GHB: Best medication to treat severe sleep disorder

Ticku
Ticku

Three Health Science Center researchers, their laboratory teams and a University of Maryland collaborator are hard at work sniffing out the clues of the effects of the drug GHB. A naturally occurring substance in our brains that people learned to make outside the body, GHB found its way into modern culture as a recreationally abused drug and as the “date-rape drug” used by sexual predators to sedate unsuspecting young women.

However, this drug in the form of medication is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, a neurological disorder characterized by fragmented sleep and daytime sleepiness. GHB normalizes sleep patterns of narcoleptics and even is used in Europe to treat alcohol dependence.

“Where this study could lead down the road is to the development of GHB-selective antidotes to help those who show up in emergency rooms with GHB overdose, either from abuse or date-rape victimization,” says Charles P. France, Ph.D., professor of pharmacology at the Health Science Center and the project co-leader with Maharaj K. Ticku, Ph.D., professor of pharmacology.

Because it rapidly clears the body, GHB is difficult to detect. “Six to eight hours after exposure, you can only find small traces, if any,” Dr. Ticku says.

GHB is a “neurotransmitter” – a courier that relays information between nerve cells. Continuous, efficient transfer of countless bits of information is essential for healthy brain function. GHB in the brain is converted into another neurotransmitter, GABA, which is the main inhibitory neurotransmitter in the body. GABA decreases activity of a third neurotransmitter, glutamate, which is the main excitatory neurotransmitter in the body. “It’s a finely tuned system,” comments GHB project contributor Wouter Koek, Ph.D., associate professor of psychiatry at the Health Science Center and holder of the START Center Medication Research Professorship.

The Health Science Center researchers contracted with Andrew Coop, Ph.D., of the University of Maryland, Baltimore, to make GHB look-alikes that no longer interact with GABA receptors and therefore are not converted to GABA. “These are chemical tools for teasing out the role of GHB,” Dr. Koek says. Dr. Ticku says Dr. Coop’s contribution is vital because no such tools exist to study the pharmacology of GHB.

Although dangerous when it is abused, GHB is the best – and currently only – FDA-approved medication to treat narcolepsy. “It normalizes sleep patterns, which is a quirky thing about GHB,” Dr. France says. Whereas sedative drugs interfere with the most restful phase of sleep, called REM or rapid eye movement, GHB increases it.

“Learning more about how GHB works could help us learn how to even more efficiently induce beneficial sleep,” Dr. Koek says. And with the problem of GHB abuse and GHB-related crime, learning how this neurotransmitter relays information among the brain’s nerve cells could save lives in hospital emergency rooms. “There are so many mechanisms with which it interacts,” Dr. Ticku says. “These are targets of future research.”

This interdisciplinary project, which extends from test-tube studies to observation of effects of GHB in rats, mice and pigeons, is funded by a $3 million grant from the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).



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