Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis

Background: Medicinal cannabinoids, including medicinal cannabis, pharmaceutical cannabinoids and their synthetic derivatives, including tetrahydrocannabinol (THC) and or cannabidiol (CBD), have been suggested to have a therapeutic role for certain mental health conditions. The primary objective was to review the evidence for cannabinoids in treating symptoms of depression, anxiety, post-traumatic stress disorder, attention-deficit hyperactivity disorder, Tic/Tourette syndrome, and psychosis, either as the primary condition or secondary to other conditions. Secondary outcomes included quality of life and global functioning.

Methods: We undertook a systematic review and meta-analysis of published and unpublished studies (1980-2018) using MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Clinical Trials, clinicaltrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We included randomised controlled trials (RCTs) and non-RCT treatment studies. Two independent reviewers screened all studies and performed data extraction. RCT evidence was synthesised, as odds ratios (ORs) for disorder remission and standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. Evidence quality was evaluated using the Cochrane Risk of Bias and GRADE approaches.

Findings: A total of k=83 studies (k=40 RCTs, n=3067) were included: k=40 for depression (k=22 RCTs, n=2524), k=31 for anxiety (k=17 RCTs, n=605), k=8 for Tic/Tourette syndrome (k=2 RCTs, n=36), k=4 for attention-deficit hyperactivity disorder (k=1 RCT, n=30), k=12 for post-traumatic stress disorder (k=1 RCT, n=10) and k=11 for psychosis (k=6 RCTs, n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms amongst those with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD=−0.25 [95% confidence interval: −0.49:−0.01]; k=7, n=252). Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD=0.36 [0.10:0.62]; n=24). Pharmaceutical THC (with or without CBD) did not improve any other primary outcomes but did increase adverse events (OR=1.99 [1.20:3.29]; k=10, n=1495) and withdrawals due to adverse events (OR=2.78 [1.59:4.86]; k=11, n=1621). Very few RCTs examined pharmaceutical CBD or medicinal cannabis.

Interpretation: There is a lack of evidence that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tic/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 amongst those with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for mental health conditions within a regulatory framework. More high-quality studies examining the effect of cannabinoids on mental disorders are needed. Review

Registration: PROSPERO CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, CRD42018102977

Funding: Therapeutic Goods Administration, Commonwealth Department of Health; Australian National Health and Medical Research Council, NIH