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

Drug Alcohol Depend. 2009 Apr 1;101(1-2):34-41. doi: 10.1016/j.drugalcdep.2008.10.016. Epub 2008 Dec 5.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / therapeutic use*
  • Cocaine-Related Disorders / psychology
  • Cocaine-Related Disorders / rehabilitation*
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Methamphetamine / administration & dosage
  • Methamphetamine / therapeutic use*
  • Middle Aged
  • Riboflavin
  • Substance Abuse Detection
  • Treatment Outcome
  • Young Adult


  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Methamphetamine
  • Riboflavin