Oral THC Sex Differences: Feeling More High Did Not Mean Every Endpoint Differed
A controlled oral-THC study found greater subjective “high” among women, but did not find matching sex differences across all measured effects. The result supports endpoint-specific interpretation, rather than a universal rule that one sex is more impaired.
The study used a fixed oral dose
Fifty-six healthy adults, including 33 women and 23 men, completed at least one test day in a randomized placebo-controlled crossover laboratory study of 10 mg oral dronabinol. Participants had recent cannabis experience but no lifetime cannabis use disorder.
Researchers measured subjective high, dissociative and psychotomimetic symptoms, heart rate, and verbal learning and memory. A fixed swallowed dose provides a different exposure scenario from self-titrated smoking, vaporization or an edible with additional cannabinoids.
The significant sex interaction was specific
The dose-by-sex interaction for subjective high was at the conventional threshold, p=0.05. Within-sex analyses found a significant THC effect among women but not men. This result should be described with its borderline interaction and sample size, rather than as a precise prediction for every individual.
THC increased dissociative and psychotomimetic measures and heart rate overall. Those endpoints did not show significant dose-by-sex interactions. Thus, the absence of a significant high response among men did not mean that men had no measurable response to the drug.
The memory null result has a defined scope
Immediate, short-delay and long-delay verbal recall did not show significant effects of dose, sex or their interaction in this experiment. That is a result for these tests and this dose, not evidence that THC leaves all memory functions intact.
Subjective intoxication, verbal recall, heart rate and driving are separate endpoints. This study did not validate a sex-specific concentration threshold for driving impairment, nor did a null recall result establish readiness for every safety-sensitive task.
Mechanism was not directly established
The authors discuss possible influences of distribution, metabolism and hormonal biology, but body-fat percentage and phase-I metabolism were not assessed to explain the observed difference. Those mechanisms remain hypotheses in relation to this dataset.
The single-dose design and selected healthy population limit generalization. Oral dronabinol also differs from complex commercial cannabis products. An expert applying the finding should state the route, dose, measured outcome and population, while avoiding a sex-based shortcut for an individual’s exposure or functional condition.
Related analysis: Concentration Is Not Impairment: THC Blood Levels in California Driving Cases.
Primary research
Ardavan Mohammad Aghaei and colleagues. Sex Differences in the Acute Effects of Oral THC: A Randomized, Placebo-Controlled, Crossover Human Laboratory Study. Psychopharmacology (2024). DOI: 10.1007/s00213-024-06625-6.
