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Introduction Studies of the rewarding and addictive properties of cannabinoids using rodents as animal models of human behaviour often fail to replicate findings from human studies. Animal studies typically employ parenteral routes of administration, whereas humans typically smoke cannabis, thus discrepancies may be related to different pharmacokinetics of parenteral and pulmonary routes of administration. Accordingly, a novel delivery system of vapourized Δ9-tetrahydrocannabinol (Δ9-THC) was developed and assessed for its pharmacokinetic, pharmacodynamic, and behavioural effects in rodents. A commercially available vapourizer was used to assess the effects of pulmonary (vapourized) administration of Δ9-THC and directly compared to parenteral (intraperitoneal, IP) administration of Δ9-THC. Methods: Sprague–Dawley rats were exposed to pure Δ9-THC vapour (1, 2, 5, 10, and 20 mg/pad), using a Volcano® vapourizing device (Storz and Bickel, Germany) or IP-administered Δ9-THC (0.1, 0.3, 0.5, 1.0 mg/kg), and drug effects on locomotor activity, food and water consumption, and cross-sensitization to morphine (5 mg/kg) were measured. Results: Vapourized Δ9-THC significantly increased feeding during the first hour following exposure, whereas IP-administered Δ9-THC failed to produce a reliable increase in feeding at all doses tested. Acute administration of 10 mg of vapourized Δ9-THC induced a short-lasting stimulation in locomotor activity compared to control in the first of four hours of testing over 7 days of repeated exposure; this chronic exposure to 10 mg of vapourized Δ9-THC did not induce behavioural sensitization to morphine. Discussion: These results suggest vapourized Δ9-THC administration produces behavioural effects qualitatively different from those induced by IP administration in rodents. Furthermore, vapourized Δ9-THC delivery in rodents may produce behavioural effects more comparable to those observed in humans. We conclude that some of the conflicting findings in animal and human cannabinoid studies may be related to pharmacokinetic differences associated with route of administration. [ABSTRACT FROM AUTHOR]

Introduction Most studies evaluating the effects of Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC delivery system for rodents was developed and used to compare the effects of pulmonary and parenteral Δ9-THC administration on blood cannabinoid levels and behaviour. Methods Sprague–Dawley rats were exposed to pulmonary Δ9-THC (1, 5, and 10 mg of inhaled vapour) delivered via a Volcano® vapourizing device (Storz and Bickel, Germany) or to parenteral Δ9-THC (0.25, 0.5, 1.0, and 1.5 mg/kg injected IP). Quantification of Δ9-THC and its psychoactive metabolite, 11-hydroxy-Δ9-THC (11-OH-Δ9-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 20 min) and number of exposed rats (1 or 2) while maintaining the same vapourization dose (10 mg). Results Blood collected at 20 min intervals showed similar dose-dependent and time-dependent changes in Δ9-THC and 11-OH-Δ9-THC for both pulmonary and parenteral administration of Δ9-THC. However, vapourized Δ9-THC induced CPP under certain conditions whereas IP-administered Δ9-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 Δ9-THC produces qualitatively different effects on behaviour depending upon the route of administration. [ABSTRACT FROM AUTHOR]