Chemical structure of GHBGamma-hydroxybutyrate powder
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Gamma-hydroxybutyrate (4-hydroxybutanoic acid, C4H8O3) is both a drug and a naturally occurring compound found in the central nervous system as well as in other organs as liver, kidneys, heart and bones. GHB is structurally similar to the ketone body beta-hydroxybutyrate. As a drug it is used most commonly in the form of a chemical salt (Na-GHB or K-GHB). The sodium salt is commercially known as sodium oxybate. more...




The precise function of GHB in body is not clear. It is an immediate precursor to GABA, a neurotransmitter which regulates awakeness, physical activity and sleep. As GABA cannot cross blood-brain barrier, GHB obtained from food may be used for converting to GABA. GHB prevents cells from oxygen starvation, which might explain presence of the compound in vital organs. GHB was also found to have neuroprotective capabilities.


It has been used as a general anesthetic, and a hypnotic in the treatment of insomnia. GHB has also been used to treat clinical depression, and improve athletic performance. In the United States, the Food and Drug Administration permits the use of GHB under the trade name Xyrem to reduce the number of cataplexy attacks in patients with narcolepsy.


GHB is an intoxicant. It may be known as G, Liquid X, Liquid E. It is less commonly known as GBH, Gamma-oh, Georgia Homeboy, Blue Verve, Gamma-G, Qi, scoop, goop, Grievous Bodily Harm, or Get Hospitalised Bitch.

Its potential for use as a date rape drug in the 1990s led to it being placed in the US on Schedule I of the Controlled Substances Act in March, 2000. On March 20, 2001, the Commission on Narcotic Drugs placed GHB in Schedule IV of the 1971 Convention on Psychotropic Substances. In the UK it was made a class C drug in June 2003.

The sodium salt of GHB has a thin, very salty, chemical taste. At low doses, GHB can cause a state of euphoria, increased sociality and intoxication. This kind of use is particularly common at rave parties. At higher doses, GHB may induce nausea, dizziness, drowsiness, visual disturbances, depressed breathing, amnesia and unconsciousness. The effects of GHB can last from 1.5 to 3 hours.

Some chemicals convert to GHB in the stomach and blood. GBL, or gamma-butyrolactone, is one such precursor. It is 1,6 times more potent than GHB, so 1ml of GBL is equivalent to 0,4g of GHB. GBL has also a shorter onset and is longer acting than GHB. GBL has an extremely bad taste and is also known to irritate innards and skin.

Other precursors include 1,4-butanediol. There may be additional toxicity concerns with these precursors.

Mode of action

The action of GHB has yet to be fully elucidated. GHB clearly has at least two sites of action, stimulating the newly characterized and aptly named "GHB receptor" as well as the GABAB. GHB, if it is indeed a neurotransmitter, will only reach concentrations high enough to act at the GHB receptor, as it only has weak affinity fo the GABAB. However, during recreational usage, GHB can reach very high concentrations in the brain, relative to basal levels, and can act at the GABAB receptor . GHBs action at the GABAB is probably responsible for its sedative effects. GHB-mediated GABAB receptor stimulation inhibits dopamine release as well as causes the release of natural sedative neurosteroids (like all other GABAB agonists e.g. Baclofen). In animals GHBs sedative effects can be stopped by GABAB antagonists (blockers).


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Xyrem approved for muscle problems in narcolepsy - Updates
From FDA Consumer, 9/1/02

The FDA recently approved Xyrem (sodium oxybate or gamma hydroxybutyrate, also known as GHB) for treating a small population of people with narcolepsy who experience episodes of cataplexy--weak or paralyzed muscles. Because of safety concerns associated with the use of the drug, the distribution of Xyrem will be tightly controlled.

In the early 1990s, GHB was marketed purporting to be a dietary supplement for enhancing athletic performance and sexual activity and for inducing sleep. It was also abused as a recreational drug and is well-known for use in date rape. As a result of a number of serious adverse events, including death, the FDA intervened to prohibit the marketing of GHB.

Xyrem has been designated as a Schedule III controlled substance for medical use, meaning it cannot be sold, distributed, or provided to anyone other than for its prescribed use. Illicit use of Xyrem will be subject to penalties under Schedule I, the most restrictive schedule of the Controlled Substances Act.

The FDA approved Xyrem based on the results of two controlled clinical trials that showed that use of the drug reduced the number of cataplectic attacks compared to a placebo. Side effects associated with Xyrem include confusion, depression, nausea, vomiting, dizziness, headache, bedwetting, and sleepwalking. Abuse of Xyrem could also lead to dependence and severe withdrawal symptoms.

Narcolepsy affects about 120,000 people in the United States. This rare condition causes an irresistible tendency to fall asleep even in unlikely circumstances, such as in the middle of a conversation. Cataplexy, a symptom of this condition, is a sudden loss of muscular control and weakness usually triggered by emotions such as amusement, anger or excitement, and is estimated to affect about 20,000 to 50,000 individuals. The effects of cataplexy range from dropping of the jaw and slumping of the head, to buckling of the legs and even collapse of the whole body. These effects can last for a few seconds or up to many minutes.

Due to serious concerns and adverse events associated with the use of Xyrem, including some events that resulted in death, the FDA worked with the drug's manufacturer, Orphan Medical Inc., to design a comprehensive risk-management program. The program includes limited distribution, physician education, patient education, the creation of a patient and physician registry, and detailed patient surveillance. Under the program, prescribers and patients will be able to obtain the product only through a single centralized pharmacy. A Medication Guide, a special patient information brochure required by the FDA, further advises patients about proper use, administration and disposal of the drug. People who have further questions are advised to talk to their doctors or to call the central pharmacy at the toll-free number 1-877-67-XYREM (1-877-679-9736).

Xyrem is approved with orphan drug status, which is available for products to treat patient populations of 200,000 or fewer.

Orphan Medical Inc. of Minnetonka, Minn., will distribute the drug. Further information on Xyrem can be found at cder/drug/infopage/xyrem/ xyrem_qa.htm.

COPYRIGHT 2002 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group

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