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 (0mg, 6x/day; n=27), (2) immediate release (IR) methamphetamine (5mg, 6x/day; n=30), (3) sustained release (SR) methamphetamine (30 mg first pill, 1x/day; 0mg 5x/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 (0mg, 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 (0mg, 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.

Figure 1

Participant enrollment and retention figure. Protocol violations indicate high absenteeism or failure to provide self-report or biological data.

Figure 2

2A. Bodyweight over the 8-week treatment period. Group differences by weight were observed, where the SR condition lost weight while the placebo (0 mg) group gained weight. 2B. Systolic blood pressure tended to change over time, and as a functioning of medication group and time. 2C. Diastolic blood pressure did not vary across group, time, or their interaction. 2D. Heart rate did not vary across group, time, or their interaction.

Figure 3

3A. Cocaine-use proportion in the intention-to-treat sample. Beginning (week 1 of treatment) and ending (week 8 of treatment) sample sizes are shown in the legend. The SR group had significantly fewer BE-positive urine tests than the placebo (0 mg) or IR conditions. 3B. Cocaine-use proportion in those completing treatment. Samples sizes are shown in the legend. The SR group had significantly fewer BE-positive urine tests than the placebo (0 mg) or IR conditions.