Utility of a controlled amphetamine withdrawal paradigm among adults who use methamphetamine: A pilot clinical trial

J Psychopharmacol. 2021 Nov;35(11):1420-1430. doi: 10.1177/02698811211050563. Epub 2021 Oct 26.

Abstract

Background: The continued increase in prevalence of methamphetamine use in the United States has resulted in a significant increase in the number of patients entering treatment for methamphetamine use. However, no robustly efficacious pharmacologic treatment for methamphetamine use or withdrawal has been identified to date after stopping methamphetamine use.

Aims: Given the association between methamphetamine withdrawal and relapse during early treatment, this study tested a controlled d-amphetamine withdrawal paradigm among methamphetamine-using individuals.

Methods: Treatment-seeking adults who used methamphetamine (N = 34; 47% female; 100% white) were enrolled in a 4-week, randomized, double-blind, placebo-controlled trial in a residential setting, in which all participants were maintained on d-amphetamine (30 mg BID) during week 1, then half were switched to placebo during weeks 2-3. All participants received placebo during week 4. Outcomes included vital signs, withdrawal, cravings for methamphetamine, mood, and cognition. Bivariate analyses tested treatment group differences on baseline demographic and outcome variables. Repeated measures models examined main and interaction effects of treatment over time.

Results/outcomes: Participants were successfully randomized and safely stabilized on d-amphetamine. Craving for methamphetamine increased during weeks 2-3 in the placebo group relative to those on d-amphetamine. Interactions with age and heart rate were noted.

Conclusions/interpretation: To our knowledge, this is the first double-blind, placebo-controlled trial measuring pharmacologic effects of abruptly stopping controlled d-amphetamine administration in adults who use methamphetamine. Results support the potential of this withdrawal paradigm to further examine the efficacy of pharmacologic agents in ameliorating methamphetamine withdrawal symptoms.

Keywords: Methamphetamine; methamphetamine withdrawal; methamphetamine withdrawal paradigm; pharmacologic treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / physiopathology*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Dextroamphetamine / administration & dosage
  • Dextroamphetamine / pharmacology*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methamphetamine / administration & dosage
  • Methamphetamine / pharmacology*
  • Pilot Projects
  • Substance Withdrawal Syndrome / physiopathology*
  • Young Adult

Substances

  • Central Nervous System Stimulants
  • Methamphetamine
  • Dextroamphetamine