A Randomized, Placebo-Controlled Trial of Sustained-Release Dextroamphetamine for Treatment of Methamphetamine Addiction

Abstract

Sixty treatment-seeking individuals with methamphetamine (MA) dependence entered a randomized, placebo-controlled, double-blind clinical trial of oral dextroamphetamine (d-AMP) as a replacement therapy for MA dependence. The subjects took 60 mg sustained-release d-AMP for 8 weeks, during which time they received eight 50-min sessions of individual psychotherapy. Adverse events and urine toxicology for MA were assessed two times a week. There were no serious adverse events. Urine samples containing <1,000 ng/ml of MA were classified as negative for MA. The MA-negative scores in the d-AMP group (3.1 ± SD 4.6) were no higher than those in the placebo group (3.3 ± SD 5.3; P > 0.05). However, withdrawal and craving scores were significantly lower in the d-AMP group (P < 0.05 for both). Although subjects taking d-AMP did not reduce their use of MA, the significant reductions observed in withdrawal and craving scores in this group support the need for further exploration of d-AMP as a pharmacologic intervention for MA dependence, possibly at higher doses.

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.…”

Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease

“…Numerous clinical trials have investigated the ability of DA reuptake inhibitors and releasers to treat cocaine AMPH dependencies. At least some studies demonstrate that DAT inhibitors are more effective than DA releasers for reducing use of DA releasers (Grabowski et al, 1997;Tiihonen et al, 2007), whereas DA releasers are more effective than DAT inhibitors for reducing use of DA inhibitors (Grabowski et al, 2001;Mooney et al, 2009;Longo et al, 2010;Galloway et al, 2011). For example, the DAT inhibitor MPD has been tested as a putative agonist replacement therapy for cocaine and METH/ AMPH dependence.…”

Methamphetamine self-administration in humans during d-amphetamine maintenance

“…Fourth, the participants in the present study were non-treatment seeking stimulant users and it is possible that damphetamine could produce greater reductions in methamphetamine use in a population that is seeking treatment, as the participants in the present study did not have any intention of decreasing their stimulant use. Non-treatment seeking stimulant users were enrolled in the present study due to ethical considerations of providing individuals who are seeking treatment with methamphetamine, but d-amphetamine has been tested in clinical trials to reduce methamphetamine abuse in treatment seeking populations and did not produce significant reductions in methamphetamine use (18,19). Fifth, demographic variables could have impacted the results of the study, as the sample size was small, which is supported by previous analyses of treatment responders in clinical trials (20).…”

“…The trend toward a decrease in self-administration of the lowest dose of methamphetamine during d-amphetamine maintenance compared to placebo maintenance supports this notion. However, higher doses, up to 110 mg/day have been tested in previous clinical trials and did not significantly reduce methamphetamine use compared to placebo (18,19), which suggests that the lack of a reduction of self-administration of methamphetamine during damphetamine maintenance may not be solely due to the dose tested. Second, methamphetamine was insufflated.…”