Sex differences in the acute effects of oral and vaporized cannabis among healthy adults

Policy changes have increased access to cannabis for individuals with little or no prior exposure. Few studies have examined sex differences in cannabis effects among individuals with sporadic cannabis use or for nonsmoked routes of cannabis administration. Data from four double-blind, placebo-controlled studies were pooled to compare the acute pharmacodynamic effects of vaporized and oral cannabis in male (n = 27) and female (n = 23) participants who used cannabis infrequently (no use ≥30 days prior to randomization). Analyses compared peak change-from-baseline scores between male and female participants for subjective drug effects, cognitive/psychomotor performance, cardiovascular effects, and blood concentrations of Δ9-tetrahydrocannabinol (THC) and its primary metabolites (11-OH-THC, THC-COOH) after exposure to placebo cannabis or cannabis containing low-dose (5 or 10 mg) or high-dose THC (20 or 25 mg). Overall, cannabis elicited dose-orderly increases in subjective effects, impairment of cognitive/psychomotor performance, heart rate, and blood cannabinoid concentrations. Females exhibited greater peak blood 11-OH-THC concentrations and reported greater peak subjective ratings of “drug effect” that remained when controlling for body weight. When controlling for both body weight and peak blood cannabinoid concentrations, ratings of “anxious/nervous,” “heart racing,” and “restless” were significantly higher for females than males. Although additional research is needed to elucidate sex differences in responses to cannabis at a wider range of THC doses, other routes of administration, and products with diverse chemical composition, the current data indicate that public health messaging and clinical decision making around the use of cannabinoids should recommend lower starting doses for females and warnings about acute anxiogenic reactions.