期刊
NEUROPSYCHOPHARMACOLOGY
卷 38, 期 8, 页码 1557-1565出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2013.54
关键词
cannabinoids; addiction and substance abuse; psychopharmacology; cesamet; cannabis; self-administration
资金
- US National Institute on Drug Abuse (NIDA) [DA09236]
- Astra-Zeneca
- Reckitt-Benckiser Pharmaceuticals
- Schering-Plough Corporation
- Johnson & Johnson Pharmaceutical Research Development
- Endo Pharmaceuticals
- MediciNova
Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Delta 9-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. The FDA-approved synthetic analog of THC, nabilone, has higher bioavailability and clearer dose-linearity than dronabinol. This study tested whether nabilone administration would decrease marijuana withdrawal symptoms and a laboratory measure of marijuana relapse relative to placebo. Daily, nontreatment-seeking marijuana smokers (8 men and 3 women), who reported smoking 8.3 +/- 3.1 marijuana cigarettes/day completed this within-subject study comprising three, 8-day inpatient phases; each phase tested a different nabilone dose (0, 6, 8 mg/day, administered in counterbalanced order on days 2-8). On the first inpatient day, participants took placebo capsules and smoked active marijuana (5.6% THC) at six timepoints. For the next 3 days, they had the opportunity to self-administer placebo marijuana (0.0% THC; withdrawal), followed by 4 days in which active marijuana was available for self-administration (5.6% THC; relapse). Both nabilone dose conditions decreased marijuana relapse and reversed withdrawal-related irritability and disruptions in sleep and food intake (p<0.05). Nabilone (8 mg/day) modestly worsened psychomotor task performance. Neither dose condition increased ratings of capsule 'liking' or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment.
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