Objective: The aim of this study was to investigate the expression of cannabinoid receptors in humanuterine smooth muscle during pregnancy and to evaluate the effects of endogenous and exogenouscannabinoids on myometrial contractility in vitro.Study design: Human myometrial biopsy specimens were obtained at elective cesarean deliveryand snap frozen or mounted for isometric recording under physiologic conditions. Cumulativedoses of the endogenous cannabinoid anandamide or the exogenous cannabinoid D9 (indicatesa double bond between carbons 9 and 10) tetrahydrocannabinol were added in the range1 nmol/L to 100 mmol/L. Selectivity of the cannabinoid receptor agonists was investigated withspecific antagonists for the CB1 and the CB2 receptors. Reverse transcriptionepolymerase chainreaction with primers for the CB1 and CB2 receptors was performed on messenger RNA that wasisolated from human pregnant myometrium.Results: Both anandamide and D9-tetrahydrocannabinol exerted a direct relaxant effect onhuman pregnant myometrium in vitro, which was of equal potency for both compounds. This relaxanteffect was antagonized by the specific CB1 receptor antagonist, SR 141716, but not by thespecific CB2 receptor antagonist, SR 144528 (n=6 specimens, P!.01). Both the CB1 and CB2receptors are expressed in human myometrium.Conclusions: Both endogenous and exogenous cannabinoids exert a potent and direct relaxanteffect on human pregnant myometrium, which is mediated through the CB1 receptor. This highlightsa possible role for endogenous cannabinoids during human parturition and pregnancy.These results also support the view that the use of exogenous cannabinoids during pregnancyis not linked independently with preterm labor.