title: Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers.
abstract: Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.
authors.affiliation: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Haney
authors.affiliation: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.|Division of Addiction Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Divya
authors.identifier: http://orcid.org/0000-0002-8985-0073
authors.initials: D
authors.lastname: Ramesh
authors.affiliation: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.|Division of Biostatistics, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Glass
authors.affiliation: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.|Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Pavlicova
authors.affiliation: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
authors.forename: Gillinder
authors.initials: G
authors.lastname: Bedi
authors.affiliation: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
authors.forename: Ziva D
authors.identifier: http://orcid.org/0000-0001-8001-2332
authors.initials: ZD
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002188:Cannabis; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008875:Middle Aged; D009271:Naltrexone / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D010349:Patient Compliance; D011897:Random Allocation; D012256:Riboflavin / Q000652:urine; D012646:Self Administration; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone; D012256:Riboflavin