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

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.

This current proof-of-concept study sought to evaluate the safety, tolerability, and effectiveness of methamphetamine as a candidate treatment for cocaine dependence.

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).

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.

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.