Forgive SWIM if the purpose of this thread was not to get answers, but rather to show others what a GHB pharmacology thread should look like. In that case his post can be deleted.
1) How does GHB work?
Gamma hydroxybutyrate (GHB) is in fact a naturally occuring substances in cells throughout the human body and is, interestingly enough, also to be found in grape wines. Generally it is to be found and is used in the form of a salt (chemical formula: Na-GHB or K-GHB), and this salt is often mixed with water for use as a recreational substance (with effects rather like those of alchohol, but more on that later), as a sleep-aid, and as a supplement for bodybuilders.
GHB works by affecting the brain's regulation of dopamine levels. It is a central nervous system depressant, which is the reason for its alcohol like recreational effects and for its negative side effects (including, among others, slowed heart rate, slowed rate of breath, and loss of consciousness).
GHB is similar to the endogenous neurotransmitter gamma-amino butyric acid (GABA; pictured at the end of the paragraph). Thus it affects the same receptor in the brain (the GABA receptor) as that substance (of note: this receptor is also influence by alcohol, Valium, and other depressive substances [not to be confused with opiates]). The GABA receptor affects neuronal transmission by encouraging the neurons not to fire, thus depressing neuronal activity and overall brain activity.[FONT=Arial][SIZE=2]
2) What pharmacology does GHB have?
Originally Posted by BilZ0r of Erowid
γ-Hydroxybutyrate (GHB) is a central nervous system depressant. It has been used as an anxiolytic, anesthetic and sedative/hypnotic, inducing a sleep-like state in experimental animals in doses ranging from 0.1 to 1.5g/kg. GHB is also a putative neurotransmitter. Treatment with GHB has been shown to affect many neurotransmitter systems, most notably, dopamine, glutamate and acetylcholine. A number of early studies focused on GHB's action at dopaminergic synapses and showed that GHB initially inhibits dopamine release and then, time-dependently, causes its release. This effect has now been shown to be due to experimental errors, such as ignoring the effects of anesthetics, or having unusually high levels of Ca2+ in the growth medium.
The mechanism of how GHB effects the CNS has been unclear up until now. Resolving the mechanism of GHB's action has been complicated by the fact that GHB acts on both the GABA-B and the newly sequenced GHB receptor. The evidence that GHB affects the GABA-B receptor is threefold. On a behavioral level, antagonizing the GABA-B receptor stops the discriminative effects of GHB. On a cellular level, GHB causes a pronounced hyper-polarization of nerve cells and this effect is blocked by GABA-B antagonists but not by GHB receptor antagonists. Finally, on a molecular level GHB binds (although weakly, KD =100µM) to the GABA-B receptor.
The GHB receptor is a novel G-protein coupled receptor, which is widely distributed throughout the cortex and certain subcortical locations (most notably the hippocampus, amygdala, septum, basal ganglia and substantia nigra) (Hechler et al., 1992). Importantly, GHB exhibits an extremely high affinity for the GHB receptor. It is obvious that GHB receptors mediate some of GHB's action because cortical neurons which are normally activated by GHB revert to their normal activity levels when GHB is added, along with its selective receptor antagonist NCS-382. The recent development of truly selective GHB receptor agonists has allowed scientists to finally understand GHB's mechanism. At low doses, GHB is binding almost exclusively to the GHB receptor, a receptor which, through pathways not yet understood, stimulates the release of glutamate (the major excitatory neurotransmitter) in the cortex. As the dose of GHB increases, more and more GHB is binding to, and activating, the inhibitory GABA-B receptor. This leads to the sedative/hypnotic effect of GHB. The selective GHB receptor agonist t-HCA (fig 1) does not cause sedation of any kind, and is presumably a stimulant as it leads to seizures.
These findings explain many things about GHB research and the subjective experience brought on by GHB. For instance, the reason why some experiments would find the GABA-B receptor to be the main mediator of GHB's effects was because they used high doses, or were measuring effects produced by the GABA-B receptor. On the other hand, experimenters using lower doses or measuring cortical excitation found the GHB receptor to be the main mediator. This also explains why people who take GHB to sleep would wake up 2-3 hours after dosing. After the initial dosing, the GABA-B receptor was being stimulated, leading to sleep, but as the GHB was being metabolized and the concentration in the body dropped, the GABA-B receptor stopped being activated, and the excititory GHB receptor became the main receptor being activated.
Note that questions 3 and 4 ("How does it affect GABA?", and "What other receptors does it hit?") are addressed above.
3) Why or how does GHB have an aphrodisiac effect?
At this point there is little scientific evidence in regards to GHB having an actual chemically aphrodisiac effect. It is speculated that people believe in this effect due to the feelings of euphoria and relaxation that it can inspire.
Originally Posted by Erowid Vaults
A low dose of GHB (usually from .5 to 1.5 grams) often causes effects similar to those of 1-3 drinks of alcohol. Users can feel a mild relaxation, increased sociability, slightly decreased motor skills, sometimes mild dizziness, and other effects similar to mild alcohol intoxication. Even at low doses it is improper and dangerous for GHB users to drive or operate heavy machinery.
A medium dose of GHB (usually from 1 to 2.5 grams) increases the relaxing effects and the physical disequilibrium experienced. Some people report an increased appreciation for music, dancing, or talking. Many people report positive mood changes. Some slurring of speech, silliness, and slight incoherency are also common. Others report increased feelings of nausea and grogginess. Some users of GHB report pro-sexual effects: an increase in tactile sensitivity, relaxation, increased male erectile capacity, and heightened experience of orgasm. Some women report that GHB makes orgasms harder to achieve.
A heavy dose of GHB (from 2.5 + grams) can increase feelings of disequilibrium in many people to point of feeling quite ill. Many people accidentally move from Medium Dose to Over Dose, only passing through Heavy Dose for a few minutes. One reason that GHB has gained notoriety as a Club Drug is that some people experience extremely positive feelings on Heavy Doses of GHB. Reports of euphoria, feeling music deeply, joyous dancing, and other very positive effects are common among aficionados. People who report these effects also describe how difficult finding one's personal dose range can be to achieve these effects. An extra quarter (.25) gram can be the difference between euphoria and vomiting.
The Overdose range for GHB can be as little as 2 grams, based on body weight and individual sensitivity. One major problem with GHB as an underground recreational substance is that it has a sharp dose-response curve, which can be difficult to manage with the various non-standard preparations available to the uninformed buyer. Another major problem is that uninformed users often mix GHB with alcohol, which drastically increases the chance of vomiting and unconsciousness. An overdose can consist of mild to extreme nausea and dizziness, and vomiting. It can also be characterized by a strong drowsy feeling followed by an temporarily unrouseable sleep (sometimes characterized as a type of coma) for 1-4 hours. Some Overdoses of GHB mix vomiting with unconsciousness which is an extremely dangerous combination for obvious reasons. When using GHB (or any substance), it is important to remember to let someone who is with you know what you're doing, so if you experience Overdose effects, they can react appropriately and let any health professionals who become involved know what substance was involved.
We're defining a level dosage above Overdose in order to highlight the effects of extreme overdoses. While many Overdoses consist mainly of heavy sleep, some are life-threatening. GHB Poisonings are characterized by very low breathing, convulsions or twitching, vomiting, complete non-responsive even to 'deep pain', fixed pupils, etc. GHB poisoning victims should receive medical care immediately.
Some people feel drowsy, sleepy, or groggy after the effects wear off or the next day after ingestion. The hangover from low and medium doses of GHB is usually mild or non-existent, although some people report feeling slightly 'fuzzy headed' the next day. Some people also report feeling refreshed, happier, and more alert the day after use. For some people, using GHB more than once a week causes significantly increased negative after effects.
Last edited by MrG; 17-06-2010 at 08:42.
Reason: Dead attachment removal