A vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part I: development and validation of a pulmonary cannabinoid route of exposure for experimental pharmacology studies in rodents

Laurie A Manwell; Armen Charchoglyan; Dyanne Brewer; Brittany A Matthews; Heather Heipel; Paul E Mallet

doi:10.1016/j.vascn.2014.06.006

A vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part I: development and validation of a pulmonary cannabinoid route of exposure for experimental pharmacology studies in rodents

J Pharmacol Toxicol Methods. 2014 Jul-Aug;70(1):120-7. doi: 10.1016/j.vascn.2014.06.006. Epub 2014 Jun 25.

Authors

Laurie A Manwell¹, Armen Charchoglyan², Dyanne Brewer², Brittany A Matthews³, Heather Heipel³, Paul E Mallet³

Affiliations

¹ Department of Psychology, Wilfrid Laurier University, Waterloo, ON N2L3C5, Canada; Department of Psychology, University of Guelph, Guelph, ON N1G2W1, Canada; Mass Spectrometry Facility, University of Guelph, Guelph, ON N1G2W1, Canada; Centre for Addiction and Mental Health, Social Aetiology of Mental Illness Program, University of Toronto, ON M5T1R8, Canada. Electronic address: laurie.manwell@camh.ca.
² Mass Spectrometry Facility, University of Guelph, Guelph, ON N1G2W1, Canada.
³ Department of Psychology, Wilfrid Laurier University, Waterloo, ON N2L3C5, Canada.

PMID: 24973534
DOI: 10.1016/j.vascn.2014.06.006

Abstract

Introduction: Most studies evaluating the effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) in animal models administer it via a parenteral route (e.g., intraperitoneal (IP) or intravenous injection (IV)), however, the common route of administration for human users is pulmonary (e.g., smoking or vapourizing marijuana). A vapourized Δ(9)-THC delivery system for rodents was developed and used to compare the effects of pulmonary and parenteral Δ(9)-THC administration on blood cannabinoid levels and behaviour.

Methods: Sprague-Dawley rats were exposed to pulmonary Δ(9)-THC (1, 5, and 10mg of inhaled vapour) delivered via a Volcano® vapourizing device (Storz and Bickel, Germany) or to parenteral Δ(9)-THC (0.25, 0.5, 1.0, and 1.5mg/kg injected IP). Quantification of Δ(9)-THC and its psychoactive metabolite, 11-hydroxy-Δ(9)-THC (11-OH-Δ(9)-THC), in blood was determined by liquid chromatography/mass spectrometry (LC/MS). In order to verify the potential for the vapourization procedure to produce a robust conditioned place preference (CPP) or conditioned place avoidance CPA, classical conditioning procedures were systematically varied by altering the exposure time (10 or 20min) and number of exposed rats (1 or 2) while maintaining the same vapourization dose (10mg).

Results: Blood collected at 20min intervals showed similar dose-dependent and time-dependent changes in Δ(9)-THC and 11-OH-Δ(9)-THC for both pulmonary and parenteral administration of Δ(9)-THC. However, vapourized Δ(9)-THC induced CPP under certain conditions whereas IP-administered Δ(9)-THC induced CPA.

Discussion: These results support and extend the limited evidence (e.g., in humans, Naef et al., 2004; in rodents, Niyuhire et al., 2007) that Δ(9)-THC produces qualitatively different effects on behaviour depending upon the route of administration.

Keywords: 11-hydroxy-Δ(9)-tetrahydrocannabinol (11-OH-THC); Liquid-chromatography/mass spectrometry (LC/MS); Plasma; Pulmonary administration; Rat; Whole blood; Δ(9)-tetrahydrocannabinol (THC).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Inhalation
Animals
Behavior, Animal / drug effects
Cannabinoids / administration & dosage*
Cannabinoids / blood
Cannabinoids / pharmacokinetics
Chromatography, Liquid / methods
Dronabinol / administration & dosage*
Dronabinol / blood
Dronabinol / pharmacokinetics
Drug Delivery Systems / methods
Injections, Intraperitoneal / methods
Lung / drug effects
Male
Mass Spectrometry / methods
Models, Animal
Morphine / administration & dosage
Morphine / adverse effects
Rats
Rats, Sprague-Dawley

Substances

Cannabinoids
Morphine
Dronabinol