The effects of acute oral naltrexone pretreatment on the abuse potential of intranasal methamphetamine, and the relationship between reward/punishment sensitivity and methamphetamine's effects

Despite many years of research, there are no FDA-approved pharmacotherapies for methamphetamine use disorder. One potential medication for treating this disorder is the opioid antagonist naltrexone (NLTX). Despite encouraging preclinical findings, however, the results of clinical studies of NLTX 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. Fourteen healthy non-medical psychostimulant users, aged 21-50 years, were recruited for this randomized, placebo-controlled, within-subjects trial. Participants completed outpatient testing sessions in which they received oral placebo (0 mg) or NLTX (50 mg) 60 minutes before intranasal methamphetamine (30 mg/70kg). Participants completed two sequential days of testing for each dose combination: On Day 1 (Sample Session) participants received the drug combination and for the following 3 hours, subjective and physiological effects were measured. On Day 2 (Choice Session), participants completed an operant self-administration task in which they chose between an additional dose of the Day 1 intranasal drug and a monetary reinforcer ($25). Primary outcome measures were peak positive subjective effects (e.g., drug “Liking”) assessed on a visual analog scale (0-100) from the Sample Session, and methamphetamine self-administration from the Choice Session. 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). Participants were primarily users of amphetamine-type stimulants (N=9) or cocaine (N=5), and all had recent experience with pharmacokinetically faster administration routes (i.e., intravenous, intranasal, or smoked). Intranasal methamphetamine significantly increased subjective ratings of drug “Liking,” “Good Effect,” and “High” from baseline (p’s