Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference.

Background: Cannabinoid-based medicines (CBMs) are being used widely in older people. However, information on the incidence of adverse events (AEs) is limited. Objective: To quantify the incidence rate difference (IRD) of AEs in middle aged and older adults of age >/=50 years receiving CBMs and also examine associations with weekly doses. Design: Systematic review and meta-analysis. Data Sources: MEDLINE, PubMed, EMBASE, CINAHL, PsychInfo, Cochrane Library and ClinicalTrials.gov (1st Jan 1990-12th June 2023). Methods: We included randomised clinical trials (RCTs) using CBMs with mean participant age >/=50 years for medicinal purposes for all clinical indications. Paired reviewers independently screened studies, extracted data and appraised risk of bias. We estimated pooled effect-sizes IRD under the random-effects model. Results: Data from 58 RCTs (37 moderate-high quality studies, pooled n = 6611, mean age range 50-87 years, 50% male, n = 3450 receiving CBMs) showed that compared with controls, the incidence of all-cause and treatment-related AEs attributable to delta-9-tetrahydrocannabinol (THC)-containing CBMs were: THC alone [IRD:18.83(95% Confidence Interval [CI], 1.47-55.79) and 16.35(95% CI, 1.25-48.56)] respectively; THC:cannabidiol (CBD) combination [IRD:19.37(95% CI, 4.24-45.47) and 11.36(95% CI, 2.55-26.48)] respectively. IRDs of serious AEs, withdrawals and deaths were not significantly greater for CBMs containing THC with or without CBD. THC dose-dependently increased the incidence of dry mouth, dizziness/lightheadedness, mobility/balance/coordination difficulties, dissociative/thinking/perception problems and somnolence/drowsiness. The interaction of weekly THC:CBD doses played a role in mostly neurological, psychiatric and cardiac side-effects. Conclusions: Although CBMs in general are safe and acceptable in middle aged and older adults, one needs to be mindful of certain common dose-dependent side-effects of THC-containing CBMs.