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Marijuana and Fertility
New Scientist
October 26, 1996

Philip Cohen, San Francisco
WOMEN who smoke marijuana may want to consider cutting back if they are trying to get pregnant. Researchers in Kansas City have found that a chemical similar to the active ingredient of cannabis will halt the development of mouse embryos and prevent them from implanting in the wall of the uterus. The chemical acts by binding to receptors on embryo cells.

Scientists know that the active ingredient in marijuana, tetrahydrocannabinol or THC, binds to specific receptors on nerve cells in the brain to produce a "high" in the user. The function of these cannabinoid receptors in normal cognition has been a mystery, but it seems likely that they do have a role, because the brain produces a chemical very like THC, called anandamide, which also binds to the receptors.

The first hint that anandamide might bind to cannabinoid receptors in the female reproductive system came last year when a team led by Sudhansu Dey, a physiologist at the University of Kansas in Kansas City, found that mouse embryo cells had cannabinoid receptors on their surfaces. He also discovered that the mouse uterus produces anandamide--- a finding that made Dey curious about whether anandamide was interacting with the receptors on the embryo's cells.

He took two-day-old embryos from mice and cultured them in dishes. In this culture medium, 90 per cent of the embryos continued to develop. But when even low levels of anandamide were added to the culture, the number of developing embryos dropped to 36 per cent.

In itself, this did not prove that cannabinoid receptors were involved: the anandamide could simply have been acting like a poison. So the researchers tried blocking the cannabinoid receptors with molecules that stopped anandamide from binding to them. When they did this, the embryos survived and continued to develop, confirming that anandamide's action on the embryos is specific and dependent on binding to the cannabinoid receptors (Reproduction and Fertility, vol 55, p 756). In research that has still to be published, Dey's team has now shown that anandamide can prevent implantation of the embryo.

No one knows why this system for preventing the implantation of embryos should have evolved, but Dey suspects it may help to ensure that the fertilised egg only implants when the uterus is at its most receptive. His team found that the levels of anandamide in the mouse uterus fluctuate through the cycle, falling to their lowest level when the mouse uterus is best prepared to receive the embryo. This suggests that the chemical acts as a signal to limit implantation to the most fertile period. "There is no question in my mind that anandamide determines the proper window for the mouse," says Dey.

Other researchers are intrigued by the findings. "This work is an important first step in understanding what role these receptors play for the embryo," says Billy Martin, a pharmacologist at the Virginia Commonwealth Universitv in Rich mond. But Martin warns that there is no strong evidence to suggest that women who use cannabis frequently suffer more problems with pregnancy. Dey accepts this, but argues that such an effect might have been easily overlooked, since cannabinoids may halt pregnancies only before implantation takes place---before a woman even knows that she has conceived.