Author:
Baglot Samantha L.,Hume Catherine,Petrie Gavin N.,Aukema Robert J.,Lightfoot Savannah H. M.,Grace Laine M.,Zhou Ruokun,Parker Linda,Rho Jong M.,Borgland Stephanie L.,McLaughlin Ryan J.,Brechenmacher Laurent,Hill Matthew N.
Abstract
AbstractUp to a third of North Americans report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human consumption are critical to study the impact of cannabis on brain and behaviour. Most animal studies to date utilize injection of delta-9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis). THC injections produce markedly different physiological and behavioural effects than inhalation, likely due to distinctive pharmacokinetics. The current study directly examined if administration route (injection versus inhalation) alters metabolism and central accumulation of THC and metabolites over time. Adult male and female Sprague–Dawley rats received either an intraperitoneal injection or a 15-min session of inhaled exposure to THC. Blood and brains were collected at 15, 30, 60, 90 and 240-min post-exposure for analysis of THC and metabolites. Despite achieving comparable peak blood THC concentrations in both groups, our results indicate higher initial brain THC concentration following inhalation, whereas injection resulted in dramatically higher 11-OH-THC concentration, a potent THC metabolite, in blood and brain that increased over time. Our results provide evidence of different pharmacokinetic profiles following inhalation versus injection. Accordingly, administration route should be considered during data interpretation, and translational animal work should strongly consider using inhalation models.
Funder
Canadian Institutes of Health Research
University of Calgary
Hotchkiss Brain Institute
Branch Out Neurological Foundation
Mathison Centre for Mental Health Research and Education
Cumming School of Medicine, University of Calgary
Hotchkiss Brain Institute, University of Calgary
Publisher
Springer Science and Business Media LLC
Cited by
38 articles.
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