Sex-Related Differences in Medical Cannabis Use: A Nationwide Database Study.

Yakirevich Amir N.; Treves N.; Davidson E.; Reuveni I.; Florentin S.; Matok I.; Bonne O. · Cannabis and cannabinoid research · 2026

**Background & Methods** This population-based retrospective cohort study analyzed medical cannabis use patterns and sex-related differences using the Israeli Medical Cannabis Agency registry from April 2018 to March 2022. The dataset included 135,698 licensed MC users, examining demographics, clinical indications, dosing parameters (THC/CBD concentrations), and adverse effect reporting, with statistical analysis conducted using time-series analyses, Cox proportional hazards models, and relative risk estimates. **Key Findings** - Men comprised 62% of the cohort and were significantly younger than women (49 ± 18.3 vs. 55.3 ± 18.1 years). The leading indications for both sexes were chronic pain, oncology-related symptoms and chemotherapy side effects, and post-traumatic stress disorder. - At treatment initiation, men received higher monthly quantities (29.3 g vs. 26.1 g; p < 0.001), higher THC concentrations (14.3% vs. 11.9%; p < 0.001), and lower CBD concentrations (5.1% vs. 6.5%; p < 0.001), with these differences persisting over the 2-year follow-up period. - Men demonstrated lower discontinuation rates (HR 0.95, 95% CI: 0.93-0.97), while women reported significantly more adverse effects (RR 1.51, 95% CI: 1.43-1.58). **Dosage & Administration** Initial monthly quantities: Men received 29.3 g versus women 26.1 g. Men received THC concentrations of 14.3% compared to women's 11.9%, while women received higher CBD concentrations (6.5% vs. 5.1%). **Safety & Adverse Effects** Women were substantially more likely to report at least one adverse effect than men (relative risk 1.51, 95% CI: 1.43-1.58). Specific adverse effects were not detailed in the abstract; however, the higher reporting rate in women may reflect biological sensitivity, hormonal factors, or differential reporting behavior between sexes. **Evidence Quality** This large registry-based study provides real-world evidence with substantial sample size and 2-year follow-up. However, significant limitations include reliance on reported adverse effects without standardized assessment tools, potential reporting bias favoring women, lack of randomization, inability to establish causation, incomplete data on confounding variables (comorbidities, concurrent medications, genetic factors), and absence of information on adherence rates or clinical outcome measures. The retrospective nature and observational design limit causal inference. Results are geographically specific to Israel's regulatory context.

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