August 4, 2006

New drugs may boost pregnancy risk: study

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S.K. Dey, Ph.D., left, and Haibin Wang, Ph.D., say that the benefit of new drugs enhancing anandamide activity must be weighed against their risk to women of reproductive age.
Photo by Mary Donaldson

New drugs may boost pregnancy risk: study

Enhancing the actions of “marijuana-like” chemicals in the body could lead to new treatments for a wide variety of disorders, from chronic pain to cancer.

But disrupting the “tone” or delicate balance of these chemicals may also increase the risk of tubal pregnancy and pregnancy failure, researchers at Vanderbilt University Medical Center reported this week in the Journal of Clinical Investigation.

The Vanderbilt scientists studied an enzyme called FAAH (fatty acid amide hydrolase), which breaks down a natural “endocannabinoid” called anandamide. When the enzyme was silenced genetically or pharmacologically in mice, anandamide levels rose.

The result was abnormal embryonic development, retention of the embryo in the oviduct (the tube leading from the ovaries to the uterus), as well as premature labor and pregnancy loss.

This suggests that a physiological anandamide “tone” is critical for normal embryonic development and successful pregnancy. “Its absence is bad for pregnancy and its over-stimulation is bad for pregnancy,” said the report's senior author, S.K. Dey, Ph.D., director of the Division of Reproductive and Developmental Biology.

Drugs that enhance anandamide activity by inhibiting its degradation are currently being investigated as possible treatments for chronic pain, anxiety, cancer, epilepsy, high blood pressure, inflammatory bowel disease and neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Their potential benefit, however, must be weighed against their risk, “especially in women of reproductive age,” the researchers concluded.

Dey and his colleagues previously reported that when the receptor that binds the main active chemical of marijuana, delta-9-tetrahydrocannabinol (THC), was blocked or over-stimulated in pregnant mice, the embryo failed to go through the oviduct. The current study suggests that higher THC levels or “tinkering” with levels of its natural version, anandamide, can produce the same effect.

The study was led by Haibin Wang, Ph.D., research assistant professor of Pediatrics, who is also the lead author on the report. Other members of the research team are Huirong Xie, Ph.D., Young Guo, Ph.D., Hao Zhang, Toshifumi Takahashi, Ph.D., Philip J. Kingsley, Lawrence J. Marnett, Ph.D., and Sanjoy K. Das, Ph.D., all of Vanderbilt, and Benjamin F. Cravatt, Ph.D., of the Scripps Research Institute in La Jolla, Calif.

The study was supported by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development.

Wang is supported by a Solvay-Mortola Research Award from The Society of Gynecologic Investigation, and Xie by a Lalor Foundation postdoctoral fellowship.