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

Abstract

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. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those <50 years of age in our primary analyses as well as limitations related to weaknesses in the included trials particularly incomplete reporting of outcomes and heterogeneity in included studies. Conclusions This pooled analysis, using data from RCTs with mean participant age ≥50 years, suggests that although THC-containing CBMs are associated with side effects, CBMs in general are safe and acceptable in older adults. However, THC:CBD combinations may be less acceptable in the dose ranges used and their tolerability may be different in adults over 65 or 75 years of age.

Medical cannabis authorization patterns, safety, and associated effects in older adults

“…No serious AEs were reported, and non-serious AEs were experienced in less than 12% of the cohort. The most common AEs observed (dizziness, nausea, dry mouth, and tinnitus) were similar with the results of a longitudinal study in older adults that observed the following most common AEs: dizziness, sleepiness/fatigue, dry mouth, and psychoactive sensation (Abuhasira et al 2018;Velayudhan et al 2021). Moreover, these AEs were similarly observed in the general population (Wang et al 2008).…”

“…Cross-sectional surveys suggest older adults generally used cannabis for pain and sleep disorders, use had a positive impact on their lives, and they were less likely to report problematic cannabis use than younger adults (Brown et al 2020;Haug et al 2017;Reynolds et al 2018;Yang et al 2021). Moreover, Page 2 of 10 MacNair et al Journal of Cannabis Research (2022) 4:50 a systematic review and meta-analysis of cannabinoidbased medicines in older adults (≥ 50 years of age) concluded that they were safe and acceptable in this population (Velayudhan et al 2021). However, only one longitudinal study has examined the safety and effectiveness of medical cannabis in this population, where patients over 65 years of age at a medical cannabis clinic in Israel were followed for 6 months and pain intensity, quality of life, and adverse events (AEs) were monitored (Abuhasira et al 2018).…”

Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline

“…The median of the mean age among eligible randomised trials we reviewed was 53; a separate review has concluded that, in general, cannabinoid based medicines are safe and acceptable in older adults. 78 Patients recruited among eligible trials were adults. However, the panel (which included a general paediatrician and a paediatric anaesthesiologist) could see no reason why the expected benefits would be systematically different among adolescents and emerging adults.…”

Medical Cannabis Use Among Older Adults in Canada: Self-Reported Data on Types and Amount Used, and Perceived Effects

“…Cannabis has also been used for mental health conditions such as anxiety, depressive symptoms, insomnia, and post-traumatic stress disorder [ 14 , 27 ]. Among older adults, adverse events, which include dizziness, dry mouth, somnolence, and falls, are of concern [ 28 , 29 ] and may be more related to tetrahydrocannabinol (THC) than cannabidiol (CBD) [ 28 ]. Other concerns surrounding cannabis use among older adults include the presence of one or more medical ailments, use of multiple medications, and altered metabolic processing of drugs [ 30 ].…”