Abstract
Although it is widely accepted that Δ9-tetrahydrocannabinol (Δ9-THC) is the primary psychoactive constituent of marijuana, questions persist as to whether other components contribute to marijuana's pharmacological activity. The present experiments assessed the cannabinoid activity of marijuana smoke exposure in mice and tested the hypothesis that Δ9-THC mediates these effects through a CB1 receptor mechanism of action. First, the effects of Δ9-THC on analgesia, hypothermia, and catalepsy were compared with those of a marijuana extract with equated Δ9-THC content after either i.v. administration or inhalation exposure. Second, mice were exposed to smoke of an ethanol-extracted placebo plant material or low-grade marijuana (with minimal Δ9-THC but similar levels of other cannabinoids) that were impregnated with varying quantities of Δ9-THC. To assess doses, Δ9-THC levels in the blood and brains of drug-exposed mice were determined following both i.v. and inhalation routes of administration. Both marijuana and Δ9-THC produced comparable levels of antinociception, hypothermia, and catalepsy regardless of the route of administration, and these effects were blocked by pretreatment with the CB1 antagonist SR141716 [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl]. Importantly, the blood and brain levels of Δ9-THC were similar in mice exhibiting similar pharmacological effects, regardless of the presence of non-Δ9-THC marijuana constituents. The present experiments provide evidence that the acute cannabinoid effects of marijuana smoke exposure on analgesia, hypothermia, and catalepsy in mice result from Δ9-THC content acting at CB1 receptors and that the non-Δ9-THC constituents of marijuana (at concentrations relevant to those typically consumed) influence these effects only minimally, if at all.
Footnotes
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This work was supported by National Institute on Drug Abuse Grant DA02396.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.104.080739.
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ABBREVIATIONS: Δ9-THC, Δ9-tetrahydrocannabinol; CBD, cannabidiol; CBC, cannnabichromene; CBN, cannabinol; SR141716, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl; ANOVA, analysis of variance; %MPE, percentage of maximum possible effect; LGM, low-grade marijuana.
- Received November 15, 2004.
- Accepted April 5, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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