A paradigm to investigate the self-regulation of cocaine administration in humans

Psychopharmacology (Berl). 2005 Jul;180(3):436-46. doi: 10.1007/s00213-005-2192-8. Epub 2005 Feb 22.

Abstract

Introduction: Current laboratory paradigms of human cocaine administration generally dictate the timing of drug access in ways that may limit assessing aspects of cocaine-taking behavior. Patient-controlled analgesia (PCA) methods, which allow individuals less restricted access to narcotic (i.e., opiate) analgesics, have proven safe and clinically effective for self-regulated treatment of pain. The current study assessed the feasibility, safety, and validity of a model of ad libitum cocaine self-administration, in which participants self-selected the timing of cocaine infusions, using PCA techniques.

Methods: Eight nontreatment seeking, otherwise medically healthy, experienced cocaine users participated in a double-blind, placebo-controlled, escalating-dose regimen of intravenous cocaine (0, 8, 16, and 32 mg per 70 kg) on 4 test days, during which time participants had 2 h of access to cocaine via manual presses of a corded PCA pump button under a fixed ratio 1: time-out 5-min schedule.

Results: Procedures were well-tolerated by participants, and no significant adverse events were noted. Measures of cocaine self-administration (e.g., number of responses and interinfusion intervals) indicated a significant main effect of cocaine dose, consistent with predicted dose-response relationships (i.e., decreasing responses and increasing interinfusion intervals with increasing injection dose). Participants appeared to regulate their cocaine intake in a carefully controlled manner, using considerably less cocaine (about half) that permitted by pump loading, PCA parameters, and session duration.

Conclusions: Data from this study support the validity of our PCA paradigm. Moreover, results suggest the apparent feasibility and safety of allowing experienced users to self-select the timing of cocaine infusions to intervals as short as 5 min. Such procedures may enhance our ability to identify effective pharmacological treatments for cocaine addiction.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analgesia, Patient-Controlled / methods*
  • Analgesia, Patient-Controlled / standards
  • Blood Pressure / drug effects
  • Cocaine / administration & dosage*
  • Cocaine / adverse effects
  • Cocaine-Related Disorders / etiology
  • Cocaine-Related Disorders / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Infusions, Intravenous
  • Male
  • Reproducibility of Results
  • Self Administration / methods
  • Self Administration / standards

Substances

  • Cocaine