GHB

There is a high incidence of death due to respiratory depression when GABAergic substances are combined with depressants such as opiates, benzodiazepines or alcohol.

GHB
The skeletal formula of GHB
Chemical Nomenclature
Common names	GHB
Substitutive name	γ-Hydroxybutyric acid
Systematic name	4-Hydroxybutanoic acid
Class Membership
Psychoactive class	Depressant
Chemical class	GABAergic
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. It is important to increase the dosage in small increments and work your way up slowly. A dose of 4g or higher can result in convulsions, unconsciousness and vomiting while 10g+ can be fatal. Light 0.5 - 1.5 g Common 1 - 2.5 g Strong 2 - 4 g Duration Total 1.5 - 2.5 hours Onset 10 - 30 minutes Peak 45 - 90 minutes Offset 15 - 30 minutes Afterglow 2 - 4 hours

Summary sheet: GHB

GHB, also known as γ-Hydroxybutyric acid and 4-hydroxybutanoic acid, is a naturally occurring substance with depressant effects which is found in the human central nervous system as well as in wine, beef, small citrus fruits, and in small amounts in almost all animals.

GHB as the sodium salt, known as sodium oxybate (INN) or by the trade name Xyrem, is used to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy. It has also been used in a medical setting as a general anesthetic; to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism; and to improve athletic performance. It is also used as an intoxicant (illegally in many jurisdictions) or as a date rape drug.

GHB is naturally produced in the human body's cells. As a supplement or drug, it is used most commonly in the form of a salt. GHB is also produced as a result of fermentation, and so is found in small quantities in some beers and wines. Succinic semialdehyde dehydrogenase deficiency is a disease that causes GHB to accumulate in the blood.

Chemistry

GHB, or gamma-Hydroxybutanoic acid, is a carboxylic acid substituted with an additional hydroxy group. GHB contains a four carbon chain with a terminal carbon bonded to a hydroxy group (OH-) and double bonded to an oxygen group to form a carboxyl unit; this is butanoic acid. At the other end of the four carbon change at R_γ, GHB is substituted with a hydroxy group.

Pharmacology

GHB has at least two distinct binding sites in the central nervous system. GHB is an agonist at the newly characterized GHB receptor, which is excitatory, and it is a weak agonist at the GABA_B receptor, which is inhibitory.

GHB induces the accumulation of either a derivative of tryptophan or tryptophan itself, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to this increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates GABA_B receptors, which are primarily responsible for its sedative effects. GHB's sedative effects are blocked by GABA_B antagonists.

There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter. Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and GABA_B agonists.

Activation of both the GHB receptor and GABA_B is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic. This means that while low concentrations stimulate dopamine release via the GHB receptor, higher concentrations inhibit dopamine release via GABA_B receptors. After an initial phase of inhibition, dopamine release is then increased via the GHB receptor.

This explains the paradoxical mix of sedative and stimulatory properties of GHB as well as the so-called "rebound" effect experienced by individuals using GHB as a sleeping agent wherein they awake suddenly after several hours of GHB-induced deep sleep. Over time, the concentration of GHB in the system decreases below the threshold for significant GABA_B receptor activation and activates predominantly the GHB receptor, leading to wakefulness.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

The physical effects of GHB can be broken down into several components which progressively intensify proportional to dosage.

The most prominent of these cognitive effects generally include:

• Stimulation and Sedation - At lower doses, GHB is physically stimulating, encouraging movement and wakefulness. At higher doses, however, it becomes physically sedating, encouraging sleep and lethargy.
• Respiratory depression - In cases of GHB overdoses, many reportedly experience an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing followed by a gradual decrease that results in a temporary stop in breathing called an apnea.
• Euphoria
• Nausea
• Motor control loss
• Dizziness
• Dehydration

Cognitive effects

The cognitive effects of GHB can be broken down into several components which progressively intensify proportional to dosage.

These are described below and generally include:

• Empathy, love and sociability enhancement - Unlike alcohol which merely increases sociability through disinhibition, GHB presents strong entactogenic effects which, although weaker than that of MDMA, are still prominent and well defined.
• Disinhibition
• Information processing suppression
• Thought deceleration
• Amnesia
• Euphoria
• Anxiety suppression

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of GHB

GHB is considered to be a safe and non-toxic substance when used responsibly or medically. The LD50 is above the active dosage, and there is no danger of acute toxicity. However, it can be dangerous when used as a recreational drug or abused. There have been many negative reports from recreational users who have overdosed, combined GHB with alcohol or other drugs, or accidentally dosed themselves unexpectedly.

One publication has investigated 226 deaths attributed to GHB. Seventy-one deaths (34%) were caused by GHB alone while the other deaths were from respiratory depression caused by interaction with alcohol or other drugs.

To avoid a possible overdose of GHB, it is important to start with a low dose and work your way up slowly by increasing the dosage in small increments. While a common recreational dose is 3g, a dose of 5g - 10g can result in convulsions, unconsciousness and vomiting. Doses above 10g+ have been known to cause death. One must also factor in the added difficulty of knowing the purity of the product (among other problems like its hygroscopy may lower the concentration of GHB in one solution, which is the form which is commonly bought and sold in the illicit market). This makes it hard for even the experienced user to dose properly.

Accidental ingestions of GHB have also occurred due to inadequate storage methods. If GHB is put into a clear liquid, glass, or bottle, it can be easily mistaken for water. It is recommended to clearly label your GHB in writing and dye the liquid with blue food coloring so it no longer resembles a drinkable beverage. It is also recommended to store your GHB in a container that no one would drink out of.

As an endogenous regulator of energy metabolism and a natural neurotransmitter, GHB is well-known to the brain and organs which are used to its effects and have highly efficient systems for metabolizing it safely. The substance is eliminated (that is, back to baseline levels) in 2-4 hours and continues to be so even after twice-daily doses for a week. In one European study, no adverse effects were reported after several years of regular recreational use.

Neurotoxicity

In multiple studies, GHB has been found to impair spatial memory, working memory, learning and memory in rats with chronic administration. These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.

One study found that repeated administration of GHB to rats for 15 days drastically reduced the number of neurons and non-neuronal cells within the hippocampus and in the prefrontal cortex. With doses of 10 mg/kg of GHB, they were decreased by 61% in the hippocampus region and 32% in the prefrontal cortex, and with 100 mg/kg, they were decreased by 38% and 9%, respectively. This paper demonstrates contradicting effects on neuronal loss, with lower doses (10 mg/kg) producing the most neurotoxicity, and higher doses (100 mg/kg) producing less.

Tolerance and addiction potential

GHB is not thought to be habit forming although it is entirely possible for one to develop a psychological dependence. There does not appear to be a particularly powerful tolerance with GHB and because of this one rarely needs to increase the amount much beyond their start dosage unless using on an extremely regular basis.

Rats forced to consume massive doses of GHB will intermittently prefer GHB solution to water but, after experiments on rats, it was noted that "no rat showed any sign of withdrawal when GHB was finally removed at the end of the 20-week period" or during periods of voluntary abstinence. Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed.

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

• Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, benzodiazepines, GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. A review of the details of 194 deaths attributed to or related to GHB over a ten-year period found that most were from respiratory depression caused by interaction with alcohol or other drugs. In humans, GHB has been shown to inhibit the elimination rate of alcohol. This may explain the respiratory arrest that has been reported after ingestion of both drugs. These substances also potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Stimulants - It is dangerous to combine GHB, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of GHB, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of GHB will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of GHB per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.

Legal issues

• USA: GHB was placed on Schedule I of the Controlled Substances Act in March 2000. However, when sold as sodium oxybate, it is considered a Schedule III substance but with Schedule I trafficking penalties, one of several drugs that are listed in multiple schedules.
• UK: GHB was made a Class C drug in June 2003.
• Hong Kong: GHB is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.
• New Zealand: GHB, 1,4-B and GBL are all Class B illegal drugs, along with any possible esters, ethers and aldehydes.
• Australia: GHB, 1,4-B and GBL are all Class B illegal drugs, along with any possible esters, ethers and aldehydes.
• Chile: GHB is a controlled drug under the law "Ley de substancias psicotropicas y estupefacientes" (psychotropic substances and narcotics).
• Norway: GHB is considered a narcotic and is only available by prescription under the trade name Xyrem.
• Switzerland: GHB is considered a narcotic and is only available by prescription under the trade name Xyrem.

See also

• Responsible use
• Depressants
• Alcohol
• GHB (Wikipedia)
• GHB (Erowid)

References

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