Further Exploration of Date-Rape Drug GHB

The naturally occurring brain chemical 4-hydroxybutyrate (4-HB), also called gamma hydroxybutyrate or GHB, can be abused or used as a date-rape drug when taken by mouth. A team of Ohio and Michigan scientists have determined new routes by which 4-HB is metabolized by the body.

"This is new and important information," said K. Michael Gibson, professor and chair of biological sciences at Michigan Technological University and a member of the research team. "It may provide new clues on how to counteract the drug’s effects, or to enhance its metabolism and decrease toxicity for chronic abusers or victims of sexual assault."

Gibson co-wrote the paper with Guo-Fang Zhang and others in the laboratory of Prof. Henri Brunengraber from the Department of Nutrition at Case Western Reserve University School of Medicine. The study was published online by the Journal of Biological Chemistry, and their findings will appear in the print edition on Nov. 27, 2009.

4-HB is a derivative of a major brain neurotransmitter in humans and other species. It occurs naturally in small amounts in the brains of most animals and humans. In a rare genetic metabolic disorder, 4-HB accumulates in extremely high levels, causing significant developmental delays and seizures.

But 4-HB is best known and most feared when it is taken orally, because it impairs the capacity to exercise judgment, like rohypnol and ketamine hydrochloride. For that reason, it can be used as a date-rape drug.

Analyzing the chemicals produced by the breakdown of 4-HB in mice and rats, Zhang, Gibson, and colleagues used very sophisticated mass spectrometry approaches to identify previously unknown enzymes and pathways that appear to act on 4-HB and other similarly structured compounds. They discovered that 4-HB is metabolized by two different chemical mechanisms or pathways. Their discovery of those pathways should open the door for future studies that can identify the enzymes involved in the following steps of the breakdown of 4-HB.

"This work may help to develop new antidotes and treatments for people who have ingested 4-HB, as well as treatment for children with the rare genetic disorder that causes the compound to accumulate in high levels," Gibson said.