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

Abstract

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.