This proposal is a component of a center grant application to investigate """"""""agonist"""""""" drugs as pharmacological adjuncts for the treatment of psychomotor stimulant dependence. Cocaine abuse and dependence represents a substantial continuing societal problem and methamphetamine abuse and dependence constitutes a substantial emerging problem. To date there is no pharmacological treatment of generally recognized of generally recognized efficacy for treatment of psychomotor stimulant dependence. The concept of substitution for these compounds with a safer stimulant, analogous to methadone and nicotine replacement therapies, is one that bears further investigation. A treatment which has a sound theoretical rationale, high likelihood of safety and reasonable probability of efficacy is l-dopa. Components of this Center Grant will investigate various aspects of l-dopa therapy. The specific objectives of this component are to evaluate l-dopa (administered with carbidopa) as to safety and possible efficacy in the University Clinical Research Center (UCRC). Four studies are proposed, the first three of which are in the nature of Phase I, II and III clinical trials, the fourth of which is a study of drug interaction. In the first study, acute dose ranging/tolerance and repeated dosing/tolerance experiments are to be conducted in normal healthy controls. In the second, stimulant abusers (cocaine dependent and methamphetamine dependent subjects) who are not seeking treatment will participate in a determination of safety and subjective effects of l-dopa. In the third study, treatment seeking stimulant-dependent individuals will be administered their first dose of carbidopa/l-dopa in the laboratory setting and adverse and subjective effects will be assessed. In the fourth study, the interaction of carbidopa/l- dopa with intranasally administered cocaine will be evaluated as will be the interaction of carbidopa/l-dopa with orally administered methamphetamine in stimulant abusers not seeking treatment. These experiments along with the associated clinical studies will provide use with the empirical evidence requisite to forming a sound opinion regarding efficacy of l-dopa in the treatment of psychomotor stimulant dependence.
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