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Only moderate-quality evidence supports medical cannabinoids

At best, only moderate-quality evidence supports the use of medical cannabinoids, and for only two conditions. And low-quality evidence only “suggests” that these agents may improve other medical conditions, but that limited effectiveness applies only to the four conditions that have been studied, according to a report published online June 23 in JAMA.

This doesn’t necessarily mean that cannabinoids have poor efficacy but instead likely reflects the dearth of high-quality research into their medical usefulness.

In what they described as the first comprehensive review to evaluate the efficacy of numerous cannabinoids across a broad range of indications, researchers analyzed data from 79 studies involving 6,462 participants performed from 1975 to early 2015. The studies assessed nabilone, dronabinol, nabiximols, levonantradol, THC, THC/CBD, and ajuvenic acid, delivered via oral capsules, cigarettes, vaporizers, oromucosal sprays, or intramuscular injection, said Penny F. Whiting, Ph.D., of University Hospitals Bristol (England) and her associates.

Most of the studies suggested that cannabinoids improved symptoms for nearly all the 10 medical conditions included in this meta-analysis, but most of the studies were of poor quality so their conclusions were questionable. These agents’ efficacy did not vary according to the type of cannabinoid assessed or the mode of delivery.

Moderate-quality evidence indicated that cannabinoids may be beneficial for chronic neuropathic or cancer pain, and moderate-quality evidence indicated that they may also be beneficial for spasticity due to multiple sclerosis or traumatic paraplegia. Low-quality evidence suggested that cannabinoids may improve nausea and vomiting due to chemotherapy, may improve appetite and induce weight gain in HIV infection, and may improve sleep in primary sleep disorders as well as in conditions that disrupt sleep such as fibromyalgia, multiple sclerosis, and chronic pain. Very low-quality evidence (due to extremely small sample sizes) suggested that cannabinoids may greatly improve tic severity in Tourette’s syndrome, Dr. Whiting and her associates said (JAMA 2015 June 23 [doi:10.1001/jama.2015.6358]).

Otherwise, the evidence did not support cannabinoids’ efficacy in anxiety, depression, psychosis, or glaucoma. Adverse events included asthenia, problems with balance, confusion, dizziness, disorientation, dry mouth, fatigue, and somnolence.

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It is unclear why medical marijuana has averted the usual Food and Drug Administration approval process required of other medications.

Adequately powered, double-blind, randomized, placebo- or treatment-controlled clinical trials are critical to establish cannabinoids’ short- and long-term efficacy and safety. Yet they already qualify by state law for use in conditions as varied as hepatitis C, Crohn’s disease, Parkinson’s disease, psoriasis, sickle cell disease, and posttraumatic stress disorder.

In particular, the risks of repeated exposure to cannabinoids needs further study. Addiction, tolerance, and a distinct withdrawal syndrome have been documented, and there is also a small but definite risk of psychotic disorder.

Dr. Deepak Cyril D’Souza and Dr. Mohini Ranganathan are in the department of psychiatry at Yale University, New Haven; in the psychiatry service at Veterans Affairs Connecticut Healthcare System, West Haven; and at Abraham Ribicoff Research Facilities at the Connecticut Mental Health Center, New Haven. Dr. D’Souza reported receiving grants from AbbVie and Pfizer, and serves on the Connecticut Board of Physicians that advises the Commissioner of Consumer Protection about the Act Concerning the Palliative Use of Marijuana. Dr. Ranganathan reported receiving grants from Insys Therapeutics. Dr. D’Souza and Dr. Ranganathan made these remarks in an editorial accompanying Dr. Whiting’s report (JAMA 2015;313:2431-2).

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It is unclear why medical marijuana has averted the usual Food and Drug Administration approval process required of other medications.

Adequately powered, double-blind, randomized, placebo- or treatment-controlled clinical trials are critical to establish cannabinoids’ short- and long-term efficacy and safety. Yet they already qualify by state law for use in conditions as varied as hepatitis C, Crohn’s disease, Parkinson’s disease, psoriasis, sickle cell disease, and posttraumatic stress disorder.

In particular, the risks of repeated exposure to cannabinoids needs further study. Addiction, tolerance, and a distinct withdrawal syndrome have been documented, and there is also a small but definite risk of psychotic disorder.

Dr. Deepak Cyril D’Souza and Dr. Mohini Ranganathan are in the department of psychiatry at Yale University, New Haven; in the psychiatry service at Veterans Affairs Connecticut Healthcare System, West Haven; and at Abraham Ribicoff Research Facilities at the Connecticut Mental Health Center, New Haven. Dr. D’Souza reported receiving grants from AbbVie and Pfizer, and serves on the Connecticut Board of Physicians that advises the Commissioner of Consumer Protection about the Act Concerning the Palliative Use of Marijuana. Dr. Ranganathan reported receiving grants from Insys Therapeutics. Dr. D’Souza and Dr. Ranganathan made these remarks in an editorial accompanying Dr. Whiting’s report (JAMA 2015;313:2431-2).

Body

It is unclear why medical marijuana has averted the usual Food and Drug Administration approval process required of other medications.

Adequately powered, double-blind, randomized, placebo- or treatment-controlled clinical trials are critical to establish cannabinoids’ short- and long-term efficacy and safety. Yet they already qualify by state law for use in conditions as varied as hepatitis C, Crohn’s disease, Parkinson’s disease, psoriasis, sickle cell disease, and posttraumatic stress disorder.

In particular, the risks of repeated exposure to cannabinoids needs further study. Addiction, tolerance, and a distinct withdrawal syndrome have been documented, and there is also a small but definite risk of psychotic disorder.

Dr. Deepak Cyril D’Souza and Dr. Mohini Ranganathan are in the department of psychiatry at Yale University, New Haven; in the psychiatry service at Veterans Affairs Connecticut Healthcare System, West Haven; and at Abraham Ribicoff Research Facilities at the Connecticut Mental Health Center, New Haven. Dr. D’Souza reported receiving grants from AbbVie and Pfizer, and serves on the Connecticut Board of Physicians that advises the Commissioner of Consumer Protection about the Act Concerning the Palliative Use of Marijuana. Dr. Ranganathan reported receiving grants from Insys Therapeutics. Dr. D’Souza and Dr. Ranganathan made these remarks in an editorial accompanying Dr. Whiting’s report (JAMA 2015;313:2431-2).

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Dearth of high-quality research
Dearth of high-quality research

At best, only moderate-quality evidence supports the use of medical cannabinoids, and for only two conditions. And low-quality evidence only “suggests” that these agents may improve other medical conditions, but that limited effectiveness applies only to the four conditions that have been studied, according to a report published online June 23 in JAMA.

This doesn’t necessarily mean that cannabinoids have poor efficacy but instead likely reflects the dearth of high-quality research into their medical usefulness.

In what they described as the first comprehensive review to evaluate the efficacy of numerous cannabinoids across a broad range of indications, researchers analyzed data from 79 studies involving 6,462 participants performed from 1975 to early 2015. The studies assessed nabilone, dronabinol, nabiximols, levonantradol, THC, THC/CBD, and ajuvenic acid, delivered via oral capsules, cigarettes, vaporizers, oromucosal sprays, or intramuscular injection, said Penny F. Whiting, Ph.D., of University Hospitals Bristol (England) and her associates.

Most of the studies suggested that cannabinoids improved symptoms for nearly all the 10 medical conditions included in this meta-analysis, but most of the studies were of poor quality so their conclusions were questionable. These agents’ efficacy did not vary according to the type of cannabinoid assessed or the mode of delivery.

Moderate-quality evidence indicated that cannabinoids may be beneficial for chronic neuropathic or cancer pain, and moderate-quality evidence indicated that they may also be beneficial for spasticity due to multiple sclerosis or traumatic paraplegia. Low-quality evidence suggested that cannabinoids may improve nausea and vomiting due to chemotherapy, may improve appetite and induce weight gain in HIV infection, and may improve sleep in primary sleep disorders as well as in conditions that disrupt sleep such as fibromyalgia, multiple sclerosis, and chronic pain. Very low-quality evidence (due to extremely small sample sizes) suggested that cannabinoids may greatly improve tic severity in Tourette’s syndrome, Dr. Whiting and her associates said (JAMA 2015 June 23 [doi:10.1001/jama.2015.6358]).

Otherwise, the evidence did not support cannabinoids’ efficacy in anxiety, depression, psychosis, or glaucoma. Adverse events included asthenia, problems with balance, confusion, dizziness, disorientation, dry mouth, fatigue, and somnolence.

At best, only moderate-quality evidence supports the use of medical cannabinoids, and for only two conditions. And low-quality evidence only “suggests” that these agents may improve other medical conditions, but that limited effectiveness applies only to the four conditions that have been studied, according to a report published online June 23 in JAMA.

This doesn’t necessarily mean that cannabinoids have poor efficacy but instead likely reflects the dearth of high-quality research into their medical usefulness.

In what they described as the first comprehensive review to evaluate the efficacy of numerous cannabinoids across a broad range of indications, researchers analyzed data from 79 studies involving 6,462 participants performed from 1975 to early 2015. The studies assessed nabilone, dronabinol, nabiximols, levonantradol, THC, THC/CBD, and ajuvenic acid, delivered via oral capsules, cigarettes, vaporizers, oromucosal sprays, or intramuscular injection, said Penny F. Whiting, Ph.D., of University Hospitals Bristol (England) and her associates.

Most of the studies suggested that cannabinoids improved symptoms for nearly all the 10 medical conditions included in this meta-analysis, but most of the studies were of poor quality so their conclusions were questionable. These agents’ efficacy did not vary according to the type of cannabinoid assessed or the mode of delivery.

Moderate-quality evidence indicated that cannabinoids may be beneficial for chronic neuropathic or cancer pain, and moderate-quality evidence indicated that they may also be beneficial for spasticity due to multiple sclerosis or traumatic paraplegia. Low-quality evidence suggested that cannabinoids may improve nausea and vomiting due to chemotherapy, may improve appetite and induce weight gain in HIV infection, and may improve sleep in primary sleep disorders as well as in conditions that disrupt sleep such as fibromyalgia, multiple sclerosis, and chronic pain. Very low-quality evidence (due to extremely small sample sizes) suggested that cannabinoids may greatly improve tic severity in Tourette’s syndrome, Dr. Whiting and her associates said (JAMA 2015 June 23 [doi:10.1001/jama.2015.6358]).

Otherwise, the evidence did not support cannabinoids’ efficacy in anxiety, depression, psychosis, or glaucoma. Adverse events included asthenia, problems with balance, confusion, dizziness, disorientation, dry mouth, fatigue, and somnolence.

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Only moderate-quality evidence supports medical cannabinoids
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Key clinical point: Only moderate-quality evidence supports the use of medical cannabinoids, and only for two conditions.

Major finding: Moderate-quality evidence indicated that cannabinoids may be beneficial for chronic neuropathic or cancer pain and for spasticity due to multiple sclerosis or traumatic paraplegia.

Data source: A comprehensive review of the literature since 1975 and a meta-analysis of 79 clinical trials involving 6,462 participants.

Disclosures: This study was funded by the Swiss Federal Office of Public Health. Dr. Whiting and her associates reported having no relevant financial conflicts of interest.