Sex differences in the acute effects of oral THC: a randomized, placebo-controlled, crossover human laboratory study.
Ardavan Mohammad Aghaei, Lia Urban Spillane, Brian Pittman, L Taylor Flynn, Joao P De Aquino, Anahita Bassir Nia, Mohini Ranganathan
Psychopharmacology October 1, 2024 Peer reviewed DOI: 10.1007/s00213-024-06625-6 via PubMed
Summary
Oral THC (10 mg) produces similar acute psychotomimetic and physiological effects in both men and women, but women report a stronger subjective 'high'. In a study with 56 participants who had prior cannabis exposure but no cannabis use disorder, significant dose-related effects were observed in psychotomimetic and physiological measures, while no differences were found in verbal learning and memory. Further research is needed to explore individual vulnerabilities related to cannabis use disorder.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 56 |
| Population | healthy men and women with prior exposure to cannabis but no history of cannabis use disorder |
| Key finding | Women reported heightened sensations of the subjective 'high' from oral THC compared to men. |
Abstract
Recent reports have shown increased cannabis use among women, leading to growing concerns about cannabis use disorder (CUD). While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the acute response to oral tetrahydrocannabinol (THC) in humans. 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. Oral THC (10 mg) 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. Oral THC (10 mg) yields similar acute 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. GOV REGISTRATION: https://clinicaltrials.gov/study/NCT02781519?term=Ranganathan&intr=THC&rank=3 .