Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis

Author summary Why was this study done? Use of cannabinoid-based medicines (CBMs) has been growing steadily in recent years, including in the elderly. However, their safety and tolerability in older adults remains unclear. With increasing interest in the use of CBMs in older people and growing unlicensed use, there is a particular need to examine their safety and tolerability in older adults. We analysed data on safety and tolerability from previously published double-blind, randomised controlled trials (RCT) using delta-9-tetrahydorcannabinol (THC) and cannabidiol (CBD), the common constituents of most CBMs, alone or in combination, to examine their effect on older adults. What did the researchers do and find? We pooled data from 46 published RCTs (with information from 6,216 patients; with mean participant age >= 50 years) on adverse events, serious adverse events or death, and withdrawal from study. We also examined the relationship between the dose of THC used in THC-containing CBMs and the incidence of adverse consequences in older adults. Our results suggest that compared with the control condition, treatment with THC-containing CBMs was associated on average with significantly greater incidence of all-cause and treatment-related adverse events. There was no significant increase in the incidence of serious adverse events or death with any CBMs. The risk of withdrawal from study was increased only in those receiving THC:CBD combination treatment, and this was related to THC dose. What do these findings mean? These findings suggest that CBMs in general are safe and acceptable in older adults. Our findings that THC-containing CBMs are associated with side effects and that THC:CBD combinations may be less acceptable at the dose ranges typically used in RCTs is critical to prescribing in older people. Background Cannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age >= 50 years. Methods and findings A systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of >= 50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Stud