Gamma-Hydroxybutyric acid


 * GHB redirects here. See also Great Highland Bagpipe.

 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.

Endogenous
The precise function of GHB in the 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.

Medical
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. In Italy, under the trade name Alcover, GHB is used in the treatment of alcoholism (50 to 100 milligrams per kilogram per day, in 3 or more divided doses), both for acute alcohol withdrawal and medium to long term detoxification.

Recreational


GHB is an intoxicant. It may be known as G, Liquid X, Liquid E. It is less commonly known as GHB, Gamma-oh, Georgia Homeboy, Georgia Hillbilly, Blue Verve, Gamma-G, Qi, scoop, or goop.

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 less 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).

The relevance of the GHB receptor in the behavioural effects induced by GHB is more controversial. It seems hard to believe that the GHB receptor is not important when it is densely expressed in many areas of the brain, including the cortex, as well as it being the high affinity site of GHB action. There is limited research into GHB receptor however evidence shows that it causes the release of glutamate which should be stimulatory. It does not seem, however, that the GHB receptor explains either GHB's sedative or rewarding/addictive properties.

One can propose a scheme where high doses of GHB are sedative through its action at the GABAB receptor, while a lower dose is somehow stimulatory. This may explain the so-called "rebound" effect, experienced by individuals using GHB as a sleeping agent, where they awake after several hours of GHB-induced sleep. That is to say, that over time, the concentration of GHB in the system decreases (because of metabolism) below a threshold for stimulating GABAB receptor function, and simply stimulates the GHB receptor, leading to wakefulness.

Dangers
The dose-response curve is very steep and as GHB often comes as a salt dissolved in water, actual amount of GHB per "capful" can vary, which makes proper dosing difficult. While small doses of GHB are considered to be safe, higher and ultra high doses can cause unconsciousness, convulsions, vomiting, suppression of the gag reflex and breathing, and death. These effects vary between persons and are dose dependent. Synergy of its sedative effects are seen when combined with other CNS depressants such as alcohol, benzodiazepines (e.g. Valium), barbiturates, and others. Deaths from GHB alone are either extremely rare or non-existent. Death while using GHB is most likely in combination with alcohol as a result of choking on vomit and asphyxiating. Death might also be possible from respiratory depression as high doses of GHB could eventually inhibit the breathing centers in the brainstem. However, it has been argued that it is extremely difficult to take a lethal dose of GHB, as a user would fall unconscious long before the lethal dose is reached. LD50 of GHB is estimated to be between 1100mg/kg and 2000mg/kg in rodents, and is almost certainly lower in humans.

There have been no long-term studies into the effect of GHB if taken chronically, and hence the question as to whether prolonged use of GHB causes any bodily harm (aside from addiction) remains unanswered.

Addiction
GHB is physically addictive and may also result in psychological addiction. Physical dependence develops when GHB is taken on a regular basis (i.e. every 2-4 hours for multiple consecutive days or weeks). Withdrawal effects may include hallucinations, 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. Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed. Unlike alcohol, it is unknown at this point if chronic use of GHB causes permanent damage to the body. However, clinical tests showed that there was no organ or brain damage in rats that were chronically administrated with GHB.

History
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 depressants.

Typically GHB has been synthesized from GBL (Gamma-butyrolactone) by adding sodium hydroxide (lye) in ethanol or water. As of late, GBL has become controlled and more circuitous routes have to be taken such as those starting with THF (tetrahydrofuran).

External references

 * streetdrugs.com
 * Erowid GHB Vault (contains also information about addiction and dangers)
 * InfoFacts - Rohypnol and GHB (National Institute on Drug Abuse)
 * Gamma Hydroxybutyrate (GHB) Fact Sheet
 * GHB alternatives

4-Hydroxybutansäure Acide gamma-hydroxybutyrique GHB GHB Gammahydroxybutyraat GHB GHB GHB