This is an unofficial archive of PsychonautWiki as of 2025-08-11T15:14:44Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
GHB: Difference between revisions
>Josikins |
>Josikins |
||
| Line 31: | Line 31: | ||
==Pharmacology== | ==Pharmacology== | ||
GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | 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 | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> and it is a weak agonist at the GABA<sub>B</sub> receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> | GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | 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 | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> and it is a weak agonist at the [[GABA]]<sub>B</sub> receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug 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 in the extracellular space, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to an 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. | GHB induces the accumulation of either a derivative of tryptophan or tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to an 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<sub>B</sub> receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABA<sub>B</sub> antagonists. | However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]<sub>B</sub> receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABA<sub>B</sub> antagonists. | ||
The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. 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> | The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. 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 | 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> 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 as do other [[GABA]]<sub>B</sub> [[agonists]] such as [[baclofen]] and [[phenibut]].<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. Both the inhibition and increase of dopamine release by GHB are inhibited by [[opioid]] [[antagonists]] such as [[naloxone]] and [[naltrexone]]. [[Dynorphin]] may play a role in the inhibition of [[dopamine]] release via kappa opioid receptors.<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> | ||
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. That is to say that, over time, the concentration of GHB in the system decreases below the threshold for significant | 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. That is to say that, 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. | ||
==Subjective effects== | ==Subjective effects== | ||