Umbrella review reveals what the benefits and risks of cannabis are and for whom

Key takeaways:

• Cannabis-based medications seem to be effective for those with chronic pain, multiple sclerosis and more.
• In the general population, cannabis worsened cognition, psychotic symptoms and psychiatric symptoms.

An umbrella review published in The BMJ provided a breakdown of the associations between cannabis and health outcomes, highlighting the uncertain potential for clinical use.

Cannabis or products that contain THC “are widely available and have increasingly high tetrahydrocannabinol content,” Marco Solmi, MD, an associate professor of psychiatry at the University of Ottawa, in Canada, and colleagues wrote. However, there has not yet been an umbrella review to systematically evaluate the existing evidence about cannabis, cannabis-based medicine and cannabinoids and associations with health outcomes from meta-analyses that encompass both randomized controlled trials and observational studies.

“We aimed to use established quantitative criteria, account for several sources of bias, and identify converging findings from different study designs,” they wrote.

For the umbrella review, the researchers searched for meta-analyses of randomized trials and observational studies on Embase, PubMed and PsychInfo. They graded the credibility of the evidence from randomized trials based on the GRADE framework (Grading of Recommendations, Assessment, Development and Evaluations) and the evidence of observational studies based on whether it was not significant, weak, suggestive, highly suggestive or convincing.

The researchers ultimately included 101 meta-analyses. In the 51 randomized controlled trials and 50 observational studies, 33 were high quality, 31 were moderate quality, 32 were low quality and five were critically low quality.

Solmi and colleagues found that converging or convincing evidence supports that cannabidiol (CBD) was effective for people with epilepsy, and cannabis-based medicines were effective for people with chronic pain, inflammatory bowel disease, multiple sclerosis and in palliative care — but there was some risk for adverse events.

The evidence also supported the idea that cannabis should be avoided in pregnancy, before and while driving, in people with mental health disorders and in adolescents and young adults.

In high-to-moderate certainty randomized controlled trials, cannabis-based medicines increased adverse events related to psychological effects (equivalent OR = 3.07; 95% CI, 1.79-5.26), vision (OR = 3; 95% CI, 1.79-5.03) and the central nervous system (OR = 2.84; 95% CI, 2.16-3.73) in people with mixed conditions (high GRADE evidence). Cannabis-based medicines also improved pain, spasticity and nausea/vomiting (moderate GRADE evidence). For those with chronic pain, cannabis-based medicines or cannabinoids lowered pain by 30% (OR = 0.59; 95% CI, 0.37-0.93) across different conditions.

Among the general population, cannabis worsened cognition and negative psychotic symptoms (moderate GRADE), as well as total psychiatric symptoms (OR = 7.49; 95% CI, 5.31-10.42) and positive psychotic symptoms (high GRADE; OR = 5.21; 95% CI, 3.36-8.01). For those who were considered healthy, cannabinoids improved unpleasantness (OR = 0.6; 95% CI, 0.41-0.88) and pain threshold (high GRADE; OR = 0.74; 95% CI, 0.59-0.91).

CBD offered improvements for seizure events (OR = 0.59; 95% CI, 0.36-0.96), including a 50% reduction of seizures (high GRADE; OR = 0.59; 95% CI, 0.38-0.92). However, it also increased somnolence, gastrointestinal adverse events and pneumonia (moderate GRADE). For epilepsy specifically, CBD reduced seizures and improved both global impression and quality of life but had no impact on sleep (high GRADE), and it heightened the risk for diarrhea (OR = 2.25; 95% CI, 1.33-3.81) and somnolence (moderate GRADE).

Solmi and colleagues concluded that “clinical relevance must be considered” before possibly implementing cannabis into clinical guidelines.

“For example, including numbers needed to treat for benefit, risk-to-benefit ratios, comparative efficacy and safety with existing treatment options, and development of patient information concerning potential adverse events. CBD appears to be safe regarding psychiatric symptoms, but more research needs to be conducted before this drug can be recommended for the treatment of any psychiatric disorder,” they concluded. “Law and public health policymakers and researchers should consider this evidence synthesis when making policy decisions on cannabinoids use regulation, and when planning a future epidemiological or experimental research agenda.”