Pregabalin: Difference between revisions

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==Chemistry==

Pregabalin is a structural analog of [[GABA]] (gamma-aminobutyric acid), with an isobutyl group substituted on the beta carbon of the aminobutyric chain. Pregabalin is similar in structure to other [[Gabapentinoid|gabapentinoids]], such as [[gabapentin]] and [[phenibut]]. Pregabalin contains a carboxylated chain of hexane called hexanoic acid. This carbon chain is substituted with an amine group through a methyl bridge in (S) conformation at R3 and a methyl group at R5.

==Pharmacology==

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The pharmacological action of pregabalin is mediated by binding to the α2δ-1 site of voltage-gated calcium channels.<ref>Field, M. J., Cox, P. J., Stott, E., Melrose, H., Offord, J., Su, T., … Williams, D. (2006). Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 17537–42. https://doi.org/10.1073/pnas.0409066103</ref><ref name="thromb">Eroglu, Ç., Allen, N. J., Susman, M. W., O’Rourke, N. A., Park, C. Y., Özkan, E., … Barres, B. A. (2009). Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis. Cell, 139(2), 380–392. https://doi.org/10.1016/j.cell.2009.09.025</ref> This site has also been referred to as the gabapentin receptor, as it is the target of the related substance [[gabapentin]] (also developed by Pfizer). Advantages to pregabalin over gabapentin include higher bioavailability and potency.

Although pregabalin is a chemical derivative of [[GABA]], it displays no activity at any GABA receptors, including GABAA, GABAB and the [[benzodiazepine]] site. Pregabalin, despite its GABA backbone, does not appear to alter GABA levels in the brain, so its pharmacological activity is presumed to be unrelated to GABA.<ref>Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel  α2–δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008</ref> Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels which appears to be the source of its subjective effects. By binding to this site, ~~Pregabalin~~ reduces the release of several excitatory neurotransmitters, including [[glutamate]], [[substance P]], [[acetylcholine]] and [[norepinephrine]].

Although pregabalin is a chemical derivative of [[GABA]], it displays no activity at any GABA receptors, including GABAA, GABAB and the [[benzodiazepine]] site. Pregabalin, despite its GABA backbone, does not appear to alter GABA levels in the brain, so its pharmacological activity is presumed to be unrelated to GABA.<ref>Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel  α2–δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008</ref> Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels which appears to be the source of its subjective effects. By binding to this site, pregabalin reduces the release of several excitatory neurotransmitters, including [[glutamate]], [[substance P]], [[acetylcholine]] and [[norepinephrine]].

One study has also shown that pregabalin promotes deep sleep, thus enhancing sleep quality. This may be substantial because reductions in slow-wave sleep have been associated with anxiety and fibromyalgia.<ref>Hindmarch, I., Dawson, J., & Stanley, N. (2005). A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep, 28(2), 187–93. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16171242</ref>

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*'''[[Effect::Double vision]]'''- This effect is quite mild and inconsistently appears at high doses. Sleep deprivation might magnify this effect.

====Hallucinatory states====

While ~~Pregabalin~~ isn't commonly thought off as a ''trip'' drug, it still can cause dissociative and even psychotic like effects at higher doses. Sleep deprivation and genetics might play a roll into the hallucinatory states of Pregabalin. Pregabalin's hallucinatory states are (but not limited to) :

While pregabalin isn't commonly thought off as a ''trip'' drug, it still can cause dissociative and even psychotic like effects at higher doses. Sleep deprivation and genetics might play a roll into the hallucinatory states of Pregabalin. Pregabalin's hallucinatory states are (but not limited to) :

*'''[[Effect::Internal hallucination]]''' - At high dosages, one may experience dream-like states and [[hypnagogia]].

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}}

{{effects/disconnective|

*'''[[Effect::Visual disconnection]]''' - This effect is generally quite mild and appears inconsistently at high doses. It results in feeling as if one's sense of vision is distant or vague and being viewed through a screen or window. However, ~~Pregabalin~~ is rarely reported to cause [[holes, spaces and voids]] or [[Visual_disconnection#Structures|hallucinatory structures]] , it can in some users (sleep deprivation might enhance this effect) but it is far from the typical experience. Pressing on your eyes while sitting in a dark room on a high - very high dose may result in very mild [[structures]] and [[sceneries]]

*'''[[Effect::Visual disconnection]]''' - This effect is generally quite mild and appears inconsistently at high doses. It results in feeling as if one's sense of vision is distant or vague and being viewed through a screen or window. However, pregabalin is rarely reported to cause [[holes, spaces and voids]] or [[Visual_disconnection#Structures|hallucinatory structures]] , it can in some users (sleep deprivation might enhance this effect) but it is far from the typical experience. Pressing on your eyes while sitting in a dark room on a high - very high dose may result in very mild [[structures]] and [[sceneries]]

}}

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*'''[[Effect::Disinhibition]]'''

*'''[[Effect::Dream potentiation]]'''

*'''[[Effect::Increased music appreciation]]''' - The music ~~enhancment~~ from ~~Pregabalin~~ can be described as music sounding more detailed, 'higher quality', and even slowed down on higher dosages.

*'''[[Effect::Increased music appreciation]]''' - The music enhancement from pregabalin can be described as music sounding more detailed, 'higher quality', and even slowed down on higher dosages.

*'''[[Effect::Motivation enhancement]]''' - Like [[kratom]], pregabalin can be mildly sedative yet increase motivation in a [[stimulant]]-like fashion.

*'''[[Effect::Immersion enhancement]]'''

*'''[[Effect::Creativity enhancement]]''' - This effect is especially noticeable on higher doses.

*'''[[Effect::Depersonalization]]''' ''and'' '''[[Effect::Derealization]]''' - At high/heavy doses, ~~Pregabalin~~ can induce a mild dissociative state. The DPDR from ~~Pregabalin~~ can be increased and made more ''negative'' (dysphoric) by sleep deprivation.

*'''[[Effect::Depersonalization]]''' ''and'' '''[[Effect::Derealization]]''' - At high/heavy doses, pregabalin can induce a mild dissociative state. The DPDR from pregabalin can be increased and made more ''negative'' (dysphoric) by sleep deprivation.

*'''[[Effect::Suicidal ideation]]''' - In very huge doses this effect can lead to suicide attempts, sleep deprivation may increase this effect.

*'''[[Effect::Psychosis]]''' - Even at medicinal doses, ~~Pregabalin~~ has been shown to have psychotic side effects in minority of it's users <ref> https://www.sciencedirect.com/science/article/pii/S105913110600029X#:~:text=Pregabalin%20is%20an%20effective%20anticonvulsant,mild%20and%20transient%20in%20nature.&text=However%2C%20physicians%20should%20be%20aware,be%20associated%20with%20psychotic%20symptoms.</ref> <ref> https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-020-0395-6</ref>. This effect is strongly potentiate by sleep deprivation and may be higher for people with genetic risks of psychosis / schizophrenia.

*'''[[Effect::Psychosis]]''' - Even at medicinal doses, pregabalin has been shown to have psychotic side effects in minority of it's users <ref> https://www.sciencedirect.com/science/article/pii/S105913110600029X#:~:text=Pregabalin%20is%20an%20effective%20anticonvulsant,mild%20and%20transient%20in%20nature.&text=However%2C%20physicians%20should%20be%20aware,be%20associated%20with%20psychotic%20symptoms.</ref> <ref> https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-020-0395-6</ref>. This effect is strongly potentiate by sleep deprivation and may be higher for people with genetic risks of psychosis / schizophrenia.

*'''[[Effect::Mania]]''' - Even if ~~Pregabalin~~ is used to treat bipolar disorder <ref> https://pubmed.ncbi.nlm.nih.gov/23040739/ </ref>,it can cause mania (even in medical doses in certain cases). <ref>https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12012 </ref>. In recreational settings, in high / very high recreational doses or/ and when the user is sleep deprived , this effect can occur, but its still not a part of the typical ~~Pregabalin~~ experience, this effect can be low in intensity (hypomania) or go hand in hand with [[Psychosis]] and appear as a full blown manic psychosis. It is important to acknowledge this effect is very, very rare.

*'''[[Effect::Mania]]''' - Even if pregabalin is used to treat bipolar disorder <ref> https://pubmed.ncbi.nlm.nih.gov/23040739/ </ref>,it can cause mania (even in medical doses in certain cases). <ref>https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12012 </ref>. In recreational settings, in high / very high recreational doses or/ and when the user is sleep deprived , this effect can occur, but its still not a part of the typical pregabalin experience, this effect can be low in intensity (hypomania) or go hand in hand with [[Psychosis]] and appear as a full blown manic psychosis. It is important to acknowledge this effect is very, very rare.

*'''[[Effect::Thought deceleration]]'''

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*'''[[Effect::Increased music appreciation]]''' - This effect is not as strong as it would be in the high, but music is noticeably enhanced and sounds more detailed.

*'''[[Effect::Muscle relaxation]]''' - This effect is not as strong as the high but its still here in the afterglow.

*'''[[Effect::Motor control loss]]''' - This effect is weaker then the ''high'' but is still noticeable to the user. Driving while in the ''afterglow'' / comedown is a bad idea.

*'''[[Effect::Dizziness]]''' - The after effects are mostly positive with ~~Pregabalin~~, but dizziness can still be here, especially after doing a high dose.

*'''[[Effect::Dizziness]]''' - The after effects are mostly positive with pregabalin, but dizziness can still be here, especially after doing a high dose.

}}

@@ Line 11: / Line 11: @@
 ==Chemistry==
-Pregabalin is a structural analog of [[GABA]] (gamma-aminobutyric acid), with an isobutyl group substituted on the beta carbon of the aminobutyric chain. Pregabalin is similar in structure to other [[Gabapentinoid|gabapentinoids]], such as [[gabapentin]] and [[phenibut]].  Pregabalin contains a carboxylated chain of hexane called hexanoic acid. This carbon chain is substituted with an amine group through a methyl bridge in (S) conformation at R<sub>3</sub> and a methyl group at R<sub>5</sub>.
+Pregabalin is a structural analog of [[GABA]] (gamma-aminobutyric acid), with an isobutyl group substituted on the beta carbon of the aminobutyric chain. Pregabalin is similar in structure to other [[Gabapentinoid|gabapentinoids]], such as [[gabapentin]] and [[phenibut]]. Pregabalin contains a carboxylated chain of hexane called hexanoic acid. This carbon chain is substituted with an amine group through a methyl bridge in (S) conformation at R<sub>3</sub> and a methyl group at R<sub>5</sub>.
 ==Pharmacology==
@@ Line 18: / Line 18: @@
 The pharmacological action of pregabalin is mediated by binding to the α2δ-1 site of voltage-gated calcium channels.<ref>Field, M. J., Cox, P. J., Stott, E., Melrose, H., Offord, J., Su, T., … Williams, D. (2006). Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 17537–42. https://doi.org/10.1073/pnas.0409066103</ref><ref name="thromb">Eroglu, Ç., Allen, N. J., Susman, M. W., O’Rourke, N. A., Park, C. Y., Özkan, E., … Barres, B. A. (2009). Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis. Cell, 139(2), 380–392. https://doi.org/10.1016/j.cell.2009.09.025</ref> This site has also been referred to as the gabapentin receptor, as it is the target of the related substance [[gabapentin]] (also developed by Pfizer). Advantages to pregabalin over gabapentin include higher bioavailability and potency.
-Although pregabalin is a chemical derivative of [[GABA]], it displays no activity at any GABA receptors, including GABA<sub>A</sub>, GABA<sub>B</sub> and the [[benzodiazepine]] site. Pregabalin, despite its GABA backbone, does not appear to alter GABA levels in the brain, so its pharmacological activity is presumed to be unrelated to GABA.<ref>Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel  α2–δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008</ref> Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels which appears to be the source of its subjective effects. By binding to this site, Pregabalin reduces the release of several excitatory neurotransmitters, including [[glutamate]], [[substance P]], [[acetylcholine]] and [[norepinephrine]].
+Although pregabalin is a chemical derivative of [[GABA]], it displays no activity at any GABA receptors, including GABA<sub>A</sub>, GABA<sub>B</sub> and the [[benzodiazepine]] site. Pregabalin, despite its GABA backbone, does not appear to alter GABA levels in the brain, so its pharmacological activity is presumed to be unrelated to GABA.<ref>Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel  α2–δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008</ref> Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels which appears to be the source of its subjective effects. By binding to this site, pregabalin reduces the release of several excitatory neurotransmitters, including [[glutamate]], [[substance P]], [[acetylcholine]] and [[norepinephrine]].
 One study has also shown that pregabalin promotes deep sleep, thus enhancing sleep quality. This may be substantial because reductions in slow-wave sleep have been associated with anxiety and fibromyalgia.<ref>Hindmarch, I., Dawson, J., & Stanley, N. (2005). A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep, 28(2), 187–93. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16171242</ref>
@@ Line 66: / Line 66: @@
 *'''[[Effect::Double vision]]'''- This effect is quite mild and inconsistently appears at high doses. Sleep deprivation might magnify this effect.
 ====Hallucinatory states====
-While Pregabalin isn't commonly thought off as a ''trip'' drug, it still can cause dissociative and even psychotic like effects at higher doses. Sleep deprivation and genetics might play a roll into the hallucinatory states of Pregabalin. Pregabalin's hallucinatory states are (but not limited to) :
+While pregabalin isn't commonly thought off as a ''trip'' drug, it still can cause dissociative and even psychotic like effects at higher doses. Sleep deprivation and genetics might play a roll into the hallucinatory states of Pregabalin. Pregabalin's hallucinatory states are (but not limited to) :
 *'''[[Effect::Internal hallucination]]''' - At high dosages, one may experience dream-like states and [[hypnagogia]].
@@ Line 72: / Line 72: @@
 }}
 {{effects/disconnective|
-*'''[[Effect::Visual disconnection]]''' - This effect is generally quite mild and appears inconsistently at  high doses. It results in feeling as if one's sense of vision is distant or vague and being viewed through a screen or window. However, Pregabalin is rarely reported to cause  [[holes, spaces and voids]] or [[Visual_disconnection#Structures|hallucinatory structures]] , it can in some users (sleep deprivation might enhance this effect) but it is far from the typical experience. Pressing on your eyes while sitting in a dark room on a high - very high dose may result in very  mild [[structures]] and [[sceneries]]
+*'''[[Effect::Visual disconnection]]''' - This effect is generally quite mild and appears inconsistently at  high doses. It results in feeling as if one's sense of vision is distant or vague and being viewed through a screen or window. However, pregabalin is rarely reported to cause [[holes, spaces and voids]] or [[Visual_disconnection#Structures|hallucinatory structures]] , it can in some users (sleep deprivation might enhance this effect) but it is far from the typical experience. Pressing on your eyes while sitting in a dark room on a high - very high dose may result in very  mild [[structures]] and [[sceneries]]
 }}
@@ Line 88: / Line 88: @@
 *'''[[Effect::Disinhibition]]'''
 *'''[[Effect::Dream potentiation]]'''
-*'''[[Effect::Increased music appreciation]]''' - The music enhancment from Pregabalin can be described as music sounding more detailed, 'higher quality', and even slowed  down on higher dosages.
+*'''[[Effect::Increased music appreciation]]''' - The music enhancement from pregabalin can be described as music sounding more detailed, 'higher quality', and even slowed down on higher dosages.
 *'''[[Effect::Motivation enhancement]]''' - Like [[kratom]], pregabalin can be mildly sedative yet increase motivation in a [[stimulant]]-like fashion.
 *'''[[Effect::Immersion enhancement]]'''
-*'''[[Effect::Creativity enhancement]]''' - This effect is especially  noticeable  on higher doses.
+*'''[[Effect::Creativity enhancement]]''' - This effect is especially noticeable on higher doses.
-*'''[[Effect::Depersonalization]]''' ''and'' '''[[Effect::Derealization]]''' - At high/heavy doses, Pregabalin can induce a mild dissociative state. The DPDR from Pregabalin can be increased and made more ''negative'' (dysphoric) by sleep deprivation.
+*'''[[Effect::Depersonalization]]''' ''and'' '''[[Effect::Derealization]]''' - At high/heavy doses, pregabalin can induce a mild dissociative state. The DPDR from pregabalin can be increased and made more ''negative'' (dysphoric) by sleep deprivation.
 *'''[[Effect::Suicidal ideation]]''' - In very huge doses this effect can lead to suicide attempts, sleep deprivation may increase this effect.
-*'''[[Effect::Psychosis]]''' - Even at medicinal doses, Pregabalin has been shown to have psychotic side effects in minority of it's users <ref> https://www.sciencedirect.com/science/article/pii/S105913110600029X#:~:text=Pregabalin%20is%20an%20effective%20anticonvulsant,mild%20and%20transient%20in%20nature.&text=However%2C%20physicians%20should%20be%20aware,be%20associated%20with%20psychotic%20symptoms.</ref> <ref> https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-020-0395-6</ref>. This effect is strongly potentiate by sleep deprivation and may be higher for people with genetic risks of psychosis / schizophrenia.
+*'''[[Effect::Psychosis]]''' - Even at medicinal doses, pregabalin has been shown to have psychotic side effects in minority of it's users <ref> https://www.sciencedirect.com/science/article/pii/S105913110600029X#:~:text=Pregabalin%20is%20an%20effective%20anticonvulsant,mild%20and%20transient%20in%20nature.&text=However%2C%20physicians%20should%20be%20aware,be%20associated%20with%20psychotic%20symptoms.</ref> <ref> https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-020-0395-6</ref>. This effect is strongly potentiate by sleep deprivation and may be higher for people with genetic risks of psychosis / schizophrenia.
-*'''[[Effect::Mania]]''' - Even if Pregabalin is used to treat bipolar disorder <ref> https://pubmed.ncbi.nlm.nih.gov/23040739/ </ref>,it can cause mania (even in medical doses in certain cases). <ref>https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12012 </ref>. In recreational settings, in high / very high recreational doses or/ and when the user is sleep deprived , this effect can occur, but its still not a part of the typical Pregabalin experience, this effect can be low in intensity (hypomania) or go hand in hand with [[Psychosis]] and appear as a full blown manic psychosis. It is important to acknowledge this effect is very, very rare.
+*'''[[Effect::Mania]]''' - Even if pregabalin is used to treat bipolar disorder <ref> https://pubmed.ncbi.nlm.nih.gov/23040739/ </ref>,it can cause mania (even in medical doses in certain cases). <ref>https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12012 </ref>. In recreational settings, in high / very high recreational doses or/ and when the user is sleep deprived , this effect can occur, but its still not a part of the typical pregabalin experience, this effect can be low in intensity (hypomania) or go hand in hand with [[Psychosis]] and appear as a full blown manic psychosis. It is important to acknowledge this effect is very, very rare.
 *'''[[Effect::Thought deceleration]]'''
@@ Line 110: / Line 110: @@
 *'''[[Effect::Increased music appreciation]]''' - This effect is not as strong as it would be in the high, but music is noticeably enhanced and sounds more detailed.
 *'''[[Effect::Muscle relaxation]]''' - This effect is not as strong as the high but its still here in the afterglow.
-*'''[[Effect::Motor control loss]]''' - This effect is weaker then the ''high'' but is still noticeable to the user. Driving while in the ''afterglow'' / comedown  is a bad idea.
+*'''[[Effect::Motor control loss]]''' - This effect is weaker then the ''high'' but is still noticeable to the user. Driving while in the ''afterglow'' / comedown is a bad idea.
-*'''[[Effect::Dizziness]]''' - The after effects are mostly positive with Pregabalin, but dizziness can still be here, especially after doing a high dose.
+*'''[[Effect::Dizziness]]''' - The after effects are mostly positive with pregabalin, but dizziness can still be here, especially after doing a high dose.
 }}