Title: Sex differences in acute hemodynamic response to delta-9-tetrahydrocannabinol: Impact of recent cannabis use frequency

Authors: Katherine Hampilos, Alisha Eversole, Elisa Pabon, Holly Middlekauff, Ziva Cooper

Area of Concentration (Petal): Basic, Clinical, Translational Research 

Specialty: Cardiology, Psychiatry

Keywords: cannabis, hemodynamic response, sex differences

Background: Combusted cannabis can trigger arrhythmia and myocardial infarction in healthy young people. While acute delta-9-tetrahydrocannabinol (THC) increases heart rate (HR) and has variable effects on blood pressure (BP), the influence of sex and cannabis use frequency on these responses remains poorly understood.

Objective: To assess how sex and recent cannabis use frequency impact acute hemodynamic responses to THC.

Methods: In this double blind, placebo-controlled, within-subjects study, healthy adult cannabis users were divided into four groups by sex and use frequency in the past month (light [≤4 days/week]; heavy [>4 days/week]). Participants attended three sessions and smoked cannabis cigarettes containing 0%, 4%, or 10% THC in random order. HR, systolic (SBP), diastolic (DBP), and mean BP (MBP) were measured at baseline and five timepoints post-exposure. Group comparisons used Kruskal-Wallis tests with Dunn’s post-hoc test and Sidak correction.

Results: 87 participants (age 30.4±7.6 years) included light females (LF; n=19), heavy females (HF; n=15), light males (LM; n=25) and heavy males (HM; n=28). Groups did not differ by age, BMI, or use frequency by sex. At baseline, HM had significantly higher SBP and lower HR than other groups; thus, post-exposure outcomes were analyzed as peak change. Compared to 0% THC, peak ΔHR increased in all groups after 4% THC (all p<0.03) but only in light users after 10% THC (all p<0.001). HM had a significantly lower peak ΔHR than LM at both 4% (p=0.02) and 10% THC (p=0.009). No differences were observed for peak ΔSBP, ΔDBP, or ΔMBP.

Conclusions: Combusted THC (vs. combustion alone) drives the acute increase in HR. Light users showed greater HR responses than heavy users, particularly among males, suggesting infrequent use may predispose to adverse acute hemodynamic changes. Further, peak ΔHR was greater in light vs. heavy male but not female users, suggesting a sex-based difference in tolerance.