|
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.
Uses
Medical
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.
Recreational
Gamma-hydroxybutyrate powder
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 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[1]. 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 [2].
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
The action of GHB has yet to be fully elucidated. GHB clearly has at least two sites of action, stimulating the newly charachterized 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 it's 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 controvertial. It seems hard to believe that the GHB receptor is not important when it is densly 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 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 doses 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 threashold for stimulating GABAB receptor function, and simpley stimulates the GHB receptor, leading to wakefulness.
Dangers
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. Synergy of its sedative effects are seen when combined with other CNS depressants such as alcohol, benzodiazepines (valium), barbiturates, and others. Deaths from GHB alone and in combination have been reported. Death occurs mainly by suffocation as high doses of GHB will eventually inhibit the breathing centers in the brain.
Addiction
GHB has a relatively high addiction potential comparable to alcohol. Severe withdrawal effects are seen after taking GHB on a regular basis (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.
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 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).
External references
|
