TY - JOUR
T1 - A paradigm to investigate the self-regulation of cocaine administration in humans
AU - Sughondhabirom, Atapol
AU - Jain, Diwakar
AU - Gueorguieva, Ralitza
AU - Coric, Vladimir
AU - Berman, Robert
AU - Lynch, Wendy J.
AU - Self, David
AU - Jatlow, Peter
AU - Malison, Robert T.
N1 - Funding Information:
Acknowledgements We are grateful for the support of the National Institute on Drug Abuse [DA00397, DA15857, DA12283 (R.T.M.); DA114038 (W.J.L.)], the Yale Interdisciplinary Women’s Health Research (IWHR) Scholar Program on Women and Drug Abuse, the Yale General Medical Clinical Research Center (funded by NIH/ NCRR/GCRC Program Grant M01-RR00125), and the Department of Mental Health and Addiction Services (DMHAS) of the State of Connecticut.
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
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U2 - 10.1007/s00213-005-2192-8
DO - 10.1007/s00213-005-2192-8
M3 - Article
C2 - 15726333
AN - SCOPUS:21344473941
SN - 0033-3158
VL - 180
SP - 436
EP - 446
JO - Psychopharmacology
JF - Psychopharmacology
IS - 3
ER -