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Effects of the NMDA antagonist memantine on human methamphetamine discrimination
Carl L Hart1, Margaret Haney, Richard W Foltin
1New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. clh42@columbia.edu
Rationale:
The discriminative stimulus effects of N-methyl- D-aspartate (NMDA) antagonists have been assessed in laboratory animals. To date, no published study has assessed their ability to alter methamphetamine-related discriminative stimulus effects in humans.
Objective:
This study investigated the discriminative stimulus, subjective (e.g. "Good Drug Effect"), psychomotor performance, and cardiovascular effects (e.g. blood pressure) of oral methamphetamine following acute oral memantine (a non-competitive NMDA antagonist) in humans.
Methods:
Initially, participants were trained to discriminate 10 mg methamphetamine from placebo using a standard two-response procedure (drug versus placebo). Then, the effects of memantine (0, 40 mg) on methamphetamine discrimination were examined across several methamphetamine doses (0, 5, 10, 20 mg) using a novel-response procedure (drug versus placebo versus novel).
Results:
Following placebo pretreatment, 10 mg methamphetamine produced 99% methamphetamine-appropriate responding and placebo produced 75% placebo-appropriate responding. Following memantine pretreatment, participants responded as if they had been given a novel compound, although memantine did not significantly alter most subjective-effects ratings following methamphetamine. Memantine alone produced "positive" subjective effects and novel drug-appropriate responding.
Conclusion:
These data indicate that the memantine-methamphetamine combination produced novel discriminative stimulus effects and that memantine produced some stimulant-like subjective effects.