Gamma-hydroxybutyrate (4-hydroxybutanoic acid, C4H8O3) is both a drug and a naturally occurring compound found in the mammalian brain, where it might function as a neurotransmitter. 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. It temporarily inhibits dopamine release in the brain and is said to stimulate pituitary growth hormone (GH) release, although this effect is mainly believed to be caused by a prolonged deep sleep that occurs when high doses of GHB are consumed.
Structural formula of gamma-hydroxybutyrate
It has been used as a general anesthetic and as a hypnotic in the treatment of insomnia. 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 Home Boy, Blue Verve, or Grievous Bodily Harm.
Its purported 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 and/or drunkenness. This kind of use is particularly common at rave parties. At higher doses, GHB may induce nausea, dizziness, drowsiness, visual disturbances, depressed breathing, amnesia, unconsciousness. These effects last for 3-6 hours.
The Australian practice of putting ice cubes into the rectum of GHB users who have fallen unconscious has no medical benefits .
Some chemicals convert to GHB in the stomach. GBL, or gamma-butyrolactone, is one such precursor. It is more potent per fluid ounce, but the effects are delayed about 20 minutes while conversion takes place. Because of the delay, there is additional risk of overdose, as users might ingest more before the first dose takes effect. GBL has a slightly oily consistency and does not taste salty.
Other precursors include 1,4-Butanediol. There may be additional toxicity concerns with these precursors.
Mode of Action
In the brain two receptors have been identified that seem to mediate the action of GHB. One is the GHB receptor which might be responsible for the physiological and some of the pharmacological effects of GHB, and the second receptor is the GABAB which might be responsible, in part, for some of the pharmacological actions of GHB. Both types of receptor are linked to intracellular G proteins which are involved in signal transduction.
The dose-response curve is very steep, and the recreationally meted-out "capfuls" are very imprecise, making proper dosing difficult. GHB can cause unconsciousness, convulsions, vomiting, and suppression of the gag reflex and of breathing. These effects may vary between persons and are dose dependent. Combination with alcohol, benzodiazepines (valium), barbiturates, and other CNS depressants is extremely dangerous because their actions are multiplied. Deaths from GHB alone and in combination have been reported.
GHB has a relatively high addiction potential comparable to alcohol. Severe withdrawal effects are seen after taking GHB on a regular base (e.g. every 4 hours for multiple consecutive days), including insomnia, anxiety, tremors, sweating, edginess, chest pain and tightness, muscle and bone aches, sensitivity to external stimuli (sound, light, touch), dysphoria, and mental dullness. These side effects will subside after 2 - 21 days depending on usage. It is possible to minimize these side effects by tapering off the drug instead of quitting abruptly.
GHB was first synthesized in the early 1960s by Dr. Henri Laborit to use in studying the neurotransmitter GABA. It quickly found a wide range of uses due to its minimal side effects and controlled action, the only difficulties being the narrow safe dosage range and the dangers presented by its combination with alcohol and other CNS depressents.
Typically GHB has been synthesized from GBL (gamma-butrylactone) by adding sodium hydroxide (lye) in ethanol or water. As of late, GBL has become controlled and more circtuitous routes have to be taken such as those starting with THF (tetrahydrofuran).