Marijuana use at the time of conception and early in pregnancy prevents embryos' safe passage from the ovary to the uterus, resulting in early pregnancy failure, suggests a new study in mice. The study appears in the August issue of the Journal of Clinical Investigation.
Marijuana, the most widely used illegal drug among women of reproductive age, binds to 2 receptors – cannabinoid receptors 1 and 2 (CB1, CB2) – which are found in the brain and other organs including sperm, eggs, and newly formed embryos. Normally, these 2 receptors are activated by the naturally occurring signaling molecule anandamide. Anandamide formation by the enzyme NAPE-PLD is carefully balanced with its degradation by the enzyme FAAH, resulting in a finely tuned local "anandamide tone" in embryos and the oviduct. This balance is required for normal embryonic development, transport along the oviduct, implantation in the uterus, and full-term pregnancy.
In the current study, Sudhansu Dey and colleagues from Vanderbilt University show that suppression of FAAH activity in the embryos and oviduct elevates anandamide levels, which inhibits embryonic development and prevents embryos from completing their passage to the uterus, causing impaired fertility. They went on to show that administration to the mice of tetrahydrocannabinol (THC), the major psychoactive component of marijuana that like anandamide also binds to CB1, swamps normal anandamide tone, causing implantation of the embryo in the earliest stages of pregnancy to fail. The results of the study show that drugs such as THC persist and swamp these finely tuned signaling systems and as such the use of THC-containing drugs such as marijuana may lead to ectopic pregnancy and/or impaired fertility in women.
In an accompanying commentary Herbert Schuel from the State University of New York discusses the sobering results of this study regarding marijuana's effects on pregnancy outcome and goes on to stress that a number of drugs currently in development or in use to suppress appetite or trigger weight-loss are also known modulators of anandamide signaling and given the results presented in the current study "such drugs need to be carefully evaluated to judge their effects on women of reproductive age and those that are pregnant."
TITLE: Fatty acid amide hydrolase deficiency limits early pregnancy events
Sudhansu K. Dey
Vanderbilt University Medical Center, Nashville, Tennessee USA.
Phone: (615) 322-8642
Fax: (615) 322-4704
View the PDF of this article at: https://www.the-jci.org/article.php?id=28621
TITLE: Tuning the oviduct to the anandamide tone
State University of New York, Buffalo, New York, USA.
Phone: (716) 829-3578
Fax: (716) 829-2911
View the PDF of this article at: https://www.the-jci.org/article.php?id=29424
Journal of Clinical Investigation