title: Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine.
abstract: Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of D-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and "positive" subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone.Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6 to 7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected.Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like "positive" subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10-mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.
authors.affiliation: From the *Department of Psychology, University of Kentucky College of Arts and Sciences; †Department of Behavioral Science, ‡Department of Psychiatry, §Department of Anatomy and Neurobiology, ∥Department of Pediatrics, and ¶Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Marks
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D003692:Delayed-Action Preparations; D018757:GABA Modulators; D009292:Narcotic Antagonists; D008694:Methamphetamine; D009271:Naltrexone; D000525:Alprazolam