Cocaine use continues to be a major public health problem, yet there are no proven medication treatments for cocaine abuse. Thus cocaine abuse represents an important target for medications development. Recent evidence primarily from preclinical studies suggests that medications which block L-type calcium channels or antagonize the function of the excitatory amino acid (EAA) gaged cation channels permeable to calcium are able to blunt the effects of cocaine. The proposed research investigates whether these medications have similar effects in humans. Three major studies, each evaluating study """""""" effects on behavioral and cardiovascular responses to intranasal cocaine 120 mg/70 kg and cocaine placebo during six laboratory test sessions, are proposed. The first study will determine whether single 60 mg and 90 mg oral doses of the L- type calcium channel blocker nimodipine given 60 minutes prior to cocaine will reduce cocaine effects in human subjects. The second study will determine whether single 120 mg and 240 mg oral doses of the EAA release inhibitor lamotrigine given 120 minutes prior to cocaine will reduce cocaine effects in human subjects. The third study will determine whether subanesthetic intravenous doses of the noncompetitive NMDA type EAA antagonist ketamine administered via a bolus and infusion paradigm will reduce cocaine effects in human subjects. Cocaine will be administered 15 minutes into the 75 minute infusion. Ketamine doses will be based on preliminary data in healthy subjects and a pilot project evaluating the effects of ketamine alone in subjects with a history of cocaine abuse.
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