Encouraging results have also been generated with agents that exhibit less specificity of action. Topiramate is commonly used as monotherapy in patients with partial onset or primary generalized tonic-clonic seizures and is FDA approved for migraine prevention. In addition to AMPAR antagonism, topiramate also enhances GABA levels in the CNS (Kuzniecky et al., 1998; Petroff et al., 1999; White et al., 2007). Interestingly, a double-blind, placebo-controlled pilot trial showed that topiramate-treated subjects were more likely to remain abstinent from cocaine use (Kampman et al., 2004) as craving intensity and duration were reduced in 25% of patients tested. Intriguingly, acute topiramate enhanced the pleasant subjective effects of methamphetamine (Johnson et al., 2007) suggesting a potential for replacement therapy. However, topiramate did not alter the rewarding properties of methamphetamine in mice (Tatsuta et al., 2007). A randomized, double-blind, placebo-controlled topiramate trial for alcohol and cocaine dependence is underway (Identifier: NCT00167245 and NCT00223626). The anticonvulsant and mood stabilizer drug lamotrigine also exhibits antagonistic effects on AMPAR and reduces glutamate release (Lee et al., 2008). Importantly, two open-label studies have correlated lamotrigine with significant
