title: The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study.
abstract: Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.
authors: 1] Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA [2] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Lara A
authors: LA
authors: Ray
authors: Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Spencer
authors: S
authors: Bujarski
authors: Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Kelly E
authors: KE
authors: Courtney
authors: Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Nathasha R
authors: NR
authors: Moallem
authors: Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Katy
authors: K
authors: Lunny
authors: Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Daniel
authors: D
authors: Roche
authors: Departments of Preventive Medicine and Psychology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors: Adam M
authors: AM
authors: Leventhal
authors: 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA [2] Department of Family Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Steve
authors: S
authors: Shoptaw
authors: 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA [2] Department of Family Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Keith
authors: K
authors: Heinzerling
authors: 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA [2] Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Edythe D
authors: ED
authors: London
authors: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Karen
authors: K
authors: Miotto
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003463:Cues; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D012727:Sex Characteristics; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D008694:Methamphetamine; D009271:Naltrexone