Abstract
Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ9-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 counter-balanced 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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Acknowledgements
The US National Institute on Drug Abuse (NIDA) supported this research (DA09236) and supplied the marijuana cigarettes. We are grateful to Laura Rolfe, Christina Hadzitheodorou, and Ashley Danies for their expert assistance in data collection and to Dr Adam Bisaga for medical supervision of the study.
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Dr Haney’s research is funded by NIDA. She and Dr Foltin have received partial salary support for an investigator-initiated study from Astra-Zeneca. Dr Haney has also served as a consultant for GW Pharmaceuticals. Dr Comer has received partial salary support from investigator-initiated studies supported by Reckitt-Benckiser Pharmaceuticals, Schering-Plough Corporation, Johnson & Johnson Pharmaceutical Research & Development, Endo Pharmaceuticals, and MediciNova. In addition, she and Dr Vosburg have received compensation from Grunenthal GmbH to conduct a meta-analysis of drug-induced subjective responses. Dr Comer has also served as a consultant to the following companies: Analgesic Solutions, BioDelivery Sciences International, Cephalon, Inflexxion, Innovative Science Solutions, Janssen, King, Neuromed, Pfizer, and Salix. Drs Cooper and Bedi declare no potential conflicts of interest.
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Haney, M., Cooper, Z., Bedi, G. et al. Nabilone Decreases Marijuana Withdrawal and a Laboratory Measure of Marijuana Relapse. Neuropsychopharmacol 38, 1557–1565 (2013). https://doi.org/10.1038/npp.2013.54
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DOI: https://doi.org/10.1038/npp.2013.54
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