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GHB: Difference between revisions
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GHB as the sodium salt, known by the trade name Xyrem,<ref>http://www.reuters.com/finance/stocks/companyProfile?rpc=66&symbol=JAZZ.O</ref> is a prescription sleep-aid which is used to treat various medical conditions such as cataplexy<ref>Sodium Oxybate | http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605032.html</ref> and excessive daytime sleepiness in patients with narcolepsy.<ref>United States Patent | Patent Number: US4738985 | Pharmaceutical composition and treatment of narcolepsy (Erowid) | https://www.erowid.org/chemicals/ghb/ghb_patent2.shtml</ref> It has also been used in a medical setting as a general anesthetic to treat conditions such as insomnia, clinical depression, and alcoholism,<ref>United States Patent | Patent Number: US4983632 | Use of Gamma-Hydroxybutyric Acid Salts for Preparing Pharmaceutical Compositions for Use in the Treatment of Alcoholism, and the Compositions Obtained (Erowid) | https://www.erowid.org/chemicals/ghb/ghb_patent.shtml</ref> and to improve athletic performance. | GHB as the sodium salt, known by the trade name Xyrem,<ref>http://www.reuters.com/finance/stocks/companyProfile?rpc=66&symbol=JAZZ.O</ref> is a prescription sleep-aid which is used to treat various medical conditions such as cataplexy<ref>Sodium Oxybate | http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605032.html</ref> and excessive daytime sleepiness in patients with narcolepsy.<ref>United States Patent | Patent Number: US4738985 | Pharmaceutical composition and treatment of narcolepsy (Erowid) | https://www.erowid.org/chemicals/ghb/ghb_patent2.shtml</ref> It has also been used in a medical setting as a general anesthetic to treat conditions such as insomnia, clinical depression, and alcoholism,<ref>United States Patent | Patent Number: US4983632 | Use of Gamma-Hydroxybutyric Acid Salts for Preparing Pharmaceutical Compositions for Use in the Treatment of Alcoholism, and the Compositions Obtained (Erowid) | https://www.erowid.org/chemicals/ghb/ghb_patent.shtml</ref> and to improve athletic performance. | ||
It is used as a recreational | It is used as a recreational substance for its [[chemical class::alcohol]]-like effects. While a common recreational dose is 3g, a dose of 5g - 10g can result in convulsions, unconsciousness (a coma-like state) and vomiting. Doses above 10g+ are associated with a risk of death.<ref name="cite">GHB Dosage by Erowid | https://www.erowid.org/chemicals/ghb/ghb_dose.shtml</ref> It is important to start with a low dose and work your way up slowly by increasing the dosage in small increments. | ||
GHB, and sometimes [[GBL]] are also commonly used as [[date rape drug]]s, in which they are secretly put dropwise into drinks. They are also referred to as "'''K.-o.-Tropfen'''" (K.-o.-drops) in German-speaking countries. Care should be taken when offered drinks from strangers. | GHB, and sometimes [[GBL]] are also commonly used as [[date rape drug]]s, in which they are secretly put dropwise into drinks. They are also referred to as "'''K.-o.-Tropfen'''" (K.-o.-drops) in German-speaking countries. Care should be taken when offered drinks from strangers. | ||
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==Pharmacology== | ==Pharmacology== | ||
GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0149763489800533</ref> in the central nervous system. GHB is an [[agonist]] at the newly characterized GHB receptor, which is excitatory.<ref>γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a | GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0149763489800533</ref> in the central nervous system. GHB is an [[agonist]] at the newly characterized GHB receptor, which is excitatory.<ref>γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a substance and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> It is also a weak [[agonist]] at the [[GABA]]<sub>B</sub> receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a substance and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> | ||
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 [[Serotonin|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. | 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 [[Serotonin|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. | ||
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==Toxicity and harm potential== | ==Toxicity and harm potential== | ||
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of GHB<ref>Development of a rational scale to assess the harm of substances of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]] | [[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of GHB<ref>Development of a rational scale to assess the harm of substances of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]] | ||
GHB is [[toxicity::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 | GHB is [[toxicity::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 substance 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.<ref>https://www.erowid.org/experiences/exp.php?ID=1926 | Erowid. "GHB Overdoses & Poisonings: An Experience with GHB (ID 1926)". Erowid.org. Jun 19, 2000. erowid.org/exp/1926 </ref> | ||
One publication has investigated 226 deaths attributed to GHB.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20825811 | Zvosec DL, Smith SW, Porrata T, Strobl AQ, Dyer JE (2011). "Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma". The American Journal of Emergency Medicine 29 (3): 319–32.</ref> 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. | One publication has investigated 226 deaths attributed to GHB.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20825811 | Zvosec DL, Smith SW, Porrata T, Strobl AQ, Dyer JE (2011). "Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma". The American Journal of Emergency Medicine 29 (3): 319–32.</ref> 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. | ||
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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.<ref> Psychotherapeutic Drugs. 1340-1375. Bibliographic information missing.</ref> 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.<ref>Ferrara, SD. Zotti, S. Tedeschi, L. Frison, G. Palatini, P. et al.. "Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent. . .". British Journal of Clinical Pharmacology. 1992. 34. 231-235. R 31 B 93. . </ref> In one European study, no adverse effects were reported after several years of regular recreational use.<ref>Laborit H . "Correlations between protein and serotonin synthesis during various activities of the central nervous system (slow and desynchronized sleep, learning and memory, sexual activity, morphine tolerance, aggressiveness, and pharmacological action of sodium ga. RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY. 1972. 3(1). </ref> | 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.<ref> Psychotherapeutic Drugs. 1340-1375. Bibliographic information missing.</ref> 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.<ref>Ferrara, SD. Zotti, S. Tedeschi, L. Frison, G. Palatini, P. et al.. "Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent. . .". British Journal of Clinical Pharmacology. 1992. 34. 231-235. R 31 B 93. . </ref> In one European study, no adverse effects were reported after several years of regular recreational use.<ref>Laborit H . "Correlations between protein and serotonin synthesis during various activities of the central nervous system (slow and desynchronized sleep, learning and memory, sexual activity, morphine tolerance, aggressiveness, and pharmacological action of sodium ga. RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY. 1972. 3(1). </ref> | ||
It is strongly recommended that one use [[responsible | It is strongly recommended that one use [[responsible substance use|harm reduction practices]] when using this drug. | ||
===Neurotoxicity=== | ===Neurotoxicity=== | ||
In multiple studies, GHB has been found to impair spatial memory, working memory, learning and memory in rats with chronic administration.<ref>Adolescent γ-hydroxybutyric acid exposure decreases cortical N-methyl-d-aspartate receptor and impairs spatial learning (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S009130570400320X</ref><ref>Effects of subchronic administration of gammahydroxybutyrate (GHB) on spatial working memory in rats (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17296081</ref><ref>γ-Hydroxybutyric Acid–Induced Cognitive Deficits in the Female Adolescent Rat | http://onlinelibrary.wiley.com/doi/10.1196/annals.1432.044/abstract</ref><ref>Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats | http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=6137924</ref> These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.<ref>https://www.ncbi.nlm.nih.gov/pubmed/15582677 (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/15582677</ref> | In multiple studies, GHB has been found to impair spatial memory, working memory, learning and memory in rats with chronic administration.<ref>Adolescent γ-hydroxybutyric acid exposure decreases cortical N-methyl-d-aspartate receptor and impairs spatial learning (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S009130570400320X</ref><ref>Effects of subchronic administration of gammahydroxybutyrate (GHB) on spatial working memory in rats (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17296081</ref><ref>γ-Hydroxybutyric Acid–Induced Cognitive Deficits in the Female Adolescent Rat | http://onlinelibrary.wiley.com/doi/10.1196/annals.1432.044/abstract</ref><ref>Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats | http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=6137924</ref> These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.<ref>https://www.ncbi.nlm.nih.gov/pubmed/15582677 (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/15582677</ref> | ||
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===Tolerance and addiction potential=== | ===Tolerance and addiction potential=== | ||
[[File:GHBwithdrawal2.png|350px|thumbnail|right|This table compares the withdrawal symptoms of GHB, [[benzodiazepines]], and [[alcohol]].<ref name="GHB">GHB Withdrawal Syndrome | Texas Commission on Alcohol and Drug Abuse | https://www.erowid.org/chemicals/ghb/ghb_addiction2.pdf</ref>]] | [[File:GHBwithdrawal2.png|350px|thumbnail|right|This table compares the withdrawal symptoms of GHB, [[benzodiazepines]], and [[alcohol]].<ref name="GHB">GHB Withdrawal Syndrome | Texas Commission on Alcohol and Drug Abuse | https://www.erowid.org/chemicals/ghb/ghb_addiction2.pdf</ref>]] | ||
GHB is [[Addiction potential::moderately physically and psychologically addictive]]. The frequent use of GHB can cause withdrawal symptoms similar to those caused by other [[depressants]] such as [[alcohol]] and [[benzodiazepines]] if abruptly discontinued.<ref>Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759403/</ref><ref>Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/</ref> These symptoms seem to depend on the dosage and the length of time the | GHB is [[Addiction potential::moderately physically and psychologically addictive]]. The frequent use of GHB can cause withdrawal symptoms similar to those caused by other [[depressants]] such as [[alcohol]] and [[benzodiazepines]] if abruptly discontinued.<ref>Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759403/</ref><ref>Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/</ref> These symptoms seem to depend on the dosage and the length of time the substance was used for. Light to moderate users often experience anxiety, insomnia, sleep-related problems, and tremors whereas heavy use can cause severe withdrawal symptoms like delirium, psychosis, and hallucinations.<ref>https://www.ncbi.nlm.nih.gov/pubmed/11174231 | Gamma-hydroxybutyrate withdrawal syndrome.</ref><ref name="GHB"></ref> | ||
Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed.<ref>Gamma-hydroxybutyrate: an emerging | Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed.<ref>Gamma-hydroxybutyrate: an emerging substance of abuse that causes physical dependence | http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.1997.tb03640.x/abstract</ref> | ||
Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within several weeks of continuous use]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::7 - 14 days]]. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. | Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within several weeks of continuous use]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::7 - 14 days]]. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. | ||
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==Legal issues== | ==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.<ref>http://web.archive.org/web/20100116121252/http://www.projectghb.org/laws.htm</ref> It is one of several substances that are listed in multiple schedules. | *'''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.<ref>http://web.archive.org/web/20100116121252/http://www.projectghb.org/laws.htm</ref> It is one of several substances that are listed in multiple schedules. | ||
*'''UK:''' GHB was made a Class C | *'''UK:''' GHB was made a Class C substance in June 2003. | ||
*'''Hong Kong:''' GHB is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. | *'''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. | *'''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. | *'''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 | *'''Chile:''' GHB is a controlled substance 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. | *'''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. | *'''Switzerland:''' GHB is considered a narcotic and is only available by prescription under the trade name Xyrem. | ||