Methamphetamine self-administration in humans during D-amphetamine maintenance

Abstract

Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of D-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that D-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested 2 D-amphetamine maintenance conditions in counterbalanced order (0 and 40 mg/d). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled 1 of 4 doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive-ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 12 items of the drug-effects questionnaires, 8 of which were attenuated by D-amphetamine maintenance (eg, increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by D-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during D-amphetamine maintenance and no adverse events occurred. Although D-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that D-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

Figure 1

Methamphetamine ratios completed on the Progressive Ratio Task (Top Left). Systolic Blood Pressure (Top Right). Subject ratings of Like Drug (Bottom Left) and Willing to Take Again (Bottom Right) from responses on a 100 mm visual analog scale on the Drug-Effect Questionnaire. Data from Systolic Blood Pressure and the Drug-Effect Questionnaire are expressed as peak effect from the sampling session. For all panels circles represent placebo maintenance and squares represent 40 mg/day d-amphetamine and brackets show 1 SEM. All data points represent mean values for 8 participants.