B Levi Bolin1, William W Stoops, Jeremy P Sites, Craig R Rush. 1. Department of Behavioral Science (BLB, WWS, CRR), University of Kentucky College of Medicine, 140 Medical Behavioral Science Building, Lexington, KY; Department of Psychology (WWS, CRR), University of Kentucky College of Arts and Sciences, 110 Kastle Hall, Lexington, KY; Department of Psychiatry (WWS, CRR), University of Kentucky College of Medicine, 3470 Blazer Parkway, Lexington, KY; and University of Kentucky College of Medicine (JPS), 138 Leader Avenue, Lexington, KY.
Abstract
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 105 mg), d-amphetamine (10, 20, and 30 mg), and placebo were assessed in quasi-random order across 8 sessions lasting for approximately 8 hours each. RESULTS:d-Amphetamine (20 and 30 mg) 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.
RCT Entities:
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 105 mg), d-amphetamine (10, 20, and 30 mg), and placebo were assessed in quasi-random order across 8 sessions lasting for approximately 8 hours each. RESULTS:d-Amphetamine (20 and 30 mg) 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.
Authors: Richard B Rothman; Marina Katsnelson; Nga Vu; John S Partilla; Christina M Dersch; Bruce E Blough; Michael H Baumann Journal: Eur J Pharmacol Date: 2002-06-28 Impact factor: 4.432
Authors: Craig R Rush; William W Stoops; Frances P Wagner; Lon R Hays; Paul E A Glaser Journal: J Clin Psychopharmacol Date: 2004-08 Impact factor: 3.153
Authors: Anushree N Karkhanis; Thomas J R Beveridge; Bruce E Blough; Sara R Jones; Mark J Ferris Journal: Drug Alcohol Depend Date: 2016-06-25 Impact factor: 4.492
Authors: Gavin McLaughlin; Michael H Baumann; Pierce V Kavanagh; Noreen Morris; John D Power; Geraldine Dowling; Brendan Twamley; John O'Brien; Gary Hessman; Folker Westphal; Donna Walther; Simon D Brandt Journal: Drug Test Anal Date: 2018-05-23 Impact factor: 3.345
Authors: William W Stoops; Justin C Strickland; Lon R Hays; Abner O Rayapati; Joshua A Lile; Craig R Rush Journal: Psychopharmacology (Berl) Date: 2016-03-01 Impact factor: 4.530