Is marijuana good or bad for you?

An umbrella review of meta-analyses on cannabis studies reveals that this psychoactive drug, more popularly known as marijuana, is only effective among people with epilepsy and should be avoided by adolescents and young adults, those who are prone to or with mental health disorders, pregnant women, and those who are driving.

In addition, medicines based on cannabis are also beneficial to people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative care, but not without adverse events (AEs).

“Cannabidiol 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,” the researchers said. “The remaining associations between cannabis and health outcomes are not supported by converging or convincing evidence.”

Using the databases of PubMed, PsychInfo, and Embase, the researchers identified systematic reviews with meta-analyses of observational studies and randomized controlled trials (RCTs) reporting on the efficacy and safety of cannabis, cannabinoids, or cannabis-based medicines up to 9 February 2022.

Credibility was assessed according to convincing, highly suggestive, suggestive, weak, or not significant observational evidence, and by Grading of Recommendations, Assessment, Development and Evaluations (GRADE). The researchers also evaluated quality using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and performed sensitivity analyses.

A total of 101 meta-analyses met the eligibility criteria (observational: n=50; RCTs: n=51; AMSTAR 2 high: n=33, moderate: n=31, low: n=32, critically low: n=5). [BMJ 2023;382:e072348]

In RCTs with high-to-moderate certainty, cannabis-based medicines resulted in more AEs related to the central nervous system (equivalent odds ratio [OR], 2.84, 95 percent confidence interval [CI], 2.16‒3.73), psychological effects (OR, 3.07, 95 percent CI, 1.79‒5.26), and vision (OR, 3.00, 95 percent CI, 1.79‒5.03) in people with mixed conditions (GRADE=high). It also improved nausea/vomiting, pain, and spasticity but increased psychiatric, gastrointestinal AEs, and somnolence, among others (GRADE=moderate).

Cannabidiol, on the other hand, reduced seizures (OR, 0.59, 95 percent CI, 0.38‒0.92) and seizure events (OR, 0.59, 95 percent CI, 0.36‒0.96; GRADE=high) but increased pneumonia, gastrointestinal AEs, and somnolence (GRADE=moderate).

Benefits and risks

Among individuals with epilepsy, cannabidiol increased diarrhoea risk (OR, 2.25, 95 percent CI, 1.33‒3.81) and showed no impact on sleep disruption (GRADE=high), but it reduced seizures across different populations and measure (n=7), improved global impression (n=2) and quality of life, and elevated the risk of somnolence (GRADE=moderate).

Cannabis-based medicines or cannabinoids were beneficial to people suffering from chronic pain, as shown by a 30-percent decrease in pain (OR, 0.59, 95 percent CI, 0.37‒0.93; GRADE=high), across different conditions. However, an increase in psychological distress was observed.

In the general population, cannabis resulted in worse positive psychotic symptoms (OR, 5.21, 95 percent CI, 3.36‒8.01) and total psychiatric symptoms (OR, 7.49, 95 percent CI< 5.31‒10.42; GRADE=high), negative psychotic symptoms, and cognition (n=11; GRADE=moderate). In healthy people, cannabinoids improved pain threshold (OR, 0.74, 95 percent CI, 0.59‒0.91) and unpleasantness (OR, 0.60, 95 percent CI, 0.41‒0.88; GRADE=high).

Furthermore, cannabinoids improved quality of life (OR, 0.34, 95 percent CI, 0.22‒0.53; GRADE=high) in people with inflammatory bowel disease; improved spasticity and pain but increased the risk of dizziness, dry mouth, nausea, and somnolence (GRADE=moderate) in those with multiple sclerosis; and improved sleep disruption but increased gastrointestinal AEs (n=2; GRADE=moderate) in cancer patients.

From observational studies, cannabis proved to be harmful to pregnant women, with increases in the likelihood of small for gestational age (OR, 1.61, 95 percent CI, 1.41‒1.83) and low birth weight (OR, 1.43, 95 percent CI, 1.27‒1.62). Cannabis also increased car crashes while driving (OR, 1.27, 95 percent CI, 1.21‒1.34), as well as psychosis (OR, 1.71, 95 percent CI, 1.47‒2.00) in the general population.

“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),” the researchers said.

“Law and public health policy makers 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, with particular attention to the tetrahydrocannabinol content of cannabinoids,” they added.