Anandamide hydrolase: a guardian angel of human reproduction?

Anandamide (AEA) is the best-studied member of the endocannabinoids, a group of bioactive fatty acid amides and esters that activate cannabinoid receptors and have several roles in both the CNS and the periphery. The tone, signaling and activity of AEA in vivo are terminated by a specific fatty acid amide hydrolase (FAAH), whose inhibition has potential therapeutic applications in pain, neurodegenerative disorders, cancer and anxiety. In this article, we discuss the participation of AEA in hormone-cytokine networks that are essential for reproduction, and support the view that FAAH plays a key role in regulating this activity of AEA. We underline the fact that FAAH in maternal lymphocytes is a molecular integrator of signals that are crucial for human gestation, and that its downregulation to date is the only early marker of spontaneous abortion, both in vivo and in vitro. We propose that drugs that are able to enhance FAAH activity might become useful therapeutic tools for the management of human infertility.