Nicotine is antagonist to cannabinoids in human sperm

Dec 4, 2006 09:38 GMT  ·  By

A new compound imitating cannabinoids from cannabis drugs may improve the fertility of tobacco smokers. Two-thirds of the male tobacco smokers will exhibit a small or a significant decrease in fertility, some with serious loss, characterized by low sperm count and low percentage sperm motility.

"Nicotine addiction is quite powerful. The best solution is to stop smoking and then wean yourself off of all nicotine products. But for smokers who can't quit, the in vitro use of AM-1346 may significantly improve their fertilizing capacity." explained Lani Burkman, associate professor in the departments of gynecology/obstetrics and urology and head of the Section on Andrology in the University of Buffalo School of Medicine and Biomedical Sciences.

The sperm from male smokers exposed to a synthetic chemical called AM-1346 - a synthetic version of a natural cannabinoid found in the human body and cannabis - doubled its fertilizing capacity. The same team previously showed that fertilizing ability of the sperm is altered by nicotine, whether in vitro, or through long-term tobacco use.

In the new study, nine selected smokers were assessed for sperm fertilizing potential checking the binding ability on the outside cover of a human egg, "zona pellucida".

4 men had a high number of sperm attaching to the egg (normal fertilizing potential, Group I), while 5 other smokers had sperm with poor egg binding (poor fertilizing potential, Group II). The researchers sought how poor fertilizing capacity from smokers could be improved. They looked at the potential interaction between two chemical systems that control sperm. "Human sperm carry the cholinergic receptor, which responds to the neurotransmitter acetylcholine," explained Burkman. "Nicotine mimics acetylcholine and binds to the cholinergic receptor."

The second chemical system involves cannabinoid receptors, which respond to cannabis (like marijuana and hash), as well as natural cannabinoids from the body. "Research from other scientists indicates that the cholinergic system and the cannabinoid system naturally regulate human sperm and help prepare them for fertilizing an egg," she said. "This natural regulation is out of balance for the majority of smokers when sperm are continuously exposed to nicotine."

"We think there is an important communication between the cannabinoid and cholinergic receptor systems in human sperm," said Burkman. "In 22 Hemizona tests, we showed that the response to AM-1346 depended on the initial fertility of the tobacco smoker, and if his semen showed poor quality, meaning low sperm count and low percentage motility."

The sperm from Group II individuals was exposed to AM-1346 for several hours and then retested. In all cases resulted an increase of sperm binding to the egg varying from 133 % to 330 % (a 201 % mean). "In contrast," said Burkman, "samples from Group I (normal fertility, normal semen quality) reacted in the opposite manner. This two-way, or biphasic, response is common for cannabinoid action. With Group I, the drug AM-1346 caused a substantial decrease in sperm binding to the egg for eight out of nine samples.

"This opposite response must be studied further," Burkman said. "It might be tied to early-versus-late steps in fertilization, where it is expected that one process is slowed down while another process is stimulated."

"It does appear that sperm functioning in tobacco smokers with low fertility and low semen quality is quite different when compared to smokers with higher fertility and good semen quality. Nicotine appears to change the sperm membranes and sperm receptors. It also raises the question of why sperm from some smokers is protected from the effects of tobacco and nicotine."