title: 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.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Laurie A
authors: LA
authors: Manwell
authors: Mass Spectrometry Facility, University of Guelph, Guelph, ON N1G2W1, Canada.
authors: Armen
authors: A
authors: Charchoglyan
authors: Mass Spectrometry Facility, University of Guelph, Guelph, ON N1G2W1, Canada.
authors: Dyanne
authors: D
authors: Brewer
authors: Department of Psychology, Wilfrid Laurier University, Waterloo, ON N2L3C5, Canada.
authors: Brittany A
authors: BA
authors: Matthews
authors: Department of Psychology, Wilfrid Laurier University, Waterloo, ON N2L3C5, Canada.
authors: Heather
authors: H
authors: Heipel
authors: Department of Psychology, Wilfrid Laurier University, Waterloo, ON N2L3C5, Canada.
authors: Paul E
authors: PE
authors: Mallet
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D013759:Dronabinol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D007274:Injections, Intraperitoneal / Q000379:methods; D008168:Lung / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D023421:Models, Animal; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002186:Cannabinoids; D009020:Morphine; D013759:Dronabinol
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)