Cannabinoids and the human uterus during pregnancy

Objective: The aim of this study was to investigate the expression of cannabinoid receptors in human uterine smooth muscle during pregnancy and to evaluate the effects of endogenous and exogenous cannabinoids on myometrial contractility in vitro. Study design: Human myometrial biopsy specimens were obtained at elective cesarean delivery and snap frozen or mounted for isometric recording under physiologic conditions. Cumulative doses of the endogenous cannabinoid anandamide or the exogenous cannabinoid Delta(9) (indicates a double bond between carbons 9 and. 10) tetrahydrocannabinol were added in the range 1 nmol/L to 100 mumol/L. Selectivity of the cannabinoid receptor agonists was investigated with specific antagonists for the CB1 and the CB2 receptors. Reverse transcription-polymerase chain reaction with primers for the CB1 and CB2 receptors was performed on messenger RNA that was isolated from human pregnant myometrium. Results: Both anandamide and Delta(9)-tetrahydrocannabinol exerted a direct relaxant effect on human pregnant myometrium in vitro, which was of equal potency for both compounds. This relaxant effect was antagonized by the specific CB1 receptor antagonist, SR 141716, but not by the specific CB2 receptor antagonist, SR 144528 (n = 6 specimens, P<.01). Both the CB1 and CB2 receptors are expressed in human myometrium. Conclusions: Both endogenous and exogenous cannabinoids exert a potent and direct relaxant effect on human pregnant myometrium, which is mediated through the CB1 receptor. This highlights a possible role for endogenous cannabinoids during human parturition and pregnancy. These results also support the view that the use of exogenous cannabinoids during pregnancy is not linked independently with preterm labor. (C) 2004 Elsevier Inc. All rights reserved.