Clinical evidence supports effectiveness of cannabis-based medicines in people with multiple sclerosis, chronic pain, and inflammatory bowel disease, and in palliative medicine, according to a review of meta-analyses, and cannabidiol is effective in people with epilepsy. However, the products are associated with adverse events, the authors report, and “convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving.”
Identified through citation databases up to Feb. 9, 2022, systematic reviews with meta-analyses of 50 observational studies and 51 randomized controlled trials (RCTs) were included that reported on the efficacy and safety of cannabis, cannabinoids, or cannabis-based medicines. Credibility of the observational evidence was graded as convincing, highly suggestive, suggestive, weak, or not significant; GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to evaluate RCTs. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2) was used to assess quality.
The AMSTAR 2 ratings for the 101 meta-analyses were high (33), moderate (31), low (32), or critically low (5). “From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE = high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE = moderate),” the authors report. “Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE = high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE = moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE = high), across different conditions (n = 7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE = high), reduced seizures across different populations and measures (n = 7), improved global impression (n = 2), quality of life, and increased risk of somnolence (GRADE = moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE = high), negative psychotic symptoms, and cognition (n = 11) (GRADE = moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE = high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE = high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE = moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).”