title: Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women.
abstract: This study examined whether the opioid receptor antagonist naltrexone is efficacious in smoking cessation and whether sex moderates the response. We assessed smoking quit rates and weight gain in a double-blind randomized trial comparing oral naltrexone (n = 162) with placebo (n = 154) in nicotine-dependent participants who wanted to quit smoking. The medication was gradually titrated up to 50 mg during the week before the quit date and then maintained at this dose for 12 weeks. For the first 4 weeks after the quit date, all participants received a nicotine patch to mitigate tobacco withdrawal and attended weekly individual cognitive-behavioral smoking cessation counseling sessions. After this time, participants continued with naltrexone or placebo through 12 weeks. Follow-up assessments were conducted at 26 and 52 weeks. During treatment, naltrexone (vs placebo) increased quit rates, attenuated smoking urge, and reduced weight gain. At follow-up, after medication discontinuation, the effect of naltrexone on improving quit rates was no longer evident. Men and women experienced different benefits from naltrexone; men showed greater reductions in smoking, whereas women showed greater reductions in weight gain. In sum, naltrexone showed acute efficacy in treating nicotine dependence, but after the medication was discontinued, the effect on quit rate was not maintained. Further study of naltrexone in smoking cessation treatment and reduction of cessation-related weight gain, as well as preclinical investigation of mechanisms underlying sex differences, is warranted.
authors.affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA. aking@bsd.uchicago.edu
authors.forename: Andrea C
authors.initials: AC
authors.lastname: King
authors.forename: Dingcai
authors.initials: D
authors.lastname: Cao
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Cai
authors.forename: Harriet
authors.initials: H
authors.lastname: deWit
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Matthews
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Stachoviak
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015928:Cognitive Behavioral Therapy / Q000379:methods; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D012737:Sex Factors; D016540:Smoking Cessation / Q000379:methods*; D013997:Time Factors; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000534:rehabilitation; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone