Effect of Afghan Ferula assa-foetida L. and Crocus Sativus L. Aqueous Extracts Combination on Withdrawal Signs in Morphine-Dependent Rats

The purpose of this study is to evaluate the effect of Afghan Ferula assa-foetida L. and Crocus Sativus L. aqueous extracts either alone or in combination on morphine withdrawal signs. For this purpose, rats were randomly divided into 13 groups (1 Normal, 1 Morphine, 4 Ferula assa-foetida-treated groups, 4 Crocus sativus-treated groups, and 3 combination groups). Morphine dependency was rendered by subcutaneous injection of morphine hydrochloride for 4 days (10, 20 and 40 mg/kg doses twice daily for 3 days and a single dose of 60 mg/kg on 4th day). Various doses of extracts were injected into extract groups simultaneously with morphine. After two hours of last morphine administration, withdrawal signs were induced by naloxone (3 mg/kg) and noted for 30 minutes. According to the results, different doses of Ferula assa-foetida and Crocus sativus extracts and their combination (in low dose) could significantly decrease the number of morphine withdrawal signs (P<0.05). However, the combination of Ferula assa-foetida and Crocus sativus extracts in high doses showed toxic effects. In conclusion, Ferula assa-foetida and Crocus sativus extract combination in low dose can decrease the morphine withdrawal signs, but without any synergic effects.