Most existing methods for evaluating the efficacy and safety of pharmacotherapies for drug abuse involve either the time and expense of clinical treatment trials or short-term experimental models which have the medical risk of drug administration and whose relevance to clinical drug abuse may be questionable. The goal of this project is to develop human experimental methods in a controlled residential research ward environment which can safely and efficiently be used to evaluate potential treatment medications. One study has used a drug self-administration paradigm analogous to those used in animal research, in which human subjects could make a stimulus-controlled operant response to earn an iv injection of low-dose cocaine or saline. Results showed that cocaine abusers could distinguish cocaine from saline injections and found the former highly reinforcing and the latter non-reinforcing. Data from the study are being analyzed to evaluate the relationship between drug self-administration and craving for cocaine, since the latter is often used as a surrogate outcome variable in studies of drug abuse treatment. Two different methods for measuring cocaine craving, visual-analogue scales and Likert scales, are also being evaluated. Another component is studying conditioned or context-specific behavioral sensitization as a method for evaluating clinically relevant effects of cocaine. While this phenomenon has been demonstrated in animals, it has never been demonstrated in humans.
