Sex differences in medical cannabis-related adverse effects

Abstract

Studies have shown that women are more susceptible to adverse effects (AEs) from conventional drugs. This study aimed to investigate the differences of medical cannabis (MC)-related AEs between women and men in patients with chronic noncancer pain (CNCP). This is a cross-sectional study of adult patients licensed for MC treatment who were also diagnosed as patients with CNCP by a physician. Data included self-reported questionnaires and comprehensive MC treatment information. Simultaneously, identification and quantification of phytocannabinoids and terpenoids from the MC cultivars were performed. Comparative statistics were used to evaluate differences between men and women. Four hundred twenty-nine patients with CNCP (64% males) reported fully on their MC treatment. Subgrouping by sex demonstrated that the weight-adjusted doses were similar between men and women (0.48 [0.33-0.6] gr for men and 0.47 [0.34-0.66] gr for women). Nonetheless, women reported more than men on MC-related AEs. Further analysis revealed that women consumed different MC cultivar combinations than men, with significantly higher monthly doses of the phytocannabinoids CBD and CBC and significantly lower monthly doses of the phytocannabinoid 373-15c and the terpenoid linalool. Our findings demonstrate sex differences in MC-related AEs among patients with CNCP. Women are more susceptible to MC-related AEs, presumably because of both the inherent sex effect and the consumption of specific phytocannabinoid compositions in the MC cultivar(s). The understanding of these differences may be crucial for planning MC treatments with safer phytocannabinoid and terpenoid compositions and to better inform patients of expected AEs.

Figure 1.

(A) Difference between absolute monthly doses of MC between women and men; (B) Difference between weight-adjusted monthly doses of MC between women and men. gr, grams; kg, kilograms; M, month; MC, medical cannabis; N.S, nonsignificant.

Figure 2.

Differences of MC-related AEs between women and men. (A) Overall (B−G) system types as stated. AEs, adverse effects; CNS, central nervous system; GI, gastrointestinal; MS, musculoskeletal; MC, medical cannabis; N.S, nonsignificant; numbers on top of the bars represent the number of patients n.

Figure 3.

Difference of overall (A), gastrointestinal (B), central nervous system (C), psychological (D), opthalmic (E), musculoskeletal (F), and cardiovascular (G) adverse events rates of sex common vs sex-specific medical cannabis cultivar combinations. AEs, adverse effects; CNS, central nervous system; GI, gastrointestinal; MS, musculoskeletal; numbers on top of the bars represent the number of patients n.