Information on clinically available activities in both peripheral and neuronal systems of crocin in saffron has been accumulated. The LTP-blocking effect of ethanol was significantly improved by oral-, intravenous-, and intracerebroventricular-administration of crocin, respectively. We investigated the effects of ethanol and crocin on synaptic potentials mediated by N-methyl-D-aspartate (NMDA) receptors in the dentate gyms of rat hippocampal slices. Crocin alone did not affect synaptic potentials mediated by non-NMDA or NMDA receptors. Crocin did not affect the inhibition of non-NMDA response by 100 mM ethanol, but significantly blocked the inhibition of NMDA response by 10-50 mM ethanol. We performed whole-cell patch recording with primary cultured rat hippocampal neurons, and confirmed that crocin blocked ethanol inhibition of inward currents evoked by the application of NMDA. We also demonstrated that crocin suppresses the effect of tumor necrosis factor (TNF)-α on neuronally differentiated PC-12 cells. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-α-induced release of cytochrome c from the mitochondoria. Crocin also blocked the cyotochrome c-induced activation of caspase-3. We found that crocin inhibited the effect of daunorubicin as well. The present paper focuses on the pharmacological actions of crocin on the central nervous system and reviews briefly the findings of such studies on the prevention of neuronal programmed cell death (apoptosis).