Phenibut: Difference between revisions

Line 25:

Phenibut has a more complex pharmacological profile than many other [[depressants]].

Unlike [[benzodiazepines]], for example, phenibut acts as a full [[agonist]] of the [[GABA]]B [[receptor]], similar to baclofen and high doses of [[GHB]].<ref name="eight">{{cite book | date=21 September 2010 | title=GABAb Receptor Pharmacology: A Tribute to Norman Bowery | publisher=Academic Press | isbn=9780123786487}}</ref> At higher doses, phenibut loses its selectivity of GABAB, and gains additional activity as a GABAA [[agonist]].<ref name="ZyablitsevaPavlova2010">{{cite journal|last1=Zyablitseva|first1=E. A.|last2=Pavlova|first2=I. V.|title=Effects of the GABA Receptor Agonist Phenibut on Spike Activity and Interactions between Neocortex and Hippocampus Neurons in Emotionally Negative Situations|journal=Neuroscience and Behavioral Physiology|volume=40|issue=9|year=2010|pages=1003–1011|issn=0097-0549|doi=10.1007/s11055-010-9360-y}}</ref>

~~Phenibut's effects at the GABAB receptor are responsible for its sedating effects.{{citation needed}}~~

Recent research has shown that phenibut binds to and blocks α2δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids such as [[gabapentin]]

and [[pregabalin]].<ref name="nine" /> Both enantiomers of phenibut show this action with similar efficacy. The R-enantiomer possesses five-fold greater affinity for α2δ subunit-containing voltage-gated calcium channels relative to the GABAB receptor, whereas the S-entantiomer does not have any efficacy at the GABAB receptor.<ref name="nine">{{cite journal | vauthors=((Dambrova, M.)), ((Zvejniece, L.)), ((Liepinsh, E.)), ((Cirule, H.)), ((Zharkova, O.)), ((Veinberg, G.)), ((Kalvinsh, I.)) | journal=European Journal of Pharmacology | title=Comparative pharmacological activity of optical isomers of phenibut | volume=583 | issue=1 | pages=128–134 | date=31 March 2008 | issn=0014-2999 | doi=10.1016/j.ejphar.2008.01.015}}</ref>

and [[pregabalin]].<ref name="nine" /> Both enantiomers of phenibut show this action with similar efficacy. The R-enantiomer possesses five-fold greater affinity for α2δ subunit-containing voltage-gated calcium channels relative to the GABAB receptor, whereas the S-entantiomer does not have any efficacy at the GABAB receptor.<ref name="nine">{{cite journal | vauthors=((Dambrova, M.)), ((Zvejniece, L.)), ((Liepinsh, E.)), ((Cirule, H.)), ((Zharkova, O.)), ((Veinberg, G.)), ((Kalvinsh, I.)) | journal=European Journal of Pharmacology | title=Comparative pharmacological activity of optical isomers of phenibut | volume=583 | issue=1 | pages=128–134 | date=31 March 2008 | issn=0014-2999 | doi=10.1016/j.ejphar.2008.01.015}}</ref> Unlike other VGCC channel blockers like [[gabapentin]], phenibut lacks anticonvulsant activity.<ref name=":0">Lapin I. Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug Rev. 2001 Winter;7(4):471-81. doi: 10.1111/j.1527-3458.2001.tb00211.x. PMID: 11830761; PMCID: PMC6494145.</ref>

The [[pain relief|analgesic]] effects of phenibut in rodents are not mediated by the GABAB receptor but by the blockage of α2δ subunit-containing voltage-gated calcium channels.<ref name="nine" />

Line 119:

Line 118:

*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2M2B]], [[alcohol]],<ref>{{cite journal | vauthors=((Koski, A.)), ((Ojanpera, I.)), ((Vuori, E.)) | journal=Alcoholism: Clinical and Experimental Research | title=Alcohol and Benzodiazepines in Fatal Poisonings | volume=26 | issue=7 | pages=956–959 | date= July 2002 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2002.tb02627.x | issn=0145-6008 | doi=10.1111/j.1530-0277.2002.tb02627.x}}</ref> [[benzodiazepines]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. 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. 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 a sudden loss of consciousness occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.

*'''[[Stimulants]]''' - Phenibut is reported to enhance the positive effects of [[stimulants]] as well as reduce jitteriness and anxiety.<ref>{{Citation | title=The Drug Classroom - Phenibut: Combinations | url=https://thedrugclassroom.com/video/phenibut/}}</ref> However, this combination can be dangerous due to the risk of excessive intoxication. Stimulants mask the [[sedation|sedative]] effects of phenibut; once the stimulant wears off, the depressant effects of phenibut will be significantly increased, leading to intensified [[disinhibition]] as well as [[Phenibut#Subjective effects|other effects]]. If combined, one should strictly limit themselves to a certain dose of phenibut prior to stimulant consumption and not redose. This combination can also potentially result in significant dehydration.

*'''[[Stimulants]]''' - Phenibut is reported to enhance the positive effects of [[stimulants]] as well as reduce jitteriness and anxiety.<ref>{{Citation | title=The Drug Classroom - Phenibut: Combinations | url=https://thedrugclassroom.com/video/phenibut/}}</ref> However, this combination can be dangerous due to the risk of excessive intoxication. Stimulants mask the [[sedation|sedative]] effects of phenibut; once the stimulant wears off, the depressant effects of phenibut will be significantly increased, leading to intensified [[disinhibition]] as well as [[Phenibut#Subjective effects|other effects]]. Unlike some other depressants, phenibut does not counteract the reduction in seizure threshold caused by most stimulants.<ref name=":0" /> If combined, one should strictly limit themselves to a certain dose of phenibut prior to stimulant consumption and not redose. This combination can also potentially result in significant dehydration.

==Legal status==

@@ Line 25: / Line 25: @@
 Phenibut has a more complex pharmacological profile than many other [[depressants]].
 Unlike [[benzodiazepines]], for example, phenibut acts as a full [[agonist]] of the [[GABA]]<sub>B</sub> [[receptor]], similar to baclofen and high doses of [[GHB]].<ref name="eight">{{cite book | date=21 September 2010 | title=GABAb Receptor Pharmacology: A Tribute to Norman Bowery | publisher=Academic Press | isbn=9780123786487}}</ref> At higher doses, phenibut loses its selectivity of GABA<sub>B</sub>, and gains additional activity as a GABA<sub>A</sub> [[agonist]].<ref name="ZyablitsevaPavlova2010">{{cite journal|last1=Zyablitseva|first1=E. A.|last2=Pavlova|first2=I. V.|title=Effects of the GABA Receptor Agonist Phenibut on Spike Activity and Interactions between Neocortex and Hippocampus Neurons in Emotionally Negative Situations|journal=Neuroscience and Behavioral Physiology|volume=40|issue=9|year=2010|pages=1003–1011|issn=0097-0549|doi=10.1007/s11055-010-9360-y}}</ref>
-Phenibut's effects at the GABA<sub>B</sub> receptor are responsible for its sedating effects.{{citation needed}}
 Recent research has shown that phenibut binds to and blocks α2δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids such as [[gabapentin]]
-and [[pregabalin]].<ref name="nine" /> Both enantiomers of phenibut show this action with similar efficacy. The R-enantiomer possesses five-fold greater affinity for α2δ subunit-containing voltage-gated calcium channels relative to the GABA<sub>B</sub> receptor, whereas the S-entantiomer does not have any efficacy at the GABA<sub>B</sub> receptor.<ref name="nine">{{cite journal | vauthors=((Dambrova, M.)), ((Zvejniece, L.)), ((Liepinsh, E.)), ((Cirule, H.)), ((Zharkova, O.)), ((Veinberg, G.)), ((Kalvinsh, I.)) | journal=European Journal of Pharmacology | title=Comparative pharmacological activity of optical isomers of phenibut | volume=583 | issue=1 | pages=128–134 | date=31 March 2008 | issn=0014-2999 | doi=10.1016/j.ejphar.2008.01.015}}</ref>
+and [[pregabalin]].<ref name="nine" /> Both enantiomers of phenibut show this action with similar efficacy. The R-enantiomer possesses five-fold greater affinity for α2δ subunit-containing voltage-gated calcium channels relative to the GABA<sub>B</sub> receptor, whereas the S-entantiomer does not have any efficacy at the GABA<sub>B</sub> receptor.<ref name="nine">{{cite journal | vauthors=((Dambrova, M.)), ((Zvejniece, L.)), ((Liepinsh, E.)), ((Cirule, H.)), ((Zharkova, O.)), ((Veinberg, G.)), ((Kalvinsh, I.)) | journal=European Journal of Pharmacology | title=Comparative pharmacological activity of optical isomers of phenibut | volume=583 | issue=1 | pages=128–134 | date=31 March 2008 | issn=0014-2999 | doi=10.1016/j.ejphar.2008.01.015}}</ref> Unlike other VGCC channel blockers like [[gabapentin]], phenibut lacks anticonvulsant activity.<ref name=":0">Lapin I. Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug Rev. 2001 Winter;7(4):471-81. doi: 10.1111/j.1527-3458.2001.tb00211.x. PMID: 11830761; PMCID: PMC6494145.</ref>
 The [[pain relief|analgesic]] effects of phenibut in rodents are not mediated by the GABA<sub>B</sub> receptor but by the blockage of α2δ subunit-containing voltage-gated calcium channels.<ref name="nine" />
@@ Line 119: / Line 118: @@
 *'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2M2B]], [[alcohol]],<ref>{{cite journal | vauthors=((Koski, A.)), ((Ojanpera, I.)), ((Vuori, E.)) | journal=Alcoholism: Clinical and Experimental Research | title=Alcohol and Benzodiazepines in Fatal Poisonings | volume=26 | issue=7 | pages=956–959 | date= July 2002 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2002.tb02627.x | issn=0145-6008 | doi=10.1111/j.1530-0277.2002.tb02627.x}}</ref> [[benzodiazepines]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. 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. 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 a sudden loss of consciousness occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
-*'''[[Stimulants]]''' -  Phenibut is reported to enhance the positive effects of [[stimulants]] as well as reduce jitteriness and anxiety.<ref>{{Citation | title=The Drug Classroom - Phenibut: Combinations | url=https://thedrugclassroom.com/video/phenibut/}}</ref> However, this combination can be dangerous due to the risk of excessive intoxication. Stimulants mask the [[sedation|sedative]] effects of phenibut; once the stimulant wears off, the depressant effects of phenibut will be significantly increased, leading to intensified [[disinhibition]] as well as [[Phenibut#Subjective effects|other effects]]. If combined, one should strictly limit themselves to a certain dose of phenibut prior to stimulant consumption and not redose. This combination can also potentially result in significant dehydration.
+*'''[[Stimulants]]''' -  Phenibut is reported to enhance the positive effects of [[stimulants]] as well as reduce jitteriness and anxiety.<ref>{{Citation | title=The Drug Classroom - Phenibut: Combinations | url=https://thedrugclassroom.com/video/phenibut/}}</ref> However, this combination can be dangerous due to the risk of excessive intoxication. Stimulants mask the [[sedation|sedative]] effects of phenibut; once the stimulant wears off, the depressant effects of phenibut will be significantly increased, leading to intensified [[disinhibition]] as well as [[Phenibut#Subjective effects|other effects]]. Unlike some other depressants, phenibut does not counteract the reduction in seizure threshold caused by most stimulants.<ref name=":0" /> If combined, one should strictly limit themselves to a certain dose of phenibut prior to stimulant consumption and not redose. This combination can also potentially result in significant dehydration.
 ==Legal status==