Abuse potential of oral phendimetrazine in cocaine-dependent individuals: Implications for agonist-like replacement therapy

B. Levi Bolin, William W. Stoops, Jeremy P. Sites, Craig R. Rush

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Objectives: Phendimetrazine is a prodrug for the monoamine releaser phenmetrazine - a drug with known abuse potential. Preclinical studies suggest that phendimetrazine has limited abuse potential and may have promise as an agonist-like replacement therapy for cocaine dependence. This study evaluated the abuse potential of phendimetrazine in humans. Methods: Nine cocaine-dependent individuals (N=9) were enrolled to investigate the abuse potential of phendimetrazine and d-amphetamine, using a double-blind, placebo-controlled, within-subject design. Subjective and cardiovascular effects of oral phendimetrazine (35, 70, and 105mg), d-amphetamine (10, 20, and 30mg), and placebo were assessed in quasi-random order across 8 sessions lasting for approximately 8hours each. Results: d-Amphetamine (20 and 30mg) significantly increased cardiovascular measures in a time and dose-related manner, but phendimetrazine did not systematically alter cardiovascular measures. Although d-amphetamine and phendimetrazine significantly increased ratings indicative of abuse potential (eg, drug liking) and stimulant-like effects relative to placebo, these increases were generally small in magnitude, with phendimetrazine producing significant effects on fewer abuse-related measures and at fewer time points than d-amphetamine. Conclusions: These preliminary findings suggest that oral phendimetrazine and d-amphetamine may have limited abuse potential in cocaine-dependent individuals. These findings collectively emphasize that the clinical utility of medications to treat cocaine-use disorders should be weighed carefully against their potential for abuse and diversion, with careful attention paid to evaluating abuse potential in a clinically relevant population of interest. Future studies are needed to further elucidate the potential utility of phendimetrazine as an agonist-like replacement therapy for cocaine dependence.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalJournal of Addiction Medicine
Issue number3
StatePublished - 2016

Bibliographical note

Funding Information:
Source of research funding: This research was supported by grants from the National Institute on Drug Abuse (R01 DA025032 and T32 DA035200).

Publisher Copyright:
Copyright © 2016 American Society of Addiction Medicine.


  • abuse potential
  • agonist replacement therapy
  • cocaine dependence
  • phendimetrazine
  • subjective effects

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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