The present study examined the effect of the MeOH extract, partially purified fraction (IV), and pure compounds from Argemone mexicana L. (Papaveraceae) on the morphine withdrawal in guinea pig isolated ileum. The MeOH extract, the partially purified fraction (IV), and the pure compounds isolated from A. mexicana significantly and in a concentration-dependent manner reduced the morphine withdrawal. Since the pure compounds were identified as protopine and allocryptopine, the observed effects could be related to these compounds. The results of the present study suggest that isoquinoline alkaloids may be potential agents in the treatment of drug abuse.