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 Δ⁹ (indicates a double bond between carbons 9 and 10) tetrahydrocannabinol were added in the range 1 nmol/L to 100 μmol/L. Selectivity of the cannabinoid receptor agonists was investigated with specific antagonists for the CB ₁ 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 Δ⁹-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, <.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 high-lights 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.