PsychonautWiki Archive

GHB: Difference between revisions

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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.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]<sub>B</sub> agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>
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.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]<sub>B</sub> agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>


Activation of both the GHB receptor and [[GABA]]<sub>B</sub> is responsible for the addictive profile of GHB. GHB's effect on [[dopamine]] release is biphasic.<ref>Drosophila [[GABA]]<sub>B</sub> receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> This means that while low concentrations stimulate [[dopamine]] release via the GHB receptor,<ref>A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and [[anticonvulsant]] properties | http://www.ncbi.nlm.nih.gov/pubmed/2173754</ref> higher concentrations inhibit [[dopamine]] release via [[GABA]]<sub>B</sub> receptors.<ref>Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.  
Activation of both the GHB receptor and [[GABA]]<sub>B</sub> is responsible for the addictive profile of GHB. GHB's effect on [[dopamine]] release is biphasic.<ref>Drosophila [[GABA]]<sub>B</sub> receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> This means that while low concentrations stimulate [[dopamine]] release via the GHB receptor,<ref>A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and [[anticonvulsant]] properties (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2173754</ref> higher concentrations inhibit [[dopamine]] release via [[GABA]]<sub>B</sub> receptors.<ref>Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> 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]]<sub>B</sub> receptor activation and activates predominantly the GHB receptor, leading to wakefulness.
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]]<sub>B</sub> receptor activation and activates predominantly the GHB receptor, leading to wakefulness.
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It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
It is strongly recommended that one use [[responsible drug 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 | http://www.sciencedirect.com/science/article/pii/S009130570400320X</ref><ref>Effects of subchronic administration of gammahydroxybutyrate (GHB) on spatial working memory in rats | 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 | 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 | 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 | https://www.ncbi.nlm.nih.gov/pubmed/15582677</ref>


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.
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.
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===Dangerous interactions===
===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. [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.  
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. [https://www.google.com/ 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]], [[gabapentin]], [[pregabalin]], [[phenibut]]'') - 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.<ref>http://web.archive.org/web/20071203005230/http://www.aafs.org/pdf/Seattleabstracts06.pdf</ref> 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.<ref>The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal to clinical studies | http://www.ncbi.nlm.nih.gov/pubmed/10075397</ref> These substances 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.<ref>https://www.erowid.org/chemicals/ghb/ghb_health.shtml</ref><ref>Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity | https://www.ncbi.nlm.nih.gov/pubmed/15274975</ref> If this occurs, users should attempt to fall asleep in the [https://www.youtube.com/watch?v=uCDa-AhrjHo recovery position] or have a friend move them into it.
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[benzodiazepines]], [[GBL]], [[methaqualone]], [[opioids]], [[gabapentin]], [[pregabalin]], [[phenibut]]'') - 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.<ref>http://web.archive.org/web/20071203005230/http://www.aafs.org/pdf/Seattleabstracts06.pdf</ref> 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.<ref>The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal to clinical studies (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/10075397</ref> These substances 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.<ref>https://www.erowid.org/chemicals/ghb/ghb_health.shtml</ref><ref>Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity | https://www.ncbi.nlm.nih.gov/pubmed/15274975</ref> If this occurs, users should attempt to fall asleep in the [https://www.youtube.com/watch?v=uCDa-AhrjHo 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 [https://www.youtube.com/watch?v=uCDa-AhrjHo 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 [https://www.youtube.com/watch?v=uCDa-AhrjHo recovery position] or have a friend move them into it.
*'''[[Stimulants]]''' -  It is dangerous to combine GHB, a [[depressant]]s, with [[stimulant]]s due to the risk of excessive intoxication. Stimulants decrease the [[sedation|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 [[GHB#Subjective effects|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.
*'''[[Stimulants]]''' -  It is dangerous to combine GHB, a [[depressant]]s, with [[stimulant]]s due to the risk of excessive intoxication. Stimulants decrease the [[sedation|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 [[GHB#Subjective effects|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.
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