10.30699/jambs.30.143.561 Background & Objective: Datura stramonium L. is a medicinal herb from the family of Solanaceae. It has been used in herbal remedies for promoting health and treating several diseases. The current study was set up to compare the effects of Datura stramonium L. extract on the naloxone-precipitated opiate-withdrawal in mice. Materials & Methods: Male BALB/c mice (30-35 g, n = 40) were arbitrarily separated into 4 groups. The control group received morphine and normal saline and other groups received three doses of D. stramonium extract (10, 20, or 30 mg/kg, intraperitoneally, i.p.). Physically dependent was made by the administration of morphine in increasing doses (50-75 mg/kg, i.p.). The withdrawal signs were elicited by intraperitoneal injections of naloxone (5 mg/kg) 2 h after the last injection of morphine. Results: Administration of D. stramonium extract in doses of 20 and 30 mg/kg markedly diminished the jumping numbers compared to the control group (P<0.05). All three doses of D. stramonium extract could significantly suppress the increase in climbing (P<0.05, P<0.001, and P<0.001, respectively) and diarrhea (P<0.001). D. stramonium in higher doses (20 or 30 mg/kg) significantly decreased rearing and itching (P<0.001). Conclusion:The study findings suggest that D. stramonium extract is effective in alleviating the signs of morphine withdrawal. Additional research is needed to determine the exact mechanisms underlying D. stramonium for inhibiting morphine withdrawal syndrome.