Prior transcranial magnetic stimulation studies showed that resting motor threshold is elevated in abstinent cocaine-dependent patients, suggesting a decrease in axonal excitability. In contrast, the increased incidence of seizures and psychosis in this group suggests increased excitability or decreased inhibition. Here, we studied long-interval intracortical facilitation and long-interval intracortical inhibition, paired-pulse transcranial magnetic stimulation measures that are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively. Ten cocaine-dependent and 10 healthy controls were examined. Resting motor threshold, long-interval intracortical facilitation and long-interval intracortical inhibition were tested from the left motor cortex. The cocaine group showed an elevated resting motor threshold and an increased long-interval intracortical facilitation, whereas long-interval intracortical inhibition was normal. Although the increase in long-interval intracortical facilitation suggests exaggerated cortical glutamatergic excitability, the increase in resting motor threshold may signify a protective mechanism against seizures and psychosis.