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Delta9-tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice.

Abstract

Although it is widely accepted that delta9-tetrahydrocannabinol (delta9-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 delta9-THC mediates these effects through a CB1 receptor mechanism of action. First, the effects of delta9-THC on analgesia, hypothermia, and catalepsy were compared with those of a marijuana extract with equated delta9-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 delta9-THC but similar levels of other cannabinoids) that were impregnated with varying quantities of delta9-THC. To assess doses, delta9-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 delta9-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 delta9-THC were similar in mice exhibiting similar pharmacological effects, regardless of the presence of non-delta9-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 delta9-THC content acting at CB1 receptors and that the non-delta9-THC constituents of marijuana (at concentrations relevant to those typically consumed) influence these effects only minimally, if at all.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology and Toxicology, Virginia Commonwealth University, Box 980613, Richmond, VA 23298-0613, USA.

    , , , ,

    Source

    MeSH

    Analgesics
    Animals
    Behavior, Animal
    Body Temperature
    Brain
    Cannabis
    Catalepsy
    Dose-Response Relationship, Drug
    Dronabinol
    Inhalation Exposure
    Injections, Intravenous
    Male
    Mice
    Mice, Inbred ICR
    Pain Measurement
    Piperidines
    Pyrazoles
    Rimonabant
    Smoke

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15831444

    Citation

    Varvel, S A., et al. "Delta9-tetrahydrocannbinol Accounts for the Antinociceptive, Hypothermic, and Cataleptic Effects of Marijuana in Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 1, 2005, pp. 329-37.
    Varvel SA, Bridgen DT, Tao Q, et al. Delta9-tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice. J Pharmacol Exp Ther. 2005;314(1):329-37.
    Varvel, S. A., Bridgen, D. T., Tao, Q., Thomas, B. F., Martin, B. R., & Lichtman, A. H. (2005). Delta9-tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice. The Journal of Pharmacology and Experimental Therapeutics, 314(1), pp. 329-37.
    Varvel SA, et al. Delta9-tetrahydrocannbinol Accounts for the Antinociceptive, Hypothermic, and Cataleptic Effects of Marijuana in Mice. J Pharmacol Exp Ther. 2005;314(1):329-37. PubMed PMID: 15831444.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Delta9-tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice. AU - Varvel,S A, AU - Bridgen,D T, AU - Tao,Q, AU - Thomas,B F, AU - Martin,B R, AU - Lichtman,A H, Y1 - 2005/04/14/ PY - 2005/4/16/pubmed PY - 2005/8/27/medline PY - 2005/4/16/entrez SP - 329 EP - 37 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 314 IS - 1 N2 - Although it is widely accepted that delta9-tetrahydrocannabinol (delta9-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 delta9-THC mediates these effects through a CB1 receptor mechanism of action. First, the effects of delta9-THC on analgesia, hypothermia, and catalepsy were compared with those of a marijuana extract with equated delta9-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 delta9-THC but similar levels of other cannabinoids) that were impregnated with varying quantities of delta9-THC. To assess doses, delta9-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 delta9-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 delta9-THC were similar in mice exhibiting similar pharmacological effects, regardless of the presence of non-delta9-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 delta9-THC content acting at CB1 receptors and that the non-delta9-THC constituents of marijuana (at concentrations relevant to those typically consumed) influence these effects only minimally, if at all. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15831444/Delta9_tetrahydrocannbinol_accounts_for_the_antinociceptive_hypothermic_and_cataleptic_effects_of_marijuana_in_mice_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15831444 DB - PRIME DP - Unbound Medicine ER -