GHB: Difference between revisions

Line 22:

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.<ref name="Dimitrijevic2005"/> This means that while low concentrations stimulate [[dopamine]] release via the GHB receptor,<ref>{{cite journal | vauthors=((Maitre, M.)), ((Hechler, V.)), ((Vayer, P.)), ((Gobaille, S.)), ((Cash, C. D.)), ((Schmitt, M.)), ((Bourguignon, J. J.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties | volume=255 | issue=2 | pages=657–663 | date= November 1990 | issn=0022-3565}}</ref> higher concentrations inhibit [[dopamine]] release via [[GABA]]B receptors.<ref>{{cite journal | vauthors=((Smolders, I.)), ((De Klippel, N.)), ((Sarre, S.)), ((Ebinger, G.)), ((Michotte, Y.)) | journal=European Journal of Pharmacology | title=Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat | volume=284 | issue=1 | pages=83–91 | date=15 September 1995 | url=https://www.sciencedirect.com/science/article/pii/001429999500369V | issn=0014-2999 | doi=10.1016/0014-2999(95)00369-V}}</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.

GHB induces the accumulation of either a derivative of tryptophan or [[tryptophan]] itself, possibly by increasing tryptophan transport across the blood–brain barrier.<ref>{{Cite journal |last=Gobaille |first=Serge |last2=Schleef |first2=Carmen |last3=Hechler |first3=Viviane |last4=Viry |first4=Sandrine |last5=Aunis |first5=Dominique |last6=Maitre |first6=Michel |date=2002-03-22 |title=Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain |url=https://pubmed.ncbi.nlm.nih.gov/12002803/ |journal=Life Sciences |volume=70 |issue=18 |pages=2101–2112 |doi=10.1016/s0024-3205(01)01526-0 |issn=0024-3205 |pmid=12002803}}</ref> 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.<ref>{{Cite journal |last=Gobaille |first=Serge |last2=Schleef |first2=Carmen |last3=Hechler |first3=Viviane |last4=Viry |first4=Sandrine |last5=Aunis |first5=Dominique |last6=Maitre |first6=Michel |date=2002-03-22 |title=Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain |url=https://pubmed.ncbi.nlm.nih.gov/12002803/ |journal=Life Sciences |volume=70 |issue=18 |pages=2101–2112 |doi=10.1016/s0024-3205(01)01526-0 |issn=0024-3205 |pmid=12002803}}</ref> 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.<ref>{{Cite journal |last=Kamal |first=Rama M. |last2=Noorden |first2=Martijn S. van |last3=Franzek |first3=Ernst |last4=Dijkstra |first4=Boukje A. G. |last5=Loonen |first5=Anton J. M. |last6=Jong |first6=Cornelius A. J. De |date=2016 |title=The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review |url=https://www.karger.com/Article/FullText/443173 |journal=Neuropsychobiology |language=english |volume=73 |issue=2 |pages=65–80 |doi=10.1159/000443173 |issn=0302-282X |pmid=27003176}}</ref>

These findings may explain the paradoxical mix of sedative and stimulatory properties of GHB as well as the so-called "rebound" effect reported 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.

@@ Line 22: / Line 22: @@
 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 name="Dimitrijevic2005"/> This means that while low concentrations stimulate [[dopamine]] release via the GHB receptor,<ref>{{cite journal | vauthors=((Maitre, M.)), ((Hechler, V.)), ((Vayer, P.)), ((Gobaille, S.)), ((Cash, C. D.)), ((Schmitt, M.)), ((Bourguignon, J. J.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties | volume=255 | issue=2 | pages=657–663 | date= November 1990 | issn=0022-3565}}</ref> higher concentrations inhibit [[dopamine]] release via [[GABA]]<sub>B</sub> receptors.<ref>{{cite journal | vauthors=((Smolders, I.)), ((De Klippel, N.)), ((Sarre, S.)), ((Ebinger, G.)), ((Michotte, Y.)) | journal=European Journal of Pharmacology | title=Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat | volume=284 | issue=1 | pages=83–91 | date=15 September 1995 | url=https://www.sciencedirect.com/science/article/pii/001429999500369V | issn=0014-2999 | doi=10.1016/0014-2999(95)00369-V}}</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.
-GHB induces the accumulation of either a derivative of tryptophan or [[tryptophan]] itself, possibly by increasing tryptophan transport across the blood–brain barrier.<ref>{{Cite journal |last=Gobaille |first=Serge |last2=Schleef |first2=Carmen |last3=Hechler |first3=Viviane |last4=Viry |first4=Sandrine |last5=Aunis |first5=Dominique |last6=Maitre |first6=Michel |date=2002-03-22 |title=Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain |url=https://pubmed.ncbi.nlm.nih.gov/12002803/ |journal=Life Sciences |volume=70 |issue=18 |pages=2101–2112 |doi=10.1016/s0024-3205(01)01526-0 |issn=0024-3205 |pmid=12002803}}</ref> 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.<ref>{{Cite journal |last=Gobaille |first=Serge |last2=Schleef |first2=Carmen |last3=Hechler |first3=Viviane |last4=Viry |first4=Sandrine |last5=Aunis |first5=Dominique |last6=Maitre |first6=Michel |date=2002-03-22 |title=Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain |url=https://pubmed.ncbi.nlm.nih.gov/12002803/ |journal=Life Sciences |volume=70 |issue=18 |pages=2101–2112 |doi=10.1016/s0024-3205(01)01526-0 |issn=0024-3205 |pmid=12002803}}</ref> 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.<ref>{{Cite journal |last=Kamal |first=Rama M. |last2=Noorden |first2=Martijn S. van |last3=Franzek |first3=Ernst |last4=Dijkstra |first4=Boukje A. G. |last5=Loonen |first5=Anton J. M. |last6=Jong |first6=Cornelius A. J. De |date=2016 |title=The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review |url=https://www.karger.com/Article/FullText/443173 |journal=Neuropsychobiology |language=english |volume=73 |issue=2 |pages=65–80 |doi=10.1159/000443173 |issn=0302-282X |pmid=27003176}}</ref>
 These findings may explain the paradoxical mix of sedative and stimulatory properties of GHB as well as the so-called "rebound" effect reported 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.