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Subst Use Misuse. 2009;44(13):1888-98. doi: 10.3109/10826080902961179.

Tolerance and sensitization to the effects of cocaine use in humans: a retrospective study of long-term cocaine users in Philadelphia.

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Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.


In the effort to develop medications to combat addiction, researchers have developed models that attempt to describe the neurobiological process of cocaine dependence. It has not, however, yet been determined which of these models, if any, best fits the behaviors and experiences of patients. This project retrospectively evaluated changes in patients' experiences with cocaine over time in order to clarify the model that best fits clinical observations. In 2005 and 2007, 100 treatment-seeking, long-term cocaine users were recruited from an urban university-based treatment center in Philadelphia, PA, United States. Each participant was administered the "Cocaine History Questionnaire" which asked them to describe the initiation and escalation of their cocaine usage, changing reward perceptions, and effects of intoxication at certain points in their drug use careers. This data was then analyzed using repeated measures, examining the within subject differences in reported information over the time points. We found evidence that while the amount of drug used increases, self-reported euphoria decreases while negative symptoms associated with cocaine use also increase. The data provide preliminary evidence for the hedonic dysregulation model of addiction. Limitations and implications of the study are discussed in the conclusion.

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