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Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.

Abstract

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.

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  • Authors+Show Affiliations

    ,

    Division on Substance Abuse, New York State Psychiatric Institute, NY, USA.

    ,

    Source

    Addiction biology 18:5 2013 Sep pg 872-81

    MeSH

    Adult
    Affect
    Analysis of Variance
    Biological Availability
    Blood Pressure
    Cannabinoid Receptor Agonists
    Dose-Response Relationship, Drug
    Double-Blind Method
    Dronabinol
    Female
    Heart Rate
    Humans
    Male
    Marijuana Abuse
    Middle Aged
    Placebos
    Psychomotor Performance
    Secondary Prevention
    Substance Withdrawal Syndrome
    Time Factors
    Young Adult

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    22260337

    Citation

    Bedi, Gillinder, et al. "Subjective, Cognitive and Cardiovascular Dose-effect Profile of Nabilone and Dronabinol in Marijuana Smokers." Addiction Biology, vol. 18, no. 5, 2013, pp. 872-81.
    Bedi G, Cooper ZD, Haney M. Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. Addict Biol. 2013;18(5):872-81.
    Bedi, G., Cooper, Z. D., & Haney, M. (2013). Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. Addiction Biology, 18(5), pp. 872-81. doi:10.1111/j.1369-1600.2011.00427.x.
    Bedi G, Cooper ZD, Haney M. Subjective, Cognitive and Cardiovascular Dose-effect Profile of Nabilone and Dronabinol in Marijuana Smokers. Addict Biol. 2013;18(5):872-81. PubMed PMID: 22260337.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. AU - Bedi,Gillinder, AU - Cooper,Ziva D, AU - Haney,Margaret, Y1 - 2012/01/19/ PY - 2012/1/21/entrez PY - 2012/1/21/pubmed PY - 2014/3/13/medline KW - Agonist treatment KW - dose-effect profile KW - dronabinol KW - marijuana dependence KW - nabilone SP - 872 EP - 81 JF - Addiction biology JO - Addict Biol VL - 18 IS - 5 N2 - Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/22260337/Subjective_cognitive_and_cardiovascular_dose_effect_profile_of_nabilone_and_dronabinol_in_marijuana_smokers_ L2 - https://doi.org/10.1111/j.1369-1600.2011.00427.x DB - PRIME DP - Unbound Medicine ER -