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.
|Number of pages||10|
|Journal||Journal of Addiction Medicine|
|State||Published - 2016|
Bibliographical noteFunding Information:
Source of research funding: This research was supported by grants from the National Institute on Drug Abuse (R01 DA025032 and T32 DA035200).
Copyright © 2016 American Society of Addiction Medicine.
- abuse potential
- agonist replacement therapy
- cocaine dependence
- subjective effects
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology (medical)