LAUSR

BACKGROUND Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. OBJECTIVE We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration. METHODS Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis. RESULTS Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment. CONCLUSION This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.