Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference.
Velayudhan et al.·Age and ageingImpact 2.2
MixedGRADEHigh6 citations
Samplek = 58 Studien n = 6.611 Pat.
DurationStudies from period 1. Jan 1990…
ControlControl group
EndpointIncidence rate difference
Blindingdoppelblind
DesignMeta-Analyse
”Key finding
THC-containing cannabinoid medicines show increased rates of adverse events (in particular dry mouth, dizziness, balance disorders, perception problems and drowsiness) in a dose-dependent manner, while serious adverse effects, discontinuations and deaths are not significantly increased.
Summary
Systematic review + meta-analysis across k=58 RCTs (n=6.611, age ≥50 years, 50% male, n=3.450 received cannabis products). Incidence Rate Difference (IRD) for all adverse events with THC-containing products: THC alone IRD=18,83 (95% CI 1,47–55,79), THC:CBD combination IRD=19,37 (95% CI 4,24–45,47). IRD for serious adverse effects, discontinuations, deaths not significantly increased. THC dose-dependent: dry mouth, dizziness, coordination difficulties, somnolence. Weekly THC:CBD dose interaction relevant for neurological, psychiatric, cardiac adverse effects.
P
PopulationAdults ≥50 years (mean age 50–87 years) under cannabinoid-based medicines, pooled n=6.611, 50% male
I
InterventionCannabinoid-based medicines (THC alone, THC:CBD combination), various indications and routes of administration
C
ControlControl group (placebo or active control)
O
OutcomeTHC alone: IRD all-cause AE 18,83 (95% CI 1,47–55,79), treatment-related AE 16,35 (95% CI 1,25–48,56); THC:CBD combination: IRD 19,37 (95% CI 4,24–45,47) and 11,36 (95% CI 2,55–26,48) respectively; no significantly increased IRDs for serious AEs, treatment discontinuations or deaths
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeMixed
Citations / year★★★★★
Authors
Velayudhan L, Pisani S, Dugonjic M, McGoohan K, Bhattacharyya S
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.