The use of medical cannabis which includes compounds like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is increasing, particularly among middle-aged and older adults. As patients and prescribers, we need to have the clearest picture possible of how these medicines are tolerated.
A recent study, comprising a comprehensive review and meta-analysis of multiple clinical trials, looked closely at the information we have on adverse events (AEs), or side effects, in patients aged 50 years and older who are using medical cannabis for a variety of conditions.
This article breaks down the key findings from this important research so you can understand the reported risks and discuss them with your prescribing specialist.
A Meta-Analysis of Current Literature
The researchers searched databases for relevant randomised controlled trials (RCTs) that used medical cannabis in participants with a mean participant age of ≥50 years for all clinical indications. Eligible studies published between January 1990 and June 2023 were included in the analysis.
All relevant available data for examination of the safety and tolerability of different medical cannabis preparations (THC:CBD combination or THC alone) was collected from eligible studies, including:
- Participant characteristics
- Indication
- Dosage and duration of intervention
- All cause and treatment-related AEs and serious adverse events (SAEs)
- AE-related withdrawals and deaths
Using this data, the researchers estimated pooled effect-sizes incident rate difference under the random-effects model.
Key Findings of the Analysis
Data from 58 RCTs was included in the final meta-analysis, with a total participant number of 6,611, of whom 3,450 received CBMPs. This was equivalent to 1,655.85 person-years of cannabinoid exposure. The mean age range of participants was 50-87 years and 50% of participants were male.
The analysis found a greater incidence of all-cause and treatment-related side effects compared to control groups in both the THC-only and THC:CBD combination treatments.
The review did not find a significantly greater risk of serious adverse events (SAEs), withdrawals from treatment, or deaths associated with medical cannabis containing THC (with or without CBD) compared to controls.
Adverse Events in THC Studies
A total of 31 RCTs from 29 articles, reporting on 1,473 patients on active and 1,265 on control interventions, were included in the analysis:
- Total AEs: All-cause and treatment-related AEs from all RCTs were 18.83 and 16.35 AEs per 1000 person-years greater than placebo, respectively.
- The most commonly reported AEs: There was a significantly higher incidence of the following AEs in active compared to control arms:
- Dizziness/light-headedness (0.819 per 1000 person-years)
- Somnolence/drowsiness (0.684 per 1000 person-years)
- Impaired mobility/balance/coordination (0.078 per 1000 person-years)
- Sedation (11.103 per 1000 person-years)
- Headache (5.287 per 1000 person-years)
- Dissociative/thinking/perception disorders (0.510 per 1000 person-years)
- Euphoria (9.117 per 1000 person-years)
- Dry mouth (1.059 per 1000 person-years)
- Pooled incident rate differences for all cause and treatment-related SAEs were 0.002 and 0.908 SAEs per 1000 person-years, respectively.
- Pooled incident rate differences for all cause and treatment-related withdrawals were 0.052 and 0.517 withdrawals per 1000 person-years, respectively.
- Pooled incident rate differences for all cause deaths were 0.023 deaths per 1000 person-years.
Meta-regression analysis suggested a significant association between cumulative THC dose per week across THC studies and incidence rate of some of the AEs, including:
- Dry mouth
- Dizziness/light-headedness
- Mobility/balance/ coordination difficulties
- Dissociative/thinking perception
- Somnolence/drowsiness
However, the researchers note that these estimates should be interpreted with caution due to heterogeneity across the studies reporting the AEs.
Adverse Events in THC:CBD Combination Studies
Data from 27 studies from 22 articles, reporting on a total of 1,977 patients on active and 1,896 on placebo intervention, were included in the analysis:
- Total AEs: All-cause and treatment-related AEs from all RCTs were 19.37 and 11.36 AEs per 1000 person-years greater than placebo, respectively.
- The most commonly reported AEs: There was a significantly higher incidence of the following AEs in active compared to control arms:
- Nausea (0.674 per 1000 person-years)
- Vomiting (0.214 per 1000 person-years)
- Dry mouth (1.227 per 1000 person-years)
- Fatigue/tiredness (0.439 per 1000 person-years)
- Dizziness/light-headedness (2.467 per 1000 person-years)
- Somnolence/drowsiness (1.650 per 1000 person-years)
- Disorientation (2.536 per 1000 person-years)
- Pooled incident rate differences for all cause and treatment-related SAEs were 0.056 and 0.058 SAEs per 1000 person-years, respectively.
- Pooled incident rate differences for all cause and treatment-related withdrawals were 0.036 and 0.489 withdrawals per 1000 person-years, respectively.
- Pooled incident rate differences for all cause deaths were 0.010 deaths per 1000 person-years.
Meta-regression analysis suggested a significant association between individual AEs and weekly doses of THC and CBD and their interaction expressed as incident rate differences for some AEs, such as:
- Palpitations (CBD and THC*CBD interaction)
- Altered taste (CBD)
- Dizziness and light-headedness (THC)
- Concentration and attention problems (THC, CBD, THC*CBD interaction)
- Disorientation (THC)
What Does This Tell Us?
This meta-analysis examined data from 58 RCTs to offer the first pooled incidence rate estimates of medical cannabis-attributable AEs, specifically in adults aged 50 years and older. The findings indicate that medical cannabis containing THC may increase the risk of mild-to-moderate AEs compared to control interventions (most commonly placebo), but were not associated with an increase in serious adverse events, withdrawal, or mortality.
The findings suggest that THC-containing medical cannabis is associated with certain side-effects in a dose-related manner, both for THC only and THC:CBD combinations, some of which may be mitigated by CBD. This provides new insights and dose-response estimates, which may be helpful in guiding clinical dosing decisions for cannabinoids, including THC and CBD.
The data analysed in this study suggest that medical cannabis is generally safe and well-tolerated in middle-aged and older individuals; however, clinicians should remain mindful of the potential dose-dependent effects of THC-containing products.
Why This Matters for Older Patients
Side effects like dizziness, lightheadedness, and impaired mobility are especially important to monitor in older people, as they can contribute to an increased risk of falls. Falls are a major cause of injury in this age group, which is why your specialist will carefully consider all potential risks when deciding on whether medical cannabis is right for you.
The ability to predict a patient’s additional risk for a specific side effect based on the dose of a medical cannabis is invaluable for specialist prescribers. These findings underscore the importance of gradual dosing and the careful consideration of the ratio of THC to CBD in a formulation.
This study strengthens the evidence that medical cannabis is generally acceptable for older adults who meet eligibility criteria, but it clearly identifies common dose-related side effects that patients and their specialists must be mindful of.
