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

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.

Author/s:

Velayudhan, Latha, McGoohan, Katie, Bhattacharyya, Sagnik

Clinicians’ Guide to Cannabidiol and Hemp Oils

Brian Desmarais — Wed, 11 Sep 2019 21:41:17 +0000

Date Added:

September 18, 2019

Journal/Publication:

Mayo Clinic Proceedings

Publisher:

Mayo Foundation for Medical Education and Research

Publication Date:

September 1, 2019

Issue:

Volume:

Pages:

1840-1851

URL:

Clinicians’ Guide to Cannabidiol and Hemp Oils

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.mayocp.2019.01.003

Keywords

cannabidoil

cannabis

PMID (1):

31447137

MeSH

This is a review of what is known about cannabidiol and other hemp-related oils from the Mayo Clinic. James W. Mold, MD, MPH

Free full text

View

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.

Author/s:

VanDolah H.J., Bauer, B.A., Mauck, K.F.