Objective(s): Evaluation of the Sophora alopecuroides var. alopecuroides seed effects on morphine withdrawal syndrome in mice and determination of the alkaloid composition of the seed total extract. Materials and Methods: The effects of the seed total extract, alkaloid fraction and major compound matrine on the mice morphine withdrawal syndrome were compared to saline and methadone. Mice were made dependent on morphine by morphine sulfate injection 3 times a day for 3 days. The withdrawal jumping and diarrhea were induced by administration of naloxone 2 hr after the 10th injection of morphine sulfate on the day 4. The total extract (100, 200, 300 mg/kg), alkaloid fraction (5, 10, 20 mg/kg), matrine (5, 15, 30 mg/kg), methadone (10 mg/kg) or saline were injected 30 min before naloxone. All drugs were administered by subcutaneous injection. The total extract alkaloid composition was also determined by gas chromatography (GC) and GC-MS analysis. Results: All doses of the total extract, alkaloid fraction and matrine as well as methadone decreased jumping and diarrhea significantly compared to the saline. The effects of the total extract and alkaloid fraction were not significantly different from methadone. But, there were significant differences between the effects of matrine and methadone. Matrine, cytisine, sophoridine, n-methyl cytisine, sophocarpine and sophoramine were the major alkaloids. There was no nicotine in the total extract. Conclusion: S. alopecuroides var. alopecuroides suppresses opioid withdrawal with efficacy comparable to methadone. Matrine may be one of the alkaloids responsible for the effect of the plant.