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Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC.

Abstract

BACKGROUND

Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment.

METHODS

Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected.

RESULTS

Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures.

CONCLUSIONS

These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.

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  • Authors+Show Affiliations

    ,

    Department of Behavioral Science, University of Kentucky College of Medicine, College of Medicine Office Building, Lexington, KY 40536-0086, USA. jalile2@email.uky.edu

    ,

    Source

    Drug and alcohol dependence 116:1-3 2011 Jul 01 pg 86-92

    MeSH

    Academic Medical Centers
    Adult
    Anti-Anxiety Agents
    Cannabinoid Receptor Agonists
    Cannabinoids
    Discrimination Learning
    Dose-Response Relationship, Drug
    Double-Blind Method
    Dronabinol
    Drug Administration Schedule
    Drug Therapy, Combination
    Female
    Humans
    Male
    Marijuana Abuse
    Outpatients
    Placebos
    Psychiatric Status Rating Scales
    Psychotropic Drugs
    Treatment Outcome
    Young Adult

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21227600

    Citation

    Lile, Joshua A., et al. "Separate and Combined Effects of the Cannabinoid Agonists Nabilone and Δ⁹-THC in Humans Discriminating Δ⁹-THC." Drug and Alcohol Dependence, vol. 116, no. 1-3, 2011, pp. 86-92.
    Lile JA, Kelly TH, Hays LR. Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug Alcohol Depend. 2011;116(1-3):86-92.
    Lile, J. A., Kelly, T. H., & Hays, L. R. (2011). Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug and Alcohol Dependence, 116(1-3), pp. 86-92. doi:10.1016/j.drugalcdep.2010.11.019.
    Lile JA, Kelly TH, Hays LR. Separate and Combined Effects of the Cannabinoid Agonists Nabilone and Δ⁹-THC in Humans Discriminating Δ⁹-THC. Drug Alcohol Depend. 2011 Jul 1;116(1-3):86-92. PubMed PMID: 21227600.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC. AU - Lile,Joshua A, AU - Kelly,Thomas H, AU - Hays,Lon R, Y1 - 2011/01/11/ PY - 2010/08/18/received PY - 2010/11/22/revised PY - 2010/11/24/accepted PY - 2011/1/14/entrez PY - 2011/1/14/pubmed PY - 2012/1/14/medline SP - 86 EP - 92 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 116 IS - 1-3 N2 - BACKGROUND: Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment. METHODS: Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected. RESULTS: Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures. CONCLUSIONS: These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/21227600/Separate_and_combined_effects_of_the_cannabinoid_agonists_nabilone_and_Δ⁹_THC_in_humans_discriminating_Δ⁹_THC_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(10)00415-1 DB - PRIME DP - Unbound Medicine ER -