Marijuana-Like Compounds May Alter Human Fertility, UB Researchers Show

SAN FRANCISCO -- Scientists at the University at Buffalo have shown that marijuana-like compounds called anandamides, found in the testis, uterus and oviduct, may play a role in regulating functions of human sperm and influence their ability to fertilize eggs.

The study, presented here today (Dec. 15, 1998) at the meeting of the American Society of Cell Biology, showed that human sperm contain receptors for cannabinoids -- chemical compounds such as THC, the active substance in marijuana smoke.

o Inhibition of acrosome reaction, the normal release of the sperm enzymes that enable sperm to penetrate the egg.

o Regulation of very active sperm swimming patterns, called hyperactivation.

o Prevention of sperm binding to the egg cover, or zona.

The findings could have significant implications for diagnosis of infertility and understanding basic human biology and molecular control, said Herbert Schuel, Ph.D., professor of anatomy and cell biology at the UB School of Medicine and Biomedical Sciences and co-author of the study.

"We've known for 30 years that very heavy marijuana smoking has a drastic effect on sperm production within the testis, which can lead to higher rates of infertility," Schuel said. "Our new findings suggest that anandamides and THC in marijuana smoke may also affect sperm functions required for fertilization in the female reproductive tract.

"The additional load of cannabinoids in the systems of people who abuse marijuana floods the natural cannabinoid receptors and appears to have adverse consequences for reproduction in both males and females."

Pioneering work by Schuel and colleagues previously had shown that sperm from the sea urchin have a recognition site, or receptor, for cannabinoids. They also provided evidence that

cannabinoids and anandamides can prevent sea-urchin sperm from fertilizing eggs by preventing the sperm acrosome reaction when they arrive at the egg surface. Washing away the cannabinoids reversed the inhibitory effects.

The current research on human fertilization was carried out in collaboration with Lani J. Burkman, Ph.D., director of the Andrology Section (the study of male fertility/infertility) in the UB medical school, and Alex Makriyannis, Ph.D., professor of medicinal chemistry at the University of Connecticut.

These researchers have found that human sperm contain functional cannabinoid receptors, allowing THC from marijuana, as well as natural cannabinoids (anandamides), to bind to sperm.

During normal reproduction, fluids within the female reproductive tract prepare the sperm to fertilize the egg -- to swim vigorously and undergo the acrosome reaction when they arrive at the egg's zona. The researchers mimicked these processes in vitro by incubating the sperm in special media, which stimulate hyperactivated swimming and can produce premature acrosome reactions without the presence of an egg.

In 30 trials using modified fertility laboratory procedures, Schuel, Burkman and colleagues incubated pre-screened human sperm in this stimulating medium containing different concentrations of THC or AM-356, a synthetic equivalent of the natural anandamide.

Samples were removed at various intervals up to six hours and assessed for changes in the acrosome, motility and vigorous swimming patterns, and for sperm binding to nonviable zona.

Results showed that after six hours, sperm exposed to THC or AM-356 had a 67 percent reduction in premature acrosome reactions, compared to controls. This finding implies that anandamides normally may prevent such premature acrosome reactions within the female reproductive tract.

Motility studies showed that higher levels of AM-356 inhibited hyperactivated swimming, while lower concentrations actually stimulated hyperactivation. These results suggest that fluctuations in anandamide levels in the oviduct may regulate sperm swimming patterns and affect the optimal timing for the sperm to meet the egg.

In the zona experiments, AM-356 inhibited sperm binding by 75 percent, and provided the first evidence that anandamides and cannabinoids can directly affect the fertilizing capacity of human sperm.