also have found that women appear to have alternative signal changes in regions germane to addiction, compared with their male counterparts. One such example was greater activity in the hippocampus and middle temporal gyrus in women, suggestive of stronger activation of regions key for memory retrieval used in craving/urge-related emotions. These data highlight the need for not only understanding how gambling and other addictions diverge between men and women, but also for how prevention and treatment of these disorders might differ based on sex.

Adolescents also get special consideration: How will they be affected by this expected growth in gambling avenues? Adolescence and young adulthood are periods of development defined by increased impulsivity and risk taking, making this population particularly vulnerable to addiction that can then persist into adulthood. It is expected that age laws will persist and prevent the legal access adults might enjoy, but shifts in opinions of harm and ease of access are likely to contribute to increased gambling exposure. To use another addictive phenomena as an example, data from the Substance Abuse and Mental Health Services Administration show a clear correlation between marijuana use, marijuana legal status, and perceptions of risk. Specifically, areas with unfettered/loosened marijuana regulation have much lower levels of perceived risk among youth and much higher levels of use. Gambling could follow a similar course.

Perhaps the most crucial observation is that the most severe pathological gamblers began gambling before adulthood. Many factors have been identified that seem to increase rates of gambling in youth: Receiving scratch-off lotto cards as gifts, gambling on school grounds, and even smoking status (quite significant given the advent of e-cigarettes now common to many high school students). All of these essentially boil down to the common pathway of proximity and social referencing. As such, the notion that an increased social presence of (what will likely be) large scale, polished, mass televised sports gambling events will be associated with increased gambling behavior (and other mental health comorbidities) among youth is not far-fetched. What also is known for gambling, as well as for other addictive disorders, is that earlier age of onset is correlated to a worse prognosis of gambling disorder in adulthood. In other words, the earlier an addiction strikes, the deeper and more severe it is in the individual – further highlighting the impetus to focus concerns about the PASPA ruling toward the impact on youth.
 

Prevention and treatment

Lastly, it is important to consider the ground gained in preventing and treating gambling addiction. Many groups focused on treating and preventing gambling already are well established, such as Gamblers Anonymous, and these groups have produced favorable results. More targeted interventions such as cognitive-behavioral therapy adjusted for addiction disorders also have proved effective, as they often not only tackle the gambling disorder but also the collection of conditions it is so often comorbid with (affective illnesses, anxiety disorders).

Pharmacotherapy also has a role, further justifying the view of gambling disorder, and indeed all addiction disorders, as biological processes with biological solutions. Examinations into opiate antagonism and glutamatergic modulation (N-acetylcysteine) also have shown some promise. Prevention programs offer perhaps the best cost-effective ratio in reducing the societal burden of gambling, which is about $7 billion annually, according to 2013 estimates by the National Council on Problem Gambling). These programs have been conducted in schools through parent-teacher groups as well as publicly through distribution of informative psychoeducation via TV and advertising channels.

All available research conducted on treatment shows that further research and validation are needed. We should not pretend that increasing access to sports betting and normalizing the activity will not have an effect on gambling prevalence and problems. Prevention, even simple cautionary public warnings, requires time, money, and planning for effective execution.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

The Supreme Court decision to overturn the federal law that prohibited state-sanctioned college and professional sports betting is bad news for clinicians who treat patients with addictions.

On May 14, the high court ruled 7-2 that the 1992 law, called the Professional and Amateur Sports Protection Act (PASPA), was unconstitutional. Now every state is free to operate, sponsor, promote, license, advertise, or authorize gambling for any college or professional sport–based event.

Optimistic outlooks on the death of PASPA include the foreseen opportunity by the states to tax and generate revenue on such gambling. Proponents of the ruling also argue that illegal activity that thrived on sports betting will now end.

But to what extent will either of those scenarios benefit the public?

If passage of various state marijuana laws is any example, assumptions that legal avenues will usurp illegal enterprises are flawed. Also, taxation likely will generate a large sum of revenue for each state. But those revenues might be offset by subsequent changes that will be needed in mental health, addiction, and wellness programs – a difficult proposition given the opioid epidemic already overburdening the country. Remember the tobacco cases and promise of state support for education, treatment, and other noble activities? Addiction medicine specialists worry that taxes collected by the states, and promises to prevent and treat gambling problems – and prevent addiction – will not end up in those coffers.

As clinicians, perhaps our most important contribution to the debates on this ruling lies in raising awareness of pathological gambling as an addiction disorder.
 

Redefining the act of gambling

Breaking down previous barriers to access and increasing convenience to gambling undoubtedly will be associated with increased pathological engagement in gambling. This conclusion is clear, based on past national experiments with substances of addiction (such as alcohol prohibition).

Since the cocaine epidemic of the 1980s, and our increased understanding that addictions need not have prominent withdrawal syndromes, we have focused on addiction as a fatal attraction. Psychiatrists and other clinicians made the case – in some quarters, at least – for sugar, sex, and Internet compulsivity as addictions. Compared with those addictions, the evidence was clearest and most compelling for pathological gambling as an addiction disorder. Indeed, gambling disorder was introduced in 2013 to the DSM-5 as the very first non–substance-based addictive disorder. This was a decisive change, as it recognizes that gambling is more than an environmental hazard for those suffering from dopamine-driven obsessive-compulsive-like dysfunction (the DSM section where it had lived previously). Instead, gambling acts as an agent that can initiate a usurpation of the brain’s reward circuitry. (In addition, this change has reopened the door for other increasingly recognized non–substance-based disorder categories such as video game and pornography addiction, and others.)

Gambling disorder certainly fits well into what many experts view as the essential phenotype of any addiction: Continued use despite harm, waning self-control over engagement, a craving state, and compulsive use. Current research is expanding rapidly and filling in the theoretical framework, strongly supporting gambling disorder based on biological evidence. Much of what we now know about the biology of addiction has been through the efforts of the Yale University–based research group, led by psychiatrist Marc N. Potenza. Dr. Potenza and his colleagues have been investigating gambling disorder in a thorough manner (Harv Rev Psychiatry. 2015 Mar-Apr;23[2]:134-46) and (Curr Treat Options Psychiatry. 2014 Jun 1;1[2]:189-203). Indeed, gambling disorder is much like the other substance-use disorders in which it is grouped, in that it has been found to share some similarities/pathways common to all addictions while also carrying its own specific nuances.

Twin studies have unearthed a wealth of information, such as knowledge that environmental factors seem to be the predominant source of the comorbid development of gambling disorder with the more socially acceptable substances as associated use disorders (alcohol, tobacco, and marijuana) through mechanisms such as peer association and place preference conditioning. Similarly, genetic influences also might be meaningful to treatment. For example, one finding showed that patients with gambling disorder and a family history of alcoholism were found to more preferentially respond to opioid-receptor antagonists as treatment for gambling disorder, compared with individuals without such family history (Psychopharmacology [Berl]. 2008;200[4]:521-7).

Explorations of neurotransmitter involvement and brain connectivity also have been conducted for gambling behaviors. Dopaminergic underpinnings of addiction have been particularly indicated in imaging studies focused on the ventral striatum and other components of reward circuitry. In addition, functional MRI studies have identified both overlapping and discordant brain imaging findings between gambling and many other substance use disorders such as cocaine. All these indicate that gambling seems, like its use-disorder counterparts, to follow a similar but distinct course of hijacking reward systems and priming the brain to seek out further gambling in a pathological manner.
 

Vulnerable populations

Another key finding of recent research exploring the biological foundations of gambling disorder is gender dimorphism. In numerous studies, women have been found to experience a “telescoping effect” from gambling, compared with their male counterparts, where they seem to more quickly advance from first exposure to problematic use. This phenomenon also is seen in women who use cocaine. Also, functional MRI studies also have found that women appear to have alternative signal changes in regions germane to addiction, compared with their male counterparts. One such example was greater activity in the hippocampus and middle temporal gyrus in women, suggestive of stronger activation of regions key for memory retrieval used in craving/urge-related emotions. These data highlight the need for not only understanding how gambling and other addictions diverge between men and women, but also for how prevention and treatment of these disorders might differ based on sex.

Adolescents also get special consideration: How will they be affected by this expected growth in gambling avenues? Adolescence and young adulthood are periods of development defined by increased impulsivity and risk taking, making this population particularly vulnerable to addiction that can then persist into adulthood. It is expected that age laws will persist and prevent the legal access adults might enjoy, but shifts in opinions of harm and ease of access are likely to contribute to increased gambling exposure. To use another addictive phenomena as an example, data from the Substance Abuse and Mental Health Services Administration show a clear correlation between marijuana use, marijuana legal status, and perceptions of risk. Specifically, areas with unfettered/loosened marijuana regulation have much lower levels of perceived risk among youth and much higher levels of use. Gambling could follow a similar course.

Perhaps the most crucial observation is that the most severe pathological gamblers began gambling before adulthood. Many factors have been identified that seem to increase rates of gambling in youth: Receiving scratch-off lotto cards as gifts, gambling on school grounds, and even smoking status (quite significant given the advent of e-cigarettes now common to many high school students). All of these essentially boil down to the common pathway of proximity and social referencing. As such, the notion that an increased social presence of (what will likely be) large scale, polished, mass televised sports gambling events will be associated with increased gambling behavior (and other mental health comorbidities) among youth is not far-fetched. What also is known for gambling, as well as for other addictive disorders, is that earlier age of onset is correlated to a worse prognosis of gambling disorder in adulthood. In other words, the earlier an addiction strikes, the deeper and more severe it is in the individual – further highlighting the impetus to focus concerns about the PASPA ruling toward the impact on youth.
 

Prevention and treatment

Lastly, it is important to consider the ground gained in preventing and treating gambling addiction. Many groups focused on treating and preventing gambling already are well established, such as Gamblers Anonymous, and these groups have produced favorable results. More targeted interventions such as cognitive-behavioral therapy adjusted for addiction disorders also have proved effective, as they often not only tackle the gambling disorder but also the collection of conditions it is so often comorbid with (affective illnesses, anxiety disorders).

Pharmacotherapy also has a role, further justifying the view of gambling disorder, and indeed all addiction disorders, as biological processes with biological solutions. Examinations into opiate antagonism and glutamatergic modulation (N-acetylcysteine) also have shown some promise. Prevention programs offer perhaps the best cost-effective ratio in reducing the societal burden of gambling, which is about $7 billion annually, according to 2013 estimates by the National Council on Problem Gambling). These programs have been conducted in schools through parent-teacher groups as well as publicly through distribution of informative psychoeducation via TV and advertising channels.

All available research conducted on treatment shows that further research and validation are needed. We should not pretend that increasing access to sports betting and normalizing the activity will not have an effect on gambling prevalence and problems. Prevention, even simple cautionary public warnings, requires time, money, and planning for effective execution.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

The Supreme Court decision to overturn the federal law that prohibited state-sanctioned college and professional sports betting is bad news for clinicians who treat patients with addictions.

On May 14, the high court ruled 7-2 that the 1992 law, called the Professional and Amateur Sports Protection Act (PASPA), was unconstitutional. Now every state is free to operate, sponsor, promote, license, advertise, or authorize gambling for any college or professional sport–based event.

Optimistic outlooks on the death of PASPA include the foreseen opportunity by the states to tax and generate revenue on such gambling. Proponents of the ruling also argue that illegal activity that thrived on sports betting will now end.

But to what extent will either of those scenarios benefit the public?

If passage of various state marijuana laws is any example, assumptions that legal avenues will usurp illegal enterprises are flawed. Also, taxation likely will generate a large sum of revenue for each state. But those revenues might be offset by subsequent changes that will be needed in mental health, addiction, and wellness programs – a difficult proposition given the opioid epidemic already overburdening the country. Remember the tobacco cases and promise of state support for education, treatment, and other noble activities? Addiction medicine specialists worry that taxes collected by the states, and promises to prevent and treat gambling problems – and prevent addiction – will not end up in those coffers.

As clinicians, perhaps our most important contribution to the debates on this ruling lies in raising awareness of pathological gambling as an addiction disorder.
 

Redefining the act of gambling

Breaking down previous barriers to access and increasing convenience to gambling undoubtedly will be associated with increased pathological engagement in gambling. This conclusion is clear, based on past national experiments with substances of addiction (such as alcohol prohibition).

Since the cocaine epidemic of the 1980s, and our increased understanding that addictions need not have prominent withdrawal syndromes, we have focused on addiction as a fatal attraction. Psychiatrists and other clinicians made the case – in some quarters, at least – for sugar, sex, and Internet compulsivity as addictions. Compared with those addictions, the evidence was clearest and most compelling for pathological gambling as an addiction disorder. Indeed, gambling disorder was introduced in 2013 to the DSM-5 as the very first non–substance-based addictive disorder. This was a decisive change, as it recognizes that gambling is more than an environmental hazard for those suffering from dopamine-driven obsessive-compulsive-like dysfunction (the DSM section where it had lived previously). Instead, gambling acts as an agent that can initiate a usurpation of the brain’s reward circuitry. (In addition, this change has reopened the door for other increasingly recognized non–substance-based disorder categories such as video game and pornography addiction, and others.)

Gambling disorder certainly fits well into what many experts view as the essential phenotype of any addiction: Continued use despite harm, waning self-control over engagement, a craving state, and compulsive use. Current research is expanding rapidly and filling in the theoretical framework, strongly supporting gambling disorder based on biological evidence. Much of what we now know about the biology of addiction has been through the efforts of the Yale University–based research group, led by psychiatrist Marc N. Potenza. Dr. Potenza and his colleagues have been investigating gambling disorder in a thorough manner (Harv Rev Psychiatry. 2015 Mar-Apr;23[2]:134-46) and (Curr Treat Options Psychiatry. 2014 Jun 1;1[2]:189-203). Indeed, gambling disorder is much like the other substance-use disorders in which it is grouped, in that it has been found to share some similarities/pathways common to all addictions while also carrying its own specific nuances.

Twin studies have unearthed a wealth of information, such as knowledge that environmental factors seem to be the predominant source of the comorbid development of gambling disorder with the more socially acceptable substances as associated use disorders (alcohol, tobacco, and marijuana) through mechanisms such as peer association and place preference conditioning. Similarly, genetic influences also might be meaningful to treatment. For example, one finding showed that patients with gambling disorder and a family history of alcoholism were found to more preferentially respond to opioid-receptor antagonists as treatment for gambling disorder, compared with individuals without such family history (Psychopharmacology [Berl]. 2008;200[4]:521-7).

Explorations of neurotransmitter involvement and brain connectivity also have been conducted for gambling behaviors. Dopaminergic underpinnings of addiction have been particularly indicated in imaging studies focused on the ventral striatum and other components of reward circuitry. In addition, functional MRI studies have identified both overlapping and discordant brain imaging findings between gambling and many other substance use disorders such as cocaine. All these indicate that gambling seems, like its use-disorder counterparts, to follow a similar but distinct course of hijacking reward systems and priming the brain to seek out further gambling in a pathological manner.
 

Vulnerable populations

Another key finding of recent research exploring the biological foundations of gambling disorder is gender dimorphism. In numerous studies, women have been found to experience a “telescoping effect” from gambling, compared with their male counterparts, where they seem to more quickly advance from first exposure to problematic use. This phenomenon also is seen in women who use cocaine. Also, functional MRI studies also have found that women appear to have alternative signal changes in regions germane to addiction, compared with their male counterparts. One such example was greater activity in the hippocampus and middle temporal gyrus in women, suggestive of stronger activation of regions key for memory retrieval used in craving/urge-related emotions. These data highlight the need for not only understanding how gambling and other addictions diverge between men and women, but also for how prevention and treatment of these disorders might differ based on sex.

Adolescents also get special consideration: How will they be affected by this expected growth in gambling avenues? Adolescence and young adulthood are periods of development defined by increased impulsivity and risk taking, making this population particularly vulnerable to addiction that can then persist into adulthood. It is expected that age laws will persist and prevent the legal access adults might enjoy, but shifts in opinions of harm and ease of access are likely to contribute to increased gambling exposure. To use another addictive phenomena as an example, data from the Substance Abuse and Mental Health Services Administration show a clear correlation between marijuana use, marijuana legal status, and perceptions of risk. Specifically, areas with unfettered/loosened marijuana regulation have much lower levels of perceived risk among youth and much higher levels of use. Gambling could follow a similar course.

Perhaps the most crucial observation is that the most severe pathological gamblers began gambling before adulthood. Many factors have been identified that seem to increase rates of gambling in youth: Receiving scratch-off lotto cards as gifts, gambling on school grounds, and even smoking status (quite significant given the advent of e-cigarettes now common to many high school students). All of these essentially boil down to the common pathway of proximity and social referencing. As such, the notion that an increased social presence of (what will likely be) large scale, polished, mass televised sports gambling events will be associated with increased gambling behavior (and other mental health comorbidities) among youth is not far-fetched. What also is known for gambling, as well as for other addictive disorders, is that earlier age of onset is correlated to a worse prognosis of gambling disorder in adulthood. In other words, the earlier an addiction strikes, the deeper and more severe it is in the individual – further highlighting the impetus to focus concerns about the PASPA ruling toward the impact on youth.
 

Prevention and treatment

Lastly, it is important to consider the ground gained in preventing and treating gambling addiction. Many groups focused on treating and preventing gambling already are well established, such as Gamblers Anonymous, and these groups have produced favorable results. More targeted interventions such as cognitive-behavioral therapy adjusted for addiction disorders also have proved effective, as they often not only tackle the gambling disorder but also the collection of conditions it is so often comorbid with (affective illnesses, anxiety disorders).

Pharmacotherapy also has a role, further justifying the view of gambling disorder, and indeed all addiction disorders, as biological processes with biological solutions. Examinations into opiate antagonism and glutamatergic modulation (N-acetylcysteine) also have shown some promise. Prevention programs offer perhaps the best cost-effective ratio in reducing the societal burden of gambling, which is about $7 billion annually, according to 2013 estimates by the National Council on Problem Gambling). These programs have been conducted in schools through parent-teacher groups as well as publicly through distribution of informative psychoeducation via TV and advertising channels.

All available research conducted on treatment shows that further research and validation are needed. We should not pretend that increasing access to sports betting and normalizing the activity will not have an effect on gambling prevalence and problems. Prevention, even simple cautionary public warnings, requires time, money, and planning for effective execution.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

The opioid epidemic continues to devastate the United States across demographic and socioeconomic groups; two-thirds of the 63,632 Americans who died of drug overdoses¹ in 2016 died of prescription or illicit opioids.

In 2015, Theodore J. Cicero, PhD, professor of psychiatry at Washington University, St. Louis, reported on a fundamental change in the nature of the ongoing opioid epidemic: What started as prescription opioid overprescribing, leading to diversion, abuse, and opioid addiction, was transitioning to illicit heroin distribution and consumption. Prescription opioids, namely, extended-release oxycodone (Oxycontin), were perceived initially as pure and safe, as they were specifically dosed and physician prescribed. In addition, filling a prescription for opioids was not associated with the shame or stigma of buying illicit drugs off the street. Because those drugs were seen as therapeutic and pharmacologically “legitimate,” many clinicians and the lay public alike were surprised to see the surge of opioid addiction and overdoses.

Dr. Cicero and others noted² that prescription opioids, whether taken originally for analgesic or recreational purposes, became a “gateway” to heroin, which already was making its way into the United States from Mexico,³ as heroin was cheap and becoming cheaper, easier to find, easy to use, and “pure.” Prescription opioids, on the other hand, were becoming more expensive, and physicians were facing increased regulations in prescribing them. Thus, as prescription opioid use became more and more stigmatized, heroin use was seen, paradoxically, as a more practical alternative. The amount of opioids prescribed in the United States has peaked; physicians are prescribing opioids less often; and the averaged dose has dropped as well, according to the Centers for Disease Control and Prevention.⁴ The first wave of deaths was attributable to prescription opioids, and the second was tied to illicitly obtained potent fentanyl analogs (manufactured in China and smuggled primarily through Mexico), which is added to heroin and sold in the United States.⁵

Many addiction experts and health policy leaders were not surprised by the increases in HIV, TB, and hepatitis B and C that followed the increasing use of intravenous opioids. However, few had experience with previous opioid epidemics in the United States, the most recent being the heroin epidemic occurring in the 1960s-1970s in the aftermath of the Vietnam War. At that time, the notion that heroin was contaminated with other psychoactive drugs, medications, fillers, and other adulterants was a foregone conclusion – though in public health and treatment discussions, this issue is hardly ever raised. We believe this to be a significant lapse in policy and planning. Surveillance by the Drug Enforcement Administration shows that acetyl fentanyl–laced heroin costs a little more on the street than regular heroin. Yet it sells, because users believe its extreme potency produces a better high, thus worth the extra cost. This phenomenon underscores an important point: Opioid addicts often are in search of a better high and will go to any lengths – even risking their lives – to get it.

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution, and selling of illicit drugs, and the motive is to increase profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects, such as caffeine, ephedra, or even paracetamol. These substances are cheaper than the main substance, have similar or complementary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes to fool the user. Some adulterants simply are the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine frequently is contaminated by nonstimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. The local anesthetic lidocaine often is added to cocaine, and the reasons are intuitive: Both drugs are fast-acting local anesthetics.

More intriguing is the story of the antiparasitic medication levamisole. The DEA has estimated that 60%-89% of the seized street cocaine contains levamisole. Levamisole appears to be partly metabolized into an amphetamine-like compound, which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids: It can mimic the effects of cocaine at a fraction of the cost. Levamisole is associated with several types of severe blood disorders, including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy, and neutropenia; a common presentation is vasculitis resulting in loss of limbs. Thus, a real danger in adulterants such as levamisole is their toxicity beyond those of the drug to which they are added, causing numerous medical consequences – including death.

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health. Dr. Srivastava is a fourth-year resident in the department of psychiatry at Washington University.

References

1 NCHS Data Brief. No. 294. December 2017.

2 N Engl J Med. 2015;373:1789-90.

3 DEA Strategic Intelligence Section. 2017 National Drug Threat Assessment: Drug Enforcement Administration, U.S. Department of Justice, 2017.

4 Centers for Disease Control and Prevention, press release. Mar 29, 2018.

5 MMWR. 2018. Mar 30;67(12):349-58.

6 Am J Public Health. 2017 Mar;107(3):430-2.

7 “Q&A: Thomas Kosten, MD: Anti-drug vaccines.” RiverMend Health.

8 “Q&A: Stacy Seikel, MD. Opioid addiction.” RiverMend Health.

9 N Engl J Med. 2018 Apr 26;378:1567-9. doi: 10.1056/NEJMp1801417.

10 Innov Clin Neurosci. 2014 Sep;11(9-10):182-90.

11 Am J Psychiatry. 187 May;144(5):563-7.

The opioid epidemic continues to devastate the United States across demographic and socioeconomic groups; two-thirds of the 63,632 Americans who died of drug overdoses¹ in 2016 died of prescription or illicit opioids.

In 2015, Theodore J. Cicero, PhD, professor of psychiatry at Washington University, St. Louis, reported on a fundamental change in the nature of the ongoing opioid epidemic: What started as prescription opioid overprescribing, leading to diversion, abuse, and opioid addiction, was transitioning to illicit heroin distribution and consumption. Prescription opioids, namely, extended-release oxycodone (Oxycontin), were perceived initially as pure and safe, as they were specifically dosed and physician prescribed. In addition, filling a prescription for opioids was not associated with the shame or stigma of buying illicit drugs off the street. Because those drugs were seen as therapeutic and pharmacologically “legitimate,” many clinicians and the lay public alike were surprised to see the surge of opioid addiction and overdoses.

Dr. Cicero and others noted² that prescription opioids, whether taken originally for analgesic or recreational purposes, became a “gateway” to heroin, which already was making its way into the United States from Mexico,³ as heroin was cheap and becoming cheaper, easier to find, easy to use, and “pure.” Prescription opioids, on the other hand, were becoming more expensive, and physicians were facing increased regulations in prescribing them. Thus, as prescription opioid use became more and more stigmatized, heroin use was seen, paradoxically, as a more practical alternative. The amount of opioids prescribed in the United States has peaked; physicians are prescribing opioids less often; and the averaged dose has dropped as well, according to the Centers for Disease Control and Prevention.⁴ The first wave of deaths was attributable to prescription opioids, and the second was tied to illicitly obtained potent fentanyl analogs (manufactured in China and smuggled primarily through Mexico), which is added to heroin and sold in the United States.⁵

Many addiction experts and health policy leaders were not surprised by the increases in HIV, TB, and hepatitis B and C that followed the increasing use of intravenous opioids. However, few had experience with previous opioid epidemics in the United States, the most recent being the heroin epidemic occurring in the 1960s-1970s in the aftermath of the Vietnam War. At that time, the notion that heroin was contaminated with other psychoactive drugs, medications, fillers, and other adulterants was a foregone conclusion – though in public health and treatment discussions, this issue is hardly ever raised. We believe this to be a significant lapse in policy and planning. Surveillance by the Drug Enforcement Administration shows that acetyl fentanyl–laced heroin costs a little more on the street than regular heroin. Yet it sells, because users believe its extreme potency produces a better high, thus worth the extra cost. This phenomenon underscores an important point: Opioid addicts often are in search of a better high and will go to any lengths – even risking their lives – to get it.

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution, and selling of illicit drugs, and the motive is to increase profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects, such as caffeine, ephedra, or even paracetamol. These substances are cheaper than the main substance, have similar or complementary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes to fool the user. Some adulterants simply are the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine frequently is contaminated by nonstimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. The local anesthetic lidocaine often is added to cocaine, and the reasons are intuitive: Both drugs are fast-acting local anesthetics.

More intriguing is the story of the antiparasitic medication levamisole. The DEA has estimated that 60%-89% of the seized street cocaine contains levamisole. Levamisole appears to be partly metabolized into an amphetamine-like compound, which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids: It can mimic the effects of cocaine at a fraction of the cost. Levamisole is associated with several types of severe blood disorders, including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy, and neutropenia; a common presentation is vasculitis resulting in loss of limbs. Thus, a real danger in adulterants such as levamisole is their toxicity beyond those of the drug to which they are added, causing numerous medical consequences – including death.

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health. Dr. Srivastava is a fourth-year resident in the department of psychiatry at Washington University.

References

1 NCHS Data Brief. No. 294. December 2017.

2 N Engl J Med. 2015;373:1789-90.

3 DEA Strategic Intelligence Section. 2017 National Drug Threat Assessment: Drug Enforcement Administration, U.S. Department of Justice, 2017.

4 Centers for Disease Control and Prevention, press release. Mar 29, 2018.

5 MMWR. 2018. Mar 30;67(12):349-58.

6 Am J Public Health. 2017 Mar;107(3):430-2.

7 “Q&A: Thomas Kosten, MD: Anti-drug vaccines.” RiverMend Health.

8 “Q&A: Stacy Seikel, MD. Opioid addiction.” RiverMend Health.

9 N Engl J Med. 2018 Apr 26;378:1567-9. doi: 10.1056/NEJMp1801417.

10 Innov Clin Neurosci. 2014 Sep;11(9-10):182-90.

11 Am J Psychiatry. 187 May;144(5):563-7.

The opioid epidemic continues to devastate the United States across demographic and socioeconomic groups; two-thirds of the 63,632 Americans who died of drug overdoses¹ in 2016 died of prescription or illicit opioids.

In 2015, Theodore J. Cicero, PhD, professor of psychiatry at Washington University, St. Louis, reported on a fundamental change in the nature of the ongoing opioid epidemic: What started as prescription opioid overprescribing, leading to diversion, abuse, and opioid addiction, was transitioning to illicit heroin distribution and consumption. Prescription opioids, namely, extended-release oxycodone (Oxycontin), were perceived initially as pure and safe, as they were specifically dosed and physician prescribed. In addition, filling a prescription for opioids was not associated with the shame or stigma of buying illicit drugs off the street. Because those drugs were seen as therapeutic and pharmacologically “legitimate,” many clinicians and the lay public alike were surprised to see the surge of opioid addiction and overdoses.

Dr. Cicero and others noted² that prescription opioids, whether taken originally for analgesic or recreational purposes, became a “gateway” to heroin, which already was making its way into the United States from Mexico,³ as heroin was cheap and becoming cheaper, easier to find, easy to use, and “pure.” Prescription opioids, on the other hand, were becoming more expensive, and physicians were facing increased regulations in prescribing them. Thus, as prescription opioid use became more and more stigmatized, heroin use was seen, paradoxically, as a more practical alternative. The amount of opioids prescribed in the United States has peaked; physicians are prescribing opioids less often; and the averaged dose has dropped as well, according to the Centers for Disease Control and Prevention.⁴ The first wave of deaths was attributable to prescription opioids, and the second was tied to illicitly obtained potent fentanyl analogs (manufactured in China and smuggled primarily through Mexico), which is added to heroin and sold in the United States.⁵

Many addiction experts and health policy leaders were not surprised by the increases in HIV, TB, and hepatitis B and C that followed the increasing use of intravenous opioids. However, few had experience with previous opioid epidemics in the United States, the most recent being the heroin epidemic occurring in the 1960s-1970s in the aftermath of the Vietnam War. At that time, the notion that heroin was contaminated with other psychoactive drugs, medications, fillers, and other adulterants was a foregone conclusion – though in public health and treatment discussions, this issue is hardly ever raised. We believe this to be a significant lapse in policy and planning. Surveillance by the Drug Enforcement Administration shows that acetyl fentanyl–laced heroin costs a little more on the street than regular heroin. Yet it sells, because users believe its extreme potency produces a better high, thus worth the extra cost. This phenomenon underscores an important point: Opioid addicts often are in search of a better high and will go to any lengths – even risking their lives – to get it.

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution, and selling of illicit drugs, and the motive is to increase profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects, such as caffeine, ephedra, or even paracetamol. These substances are cheaper than the main substance, have similar or complementary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes to fool the user. Some adulterants simply are the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine frequently is contaminated by nonstimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. The local anesthetic lidocaine often is added to cocaine, and the reasons are intuitive: Both drugs are fast-acting local anesthetics.

More intriguing is the story of the antiparasitic medication levamisole. The DEA has estimated that 60%-89% of the seized street cocaine contains levamisole. Levamisole appears to be partly metabolized into an amphetamine-like compound, which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids: It can mimic the effects of cocaine at a fraction of the cost. Levamisole is associated with several types of severe blood disorders, including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy, and neutropenia; a common presentation is vasculitis resulting in loss of limbs. Thus, a real danger in adulterants such as levamisole is their toxicity beyond those of the drug to which they are added, causing numerous medical consequences – including death.

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health. Dr. Srivastava is a fourth-year resident in the department of psychiatry at Washington University.

References

1 NCHS Data Brief. No. 294. December 2017.

2 N Engl J Med. 2015;373:1789-90.

3 DEA Strategic Intelligence Section. 2017 National Drug Threat Assessment: Drug Enforcement Administration, U.S. Department of Justice, 2017.

4 Centers for Disease Control and Prevention, press release. Mar 29, 2018.

5 MMWR. 2018. Mar 30;67(12):349-58.

6 Am J Public Health. 2017 Mar;107(3):430-2.

7 “Q&A: Thomas Kosten, MD: Anti-drug vaccines.” RiverMend Health.

8 “Q&A: Stacy Seikel, MD. Opioid addiction.” RiverMend Health.

9 N Engl J Med. 2018 Apr 26;378:1567-9. doi: 10.1056/NEJMp1801417.

10 Innov Clin Neurosci. 2014 Sep;11(9-10):182-90.

11 Am J Psychiatry. 187 May;144(5):563-7.