The effects of memantine on the subjective, reinforcing and cardiovasculareffects of cocaine in humans

Eight male frequent cocaine smokers participated in a 44- to 47-day inpatie nt and outpatient study to assess the effects of the noncompetitive N-methy l-D-aspartate (NMDA) antagonist, memantine, on cocaine self-administration, subjective effects, and psychomotor performance. Participants were maintai ned on memantine (0 and 20 mg daily) for 7-10 days prior to laboratory test ing, using a double-blind crossover design. Under each medication condition , participants smoked four doses of cocaine base (0, 12, 25 and 50 mg), and were subsequently given five opportunities, 14 min apart, to self-administ er that dose of cocaine or receive a merchandise voucher ($5.00). Each coca ine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose was systematically varied. Vital sig ns were recorded every 2 min, and subjective effects were assessed at basel ine and after each cocaine or voucher delivery. In addition, psychomotor pe rformance was assessed before and after each self-administration session. M emantine maintenance was not associated with changes in psychomotor perform ance or the number of cocaine doses chosen each session. Memantine maintena nce was, however, associated with significant increases in some subjective effects of cocaine, including ratings of 'good drug effect', 'high', 'poten cy', 'quality', and street value. These data suggest that NMDA antagonists may have limited usefulness as treatment medications for cocaine abuse. Beh av Pharmacol 1998; 9:587-598 (C) 1998 Lippincott Williams & Wilkins.