Little evidence to support idea that medical cannabis can treat, improve mental health disorders, say experts
There is insufficient evidence to suggest that medical cannabis and medicinal cannabinoids can treat or improve mental health disorders or relieve their symptoms.
Researchers, who conducted a comprehensive analysis of medicinal cannabinoids and their impact on six mental health disorders - depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder (PTSD), and psychosis - conclude that the use of cannabinoids for mental health conditions cannot be justified due to a lack of evidence currently for their effectiveness, and because of the known risks of cannabinoids. The findings have been published in The Lancet Psychiatry journal.
"Our findings have important implications in countries where cannabis and cannabinoids are being made available for medical use. There is a notable absence of high-quality evidence to properly assess the effectiveness and safety of medicinal cannabinoids compared with placebo, and until evidence from randomized controlled trials is available, clinical guidelines cannot be drawn up around their use in mental health disorders," says lead author of the study Professor Louisa Degenhardt from the National Drug and Alcohol Research Centre (NDARC) at University of New South Wales (UNSW) in Sydney, Australia.
Professor Degenhardt further says, "In countries where medicinal cannabinoids are already legal, doctors and patients must be aware of the limitations of existing evidence and the risks of cannabinoids. These must be weighed when considering the use to treat symptoms of common mental health disorders. Those who decide to proceed should be carefully monitored for positive and negative mental health effects of using medicinal cannabinoids."
Medicinal cannabinoids include medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, Tetrahydrocannabinol (THC), and cannabidiol (CBD). A recent study, which was published in The Lancet, says that cannabis remains an illicit drug under international drug control treaties that have been ratified by most UN member states, including Canada and the USA. Despite this illegality, an estimated 192 million adults or 3.9% of the global adult population used cannabis in 2015, says the study.
According to experts, after chronic non-cancer pain, mental health is one of the most common reasons for using medicinal cannabinoids. These are being increasingly made available for medicinal purposes globally, for example, in the US, Australia, and Canada, including for the treatment of mental health disorders. However, says the research team, there are concerns around the adverse effects of this availability, as there is a large body of evidence indicating that non-medicinal cannabis use can increase the occurrence of depression, anxiety, and psychotic symptoms.
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The research team examined the available evidence for all types of medicinal cannabinoids. They included all study designs and investigated the impact on remission from and symptoms of six mental health disorders in adults.
The team assessed published and unpublished studies between 1980 and 2018 and included 83 eligible studies (including 3,000 people), 40 of which were randomized controlled trials (RCTs). The others were open-label trials, where participants knew which treatment they were taking. Of the 83 studies, 42 looked at depression (including 23 RCTs), 31 looked at anxiety (17 RCTs), eight looked at Tourette syndrome (two RCTs), three were on ADHD (one RCT), 12 were on PTSD (one RCT), and 11 were on psychosis (six RCTs). The analysis, says the team, shows that there is scarce evidence to suggest that cannabinoids improve mental conditions.
"However, 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," says the study.
According to the research team, in most randomized controlled trials that examined depression and anxiety, the primary reason for cannabinoid use was for another medical condition such as chronic non-cancer pain or multiple sclerosis. In the studies looking at the other four disorders, the cannabinoid was used to treat mental health disorders. Few randomized controlled trials examined the role of pharmaceutical CBD or medicinal cannabis; most looked at THC, with or without CBD, says the team.
"There is a notable absence of high-quality evidence where mental disorders are the primary target of treatment, and most evidence is derived from studies where mental disorders are secondary to another medical condition, commonly chronic non-cancer pain and multiple sclerosis. Most of the included studies were done among individuals in whom depression or anxiety was secondary to another medical condition, and in these studies, we found no impact of pharmaceutical THC (with or without CBD) on depression symptoms, and a small reduction in anxiety symptoms," state the findings.
It adds, "Of the few studies in which participants had an anxiety disorder, we did not see a significant benefit of CBD on symptoms of anxiety."
The researchers found that pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (seven studies of 252 people), though this may have been due to improvements in the primary medical condition. The team suggests that further research should explicitly study the effects of cannabinoids on anxiety and depression.
Pharmaceutical THC (with or without CBD), shows analysis, worsened negative symptoms of psychosis (one study, 24 people) and did not significantly affect any other primary outcomes for the mental health disorders examined. It also increased the number of people who had adverse events (10 studies; 1,495 people), and withdrawals due to adverse events (11 studies; 1,621 people) compared with placebo across all mental health disorders examined.
"Cannabinoids are often advocated as a treatment for various mental health conditions. Countries that allow medicinal cannabinoid use will probably see increased demand for such use. Clinicians and consumers need to be aware of the low quality and quantity of evidence for the effectiveness of medicinal cannabinoids in treating mental health disorders and the potential risk of adverse events. Most studies are based on pharmaceutical cannabinoids, rather than medicinal cannabis, but plant products are most often used by those taking cannabinoids for medicinal purposes in the USA," says the study.
Based on their analysis, the researchers say that there is a need for high-quality research to understand the effects of different cannabinoids on a range of outcomes for people with mental health disorders. Such evidence, they explain, is essential before clinical guidelines can be provided about the medicinal use of cannabinoids for these disorders.
"Given the likely interest but scant evidence to guide patient and clinician decisions around cannabinoids for mental health, there is an urgent need for randomized controlled trials to inform whether there are benefits of cannabinoids for these indications," says Professor Degenhardt.
In a linked comment, Professor Deepak Cyril D'Souza from Yale University School of Medicine, US, says that there is a pressing need to develop new medications for the treatment of psychiatric disorders. While there is growing public interest in the use of cannabis and its principal constituent cannabinoids, in parallel, there is considerable commercial interest in touting these products as treatments for various disorders, says the expert. As a result, says Professor D'Souza, health practitioners need to be well informed about this topic.
"In light of the results of this comprehensive review and meta-analysis, it would be hard for practitioners to justify recommending the use of cannabinoids for psychiatric conditions at this time. What is clear is that more high-quality randomized controlled trials are needed to test the efficacy and safety of cannabinoids in psychiatric disorders before these compounds can be recommended for clinical use. This can only be accomplished by removing any barriers to research", says Professor D'Souza.
He adds, "The process of drug development in modern medicine is to first demonstrate efficacy and safety in clinical trials before using the drug clinically. With cannabinoids, it seems that the cart (use) is before the horse (evidence). If cannabinoids are to be used in the treatment of psychiatric disorders, they should first be tested in randomized controlled trials and subjected to the same regulatory approval process as other prescription medications."