Title:Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female Sprague Dawley
Rats: A Pharmacokinetic and Behavioral Assessment
Volume: 29
Issue: 27
Author(s): Samantha L. Penman, Erin C. Berthold, Abrianna Mihalkovic, Nikki Hammond, Christopher R. McCurdy, Kenneth Blum, Rina D. Eiden, Abhisheak Sharma and Panayotis K. Thanos*
Affiliation:
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions,
Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo,
NY, USA
- Department of Psychology, University at Buffalo, Buffalo, NY, USA
Keywords:
Delta-9-tetrahydrocannabinol (THC), cannabis, liquid-chromatography/mass-spectrometry, rodent, serum, locomotor activity.
Abstract:
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.
