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Safety and tolerability of intranasal cocaine during phendimetrazine maintenance

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Abstract

Rationale

Phendimetrazine appears to have limited abuse potential and reduces cocaine self-administration in preclinical studies. No human studies have evaluated the safety and tolerability of cocaine in combination with phendimetrazine, which is a necessary next step in evaluating the efficacy of phendimetrazine for treating cocaine use disorder.

Objectives

This study determined the safety and tolerability of acute cocaine doses during chronic phendimetrazine treatment.

Methods

Ten subjects completed this within-subject, placebo-controlled, inpatient study. Subjects were maintained on ascending oral phendimetrazine doses (0, 70, 140, and 210 mg/day). After at least seven maintenance days at each dose, subjects received ascending doses of intranasal cocaine (0, 10, 20, 40, and 80 mg), separated by 90 min, within one session.

Results

Cocaine produced prototypical cardiovascular and subject-rated effects (e.g., increased blood pressure and ratings of like drug). The cardiovascular effects of cocaine alone were not clinically significant for an acute drug response (e.g., average heart rate did not approach tachycardia, 100 beats/min). Phendimetrazine enhanced peak heart rate following placebo and low cocaine doses, but these effects were also not clinically significant. Phendimetrazine was otherwise devoid of effects alone and did not alter the subject-rated effects of cocaine or hypothetical demand for cocaine on a purchase task.

Conclusions

Cocaine was safe and well tolerated during maintenance on a threefold range of phendimetrazine doses. Given this safety profile, the reduced abuse potential of phendimetrazine and promising preclinical research, future human laboratory studies, and possibly clinical trials should evaluate the efficacy of phendimetrazine for reducing cocaine use.

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Acknowledgments

The authors gratefully acknowledge the staff of the University of Kentucky Laboratory of Human Behavioral Pharmacology for the technical assistance, the staff of the University of Kentucky Center for Clinical and Translational Science Clinical Research Inpatient Unit for the medical assistance, and the University of Kentucky Investigative Drug Service for the preparation of study medications. This study complied with all laws of the United States of America.

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Authors and Affiliations

  1. Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Room 140, Lexington, KY, 40536-0086, USA

    William W. Stoops, Joshua A. Lile & Craig R. Rush

  2. Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY, 40509-1810, USA

    William W. Stoops, Lon R. Hays, Abner O. Rayapati, Joshua A. Lile & Craig R. Rush

  3. Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY, 40506-0044, USA

    William W. Stoops, Justin C. Strickland, Joshua A. Lile & Craig R. Rush

Authors
  1. William W. Stoops
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  2. Justin C. Strickland
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  3. Lon R. Hays
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  4. Abner O. Rayapati
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  5. Joshua A. Lile
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  6. Craig R. Rush
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Corresponding author

Correspondence to William W. Stoops.

Ethics declarations

The Medical Institutional Review Board of the University of Kentucky approved this study, which was conducted in accordance with all relevant guidelines, including the 1964 Declaration of Helsinki. Subjects provided sober, written informed consent to participate in this within-subject, placebo-controlled, inpatient study.

Conflict of interest

The authors declare that they have no conflicts of interest. The authors gratefully acknowledge the research support from the National Institute on Drug Abuse (R01DA036553) and from the National Center for Advancing Translational Sciences (UL1TR000117) of the National Institutes of Health. These funding agencies had no role in the study design, data collection or analysis, or preparation and submission of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Stoops, W.W., Strickland, J.C., Hays, L.R. et al. Safety and tolerability of intranasal cocaine during phendimetrazine maintenance. Psychopharmacology 233, 2055–2063 (2016). https://doi.org/10.1007/s00213-016-4260-7

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  • DOI: https://doi.org/10.1007/s00213-016-4260-7

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