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 d-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested two d-amphetamine maintenance conditions in counter-balanced order (0 and 40 mg/day). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled one of four 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 13 items of the drug-effects questionnaires, 10 of which were attenuated by d-amphetamine maintenance (e.g., 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.

Effects of 7-day continuous d-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys

“…Consistent with previous methamphetamine self-administration studies in nonhuman primates (Banks and Blough, 2015; John et al, 2014, 2015) and humans (Kirkpatrick et al, 2012; Pike et al, 2014), increasing methamphetamine doses resulted in an increased preference over an alternative, nondrug reinforcer. In contrast, the present study was inconsistent with two previous rat methamphetamine choice studies (Caprioli et al, 2015; Ping and Kruzich, 2008).…”

“…Methylphenidate treatment effects have been equivocal with three clinical trials (Konstenius et al, 2014; Rezaei et al, 2015; Tiihonen et al, 2007) demonstrating a reduction in amphetamine/methamphetamine use and three clinical trials (Konstenius et al, 2010; Ling et al, 2014; Miles et al, 2013) demonstrating no effect on amphetamine/methamphetamine use. Furthermore, d-amphetamine treatment efficacy has not been significant in either clinical trials (Galloway et al, 2011; Longo et al, 2010) or a human laboratory methamphetamine self-administration study (Pike et al, 2014). However, there are two potential reasons for these equivocal or negative clinical results.…”

Acute buspirone dosing enhances abuse-related subjective effects of oral methamphetamine

“…D-amphetamine, a dopamine releaser, did not promote methamphetamine abstinence (Galloway et al, 2011). D-amphetamine decreased some of the subjective effects of methamphetamine, but did not reduce self-administration in the human laboratory (Rush et al, 2011; Pike et al, 2014, respectively). Aripiprazole, a dopamine partial agonist, increased amphetamine use (Tiihonen et al, 2007).…”

Agonist Medications for the Treatment of Cocaine Use Disorder

“…The general class of abused stimulants also includes drugs such as amphetamine, methamphetamine, and emerging cathinone analogs that function as substrates at dopamine transporters to promote dopamine release (Baumann et al, 2012a;Cameron et al, 2013;Rothman et al, 2001). Recent clinical trials and a human laboratory study found that amphetamine maintenance failed to produce significant decreases in methamphetamine consumption (Galloway et al, 2011;Longo et al, 2010;Pike et al, 2014). These and related results have been interpreted to suggest that dopamine releasers such as amphetamine may be more effective to treat abuse of dopamine uptake inhibitors (eg, cocaine) than abuse of other dopamine releasers.…”