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Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.
Addict Biol 2013; 18(5):872-81AB

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.

Authors+Show Affiliations

Division on Substance Abuse, New York State Psychiatric Institute, NY, USA.No affiliation info availableNo affiliation info available

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 -