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Medical cannabis not proven in mental health — research review

Evidence is weak for whether medicinal cannabis treatments can relieve mental illnesses such as anxiety, depression and psychosis, and doctors should prescribe them with great caution, researchers said. They found that pharmaceutical THC – either with or without cannabidiol – made psychosis worse.

Reuters Health reports that in a review of scientific studies that analysed the impact of medicinal cannabinoids on six mental health disorders, the researchers found “a lack of evidence for their effectiveness.”

Their findings have important implications for countries such as the US, Australia, Britain and Canada, where medical cannabis is being made available for patients with certain illness, said Louisa Degenhardt, a drug and alcohol expert at Australias University of New South Wales in Sydney. “There is a notable absence of high-quality evidence to properly assess the effectiveness and safety of medicinal cannabinoids … and until evidence from randomised controlled trials is available, clinical guidelines cannot be drawn up around their use in mental health disorders,” she said.

Despite a lack of clinical trial evidence, anecdotally some military veterans and others who suffer post-traumatic stress disorder (PTSD), depression and anxiety say they have found cannabis helpful in easing some of their symptoms. Other conditions cannabis is used for include nausea, epilepsy, and traumatic brain injury, but this study did not examine its impact on those.

Medicinal cannabinoids include medicinal cannabis and pharmaceutical cannabinoids, as well as their synthetic derivatives, THC, or delta-9-tetrahydrocannabinol – the main psychoactive ingredient of cannabis – and cannabidiol, or CBD.

“Cannabinoids are often advocated as a treatment for various mental health conditions,” Degenhardt said. “(But) clinicians and consumers need to be aware of the low quality and quantity of evidence … and the potential risk of adverse events.”

Degenhardt’s team sought to look at all available evidence for all types of medicinal cannabinoids. They included all study designs and investigated the impact on remission from and symptoms of depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, PTSD and psychosis. They analysed 83 published and unpublished studies covering around 3,000 people between 1980 and 2018.

They found that pharmaceutical THC – either with or without CBD – made psychosis worse, and did not significantly affect any other primary outcomes for the mental illnesses analysed.

It also increased the number of people who reported side effects, and the number who decided to withdraw from a study due to side effects.

Tom Freeman, an addiction and mental health expert at Britain’s Bath University who was not involved with the study, said the findings highlighted an urgent need for high-quality trials of medical cannabis to strengthen the evidence – particularly given what he said was “significant demand” from patients.

Deepak Cyril D’Souza of Yale University School of Medicine in New Haven, Connecticut, said that “in light of the paucity of evidence, the absence of good quality evidence for efficacy, and the known risk of cannabinoids, their use as treatments for psychiatric disorders cannot be justified at present.”

The Guardian reports that in modern medicine, it is normal practice to prove safety and efficacy in trials before drugs are allowed to be given out to patients. “If cannabinoids are to be used in the treatment of psychiatric disorders, they should first be tested in randomised controlled trials and subjected to the same regulatory approval process as other prescription medications,” he add.

Abstract
Background: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.
Methods: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry.
We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).
Findings: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD −0·25 [95% CI −0·49 to −0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.
Interpretation: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.
Funding: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.

Authors
Nicola Black, Emily Stockings, Gabrielle Campbell, Lucy T Tran, Dino Zagic, Wayne D Hall, Michael Farrell, Louisa Degenhardt

[link url="https://www.reuters.com/article/us-health-mental-cannabis/medicinal-cannabis-not-proven-in-mental-health-study-finds-idUSKBN1X72AV"]Reuters Health report[/link]

[link url="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-03661930401-8/fulltext"]The Lancet Psychiatry article summary[/link]

[link url="https://www.theguardian.com/society/2019/oct/28/risks-of-cannabis-use-for-mental-health-treatment-outweigh-benefits?CMP=Share_iOSApp_Other"]The Guardian report[/link]

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