Effects of oral methamphetamine on cocaine use: A randomized, double-blind, placebo-controlled trial

Abstract

Background No medication is currently approved for the treatment of cocaine dependence, but several preclinical and clinical reports suggest agonist-like medications, e.g. amphetamine analogues, may be a productive strategy for medication development. Objective This current proof-of-concept study sought to evaluate the safety, tolerability, and effectiveness of methamphetamine as a candidate treatment for cocaine dependence. Methods A randomized, double-blind, placebo-controlled study served to evaluate three treatment conditions in 82 cocaine-dependent individuals: (1) placebo (0 mg, 6×/day; n = 27), (2) immediate release (IR) methamphetamine (5 mg, 6×/day; n = 30), (3) sustained release (SR) methamphetamine (30 mg first pill, 1×/day; 0 mg 5×/day; n = 25). The study employed a sequential, two-phase design (i.e., 4 weeks of medication and counseling followed by 4 weeks of medication/counseling plus a contingency management procedure). Results Both preparation forms of methamphetamine were well tolerated, with similar retention to placebo (0 mg, 33%; 30 mg IR, 30%, 30 mg SR, 32%). Methamphetamine SR was associated with decreased sleep and increased weight loss. Medication adherence rates were high for the first dose of the day (95%), while adherence for subsequent capsules was lower. Those in the SR condition exhibited consistently lower rates of cocaine-positive urine samples (0 mg, 60%; 30 mg IR, 66%, 30 mg SR, 29%), p<0.0001, and reported the greatest reduction in craving for cocaine, p<0.05. Conclusions SR methamphetamine significantly reduced cocaine use and craving. Additional research is warranted to develop and evaluate agonist-like medications that may effectively treat cocaine dependence.

Interaction Between Behavioral and Pharmacological Treatment Strategies to Decrease Cocaine Choice in Rhesus Monkeys

“…Thus, in preclinical studies that aspire to evaluate pharmacological or behavioral treatment strategies for drug dependence, choice procedures can play a critical role in the preclinical evaluation process to determine whether a given experimental manipulation produces this critical reallocation of behavior (Haney and Spealman, 2008;Negus et al, 2011). Second, although dopamine/norepinephrine-selective releasers have consistently demonstrated efficacy to decrease cocaine choice in nonhuman primates Negus, 2003;present study), human laboratory studies (Greenwald et al, 2010;Rush et al, 2010), and clinical trials (Grabowski et al, 2001;Mooney et al, 2009), the magnitude of this therapeutic effect is limited by untoward effects and lower than the magnitude of effect that can potentially be achieved with behavioral economic approaches. However, the present results suggest that phenmetrazine or related compounds may nonetheless be therapeutically useful under circumstances in which cocaine is relatively inexpensive, cocaine consumption is maintained by relatively low cocaine doses, and behavioral options are limited.…”

“…The other category of strategies consists of pharmacological approaches, such as maintenance on an agonist-based pharmacotherapy, and clinical trials have demonstrated efficacy of maintenance on the dopamine/norepinephrine vs serotonin-selective monoamine releaser d-amphetamine to decrease cocaine abuse (Grabowski et al, 2001(Grabowski et al, , 2004Mooney et al, 2009). However, interactions between behavioral and pharmacological approaches in the treatment of cocaine abuse are poorly understood and understudied.…”

Incubation of Methamphetamine and Palatable Food Craving after Punishment-Induced Abstinence

“…We trained the rats in seven cycles of 2 days of methamphetamine self-administration and one off day in order to prevent loss of body weight during the training phase (under our training conditions of 6 or 9 h daily sessions, rats lose weight after each training day and regain the lost weight during the off days (Shepard et al, 2004;Theberge et al, 2013)). Weight loss is a common side effect of methamphetamine use by humans (Mooney et al, 2009;Neale et al, 2009) or laboratory animals (Krasnova et al, 2010) because of the drug's anorexic effects (Saito et al, 1995). We dissolved methamphetamine HCl in sterile saline and the rats self-administered the drug at a dose of 0.1 mg/kg/infusion over 3.5 s (0.10 ml/infusion) (Shepard et al, 2004;Theberge et al, 2013).…”

Effects of Oral and Intravenous Administration of Buspirone on Food–Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

“…A great deal of preclinical and clinical evidence has implicated D2-like dopamine receptors (composed of D 2 , D 3 , and D 4 subtypes) in the abuse-related behavioral effects of cocaine (see, eg, Woolverton et al, 1984;Callahan et al, 1991;Caine et al, 2000). Drugs that nonselectively and indirectly stimulate D2-like receptors such as d-amphetamine and methamphetamine can reduce cocaine use (Grabowski et al, 2004;Mooney et al, 2009), but themselves possess high abuse liability. Negative results have been obtained using direct-acting D2-like receptor agonists (cf, Amato et al, 2011).…”