Pharmacokinetic and pharmacodynamic properties of aerosolized (vaped) THC in adolescent male and female rats.
Adolescent exposure to ∆ We investigated the pharmacokinetics and pharmacodynamics of aerosolized THC (30 min inhalation exposure, 25 or 100 mgml) in adolescent Wistar rats of both sexes. Liquid chromatographymass spectrometry analysis of THC and its major metabolites was conducted on blood plasma and brain tissue at 5, 30, 60, and 120 min following a 30-min aerosol dosing session. Effects on activity in a novel environment for 120 min after aerosol, and temperature, were measured in separate rats. We found sex-dependent differences in the pharmacokinetics of THC and its active (11-OH-THC) and inactive (11-COOH-THC) metabolites in the blood and brain, along with dose- and sex-dependent effects on anxiety-like and exploratory behaviors namely, greater 11-OH-THC levels accompanied by greater behavioral effects in females at the low dose but similar hypothermic effects in both sexes at the high dose. These results provide a benchmark for dosing adolescent rats with aerosolized (or vaped) THC, which could facilitate adoption by other labs of this potentially human-relevant THC exposure model to understand cannabis effects on the developing brain.