Effect of Crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice.

Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5 h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3 mg/kg) or normal saline. Naloxone was injected (5 mg/kg i.p.) 2 h after the final dose of morphine and the number of episodes of jumping during 30 mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30 mm prior and 1 and 2 h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320 mg/kg) and the ethanolic extract decreased it in the dose of 800 mg/kg in open field test. But crocin and the dose of 400 mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome.