Cannabinoids and reproduction

The success of implantation depends on the synchronous development of the embryo and the endometrium. This process is recognised to be regulated by the endocannabinoid system, the most widely studied of which is anandamide.;The first part of this study was the development of a robust assay to measure anandamide in human plasma. The assay was then applied to measure anandamide concentrations during the menstrual cycle, pregnancy, labour and in a group of women presenting with threatened miscarriage. The mean plasma anandamide levels in the follicular phase were 1.68 nM compared to 0.87 in the luteal phase. In pregnancy, the mean levels in the first trimester were 0.89 nM and 0.44 in both the second and third trimesters. At term, the mean levels were 0.68 in the non-labour group and to 2.5 nM in labour. In the threatened miscarriage group, anandamide levels >2.0 nM were predictive of subsequent miscarriage with sensitivity of 100%, specificity of 94.4%, negative predictive value of 100% and positive predictive value of 81.8%.;Finally, to try and identify potential targets of anandamide action, the expression of the cannabinoid receptors (CB1 & CB2) and the enzyme FAAH was studied in first trimester placentas. All proteins studied were present in the tissues examined with the expression of the CB1 diminishing after 9 weeks and FAAH disappearing by 11 weeks gestation. Similarly, anandamide inhibited the growth of BeWo cells in culture. Taken together, these findings suggest that anandamide plays a role in the maintenance of early pregnancy.