Addiction Medicine

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

On a recent Sunday morning in Los Angeles, 10 members of Gamblers Anonymous gathered in a park for their regular meeting. After, they shared advice for how physicians can best help patients with problem gambling.

“If a patient talks about financial distress, spouse issues, physical issues, or has blood pressure issues, suspect gambling,” one woman said. Another said, if a physician asks about gambling and the patient says, “Just a little,” chances are that person is an active gambler.

The bottom line: None of the people — who spoke for themselves and not on behalf of Gamblers Anonymous — said they had been asked by their doctors about gambling issues. All said they would welcome such questions.

Gambling is on the rise, and gambling disorder is now recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The condition is viewed as similar to substance-related disorders in its clinical expression, brain origin, comorbidity, physiology, and treatment.

Primary care physicians (PCPs), more than any of their colleagues, are likely to encounter a patient with an undetected gambling disorder, according to experts, as it often intertwines with physical and mental health concerns. Those conditions bring the patient to their clinicians, although the patients may not link those issues with their gambling. The physicians may not either.

Few PCPs broach the topic. “I would say the majority of physicians do not screen for it,” said Brian K. Unwin, MD, FAAFP, AGSF, a family medicine physician and geriatrician at the Carilion Center for Healthy Aging and professor at the Virginia Tech Carilion School of Medicine, Roanoke.

The clinician who does take steps to screen for the problem is “exceptionally rare,” said Timothy W. Fong, MD, clinical professor of psychiatry at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gambling Studies Program. Launched in 2005, the program conducts research, provides prevention and treatment services, and offers training to healthcare providers and the community.

A Las Vegas physician said colleagues in her area are likewise largely unaware, despite the strong connection with the city and gaming. “I do not think most primary care physicians are routinely asking about gambling,” said Maureen Strohm, MD, president of the Nevada Society of Addiction Medicine. Strohm also directs the addiction medicine fellowship at HCA Sunrise Health GME Consortium at Southern Hills Hospital & Medical Center in Las Vegas and cares for patients with substance abuse issues.

But physicians should look for gambling issues, she said, especially in those with known substance abuse disorders. “We encourage incorporation of gambling as another question in comprehensive assessment of patients, since it’s rarely an isolated issue in our treatment settings,” Strohm said.

 

Gritty Reputation Goes Glam, With No Shortage of Opportunities

Why a rise in gambling? Its reputation, for one thing. “It used to be, if you enjoyed gambling, you were viewed as, what — a person of vice, a person of sin,” Fong said. “That’s completely changed. Engaging in gambling is more accepted — and not just accepted but normalized and even glamorized. In some circles, if you don’t gamble, it’s like, ‘What is wrong with you?’ ”

Opportunities to gamble have increased, including a boom in mobile sports betting. Sports betting online, in person, or both now is legal in 39 states and the District of Columbia. The rate of gambling problems among sports bettors is at least twice as high as that for other gamblers, the National Council on Problem Gambling found. As Fong puts it: “The casino comes to you.”

With the rise in opportunities to bet has come an increase in gambling-related disorders. Statistics vary greatly, but Unwin cites a meta-analysis published in 2023 that found moderate-risk or at-risk gambling affects 2.4% of the adult population and pathologic or problem gambling affects 1.29%. He first noticed problem gambling in young soldiers when he was a military doctor and published on it in 2000.

However, the percentage of people with gambling issues seeking care in PCPs’ offices is much higher, probably from 5% to 16%, research has found. “When you survey people who go to the primary care physicians, the number [with a gambling issue] could be as high as 10%-15% of those going for any medical reason,” Fong said. “Many times, their stories are hidden.”

In November, The Lancet Public Health Commission said it views problem gambling as an expanding public health threat.

 

Seeing the Red Flags

“In a perfect world, it would be great to ask all patients” about gambling issues, Unwin said. A more realistic approach, given clinical workloads, is to be alert to the possibility, especially in patients with depression or substance abuse, which often accompany gambling issues.

Learn to look at patterns, Unwin said. “If a patient has had impulsivity issues, is a young male, has had depression and alcohol issues, let’s look and see what else is going on.” 

Other red flags include anyone with an active mental health problem or with a family history of known gambling problems, Fong said.

Some personality traits are linked with a higher likelihood of gambling issues, including highly impulsive behavior and risk-taking behavior. Many problem gamblers are “not very good with loss aversion. They lose a bunch and shrug it off and go back the next day,” Fong noted.

Often, however, the clues are not obvious. Unwin remembers caring for an older couple, and the wife set up an appointment with him — not to talk about her health but to discuss his gambling. “My husband has spent us into debt,” she said. Unwin recalled being completely surprised.

The situation illustrates the flaw in the stereotypical profile of a problem. “In our mind’s eye, it’s often an older White male who talks loudly, is perhaps counterculture,” Fong said. But he often sees young and older people from all cultures and all economic levels struggling with gambling: “Like other forms of addiction, it cuts across all demographics.”

 

Inside a Gambler’s Brain

Many physicians struggle to understand the attraction of gambling, Fong said. They ask: “How can you be addicted to a behavior? Why can’t you just stop?” He tells them: “If people could do that, they would not have a biological psychiatric disorder,” which is what gambling disorder is.

The urge to gamble can be so strong, “You can’t think of anything else,” Fong said. “It screws up your day.” Gamblers say they’re after the “action,” the euphoric state similar to the highs produced from some drugs. Compared with recreational gamblers, problem gamblers rely more on long-term learning than short-term reward?, and so are less able to learn from their losses in the immediate past, research by Fong and others found.

 

Seeking Treatment

One in five problem gamblers seeks help, and 1 in 25 with a moderate-risk habit do so, Unwin said, citing a 2022 study.

To identify concerning behaviors, physicians can turn to two brief screeners that take just minutes:

• The Brief Biosocial Gambling Screen includes just three questions; a yes to any one suggests a gambling problem.
• The Lie-Bet two-question screener can help determine if a person needs a referral for a gambling problem.

“People tend to be pretty honest with their doctor when asked about gambling,” Fong said. “Even the act of asking is enough to get people to start thinking.”

To meet the DSM-5 criteria for gambling disorder, patients must exhibit at least four or more concerning behaviors in the previous 12 months.

For available treatments, “our toolbox is growing,” Fong said. “Psychotherapy probably works best,” including cognitive-behavioral therapy and relapse prevention approaches. “Twelve-step programs work very well,” Fong added.

Medications used for alcohol use disorder, such as naltrexone, an opioid antagonist, are prescribed for gambling disorder, with some success, he said. Often, developing a positive therapeutic relationship with a person who does not judge them is enough to change behavior, Fong said.

To provide treatment and other services, the UCLA program collaborates with the state Office of Problem Gambling. “We know that at least 70% of our patients who stay in treatment and participate in treatment make really meaningful gains and improvement in some part of their lives,” Fong said. “They do gamble less; they do gamble with less money.

 

Goal: Cold Turkey or Harm Reduction?

Fong tells gamblers seeking help: “My goal is to reduce the harm related to your gambling.” In working with patients, he identifies forms that are most problematic and those less likely to cause problems. For some, sports betting may be an issue, but going to Las Vegas a few times a year to play the slots may not generate harm for them. Many patients still gamble, he said, but have a better quality of life if they focus on health and wellness.

“Abstinence is just one domain,” Fong said. The others — home, health, self-care, a sense of purpose, community — are important, too. He helps patients to focus on those.”

Of all the addictions, gambling is one physicians are largely unaware of, Fong said. “And the patients have something that can be treated.”

Unwin, Strohm, and Fong reported no relevant financial disclosures. Physicians can attend open meetings of Gamblers Anonymous to find out more. Members of the group are available to speak to clinicians.

A version of this article appeared on Medscape.com.

On a recent Sunday morning in Los Angeles, 10 members of Gamblers Anonymous gathered in a park for their regular meeting. After, they shared advice for how physicians can best help patients with problem gambling.

“If a patient talks about financial distress, spouse issues, physical issues, or has blood pressure issues, suspect gambling,” one woman said. Another said, if a physician asks about gambling and the patient says, “Just a little,” chances are that person is an active gambler.

The bottom line: None of the people — who spoke for themselves and not on behalf of Gamblers Anonymous — said they had been asked by their doctors about gambling issues. All said they would welcome such questions.

Gambling is on the rise, and gambling disorder is now recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The condition is viewed as similar to substance-related disorders in its clinical expression, brain origin, comorbidity, physiology, and treatment.

Primary care physicians (PCPs), more than any of their colleagues, are likely to encounter a patient with an undetected gambling disorder, according to experts, as it often intertwines with physical and mental health concerns. Those conditions bring the patient to their clinicians, although the patients may not link those issues with their gambling. The physicians may not either.

Few PCPs broach the topic. “I would say the majority of physicians do not screen for it,” said Brian K. Unwin, MD, FAAFP, AGSF, a family medicine physician and geriatrician at the Carilion Center for Healthy Aging and professor at the Virginia Tech Carilion School of Medicine, Roanoke.

The clinician who does take steps to screen for the problem is “exceptionally rare,” said Timothy W. Fong, MD, clinical professor of psychiatry at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gambling Studies Program. Launched in 2005, the program conducts research, provides prevention and treatment services, and offers training to healthcare providers and the community.

A Las Vegas physician said colleagues in her area are likewise largely unaware, despite the strong connection with the city and gaming. “I do not think most primary care physicians are routinely asking about gambling,” said Maureen Strohm, MD, president of the Nevada Society of Addiction Medicine. Strohm also directs the addiction medicine fellowship at HCA Sunrise Health GME Consortium at Southern Hills Hospital & Medical Center in Las Vegas and cares for patients with substance abuse issues.

But physicians should look for gambling issues, she said, especially in those with known substance abuse disorders. “We encourage incorporation of gambling as another question in comprehensive assessment of patients, since it’s rarely an isolated issue in our treatment settings,” Strohm said.

 

Gritty Reputation Goes Glam, With No Shortage of Opportunities

Why a rise in gambling? Its reputation, for one thing. “It used to be, if you enjoyed gambling, you were viewed as, what — a person of vice, a person of sin,” Fong said. “That’s completely changed. Engaging in gambling is more accepted — and not just accepted but normalized and even glamorized. In some circles, if you don’t gamble, it’s like, ‘What is wrong with you?’ ”

Opportunities to gamble have increased, including a boom in mobile sports betting. Sports betting online, in person, or both now is legal in 39 states and the District of Columbia. The rate of gambling problems among sports bettors is at least twice as high as that for other gamblers, the National Council on Problem Gambling found. As Fong puts it: “The casino comes to you.”

With the rise in opportunities to bet has come an increase in gambling-related disorders. Statistics vary greatly, but Unwin cites a meta-analysis published in 2023 that found moderate-risk or at-risk gambling affects 2.4% of the adult population and pathologic or problem gambling affects 1.29%. He first noticed problem gambling in young soldiers when he was a military doctor and published on it in 2000.

However, the percentage of people with gambling issues seeking care in PCPs’ offices is much higher, probably from 5% to 16%, research has found. “When you survey people who go to the primary care physicians, the number [with a gambling issue] could be as high as 10%-15% of those going for any medical reason,” Fong said. “Many times, their stories are hidden.”

In November, The Lancet Public Health Commission said it views problem gambling as an expanding public health threat.

 

Seeing the Red Flags

“In a perfect world, it would be great to ask all patients” about gambling issues, Unwin said. A more realistic approach, given clinical workloads, is to be alert to the possibility, especially in patients with depression or substance abuse, which often accompany gambling issues.

Learn to look at patterns, Unwin said. “If a patient has had impulsivity issues, is a young male, has had depression and alcohol issues, let’s look and see what else is going on.” 

Other red flags include anyone with an active mental health problem or with a family history of known gambling problems, Fong said.

Some personality traits are linked with a higher likelihood of gambling issues, including highly impulsive behavior and risk-taking behavior. Many problem gamblers are “not very good with loss aversion. They lose a bunch and shrug it off and go back the next day,” Fong noted.

Often, however, the clues are not obvious. Unwin remembers caring for an older couple, and the wife set up an appointment with him — not to talk about her health but to discuss his gambling. “My husband has spent us into debt,” she said. Unwin recalled being completely surprised.

The situation illustrates the flaw in the stereotypical profile of a problem. “In our mind’s eye, it’s often an older White male who talks loudly, is perhaps counterculture,” Fong said. But he often sees young and older people from all cultures and all economic levels struggling with gambling: “Like other forms of addiction, it cuts across all demographics.”

 

Inside a Gambler’s Brain

Many physicians struggle to understand the attraction of gambling, Fong said. They ask: “How can you be addicted to a behavior? Why can’t you just stop?” He tells them: “If people could do that, they would not have a biological psychiatric disorder,” which is what gambling disorder is.

The urge to gamble can be so strong, “You can’t think of anything else,” Fong said. “It screws up your day.” Gamblers say they’re after the “action,” the euphoric state similar to the highs produced from some drugs. Compared with recreational gamblers, problem gamblers rely more on long-term learning than short-term reward?, and so are less able to learn from their losses in the immediate past, research by Fong and others found.

 

Seeking Treatment

One in five problem gamblers seeks help, and 1 in 25 with a moderate-risk habit do so, Unwin said, citing a 2022 study.

To identify concerning behaviors, physicians can turn to two brief screeners that take just minutes:

• The Brief Biosocial Gambling Screen includes just three questions; a yes to any one suggests a gambling problem.
• The Lie-Bet two-question screener can help determine if a person needs a referral for a gambling problem.

“People tend to be pretty honest with their doctor when asked about gambling,” Fong said. “Even the act of asking is enough to get people to start thinking.”

To meet the DSM-5 criteria for gambling disorder, patients must exhibit at least four or more concerning behaviors in the previous 12 months.

For available treatments, “our toolbox is growing,” Fong said. “Psychotherapy probably works best,” including cognitive-behavioral therapy and relapse prevention approaches. “Twelve-step programs work very well,” Fong added.

Medications used for alcohol use disorder, such as naltrexone, an opioid antagonist, are prescribed for gambling disorder, with some success, he said. Often, developing a positive therapeutic relationship with a person who does not judge them is enough to change behavior, Fong said.

To provide treatment and other services, the UCLA program collaborates with the state Office of Problem Gambling. “We know that at least 70% of our patients who stay in treatment and participate in treatment make really meaningful gains and improvement in some part of their lives,” Fong said. “They do gamble less; they do gamble with less money.

 

Goal: Cold Turkey or Harm Reduction?

Fong tells gamblers seeking help: “My goal is to reduce the harm related to your gambling.” In working with patients, he identifies forms that are most problematic and those less likely to cause problems. For some, sports betting may be an issue, but going to Las Vegas a few times a year to play the slots may not generate harm for them. Many patients still gamble, he said, but have a better quality of life if they focus on health and wellness.

“Abstinence is just one domain,” Fong said. The others — home, health, self-care, a sense of purpose, community — are important, too. He helps patients to focus on those.”

Of all the addictions, gambling is one physicians are largely unaware of, Fong said. “And the patients have something that can be treated.”

Unwin, Strohm, and Fong reported no relevant financial disclosures. Physicians can attend open meetings of Gamblers Anonymous to find out more. Members of the group are available to speak to clinicians.

A version of this article appeared on Medscape.com.

On a recent Sunday morning in Los Angeles, 10 members of Gamblers Anonymous gathered in a park for their regular meeting. After, they shared advice for how physicians can best help patients with problem gambling.

“If a patient talks about financial distress, spouse issues, physical issues, or has blood pressure issues, suspect gambling,” one woman said. Another said, if a physician asks about gambling and the patient says, “Just a little,” chances are that person is an active gambler.

The bottom line: None of the people — who spoke for themselves and not on behalf of Gamblers Anonymous — said they had been asked by their doctors about gambling issues. All said they would welcome such questions.

Gambling is on the rise, and gambling disorder is now recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The condition is viewed as similar to substance-related disorders in its clinical expression, brain origin, comorbidity, physiology, and treatment.

Primary care physicians (PCPs), more than any of their colleagues, are likely to encounter a patient with an undetected gambling disorder, according to experts, as it often intertwines with physical and mental health concerns. Those conditions bring the patient to their clinicians, although the patients may not link those issues with their gambling. The physicians may not either.

Few PCPs broach the topic. “I would say the majority of physicians do not screen for it,” said Brian K. Unwin, MD, FAAFP, AGSF, a family medicine physician and geriatrician at the Carilion Center for Healthy Aging and professor at the Virginia Tech Carilion School of Medicine, Roanoke.

The clinician who does take steps to screen for the problem is “exceptionally rare,” said Timothy W. Fong, MD, clinical professor of psychiatry at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gambling Studies Program. Launched in 2005, the program conducts research, provides prevention and treatment services, and offers training to healthcare providers and the community.

A Las Vegas physician said colleagues in her area are likewise largely unaware, despite the strong connection with the city and gaming. “I do not think most primary care physicians are routinely asking about gambling,” said Maureen Strohm, MD, president of the Nevada Society of Addiction Medicine. Strohm also directs the addiction medicine fellowship at HCA Sunrise Health GME Consortium at Southern Hills Hospital & Medical Center in Las Vegas and cares for patients with substance abuse issues.

But physicians should look for gambling issues, she said, especially in those with known substance abuse disorders. “We encourage incorporation of gambling as another question in comprehensive assessment of patients, since it’s rarely an isolated issue in our treatment settings,” Strohm said.

 

Gritty Reputation Goes Glam, With No Shortage of Opportunities

Why a rise in gambling? Its reputation, for one thing. “It used to be, if you enjoyed gambling, you were viewed as, what — a person of vice, a person of sin,” Fong said. “That’s completely changed. Engaging in gambling is more accepted — and not just accepted but normalized and even glamorized. In some circles, if you don’t gamble, it’s like, ‘What is wrong with you?’ ”

Opportunities to gamble have increased, including a boom in mobile sports betting. Sports betting online, in person, or both now is legal in 39 states and the District of Columbia. The rate of gambling problems among sports bettors is at least twice as high as that for other gamblers, the National Council on Problem Gambling found. As Fong puts it: “The casino comes to you.”

With the rise in opportunities to bet has come an increase in gambling-related disorders. Statistics vary greatly, but Unwin cites a meta-analysis published in 2023 that found moderate-risk or at-risk gambling affects 2.4% of the adult population and pathologic or problem gambling affects 1.29%. He first noticed problem gambling in young soldiers when he was a military doctor and published on it in 2000.

However, the percentage of people with gambling issues seeking care in PCPs’ offices is much higher, probably from 5% to 16%, research has found. “When you survey people who go to the primary care physicians, the number [with a gambling issue] could be as high as 10%-15% of those going for any medical reason,” Fong said. “Many times, their stories are hidden.”

In November, The Lancet Public Health Commission said it views problem gambling as an expanding public health threat.

 

Seeing the Red Flags

“In a perfect world, it would be great to ask all patients” about gambling issues, Unwin said. A more realistic approach, given clinical workloads, is to be alert to the possibility, especially in patients with depression or substance abuse, which often accompany gambling issues.

Learn to look at patterns, Unwin said. “If a patient has had impulsivity issues, is a young male, has had depression and alcohol issues, let’s look and see what else is going on.” 

Other red flags include anyone with an active mental health problem or with a family history of known gambling problems, Fong said.

Some personality traits are linked with a higher likelihood of gambling issues, including highly impulsive behavior and risk-taking behavior. Many problem gamblers are “not very good with loss aversion. They lose a bunch and shrug it off and go back the next day,” Fong noted.

Often, however, the clues are not obvious. Unwin remembers caring for an older couple, and the wife set up an appointment with him — not to talk about her health but to discuss his gambling. “My husband has spent us into debt,” she said. Unwin recalled being completely surprised.

The situation illustrates the flaw in the stereotypical profile of a problem. “In our mind’s eye, it’s often an older White male who talks loudly, is perhaps counterculture,” Fong said. But he often sees young and older people from all cultures and all economic levels struggling with gambling: “Like other forms of addiction, it cuts across all demographics.”

 

Inside a Gambler’s Brain

Many physicians struggle to understand the attraction of gambling, Fong said. They ask: “How can you be addicted to a behavior? Why can’t you just stop?” He tells them: “If people could do that, they would not have a biological psychiatric disorder,” which is what gambling disorder is.

The urge to gamble can be so strong, “You can’t think of anything else,” Fong said. “It screws up your day.” Gamblers say they’re after the “action,” the euphoric state similar to the highs produced from some drugs. Compared with recreational gamblers, problem gamblers rely more on long-term learning than short-term reward?, and so are less able to learn from their losses in the immediate past, research by Fong and others found.

 

Seeking Treatment

One in five problem gamblers seeks help, and 1 in 25 with a moderate-risk habit do so, Unwin said, citing a 2022 study.

To identify concerning behaviors, physicians can turn to two brief screeners that take just minutes:

• The Brief Biosocial Gambling Screen includes just three questions; a yes to any one suggests a gambling problem.
• The Lie-Bet two-question screener can help determine if a person needs a referral for a gambling problem.

“People tend to be pretty honest with their doctor when asked about gambling,” Fong said. “Even the act of asking is enough to get people to start thinking.”

To meet the DSM-5 criteria for gambling disorder, patients must exhibit at least four or more concerning behaviors in the previous 12 months.

For available treatments, “our toolbox is growing,” Fong said. “Psychotherapy probably works best,” including cognitive-behavioral therapy and relapse prevention approaches. “Twelve-step programs work very well,” Fong added.

Medications used for alcohol use disorder, such as naltrexone, an opioid antagonist, are prescribed for gambling disorder, with some success, he said. Often, developing a positive therapeutic relationship with a person who does not judge them is enough to change behavior, Fong said.

To provide treatment and other services, the UCLA program collaborates with the state Office of Problem Gambling. “We know that at least 70% of our patients who stay in treatment and participate in treatment make really meaningful gains and improvement in some part of their lives,” Fong said. “They do gamble less; they do gamble with less money.

 

Goal: Cold Turkey or Harm Reduction?

Fong tells gamblers seeking help: “My goal is to reduce the harm related to your gambling.” In working with patients, he identifies forms that are most problematic and those less likely to cause problems. For some, sports betting may be an issue, but going to Las Vegas a few times a year to play the slots may not generate harm for them. Many patients still gamble, he said, but have a better quality of life if they focus on health and wellness.

“Abstinence is just one domain,” Fong said. The others — home, health, self-care, a sense of purpose, community — are important, too. He helps patients to focus on those.”

Of all the addictions, gambling is one physicians are largely unaware of, Fong said. “And the patients have something that can be treated.”

Unwin, Strohm, and Fong reported no relevant financial disclosures. Physicians can attend open meetings of Gamblers Anonymous to find out more. Members of the group are available to speak to clinicians.

A version of this article appeared on Medscape.com.

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A 40-year-old woman presents for a wellness visit. She says that she feels well but admits to high levels of stress and occasional fatigue. She works about 60 hours per week as an executive in a finance company. In addition, she is married and has two children, ages 12 and 10 years. She says that she has no time for herself and has noticed that she gets frustrated faster than she used to, but she does not think she has depression. Her score on a Patient Health Questionnaire 9 (PHQ-9) is 5, indicating a low level of depression symptoms.

Regarding health habits, she has never used nicotine products. She reports having one to two alcoholic drinks per day, either wine or a cocktail, and has four drinks per day on a couple of weekend days per month (such as on “date night” with her spouse). She says she does not use any other drugs, including cannabis, and is not taking any medications.

Her vital signs and physical examination are unremarkable. You note that she had an evaluation with a complete blood count, comprehensive metabolic panel, and thyroid-stimulating hormone level performed 7 months ago, with normal results.

What would be the best next step in caring for this patient?

A. Ask her to consider talk therapy to address her fatigue and stress

B. Have her complete a tool (such as the AUDIT-C) to identify hazardous drinking

C. Consider prescribing a selective serotonin reuptake inhibitor

D. Repeat her previous labs, adding vitamin B12 and vitamin D levels

Dr. Vega’s Take

Although all of the answer choices above could apply to this patient, a more formal screening for problem drinking is the most important intervention to make now.

This patient’s story is not unique, particularly in the wake of the COVID-19 pandemic. According to data from the National Institute on Alcohol Abuse and Alcoholism, 64% and 61% of males and females, respectively, at least 12 years of age, reported consuming alcohol in 2023, and 21.7% of these individuals reported binge drinking. 

Alcohol consumption is taking an increasing toll on public health. Between 2016 and 2021, the number of US deaths caused by excessive alcohol use increased by 29%, to a total of 47.6 cases per 100,000 population. The death rate increased faster among females vs males.

The US Preventive Services Task Force (USPSTF) recommends screening for alcohol misuse among adults at least 18 years of age, with no specific interval for repeat screening. USPSTF does recommend two specific screening instruments because of their ease of use and accuracy: the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and Single Alcohol Screening Question (SASQ): How many times in the past year have you had more than four drinks (for women) or five drinks (for men) in a day? 

The AUDIT-C features three questions about alcohol use, the amount of alcohol consumed, and the frequency of heavy alcohol use. The instrument is scored from 0 to 12, with a higher score indicating a high risk for problem drinking. Generally, an AUDIT-C score is considered a positive screen at a score of 4 for men and 3 for women. The SASQ focuses on the number of heavy drinking days in the past year, with a current cutoff of five drinks for men and four drinks for women and anyone age 65 years or older.

Both the AUDIT-C and SASQ should be followed up with a more extensive history to make the diagnosis of alcohol use disorder (AUD). The USPSTF also recommends at least brief follow-up counseling for adults with possible AUD, noting that the most common form of counseling is personalized normative feedback, which compares a patient’s alcohol use pattern with that of others. 

What is your practice in screening for AUD, and what have you found effective in counseling patients? I look forward to hearing your thoughts.

Dr. Vega is Health Sciences Clinical Professor, Family Medicine, University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A 40-year-old woman presents for a wellness visit. She says that she feels well but admits to high levels of stress and occasional fatigue. She works about 60 hours per week as an executive in a finance company. In addition, she is married and has two children, ages 12 and 10 years. She says that she has no time for herself and has noticed that she gets frustrated faster than she used to, but she does not think she has depression. Her score on a Patient Health Questionnaire 9 (PHQ-9) is 5, indicating a low level of depression symptoms.

Regarding health habits, she has never used nicotine products. She reports having one to two alcoholic drinks per day, either wine or a cocktail, and has four drinks per day on a couple of weekend days per month (such as on “date night” with her spouse). She says she does not use any other drugs, including cannabis, and is not taking any medications.

Her vital signs and physical examination are unremarkable. You note that she had an evaluation with a complete blood count, comprehensive metabolic panel, and thyroid-stimulating hormone level performed 7 months ago, with normal results.

What would be the best next step in caring for this patient?

A. Ask her to consider talk therapy to address her fatigue and stress

B. Have her complete a tool (such as the AUDIT-C) to identify hazardous drinking

C. Consider prescribing a selective serotonin reuptake inhibitor

D. Repeat her previous labs, adding vitamin B12 and vitamin D levels

Dr. Vega’s Take

Although all of the answer choices above could apply to this patient, a more formal screening for problem drinking is the most important intervention to make now.

This patient’s story is not unique, particularly in the wake of the COVID-19 pandemic. According to data from the National Institute on Alcohol Abuse and Alcoholism, 64% and 61% of males and females, respectively, at least 12 years of age, reported consuming alcohol in 2023, and 21.7% of these individuals reported binge drinking. 

Alcohol consumption is taking an increasing toll on public health. Between 2016 and 2021, the number of US deaths caused by excessive alcohol use increased by 29%, to a total of 47.6 cases per 100,000 population. The death rate increased faster among females vs males.

The US Preventive Services Task Force (USPSTF) recommends screening for alcohol misuse among adults at least 18 years of age, with no specific interval for repeat screening. USPSTF does recommend two specific screening instruments because of their ease of use and accuracy: the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and Single Alcohol Screening Question (SASQ): How many times in the past year have you had more than four drinks (for women) or five drinks (for men) in a day? 

The AUDIT-C features three questions about alcohol use, the amount of alcohol consumed, and the frequency of heavy alcohol use. The instrument is scored from 0 to 12, with a higher score indicating a high risk for problem drinking. Generally, an AUDIT-C score is considered a positive screen at a score of 4 for men and 3 for women. The SASQ focuses on the number of heavy drinking days in the past year, with a current cutoff of five drinks for men and four drinks for women and anyone age 65 years or older.

Both the AUDIT-C and SASQ should be followed up with a more extensive history to make the diagnosis of alcohol use disorder (AUD). The USPSTF also recommends at least brief follow-up counseling for adults with possible AUD, noting that the most common form of counseling is personalized normative feedback, which compares a patient’s alcohol use pattern with that of others. 

What is your practice in screening for AUD, and what have you found effective in counseling patients? I look forward to hearing your thoughts.

Dr. Vega is Health Sciences Clinical Professor, Family Medicine, University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A 40-year-old woman presents for a wellness visit. She says that she feels well but admits to high levels of stress and occasional fatigue. She works about 60 hours per week as an executive in a finance company. In addition, she is married and has two children, ages 12 and 10 years. She says that she has no time for herself and has noticed that she gets frustrated faster than she used to, but she does not think she has depression. Her score on a Patient Health Questionnaire 9 (PHQ-9) is 5, indicating a low level of depression symptoms.

Regarding health habits, she has never used nicotine products. She reports having one to two alcoholic drinks per day, either wine or a cocktail, and has four drinks per day on a couple of weekend days per month (such as on “date night” with her spouse). She says she does not use any other drugs, including cannabis, and is not taking any medications.

Her vital signs and physical examination are unremarkable. You note that she had an evaluation with a complete blood count, comprehensive metabolic panel, and thyroid-stimulating hormone level performed 7 months ago, with normal results.

What would be the best next step in caring for this patient?

A. Ask her to consider talk therapy to address her fatigue and stress

B. Have her complete a tool (such as the AUDIT-C) to identify hazardous drinking

C. Consider prescribing a selective serotonin reuptake inhibitor

D. Repeat her previous labs, adding vitamin B12 and vitamin D levels

Dr. Vega’s Take

Although all of the answer choices above could apply to this patient, a more formal screening for problem drinking is the most important intervention to make now.

This patient’s story is not unique, particularly in the wake of the COVID-19 pandemic. According to data from the National Institute on Alcohol Abuse and Alcoholism, 64% and 61% of males and females, respectively, at least 12 years of age, reported consuming alcohol in 2023, and 21.7% of these individuals reported binge drinking. 

Alcohol consumption is taking an increasing toll on public health. Between 2016 and 2021, the number of US deaths caused by excessive alcohol use increased by 29%, to a total of 47.6 cases per 100,000 population. The death rate increased faster among females vs males.

The US Preventive Services Task Force (USPSTF) recommends screening for alcohol misuse among adults at least 18 years of age, with no specific interval for repeat screening. USPSTF does recommend two specific screening instruments because of their ease of use and accuracy: the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and Single Alcohol Screening Question (SASQ): How many times in the past year have you had more than four drinks (for women) or five drinks (for men) in a day? 

The AUDIT-C features three questions about alcohol use, the amount of alcohol consumed, and the frequency of heavy alcohol use. The instrument is scored from 0 to 12, with a higher score indicating a high risk for problem drinking. Generally, an AUDIT-C score is considered a positive screen at a score of 4 for men and 3 for women. The SASQ focuses on the number of heavy drinking days in the past year, with a current cutoff of five drinks for men and four drinks for women and anyone age 65 years or older.

Both the AUDIT-C and SASQ should be followed up with a more extensive history to make the diagnosis of alcohol use disorder (AUD). The USPSTF also recommends at least brief follow-up counseling for adults with possible AUD, noting that the most common form of counseling is personalized normative feedback, which compares a patient’s alcohol use pattern with that of others. 

What is your practice in screening for AUD, and what have you found effective in counseling patients? I look forward to hearing your thoughts.

Dr. Vega is Health Sciences Clinical Professor, Family Medicine, University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonist (GLP-1) prescriptions for diabetes and obesity treatment are soaring, as is the interest in their potential for treating an array of other conditions. One area in particular is addiction, which, like obesity and diabetes, has been increasing, both in terms of case numbers and deaths from drug overdose, excessive alcohol use, and tobacco/e-cigarettes.

So far, data supporting GLP-1 use in addiction are limited to preclinical studies, anecdotal evidence, a few cohort analyses, and randomized clinical trials. But the chatter among researchers and clinicians, not to mention patients, portends its promise. 

 

“The evidence is very preliminary and very exciting,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “The studies have been going on for more than a decade looking at the effects of GLP medications, mostly first generation and predominantly in rodents,” she said.

GLP “drugs like exenatide and liraglutide all reduced consumption of nicotine, of alcohol, of cocaine, and response to opioids,” Volkow said.

 

Clinical, Real-World Data Promising

Second-generation agents like semaglutide appear to hold greater promise than their first-generation counterparts. Volkow noted that not only is semaglutide a “much more potent drug,” but pointed to recent findings that saw significant declines in heavy drinking days among patients with alcohol use disorder (AUD).

At the Research Society on Alcohol’s annual meeting in June, researchers from the University of North Carolina at Chapel Hill presented findings of a 2-month, phase 2, randomized clinical trial comparing two low doses (0.25 mg/wk, 0.5 mg/wk) of semaglutide with placebo in 48 participants reporting symptoms of AUD. Though preliminary and unpublished, the data showed a reduction in drinking quantity and heavy drinking in the semaglutide vs placebo groups.

Real-world evidence from electronic health records has also underscored the potential benefit of semaglutide in AUD. In a 12-month retrospective cohort analysis of the records of patients with obesity and no prior AUD diagnosis prescribed semaglutide (n = 45,797) or non-GLP-1 anti-obesity medications (naltrexone, topiramate, n = 38,028), semaglutide was associated with a 50% lower risk for a recurrent AUD diagnosis and a 56% significantly lower risk for incidence AUD diagnosis across gender, age group, and race, and in patients with/without type 2 diabetes.

Likewise, findings from another cohort analysis assigned 1306 treatment-naive patients with type 2 diabetes and no prior AUD diagnosis to semaglutide or non-GLP-1 anti-diabetes medications and followed them for 12 months. Compared with people prescribed non-GLP-1 diabetes medications, those who took semaglutide had a 42% lower risk for recurrent alcohol use diagnosis, consistent across gender, age group, and race, whether the person had been diagnosed with obesity.

However, AUD is not the only addiction where semaglutide appears to have potential benefit. Cohort studies conducted by Volkow and her colleagues have suggested as much as a 78% reduced risk or opioid overdose in patients with comorbid obesity and type 2 diabetes) and a 44% reduction in cannabis use disorder in type 2 diabetes patients without a prior cannabis use disorder history.

 

Unclear Mechanisms, Multiple Theories

It’s not entirely clear how semaglutide provides a path for addicts to reduce their cravings or which patients might benefit most.

Preclinical studies have suggested that GLP-1 receptors are expressed throughout the mesolimbic dopamine system and transmit dopamine directly to reward centers in the forebrain, for example, the nucleus accumbens. The drugs appear to reduce dopamine release and transmission to these reward centers, as well as to areas that are responsible for impulse control.

“What we’re seeing is counteracting mechanisms that allow you to self-regulate are also involved in addiction, but I don’t know to what extent these medications could help strengthen that,” said Volkow.

Henry Kranzler, MD, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, has a paper in press looking at genetic correlation between body mass index (BMI) and AUD. “Genetic analysis showed that many of the same genes are working in both disorders but in opposite directions,” he said.

The bottom line is that “they share genetics, but by no means are they the same; this gives us reason to believe that the GLP-1s could be beneficial in obesity but not nearly as beneficial for treating addiction,” said Kranzler.

 

Behind Closed Doors

Like many people with overweight or obesity who are on semaglutide, Bridget Pilloud, a writer who divides her time between Washington State and Arizona, no longer has any desire to drink.

“I used to really enjoy sitting and slowly sipping an Old Fashioned. I used to really enjoy specific whiskeys. Now, I don’t even like the flavor; the pleasure of drinking is gone,” she said.

Inexplicably, Pilloud said that she’s also given up compulsive shopping; “The hunt and acquisition of it was always really delicious to me,” she said.

Pilloud’s experience is not unique. Angela Fitch, MD, an obesity medicine specialist, co-founder and CMO of knownwell health, and former president of the Obesity Medicine Association, has had patients on semaglutide tell her that they’re not shopping as much.

But self-reports about alcohol consumption are far more common.

A 2023 analysis of social media posts reinforced that the experience is quite common, albeit self-reported.

Researchers used machine learning attribution mapping of 68,250 posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists on the Reddit platform. Among the 1580 alcohol-related posts, 71% (1134/1580) of users of either drug said they had reduced cravings and decreased desire to drink. In a remote companion study of 153 people with obesity taking semaglutide (n = 56), tirzepatide (n = 50), or neither (n = 47), there appeared to be a reduced suppression of the desire to consume alcohol, with users reporting fewer drinks and binge episodes than control individuals.

Self-reports also underscored the association between either of the medications and less stimulating/sedative effects of alcohol compared with before starting the medications and to controls.

Behind closed doors, there appears to be as much chatter about the potential of these agents for AUD and other addiction disorders as there are questions about factors like treatment duration, safety of long-term, chronic use, and dosage.

“We don’t have data around people with normal weight and how much risk that is to them if they start taking these medications for addiction and reduce their BMI as low as 18,” said Fitch.

There’s also the question of when and how to wean patients off the medications, a consideration that is quite important for patients with addiction problems, said Volkow.

“What happens when you become addicted to drugs is that you start to degrade social support systems needed for well-being,” she explained. “The big difference with drugs versus foods is that you can live happily with no drugs at all, whereas you die if you don’t eat. So, there are greater challenges in the ability to change the environment (eg, help stabilize everyday life so people have alternative reinforcers) when you remove the reward.” 

Additional considerations range from overuse and the development of treatment-resistant obesity to the need to ensure that patients on these drugs receive ongoing management and, of course, access, noted Fitch.

Still, the NIDA coffers are open. “We’re waiting for proposals,” said Volkow.

Fitch is cofounder and CMO of knownwell health. Volkow reported no relevant financial relationships. Kranzler is a member of advisory boards for Altimmune, Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, Eli Lilly and Company, and Sophrosyne Pharmaceuticals; a consultant to Sobrera Pharma and Altimmune; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna Pharmaceuticals, Ethypharm, Imbrium, Indivior, Kinnov, Eli Lilly, Otsuka, and Pear; and a holder of US patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued on January 26, 2021.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonist (GLP-1) prescriptions for diabetes and obesity treatment are soaring, as is the interest in their potential for treating an array of other conditions. One area in particular is addiction, which, like obesity and diabetes, has been increasing, both in terms of case numbers and deaths from drug overdose, excessive alcohol use, and tobacco/e-cigarettes.

So far, data supporting GLP-1 use in addiction are limited to preclinical studies, anecdotal evidence, a few cohort analyses, and randomized clinical trials. But the chatter among researchers and clinicians, not to mention patients, portends its promise. 

 

“The evidence is very preliminary and very exciting,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “The studies have been going on for more than a decade looking at the effects of GLP medications, mostly first generation and predominantly in rodents,” she said.

GLP “drugs like exenatide and liraglutide all reduced consumption of nicotine, of alcohol, of cocaine, and response to opioids,” Volkow said.

 

Clinical, Real-World Data Promising

Second-generation agents like semaglutide appear to hold greater promise than their first-generation counterparts. Volkow noted that not only is semaglutide a “much more potent drug,” but pointed to recent findings that saw significant declines in heavy drinking days among patients with alcohol use disorder (AUD).

At the Research Society on Alcohol’s annual meeting in June, researchers from the University of North Carolina at Chapel Hill presented findings of a 2-month, phase 2, randomized clinical trial comparing two low doses (0.25 mg/wk, 0.5 mg/wk) of semaglutide with placebo in 48 participants reporting symptoms of AUD. Though preliminary and unpublished, the data showed a reduction in drinking quantity and heavy drinking in the semaglutide vs placebo groups.

Real-world evidence from electronic health records has also underscored the potential benefit of semaglutide in AUD. In a 12-month retrospective cohort analysis of the records of patients with obesity and no prior AUD diagnosis prescribed semaglutide (n = 45,797) or non-GLP-1 anti-obesity medications (naltrexone, topiramate, n = 38,028), semaglutide was associated with a 50% lower risk for a recurrent AUD diagnosis and a 56% significantly lower risk for incidence AUD diagnosis across gender, age group, and race, and in patients with/without type 2 diabetes.

Likewise, findings from another cohort analysis assigned 1306 treatment-naive patients with type 2 diabetes and no prior AUD diagnosis to semaglutide or non-GLP-1 anti-diabetes medications and followed them for 12 months. Compared with people prescribed non-GLP-1 diabetes medications, those who took semaglutide had a 42% lower risk for recurrent alcohol use diagnosis, consistent across gender, age group, and race, whether the person had been diagnosed with obesity.

However, AUD is not the only addiction where semaglutide appears to have potential benefit. Cohort studies conducted by Volkow and her colleagues have suggested as much as a 78% reduced risk or opioid overdose in patients with comorbid obesity and type 2 diabetes) and a 44% reduction in cannabis use disorder in type 2 diabetes patients without a prior cannabis use disorder history.

 

Unclear Mechanisms, Multiple Theories

It’s not entirely clear how semaglutide provides a path for addicts to reduce their cravings or which patients might benefit most.

Preclinical studies have suggested that GLP-1 receptors are expressed throughout the mesolimbic dopamine system and transmit dopamine directly to reward centers in the forebrain, for example, the nucleus accumbens. The drugs appear to reduce dopamine release and transmission to these reward centers, as well as to areas that are responsible for impulse control.

“What we’re seeing is counteracting mechanisms that allow you to self-regulate are also involved in addiction, but I don’t know to what extent these medications could help strengthen that,” said Volkow.

Henry Kranzler, MD, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, has a paper in press looking at genetic correlation between body mass index (BMI) and AUD. “Genetic analysis showed that many of the same genes are working in both disorders but in opposite directions,” he said.

The bottom line is that “they share genetics, but by no means are they the same; this gives us reason to believe that the GLP-1s could be beneficial in obesity but not nearly as beneficial for treating addiction,” said Kranzler.

 

Behind Closed Doors

Like many people with overweight or obesity who are on semaglutide, Bridget Pilloud, a writer who divides her time between Washington State and Arizona, no longer has any desire to drink.

“I used to really enjoy sitting and slowly sipping an Old Fashioned. I used to really enjoy specific whiskeys. Now, I don’t even like the flavor; the pleasure of drinking is gone,” she said.

Inexplicably, Pilloud said that she’s also given up compulsive shopping; “The hunt and acquisition of it was always really delicious to me,” she said.

Pilloud’s experience is not unique. Angela Fitch, MD, an obesity medicine specialist, co-founder and CMO of knownwell health, and former president of the Obesity Medicine Association, has had patients on semaglutide tell her that they’re not shopping as much.

But self-reports about alcohol consumption are far more common.

A 2023 analysis of social media posts reinforced that the experience is quite common, albeit self-reported.

Researchers used machine learning attribution mapping of 68,250 posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists on the Reddit platform. Among the 1580 alcohol-related posts, 71% (1134/1580) of users of either drug said they had reduced cravings and decreased desire to drink. In a remote companion study of 153 people with obesity taking semaglutide (n = 56), tirzepatide (n = 50), or neither (n = 47), there appeared to be a reduced suppression of the desire to consume alcohol, with users reporting fewer drinks and binge episodes than control individuals.

Self-reports also underscored the association between either of the medications and less stimulating/sedative effects of alcohol compared with before starting the medications and to controls.

Behind closed doors, there appears to be as much chatter about the potential of these agents for AUD and other addiction disorders as there are questions about factors like treatment duration, safety of long-term, chronic use, and dosage.

“We don’t have data around people with normal weight and how much risk that is to them if they start taking these medications for addiction and reduce their BMI as low as 18,” said Fitch.

There’s also the question of when and how to wean patients off the medications, a consideration that is quite important for patients with addiction problems, said Volkow.

“What happens when you become addicted to drugs is that you start to degrade social support systems needed for well-being,” she explained. “The big difference with drugs versus foods is that you can live happily with no drugs at all, whereas you die if you don’t eat. So, there are greater challenges in the ability to change the environment (eg, help stabilize everyday life so people have alternative reinforcers) when you remove the reward.” 

Additional considerations range from overuse and the development of treatment-resistant obesity to the need to ensure that patients on these drugs receive ongoing management and, of course, access, noted Fitch.

Still, the NIDA coffers are open. “We’re waiting for proposals,” said Volkow.

Fitch is cofounder and CMO of knownwell health. Volkow reported no relevant financial relationships. Kranzler is a member of advisory boards for Altimmune, Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, Eli Lilly and Company, and Sophrosyne Pharmaceuticals; a consultant to Sobrera Pharma and Altimmune; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna Pharmaceuticals, Ethypharm, Imbrium, Indivior, Kinnov, Eli Lilly, Otsuka, and Pear; and a holder of US patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued on January 26, 2021.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonist (GLP-1) prescriptions for diabetes and obesity treatment are soaring, as is the interest in their potential for treating an array of other conditions. One area in particular is addiction, which, like obesity and diabetes, has been increasing, both in terms of case numbers and deaths from drug overdose, excessive alcohol use, and tobacco/e-cigarettes.

So far, data supporting GLP-1 use in addiction are limited to preclinical studies, anecdotal evidence, a few cohort analyses, and randomized clinical trials. But the chatter among researchers and clinicians, not to mention patients, portends its promise. 

 

“The evidence is very preliminary and very exciting,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “The studies have been going on for more than a decade looking at the effects of GLP medications, mostly first generation and predominantly in rodents,” she said.

GLP “drugs like exenatide and liraglutide all reduced consumption of nicotine, of alcohol, of cocaine, and response to opioids,” Volkow said.

 

Clinical, Real-World Data Promising

Second-generation agents like semaglutide appear to hold greater promise than their first-generation counterparts. Volkow noted that not only is semaglutide a “much more potent drug,” but pointed to recent findings that saw significant declines in heavy drinking days among patients with alcohol use disorder (AUD).

At the Research Society on Alcohol’s annual meeting in June, researchers from the University of North Carolina at Chapel Hill presented findings of a 2-month, phase 2, randomized clinical trial comparing two low doses (0.25 mg/wk, 0.5 mg/wk) of semaglutide with placebo in 48 participants reporting symptoms of AUD. Though preliminary and unpublished, the data showed a reduction in drinking quantity and heavy drinking in the semaglutide vs placebo groups.

Real-world evidence from electronic health records has also underscored the potential benefit of semaglutide in AUD. In a 12-month retrospective cohort analysis of the records of patients with obesity and no prior AUD diagnosis prescribed semaglutide (n = 45,797) or non-GLP-1 anti-obesity medications (naltrexone, topiramate, n = 38,028), semaglutide was associated with a 50% lower risk for a recurrent AUD diagnosis and a 56% significantly lower risk for incidence AUD diagnosis across gender, age group, and race, and in patients with/without type 2 diabetes.

Likewise, findings from another cohort analysis assigned 1306 treatment-naive patients with type 2 diabetes and no prior AUD diagnosis to semaglutide or non-GLP-1 anti-diabetes medications and followed them for 12 months. Compared with people prescribed non-GLP-1 diabetes medications, those who took semaglutide had a 42% lower risk for recurrent alcohol use diagnosis, consistent across gender, age group, and race, whether the person had been diagnosed with obesity.

However, AUD is not the only addiction where semaglutide appears to have potential benefit. Cohort studies conducted by Volkow and her colleagues have suggested as much as a 78% reduced risk or opioid overdose in patients with comorbid obesity and type 2 diabetes) and a 44% reduction in cannabis use disorder in type 2 diabetes patients without a prior cannabis use disorder history.

 

Unclear Mechanisms, Multiple Theories

It’s not entirely clear how semaglutide provides a path for addicts to reduce their cravings or which patients might benefit most.

Preclinical studies have suggested that GLP-1 receptors are expressed throughout the mesolimbic dopamine system and transmit dopamine directly to reward centers in the forebrain, for example, the nucleus accumbens. The drugs appear to reduce dopamine release and transmission to these reward centers, as well as to areas that are responsible for impulse control.

“What we’re seeing is counteracting mechanisms that allow you to self-regulate are also involved in addiction, but I don’t know to what extent these medications could help strengthen that,” said Volkow.

Henry Kranzler, MD, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, has a paper in press looking at genetic correlation between body mass index (BMI) and AUD. “Genetic analysis showed that many of the same genes are working in both disorders but in opposite directions,” he said.

The bottom line is that “they share genetics, but by no means are they the same; this gives us reason to believe that the GLP-1s could be beneficial in obesity but not nearly as beneficial for treating addiction,” said Kranzler.

 

Behind Closed Doors

Like many people with overweight or obesity who are on semaglutide, Bridget Pilloud, a writer who divides her time between Washington State and Arizona, no longer has any desire to drink.

“I used to really enjoy sitting and slowly sipping an Old Fashioned. I used to really enjoy specific whiskeys. Now, I don’t even like the flavor; the pleasure of drinking is gone,” she said.

Inexplicably, Pilloud said that she’s also given up compulsive shopping; “The hunt and acquisition of it was always really delicious to me,” she said.

Pilloud’s experience is not unique. Angela Fitch, MD, an obesity medicine specialist, co-founder and CMO of knownwell health, and former president of the Obesity Medicine Association, has had patients on semaglutide tell her that they’re not shopping as much.

But self-reports about alcohol consumption are far more common.

A 2023 analysis of social media posts reinforced that the experience is quite common, albeit self-reported.

Researchers used machine learning attribution mapping of 68,250 posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists on the Reddit platform. Among the 1580 alcohol-related posts, 71% (1134/1580) of users of either drug said they had reduced cravings and decreased desire to drink. In a remote companion study of 153 people with obesity taking semaglutide (n = 56), tirzepatide (n = 50), or neither (n = 47), there appeared to be a reduced suppression of the desire to consume alcohol, with users reporting fewer drinks and binge episodes than control individuals.

Self-reports also underscored the association between either of the medications and less stimulating/sedative effects of alcohol compared with before starting the medications and to controls.

Behind closed doors, there appears to be as much chatter about the potential of these agents for AUD and other addiction disorders as there are questions about factors like treatment duration, safety of long-term, chronic use, and dosage.

“We don’t have data around people with normal weight and how much risk that is to them if they start taking these medications for addiction and reduce their BMI as low as 18,” said Fitch.

There’s also the question of when and how to wean patients off the medications, a consideration that is quite important for patients with addiction problems, said Volkow.

“What happens when you become addicted to drugs is that you start to degrade social support systems needed for well-being,” she explained. “The big difference with drugs versus foods is that you can live happily with no drugs at all, whereas you die if you don’t eat. So, there are greater challenges in the ability to change the environment (eg, help stabilize everyday life so people have alternative reinforcers) when you remove the reward.” 

Additional considerations range from overuse and the development of treatment-resistant obesity to the need to ensure that patients on these drugs receive ongoing management and, of course, access, noted Fitch.

Still, the NIDA coffers are open. “We’re waiting for proposals,” said Volkow.

Fitch is cofounder and CMO of knownwell health. Volkow reported no relevant financial relationships. Kranzler is a member of advisory boards for Altimmune, Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, Eli Lilly and Company, and Sophrosyne Pharmaceuticals; a consultant to Sobrera Pharma and Altimmune; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna Pharmaceuticals, Ethypharm, Imbrium, Indivior, Kinnov, Eli Lilly, Otsuka, and Pear; and a holder of US patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued on January 26, 2021.

A version of this article appeared on Medscape.com.