title: Safety and tolerability of intranasal cocaine during phendimetrazine maintenance.
abstract: 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.
  
  
  
  This study determined the safety and tolerability of acute cocaine doses during chronic phendimetrazine treatment.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.stoops@uky.edu.|Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY, 40509-1810, USA. william.stoops@uky.edu.|Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY, 40506-0044, USA. william.stoops@uky.edu.
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.affiliation: Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY, 40506-0044, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Strickland
authors.affiliation: Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY, 40509-1810, USA.
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
authors.affiliation: Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY, 40509-1810, USA.
authors.forename: Abner O
authors.initials: AO
authors.lastname: Rayapati
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Room 140, Lexington, KY, 40536-0086, USA.|Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY, 40509-1810, USA.|Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY, 40506-0044, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Room 140, Lexington, KY, 40536-0086, USA.|Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY, 40509-1810, USA.|Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY, 40506-0044, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000191:economics / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D009025:Morpholines; C100294:phendimetrazine; D003042:Cocaine
keywords: Cocaine; Humans; Pharmacotherapy; Phendimetrazine; Physiological effects