title: A single-day paradigm of self-regulated human cocaine administration.
abstract: Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs.
  
  
  METHODS
  Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed.
  
  
  RESULTS
  Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects (“high”) were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses.
  
  
  CONCLUSIONS
  These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: D
authors.initials: D
authors.lastname: Matuskey
authors.forename: B
authors.initials: B
authors.lastname: Pittman
authors.forename: J I
authors.initials: JI
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Wanyiri
authors.forename: H
authors.initials: H
authors.lastname: Nadim
authors.forename: P
authors.initials: P
authors.lastname: Jatlow
authors.forename: R
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: M N
authors.initials: MN
authors.lastname: Potenza
authors.forename: P T
authors.initials: PT
authors.lastname: Morgan
authors.forename: Z
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: R T
authors.initials: RT
authors.lastname: Malison
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002985:Clinical Protocols; D003042:Cocaine / Q000008:administration & dosage* / Q000097:blood; D019970:Cocaine-Related Disorders / Q000097:blood / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D012646:Self Administration; D013997:Time Factors
chemical_list: D003042:Cocaine