A paradigm to investigate the self-regulation of cocaine administration in humans.
BACKGROUND
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.
Sughondhabirom
Atapol
A
Department of Psychiatry, Yale University, New Haven, CT 06519, USA.
Jain
Diwakar
D
Gueorguieva
Ralitza
R
Coric
Vladimir
V
Berman
Robert
R
Lynch
Wendy J
WJ
Self
David
D
Jatlow
Peter
P
Malison
Robert T
RT
D000328:Adult; D016058:Analgesia, Patient-Controlled / Q000379:methods* / Q000592:standards; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D015203:Reproducibility of Results; D012646:Self Administration / Q000379:methods / Q000592:standards
D003042:Cocaine
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