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

• Published in: Addiction biology Vol. 18; no. 5; pp. 872 - 881
• Main Authors: Bedi, Gillinder, Cooper, Ziva D., Haney, Margaret
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2013; John Wiley & Sons, Inc
• Subjects: Addiction; Adult; Affect - drug effects; Agonist treatment; Analysis of Variance; Biological Availability; Blood Pressure - drug effects; Cannabinoid Receptor Agonists - pharmacokinetics; Cannabinoid Receptor Agonists - pharmacology; Cannabinoid Receptor Agonists - therapeutic use; dose-effect profile; Dose-Response Relationship, Drug; Double-Blind Method; dronabinol; Dronabinol - analogs & derivatives; Dronabinol - pharmacokinetics; Dronabinol - pharmacology; Dronabinol - therapeutic use; Female; Heart Rate - drug effects; Humans; Male; Marijuana Abuse - drug therapy; marijuana dependence; Middle Aged; nabilone; Placebos; Psychomotor Performance - drug effects; Secondary Prevention; Substance Withdrawal Syndrome - prevention & control; Time Factors; Young Adult; Agonist treatment; dose-effect profile; marijuana dependence; dronabinol; nabilone
• ISSN: 1355-6215; 1369-1600; 1369-1600
• DOI: 10.1111/j.1369-1600.2011.00427.x

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.