Sex Differences in the Acute Effects of Oral THC: A Randomized, Placebo-Controlled, Crossover Human Laboratory Study.

Rationale: Recent reports have shown increased cannabis use among women, leading to growing concerns about cannabis use disorder (CUD). Some evidence suggests a faster progression to addiction in women, known as the "telescoping effect." While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the response to oral tetrahydrocannabinol (THC) in humans. Methods: 56 healthy men and women with prior exposure to cannabis but no history of CUD participated in a randomized, placebo-controlled, human laboratory study where they received a single 10 mg dose of oral THC (dronabinol). Subjective psychoactive effects were assessed by the visual analog scale of "high", psychotomimetic effects by the Clinician-Administered Dissociative Symptoms Scale and Psychotomimetic States Inventory, verbal learning and memory by Rey Auditory Verbal Learning Test (RAVLT), and physiological effects by heart rate. Outcomes were regularly measured on the test day, except for the RAVLT, which was assessed once. Peak differences from baseline were analyzed using a nonparametric method for repeated measures. Results: Oral THC demonstrated significant dose-related effects in psychotomimetic and physiological domains, but not in RAVLT outcomes. A notable interaction between THC dose and sex emerged concerning the subjective "high" scores, with women reporting heightened sensations (p=0.05). No other significant effects of sex and THC dose interaction were observed. Conclusion: Oral THC yields similar psychotomimetic and physiological effects across sexes, but women may experience a pronounced subjective psychoactive effect. Further research is needed to identify individual vulnerabilities and facilitate tailored interventions addressing CUD.

Cannabis Use: Neurobiological, Behavioral, and Sex/Gender Considerations.

PURPOSE OF REVIEW: To summarize the current literature on the effects of cannabinoids in humans and to discuss the existing literature on the sex- and gender-related differences in the effects of cannabinoids. RECENT FINDINGS: Cannabis and its constituent cannabinoids are associated with risk of addiction, cognitive deficits and mood/psychotic disorders. Preclinical and emerging clinical data suggest greater sensitivity to the effects of cannabinoids in women. SUMMARY: Cannabis is one of the most commonly used drugs with increasing rates of use. Women in particular may be at a greater risk of adverse outcomes given the previously described "telescoping effect" of substance use in women. Human data examining the sex- and gender-related differences in the effects of cannabinoids and factors underlying these differences are very limited. This represents a critical gap in the literature and needs to be systematically examined in future studies.