Research ReportsThe effects of acute oral naltrexone pretreatment on the abuse potential of intranasal methamphetamine, and the relationship between reward/punishment sensitivity and methamphetamine’s effectsJones, Jermaine D.a; Mumtaz, Mudassirb; Vadhan, Nehal P.c; Martinez, Sukya; Pramanik, Satadrud; Manubay, Jeannea; Mogali, Shanthia; Perez, Freymona; Castillo, Felipea; Kranzler, Henry R.e; Comer, Sandra D.a Author Information aDivision on Substance Use Disorders, Department of Psychiatry, New York State Psychiatric Institute, and Columbia University Irving Medical Center bDepartments of Psychiatry and Molecular Medicine, The City University of New York School of Medicine cDepartments of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell Feinstein Institute for Medical Research dMailman School of Public Health, Columbia University, New York eCenter for Studies of Addiction, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Received 9 September 2021 Accepted as revised 29 January 2022 Correspondence to Jermaine D. Jones, PhD, Division on Substance Use Disorders, Department of Psychiatry, New York State Psychiatric Institute, and Columbia University Irving Medical Center, 1051 Riverside Drive, NY 10032, USA, E-mail: [email protected], [email protected] Behavioural Pharmacology: June 2022 - Volume 33 - Issue 4 - p 255-265 doi: 10.1097/FBP.0000000000000671 Buy Metrics Abstract One potential medication for treating methamphetamine use disorder is the opioid antagonist naltrexone (NLTX). Despite encouraging preclinical findings, the results of clinical studies have been mixed. The primary aim of the current trial was to examine the effects of acute NLTX pretreatment on the subjective and reinforcing effects of intranasal methamphetamine. Nonmedical psychostimulant users completed outpatient testing sessions in which they received oral placebo (0 mg) or NLTX (50 mg) before intranasal methamphetamine (30 mg/70 kg). Primary outcome measures were peak positive subjective effects (e.g. drug ‘Liking’) assessed on a visual analog scale (0–100), and methamphetamine self-administration using an operant self-administration task. Participants also completed a probabilistic categorization task to assess reward and punishment learning sensitivity. Complete data were available from 13 male and 1 transgender (male-to-female) participant (age: 33.4 ± 7.6 years). Intranasal methamphetamine significantly increased subjective ratings of drug ‘Liking’, ‘Good Effect’ and ‘High’ from baseline (P’s < 0.01), but did not significantly vary as a function of placebo or NLTX pretreatment. Similarly, methamphetamine self-administration did not vary between the placebo and NLTX pretreatment conditions. This sample did not demonstrate a significant ‘bias’ in learning from positive and negative outcomes (i.e. reward and punishment sensitivity), and reward/punishment sensitivity was not correlated with the effects of methamphetamine or the effects of NLTX on methamphetamine. The current study argues against the use of NLTX as a stand-alone medication for treating methamphetamine use disorder. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.