Lancet study finds insufficient evidence that medicinal cannabinoids improve mental health

A new meta-analysis published in The Lancet Psychiatry found inadequate evidence that cannabinoids relieve depression, anxiety disorders, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis.

Medicinal cannabinoids include medicinal cannabis and pharmaceutical cannabinoids, and their synthetic derivatives, THC and cannabidiol (CBD). Around the world, these are increasingly being made available for medicinal purposes, including for the treatment of mental health disorders. However, 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.

For the study, researchers analyzed medicinal cannabinoids and their impact on six mental health disorders. They included published and unpublished studies between 1980 and 2018 and included 83 eligible studies, 40 of which were randomized controlled trials (RCTs), and the remaining of which were open-label trials. Of the 83 studies, 42 looked at depression (including 23 RCTs), 31 looked at anxiety (including 17 RCTs), eight looked at Tourette syndrome (including two RCTs), three were on ADHD (including one RCT), 12 were on PTSD (including one RCT), and 11 were on psychosis (including six RCTs).

In most RCTs examining 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 the mental health disorder. Few randomized controlled trials examined the role of pharmaceutical CBD or medicinal cannabis, and most looked at THC, with or without CBD.

The authors found that pharmaceutical THC with or without CBD improved anxiety symptoms among individuals with other medical conditions, which encompassed seven studies of 252 people, though this may have been due to improvements in the primary medical condition. The authors suggest further research should explicitly study the effects of cannabinoids on anxiety and depression.

Pharmaceutical THC with or without CBD worsened negative symptoms of psychosis 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 and withdrawals due to adverse events compared with placebo across all mental health disorders examined, the researchers said.

The study highlights the limited evidence and the low quality of the evidence that exists around using cannabinoids for treatment of mental health conditions. 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, researchers said.

The authors also highlight that their analysis and conclusions are limited by the small amount of available data, small study sizes, and the differences in findings between small studies. There is no recommended approach for addressing these issues in systematic reviews, but they tried to minimize them by keeping the focus of the review narrow. They also note that 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 United States.

"Cannabinoids are often advocated as a treatment for various mental health conditions,” said Louisa Degenhardt, PhD, lead author of the study and professor at the National Drug and Alcohol Research Centre in Sydney, Australia, in a statement. “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.”