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Pregabalin: Difference between revisions
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{{SubstanceBox/Pregabalin}} | {{SubstanceBox/Pregabalin}} | ||
'''Pregabalin''' (also known as '''3-isobutyl GABA''' and by the trade-name '''Lyrica''') is a [[psychoactive class::depressant]] substance of the [[chemical class::gabapentinoid]] class. Pregabalin is a common prescription drug, which is typically used to treat neuropathic pain, [[anxiety]], [[restless leg syndrome]], and as an adjunct drug in the treatment of [[seizures]].<ref>https://www.ema.europa.eu/en/medicines/human/EPAR/lyrica</ref><ref>https://n.neurology.org/content/74/23/1897. | '''Pregabalin''' (also known as '''3-isobutyl GABA''' and by the trade-name '''Lyrica''') is a [[psychoactive class::depressant]] substance of the [[chemical class::gabapentinoid]] class. Pregabalin is a common prescription drug, which is typically used to treat neuropathic pain, [[anxiety]], [[restless leg syndrome]], and as an adjunct drug in the treatment of [[seizures]].<ref>{{Citation | vauthors=EMA | year=2018 | title=Lyrica | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lyrica}}</ref><ref>{{cite journal | vauthors=((Garcia-Borreguero, D.)), ((Larrosa, O.)), ((Williams, A.-M.)), ((Albares, J.)), ((Pascual, M.)), ((Palacios, J. C.)), ((Fernandez, C.)) | journal=Neurology | title=Treatment of restless legs syndrome with pregabalin: A double-blind, placebo-controlled study | volume=74 | issue=23 | pages=1897–1904 | date=8 June 2010 | url=https://n.neurology.org/content/74/23/1897 | issn=0028-3878 | doi=10.1212/WNL.0b013e3181e1ce73}}</ref> | ||
Pregabalin has a pharmacological profile comparable to that of [[gabapentin]] as they both share similar mechanisms of action and induce similar subjective effects. The advantages pregabalin has over gabapentin include greater bioavailability and potency,<ref>A pharmacokinetic comparison of pregabalin and gabapentin | Pregabalin has a pharmacological profile comparable to that of [[gabapentin]] as they both share similar mechanisms of action and induce similar subjective effects. The advantages pregabalin has over gabapentin include greater bioavailability and potency,<ref>{{cite journal | vauthors=((Wesche, D.)), ((Bockbrader, H.)) | journal=The Journal of Pain | title=A pharmacokinetic comparison of pregabalin and gabapentin | volume=6 | issue=3 | pages=S29 | date= March 2005 | url=https://linkinghub.elsevier.com/retrieve/pii/S152659000500129X | issn=15265900 | doi=10.1016/j.jpain.2005.01.114}}</ref> as well as a wider variety of accepted medical applications for pregabalin not seen with gabapentin, such as its successful use in the treatment of anxiety, in which the use of gabapentin was not successful, excluding some more severe cases.<ref>{{cite journal | vauthors=((Feltner, D. E.)), ((Crockatt, J. G.)), ((Dubovsky, S. J.)), ((Cohn, C. K.)), ((Shrivastava, R. K.)), ((Targum, S. D.)), ((Liu-Dumaw, M.)), ((Carter, C. M.)), ((Pande, A. C.)) | journal=Journal of Clinical Psychopharmacology | title=A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study of Pregabalin in Patients With Generalized Anxiety Disorder: | volume=23 | issue=3 | pages=240–249 | date= June 2003 | url=http://journals.lww.com/00004714-200306000-00005 | issn=0271-0749 | doi=10.1097/01.jcp.0000084032.22282.ff}}</ref> <ref>{{cite journal | vauthors=((Pande, A. C.)), ((Pollack, M. H.)), ((Crockatt, J.)), ((Greiner, M.)), ((Chouinard, G.)), ((Lydiard, R. B.)), ((Taylor, C. B.)), ((Dager, S. R.)), ((Shiovitz, T.)) | journal=Journal of Clinical Psychopharmacology | title=Placebo-Controlled Study of Gabapentin Treatment of Panic Disorder: | volume=20 | issue=4 | pages=467–471 | date= August 2000 | url=http://journals.lww.com/00004714-200008000-00011 | issn=0271-0749 | doi=10.1097/00004714-200008000-00011}}</ref> | ||
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==Chemistry== | ==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 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== | ==Pharmacology== | ||
[[File:Gabapentinoids.png|thumb|right|Pregabalin is neither a GABA<sub>A</sub> or GABA<sub>B</sub> receptor agonist]] | [[File:Gabapentinoids.png|thumb|right|Pregabalin is neither a GABA<sub>A</sub> or GABA<sub>B</sub> receptor agonist]] | ||
===Pharmacodynamics=== | ===Pharmacodynamics=== | ||
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., | The pharmacological action of pregabalin is mediated by binding to the α2δ-1 site of voltage-gated calcium channels.<ref>{{cite journal | vauthors=((Field, M. J.)), ((Cox, P. J.)), ((Stott, E.)), ((Melrose, H.)), ((Offord, J.)), ((Su, T.-Z.)), ((Bramwell, S.)), ((Corradini, L.)), ((England, S.)), ((Winks, J.)), ((Kinloch, R. A.)), ((Hendrich, J.)), ((Dolphin, A. C.)), ((Webb, T.)), ((Williams, D.)) | journal=Proceedings of the National Academy of Sciences | title=Identification of the α 2 -δ-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin | volume=103 | issue=46 | pages=17537–17542 | date=14 November 2006 | url=https://pnas.org/doi/full/10.1073/pnas.0409066103 | issn=0027-8424 | doi=10.1073/pnas.0409066103}}</ref><ref name="thromb">{{cite journal | vauthors=((Eroglu, Ç.)), ((Allen, N. J.)), ((Susman, M. W.)), ((O’Rourke, N. A.)), ((Park, C. Y.)), ((Özkan, E.)), ((Chakraborty, C.)), ((Mulinyawe, S. B.)), ((Annis, D. S.)), ((Huberman, A. D.)), ((Green, E. M.)), ((Lawler, J.)), ((Dolmetsch, R.)), ((Garcia, K. C.)), ((Smith, S. J.)), ((Luo, Z. D.)), ((Rosenthal, A.)), ((Mosher, D. F.)), ((Barres, B. A.)) | journal=Cell | title=Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis | volume=139 | issue=2 | pages=380–392 | date= October 2009 | url=https://linkinghub.elsevier.com/retrieve/pii/S0092867409011854 | issn=00928674 | doi=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., | 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>{{cite journal | vauthors=((Taylor, C. P.)), ((Angelotti, T.)), ((Fauman, E.)) | journal=Epilepsy Research | title=Pharmacology and mechanism of action of pregabalin: The calcium channel α2–δ (alpha2–delta) subunit as a target for antiepileptic drug discovery | volume=73 | issue=2 | pages=137–150 | date= February 2007 | url=https://linkinghub.elsevier.com/retrieve/pii/S0920121106003895 | issn=09201211 | doi=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]].<ref>{{Cite journal| doi = 10.1124/mol.106.023309| issn = 1521-0111| volume = 70| issue = 2| pages = 467–476| last1 = Micheva| first1 = Kristina D.| last2 = Taylor| first2 = Charles P.| last3 = Smith| first3 = Stephen J.| title = Pregabalin Reduces the Release of Synaptic Vesicles from Cultured Hippocampal Neurons| journal = Molecular Pharmacology| accessdate = 2023-07-14| date = 2006-08-01| url = https://molpharm.aspetjournals.org/content/70/2/467| pmid = 16641316}}</ref> | ||
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., | Reduction in the release of glutamate and acetylcholine might be the cause of dissociative / deliriant like effects in high doses.{{citation needed}} | ||
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>{{cite journal | vauthors=((Hindmarch, I.)), ((Dawson, J.)), ((Stanley, N.)) | journal=Sleep | title=A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo | volume=28 | issue=2 | pages=187–193 | date= February 2005 | issn=0161-8105 | doi=10.1093/sleep/28.2.187}}</ref> | |||
Also, an independent action of the gabapentin site on the neurogenesis of excitatory synapses has been discovered. The endogenous neurochemical thrombospondin also binds to this site and is important for the generation of new excitatory synapses. Gabapentin and pregabalin, having a high affinity for this site, block this action and result in lower levels of excitatory synapses in animal models.<ref name="thromb" /> | Also, an independent action of the gabapentin site on the neurogenesis of excitatory synapses has been discovered. The endogenous neurochemical thrombospondin also binds to this site and is important for the generation of new excitatory synapses. Gabapentin and pregabalin, having a high affinity for this site, block this action and result in lower levels of excitatory synapses in animal models.<ref name="thromb" /> | ||
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Pregabalin undergoes negligible metabolism in humans. In experiments using nuclear medicine techniques, it was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The primary metabolite is N-methyl pregabalin. | Pregabalin undergoes negligible metabolism in humans. In experiments using nuclear medicine techniques, it was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The primary metabolite is N-methyl pregabalin. | ||
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged substance | Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged substance.<ref>{{Citation | year=2016 | title=LYRICA 200 mg | url=http://web.archive.org/web/20160305071130/http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=41099}}</ref> The elimination half life is 6.3 hours.<ref>{{Citation | title=Pregabalin | url=https://go.drugbank.com/drugs/DB00230}}</ref> | ||
==Subjective effects== | ==Subjective effects== | ||
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|{{effects/physical| | |{{effects/physical| | ||
*'''[[Effect::Sedation]]''' - Pregabalin produces mild sedation and improves sleep onset latency modestly. Several studies have shown pregabalin improves sleep quality of those who take it for various indications. It is unknown if this effect is carried over to those who take it recreationally.<ref> Time to improvement of pain and sleep quality in clinical trials of pregabalin for the treatment of fibromyalgia. | *'''[[Effect::Stimulation]]''' & '''[[Effect::Sedation]]''' - Pregabalin produces mild sedation and improves sleep onset latency modestly. Several studies have shown pregabalin improves sleep quality of those who take it for various indications. It is unknown if this effect is carried over to those who take it recreationally.<ref>{{cite journal | vauthors=((Arnold, L. M.)), ((Emir, B.)), ((Pauer, L.)), ((Resnick, M.)), ((Clair, A.)) | journal=Pain Medicine (Malden, Mass.) | title=Time to improvement of pain and sleep quality in clinical trials of pregabalin for the treatment of fibromyalgia | volume=16 | issue=1 | pages=176–185 | date= January 2015 | issn=1526-4637 | doi=10.1111/pme.12636}}</ref><ref>{{cite journal | vauthors=((Perez-Lloret, S.)), ((Rojas, G. M.)), ((Menoni, M. C.)), ((Ruiz, G.)), ((Velásquez, C.)), ((Rodriguez, H.)), ((Rey, M. V.)), ((Cardinali, A. D. P.)), ((PGB Study Team)) | journal=Clinical Neuropharmacology | title=Pregabalin beneficial effects on sleep quality or health-related quality of life are poorly correlated with reduction on pain intensity after an 8-week treatment course | volume=35 | issue=1 | pages=21–24 | date= February 2012 | issn=1537-162X | doi=10.1097/WNF.0b013e31823df2dc}}</ref> However, it is not an overly sedating substance when taken in the daytime. | ||
*'''[[Effect::Appetite enhancement]]''' - This effect is not particularly prominent, but is reported to occur in some people. It can have a synergistic effect when combined with [[cannabis]]. | *'''[[Effect::Appetite enhancement]]''' - This effect is not particularly prominent, but is reported to occur in some people. It can have a synergistic effect when combined with [[cannabis]]. | ||
*'''[[Effect::Pain relief]]''' - Pregabalin is effective against certain types of chronic pain, particularly neuropathic pain, but not against acute pain.<ref> Pregabalin in Neuropathic Pain: Evidences and Possible Mechanisms | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915349/</ref> | *'''[[Effect::Pain relief]]''' - Pregabalin is effective against certain types of chronic pain, particularly neuropathic pain, but not against acute pain.<ref>{{cite journal | vauthors=((Verma, V.)), ((Singh, N.)), ((Singh Jaggi, A.)) | journal=Current Neuropharmacology | title=Pregabalin in Neuropathic Pain: Evidences and Possible Mechanisms | volume=12 | issue=1 | pages=44–56 | date= January 2014 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915349/ | issn=1570-159X | doi=10.2174/1570159X1201140117162802}}</ref> | ||
*'''[[Effect::Spontaneous bodily sensations]]''' - The general "body high" of pregabalin can be described as a sharp, pleasurable tingling sensation which is location specific to the hands, feet, and head. | *'''[[Effect::Spontaneous bodily sensations]]''' - The general "body high" of pregabalin can be described as a sharp, pleasurable tingling sensation which is location specific to the hands, feet, and head. | ||
*'''[[Effect::Physical euphoria]]''' - This component, while prominent in the experience, is generally not as strong as the cognitive euphoria that can be induced. The sensation itself can be described as feelings of physical comfort, warmth and bliss. | *'''[[Effect::Physical euphoria]]''' - This component, while prominent in the experience, is generally not as strong as the cognitive euphoria that can be induced. The sensation itself can be described as feelings of physical comfort, warmth and bliss. | ||
*'''[[Effect::Tactile enhancement]]''' | *'''[[Effect::Tactile enhancement]]''' - Although the user’s body may feel numb, the sense of touch can be heightened at the same time. | ||
*'''[[Effect::Muscle twitching]]''' - Somewhat paradoxically, since pregabalin is used as an adjunct treatment for epilepsy, pregabalin, especially in higher doses, can produce muscle spasms.{{citation needed}} Anecdotally, seizures have been reported in overdose.{{citation needed}} | *'''[[Effect::Muscle twitching]]''' - Somewhat paradoxically, since pregabalin is used as an adjunct treatment for epilepsy, pregabalin, especially in higher doses, can produce muscle spasms.{{citation needed}} Anecdotally, seizures have been reported in overdose.{{citation needed}} | ||
*'''[[Effect::Respiratory depression]]''' - While pregabalin may cause respiratory depression, this effect is not as strong as those with [[opioids]] and [[benzodiazepines]].<ref> Postoperative respiratory depression associated with pregabalin: A case series and a preoperative decision algorithm | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206785/</ref> | *'''[[Effect::Respiratory depression]]''' - While pregabalin may cause respiratory depression, this effect is not as strong as those with [[opioids]] and [[benzodiazepines]].<ref>{{cite journal | vauthors=((Eipe, N.)), ((Penning, J.)) | journal=Pain Research & Management : The Journal of the Canadian Pain Society | title=Postoperative respiratory depression associated with pregabalin: A case series and a preoperative decision algorithm | volume=16 | issue=5 | pages=353–356 | date= 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206785/ | issn=1203-6765}}</ref> | ||
*'''[[Effect::Muscle relaxation]]''' - While the muscle relaxation experienced on pregabalin is not as powerful as that of [[diazepam]] or other [[benzodiazepines]], it is still prominent. | *'''[[Effect::Muscle relaxation]]''' - While the muscle relaxation experienced on pregabalin is not as powerful as that of [[diazepam]] or other [[benzodiazepines]], it is still prominent. | ||
*'''[[Effect::Dizziness]]''' - This effect is fairly prevalent at higher doses. | *'''[[Effect::Dizziness]]''' - This effect is fairly prevalent at higher doses. | ||
*'''[[Effect::Perception of bodily lightness]]''' - At very high doses, some users report feeling lighter. | *'''[[Effect::Perception of bodily lightness]]''' - At very high doses, some users report feeling lighter. | ||
*'''[[Effect::Increased libido]]''' ''or'' '''[[Effect::Decreased libido]]''' | *'''[[Effect::Increased libido]]''' ''or'' '''[[Effect::Decreased libido]]''' | ||
*'''[[Effect::Orgasm | *'''[[Effect::Orgasm depression]]''' - Some may experience a delayed but stronger orgasm even if they experience an increase in libido. | ||
*'''[[Effect::Motor control loss]]''' | *'''[[Effect::Difficulty urinating]]''' - This effect is commonly reported by users. | ||
*'''[[Effect::Seizure suppression]]'''<ref> Pregabalin | | *'''[[Effect::Frequent urination]]''' | ||
*'''[[Effect::Motor control loss]]''' - At higher doses this effect resembles that of [[benzodiazepines]] and [[alcohol]]. Users report stumbling and bumping in to walls. | |||
*'''[[Tactile suppression]]''' - This effect can result in the whole body feeling numb, particularly one’s face. At the same time the user’s sense of touch can be enhanced. | |||
*'''[[Effect::Seizure suppression]]''' - Pregabalin is effective at reducing certain types of seizures such as focal seizures and partial seizures.<ref>{{Citation | title=Pregabalin | url=https://www.epilepsy.com/tools-resources/seizure-medication-list/pregabalin}}</ref><ref>{{cite journal | vauthors=((Ryvlin, P.)), ((Perucca, E.)), ((Rheims, S.)) | journal=Neuropsychiatric Disease and Treatment | title=Pregabalin for the management of partial epilepsy | volume=4 | issue=6 | pages=1211–1224 | date= December 2008 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646650/ | issn=1176-6328}}</ref> | |||
*'''[[Effect::Pupil dilation]]''' | |||
}} | }} | ||
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*'''[[Effect::Tracers]]''' - This effect can be seen at high doses and is generally quite mild. It generally does not extend past level 2. | *'''[[Effect::Tracers]]''' - This effect can be seen at high doses and is generally quite mild. It generally does not extend past level 2. | ||
*'''[[Effect::Depth perception distortions]]''' - This effect is quite mild and only appears at very high doses. | *'''[[Effect::Depth perception distortions]]''' - This effect is quite mild and only appears at very high doses. | ||
*'''[[Effect::Object alteration]]''' | *'''[[Effect::Object alteration]]''' - Although this effect is rare, it can still occur spontaneously, typically with heavy doses. | ||
*'''[[Effect::Drifting]]''' | *'''[[Effect::Drifting]]''' | ||
*'''[[Effect::After images]]''' and *'''[[Effect::Frame rate suppression]]''' at high / very high doses. These 2 effects together can make your vision feel more 'slow'. | *'''[[Effect::After images]]''' and *'''[[Effect::Frame rate suppression]]''' at high / very high doses. These 2 effects together can make your vision feel more 'slow'. | ||
*'''[[Effect::Double vision]]'''- This effect is quite mild and inconsistently appears at high doses | *'''[[Effect::Double vision]]'''- This effect is quite mild and inconsistently appears at high doses. | ||
====Hallucinatory states==== | ====Hallucinatory states==== | ||
While | While pregabalin isn't commonly thought off as a hallucinogenic drug, it still can cause dissociative and even psychotic like effects at higher doses. Sleep deprivation and genetics might play a role 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]]. | *'''[[Effect::Internal hallucination]]''' - At high dosages, one may experience dream-like states and [[hypnagogia]]. | ||
*'''[[Effect::External hallucination]]''' - This effect is rare and only | *'''[[Effect::External hallucination]]''' - This effect is rare and only occurs on heavy doses and/or when the user is sleep deprived. This effect can be delirious / psychotic in nature. It can include : [[Object activation]], [[Shadow people]] and [[Transformations]]. It may include even non existent people and animals from a distance, but once the user comes closer they may disappear. | ||
}} | }} | ||
{{effects/disconnective| | {{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, | *'''[[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]]. | ||
}} | }} | ||
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The most prominent of these cognitive effects generally include: | The most prominent of these cognitive effects generally include: | ||
*'''[[Effect::Analysis suppression]]''' | *'''[[Effect::Analysis suppression]]''' | ||
* '''[[Effect::Empathy, affection, and sociability enhancement]]''' - Pregabalin presents distinct [[entactogen|entactogen/empathogenic]] effects. In | * '''[[Effect::Empathy, affection, and sociability enhancement]]''' - Pregabalin presents distinct [[entactogen|entactogen/empathogenic]] effects. In contrast to [[benzodiazepines]] (which merely increase sociability through [[disinhibition]]), at high dosages pregabalin directly increases the urge to communicate with others with feelings of empathy, love, closeness and connection being well-defined. These effects, although weaker than that of [[MDMA]], are still prominent. | ||
*'''[[Effect::Ego inflation]]''' | |||
*'''[[Effect::Novelty enhancement]]''' | |||
*'''[[Effect::Suggestibility enhancement]]''' | *'''[[Effect::Suggestibility enhancement]]''' | ||
*'''[[Effect::Amnesia]]''' - Compared to [[benzodiazepines]], pregabalin is only mildly amnesiac if not combined with other depressants. With chronic usage or high dosages, one should expect more "tip of the tongue" moments and impaired short-term memory (e.g., walking into a room and forgetting what you were supposed to do there). Total blackouts do not seem to occur except in combination with other substances. | *'''[[Effect::Amnesia]]''' - Compared to [[benzodiazepines]], pregabalin is only mildly amnesiac if not combined with other depressants. With chronic usage or high dosages, one should expect more "tip of the tongue" moments and impaired short-term memory (e.g., walking into a room and forgetting what you were supposed to do there). Total blackouts do not seem to occur except in combination with other substances. | ||
*'''[[Effect::Anxiety suppression]]''' | *'''[[Effect::Anxiety suppression]]''' | ||
*'''[[Effect::Emotion enhancement]]''' | *'''[[Effect::Emotion enhancement]]''' | ||
*'''[[Effect::Cognitive euphoria]]'''<ref> Abuse and Misuse Potential of Pregabalin: A Review of the Clinical Evidence | *'''[[Effect::Cognitive euphoria]]'''<ref>{{cite book | date= 2012 | title=Abuse and Misuse Potential of Pregabalin: A Review of the Clinical Evidence | publisher=Canadian Agency for Drugs and Technologies in Health}}</ref> - Many users who take pregabalin describe a moderate to even intense euphoria, even at lower doses. Many users describe it as similar to [[opioid]] induced euphoria. The sensation itself can be described as powerful and overwhelming feelings of emotional bliss, contentment, and happiness. | ||
*'''[[Effect::Disinhibition]]''' | *'''[[Effect::Disinhibition]]''' | ||
*'''[[Effect::Dream potentiation]]''' | *'''[[Effect::Dream potentiation]]''' | ||
*'''[[Effect::Increased music appreciation]]''' - The music | *'''[[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::Motivation enhancement]]''' - Like [[kratom]], pregabalin can be mildly sedative yet increase motivation in a [[stimulant]]-like fashion. | ||
*'''[[Effect::Immersion enhancement]]''' | *'''[[Effect::Immersion enhancement]]''' | ||
*'''[[Effect::Creativity enhancement]]''' - This effect is especially | *'''[[Effect::Creativity enhancement]]''' - This effect is especially noticeable on higher doses. | ||
*'''[[Effect::Depersonalization]]''' ''and'' '''[[Effect::Derealization]]''' - At | *'''[[Effect::Depersonalization]]''' ''and'' '''[[Effect::Derealization]]''' - At 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 | *'''[[Effect::Suicidal ideation]]''' - In heavy doses, this can lead to suicide attempts. | ||
*'''[[Effect::Psychosis]]''' - Even at | *'''[[Effect::Psychosis]]''' - Even at therapeutic doses, pregabalin has been shown to have psychotic side effects in a minority of it's users <ref>{{cite journal | vauthors=((Olaizola, I.)), ((Ellger, T.)), ((Young, P.)), ((Bösebeck, F.)), ((Evers, S.)), ((Kellinghaus, C.)) | journal=Seizure | title=Pregabalin-associated acute psychosis and epileptiform EEG-changes | volume=15 | issue=3 | pages=208–210 | date=1 April 2006 | url=https://www.sciencedirect.com/science/article/pii/S105913110600029X | issn=1059-1311 | doi=10.1016/j.seizure.2006.02.004}}</ref><ref>{{cite journal | vauthors=((Mousailidis, G.)), ((Papanna, B.)), ((Salmon, A.)), ((Sein, A.)), ((Al-Hillawi, Q.)) | journal=BMC Pharmacology and Toxicology | title=Pregabalin induced visual hallucinations – a rare adverse reaction | volume=21 | issue=1 | pages=16 | date=28 February 2020 | url=https://doi.org/10.1186/s40360-020-0395-6 | issn=2050-6511 | doi=10.1186/s40360-020-0395-6}}</ref>. Sleep deprivation strongly potentiates this effect, which may be higher for people genetically predisposed to schizophrenia. | ||
*'''[[Effect::Mania]]''' - | *'''[[Effect::Mania]]''' - When used to treat bipolar disorder <ref>{{cite journal | vauthors=((Schaffer, L. C.)), ((Schaffer, C. B.)), ((Miller, A. R.)), ((Manley, J. L.)), ((Piekut, J. A.)), ((Nordahl, T. E.)) | journal=Journal of Affective Disorders | title=An open trial of pregabalin as an acute and maintenance adjunctive treatment for outpatients with treatment resistant bipolar disorder | volume=147 | issue=1–3 | pages=407–410 | date= May 2013 | issn=1573-2517 | doi=10.1016/j.jad.2012.09.005}}</ref>,it can cause mania, even from therapeutic doses.<ref>{{cite journal | vauthors=((Yukawa, T.)), ((Suzuki, Y.)), ((Fukui, N.)), ((Otake, M.)), ((Sugai, T.)), ((Someya, T.)) | journal=Psychiatry and Clinical Neurosciences | title=Manic symptoms associated with pregabalin in a patient with conversion disorder | volume=67 | issue=2 | pages=129–130 | date= February 2013 | url=https://onlinelibrary.wiley.com/doi/10.1111/pcn.12012 | issn=13231316 | doi=10.1111/pcn.12012}}</ref>. This effect typically occurs in a recreational settings, with heavy doses, or when the user is sleep-deprived. It can appear low in intensity (hypomania) or synergize with [[psychosis]]. However, this effect is rare, and it's not a part of the typical experience. | ||
*'''[[Effect::Thought deceleration]]''' | *'''[[Effect::Thought deceleration]]''' | ||
}} | }} | ||
{{effects/auditory| | {{effects/auditory| | ||
*'''[[Effect::Auditory enhancement | *'''[[Effect::Auditory enhancement]]''' | ||
*'''[[Effect::Auditory distortion | *'''[[Effect::Auditory distortion]]''' - These are usually mild and only present at extremely high doses. | ||
*'''[[Effect::Auditory hallucination]]''' - | *'''[[Effect::Auditory hallucination]]''' - At heavier dosages, one may experience tinnitus or the perception of imagined sounds, such as voices. | ||
}} | }} | ||
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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::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::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 | *'''[[Effect::Motor control loss]]''' - This effect is weaker than 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 | *'''[[Effect::Dizziness]]''' - The after effects are mostly positive with pregabalin, but dizziness can still be here, especially after doing a high dose. | ||
}} | }} | ||
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Pregabalin is used in a medical setting, usually prescribed in capsules, to treat epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. Its use for epilepsy is as an add-on therapy for partial seizures with or without secondary generalization in adults. Some off-label uses of pregabalin include restless leg syndrome, prevention of migraines, social anxiety disorder, and alcohol withdrawal. | Pregabalin is used in a medical setting, usually prescribed in capsules, to treat epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. Its use for epilepsy is as an add-on therapy for partial seizures with or without secondary generalization in adults. Some off-label uses of pregabalin include restless leg syndrome, prevention of migraines, social anxiety disorder, and alcohol withdrawal. | ||
=== | ===Seizure Prevention=== | ||
Pregabalin is useful when added to other treatments, when those other treatments are not controlling partial epilepsy. Its use alone is less effective than some other seizure medications. It is unclear how it compares to gabapentin for this use. | Pregabalin is useful when added to other treatments, when those other treatments are not controlling partial epilepsy. Its use alone is less effective than some other seizure medications. It is unclear how it compares to gabapentin for this use. Pregabalin has also been shown to be effective against alcohol withdrawal induced seizures <ref>{{cite journal | vauthors=((Becker, H. C.)), ((Myrick, H.)), ((Veatch, L. M.)) | journal=Alcohol and Alcoholism | title=PREGABALIN IS EFFECTIVE AGAINST BEHAVIORAL AND ELECTROGRAPHIC SEIZURES DURING ALCOHOL WITHDRAWAL | volume=41 | issue=4 | pages=399–406 | date=1 July 2006 | url=http://academic.oup.com/alcalc/article/41/4/399/162460/PREGABALIN-IS-EFFECTIVE-AGAINST-BEHAVIORAL-AND | issn=1464-3502 | doi=10.1093/alcalc/agl029}}</ref>. | ||
===Neuropathic pain=== | ===Neuropathic pain=== | ||
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====Opioids==== | ====Opioids==== | ||
Anecdotal reports<ref>Kämmerer, N., Lemenager, T., Grosshans, M., Kiefer, F., | Anecdotal reports<ref>{{cite journal | vauthors=((Kämmerer, N.)), ((Lemenager, T.)), ((Grosshans, M.)), ((Kiefer, F.)), ((Hermann, D.)) | journal=Psychiatrische Praxis | title=Pregabalin zur Reduktion von Opiatentzugssymptomen | volume=39 | issue=07 | pages=351–352 | date=11 June 2012 | url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-0032-1305042 | issn=0303-4259 | doi=10.1055/s-0032-1305042}}</ref> exist of successful discontinuation of opioid use by supplementing with pregabalin. | ||
====Tobacco==== | ====Tobacco==== | ||
One placebo-controlled four-day trial (n=24 completed) investigated the effects of pregabalin on smoking cessation in non-treatment-seeking smokers.<ref>Herman, A. I., Waters, A. J., McKee, S. A., | One placebo-controlled four-day trial (n=24 completed) investigated the effects of pregabalin on smoking cessation in non-treatment-seeking smokers.<ref>{{cite journal | vauthors=((Herman, A. I.)), ((Waters, A. J.)), ((McKee, S. A.)), ((Sofuoglu, M.)) | journal=Psychopharmacology | title=Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive performance in smokers | volume=220 | issue=3 | pages=611–617 | date= April 2012 | url=http://link.springer.com/10.1007/s00213-011-2507-x | issn=0033-3158 | doi=10.1007/s00213-011-2507-x}}</ref> This study did not find any statistically significant effect on smoking behavior, although pregabalin reduced some withdrawal symptoms: anxiety, irritability, and frustration. Pregabalin also reduced the measure of subjective "liking" after smoking a cigarette. | ||
====Alcohol==== | ====Alcohol==== | ||
A meta-review of five studies concerning the use of pregabalin in treating alcoholism or alcohol withdrawal found positive results for relapse prevention in sober patients at dosages of 150-450 mg/day, but conflicting results for the treatment of acute alcohol withdrawal.<ref>Guglielmo, R., Martinotti, G., Clerici, M., | A meta-review of five studies concerning the use of pregabalin in treating alcoholism or alcohol withdrawal found positive results for relapse prevention in sober patients at dosages of 150-450 mg/day, but conflicting results for the treatment of acute alcohol withdrawal.<ref>{{cite journal | vauthors=((Guglielmo, R.)), ((Martinotti, G.)), ((Clerici, M.)), ((Janiri, L.)) | journal=Advances in Therapy | title=Pregabalin for Alcohol Dependence: A Critical Review of the Literature | volume=29 | issue=11 | pages=947–957 | date= November 2012 | url=http://link.springer.com/10.1007/s12325-012-0061-5 | issn=0741-238X | doi=10.1007/s12325-012-0061-5}}</ref> Two of the studies concerned the only maintenance of abstinence. Both showed positive results. In one of them (n=59), pregabalin compared favorably to naltrexone on the measure of days abstinent from any amount of alcohol. | ||
====Benzodiazepines==== | ====Benzodiazepines==== | ||
One open-label pilot study<ref>Oulis, P., Konstantakopoulos, G., Kouzoupis, A. V., Masdrakis, V. G., Karakatsanis, N. A., Karapoulios, E., | One open-label pilot study<ref>{{cite journal | vauthors=((Oulis, P.)), ((Konstantakopoulos, G.)), ((Kouzoupis, A. V.)), ((Masdrakis, V. G.)), ((Karakatsanis, N. A.)), ((Karapoulios, E.)), ((Kontoangelos, K. A.)), ((Papadimitriou, G. N.)) | journal=Human Psychopharmacology: Clinical and Experimental | title=Pregabalin in the discontinuation of long-term benzodiazepines’ use | volume=23 | issue=4 | pages=337–340 | date= June 2008 | url=https://onlinelibrary.wiley.com/doi/10.1002/hup.937 | issn=08856222 | doi=10.1002/hup.937}}</ref> of 15 individuals with high-dose [[benzodiazepine]] dependence reported that all subjects have successfully discontinued benzodiazepines within 14 weeks, while taking supplemental doses of 225-900mg pregabalin/day. The patients also showed reduced anxiety levels and better cognitive functioning. Pregabalin was well tolerated. | ||
==Toxicity and harm potential== | ==Toxicity and harm potential== | ||
Pregabalin likely has a [[Toxicity::low toxicity]] relative to dose. However, it is potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]. | Pregabalin likely has a [[Toxicity::low toxicity]] relative to dose. However, it is potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]. | ||
===Seizure Risk=== | |||
Pregabalin has been shown to induce and or increase the risk of seizures at recreational dosages.<ref>https://doi.org/10.1101/cshperspect.a022863</ref><ref>https://doi.org/10.1111/j.0013-9580.2004.455003.x</ref><ref>https://doi.org/10.1111/j.0013-9580.2004.455003.x</ref> There is little evidence showing there is a concern at medical dosages (600mg and under). This risk may be increased when mixed with other drugs that lower seizure threshold. Caution is recommended when using doses of higher than 600mg. Reducing various susceptibility factors may also be beneficial in lowering this risk. Susceptibility factors may include things such as low sodium, lack of sleep, and intensive physical activity. | |||
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance. | It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance. | ||
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The [[LD50|LD<sub>50</sub>]] for rodents has been established to be greater than 5000mg/kg. Rat IV LD50 was also determined to be greater than 300mg/kg.<ref>Lyrica material data sheet | http://web.archive.org/web/20161203214718/http://www.pfizer.com/files/products/material_safety_data/722.pdf</ref> | The [[LD50|LD<sub>50</sub>]] for rodents has been established to be greater than 5000mg/kg. Rat IV LD50 was also determined to be greater than 300mg/kg.<ref>Lyrica material data sheet | http://web.archive.org/web/20161203214718/http://www.pfizer.com/files/products/material_safety_data/722.pdf</ref> | ||
In terms of humans, there exists a case report of a man who ingested 8,400mg pregabalin and eventually fell into a coma but was managed with supportive care alone until he regained consciousness.<ref>Wood, D. M., Berry, D. J., Glover, G., Eastwood, J., | In terms of humans, there exists a case report of a man who ingested 8,400mg pregabalin and eventually fell into a coma but was managed with supportive care alone until he regained consciousness.<ref>{{cite journal | vauthors=((Wood, D. M.)), ((Berry, D. J.)), ((Glover, G.)), ((Eastwood, J.)), ((Dargan, P. I.)) | journal=Journal of Medical Toxicology | title=Significant Pregabalin Toxicity Managed with Supportive Care Alone | volume=6 | issue=4 | pages=435–437 | date= December 2010 | url=http://link.springer.com/10.1007/s13181-010-0052-3 | issn=1556-9039 | doi=10.1007/s13181-010-0052-3}}</ref> For comparison, the maximum recommended a therapeutic dose of pregabalin is 600mg/day.<ref>{{Citation | title=Lyrica (pregabalin) for Fibromyalgia: Uses, Dosage, Side Effects, Interactions, Warnings | url=https://www.rxlist.com/lyrica-drug.htm}}</ref> Pfizer's official package insert for Lyrica states that the highest accidental ingestion of pregabalin during clinical trials was 8 g, with no significant consequences.<ref>Lyrica package insert | http://labeling.pfizer.com/ShowLabeling.aspx?id=561#section-10 </ref> | ||
===Tolerance and addiction potential=== | ===Tolerance and addiction potential=== | ||
Pregabalin was initially thought to be non-addictive with a low abuse potential and little tolerance development. However, recreational use of the substance has caused a re-evaluation of this assessment. The euphoric effects of the substance and the development of tolerance can lead to the use of dosages far above the therapeutic range, which suggests both the potential for recreational use and addiction.<ref>Ja, pregabalin kan misbrukes! | http://web.archive.org/web/20160407131805/http://tidsskriftet.no/article/2029812 </ref><ref>Gabapentin and pregabalin: abuse and addiction | Pregabalin was initially thought to be non-addictive with a low abuse potential and little tolerance development. However, recreational use of the substance has caused a re-evaluation of this assessment. The euphoric effects of the substance and the development of tolerance can lead to the use of dosages far above the therapeutic range, which suggests both the potential for recreational use and addiction.<ref>{{Citation | year=2016 | title=Ja, pregabalin kan misbrukes! - Tidsskrift for Den norske legeforening | url=http://web.archive.org/web/20160407131805/http://tidsskriftet.no/article/2029812}}</ref><ref>{{cite journal | journal=Prescrire International | title=Gabapentin and pregabalin: abuse and addiction | volume=21 | issue=128 | pages=152–154 | date= June 2012 | issn=1167-7422}}</ref> | ||
Tolerance will develop to the depressant effects [[Time to full tolerance::within several months of continuous use]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::7 - 14 days]]. Withdrawal symptoms or rebound symptoms are likely to occur after ceasing usage abruptly following a few months or longer of steady dosing and may necessitate a gradual dose reduction. | Tolerance will develop to the depressant effects [[Time to full tolerance::within several months of continuous use]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::7 - 14 days]]. Withdrawal symptoms or rebound symptoms are likely to occur after ceasing usage abruptly following a few months or longer of steady dosing and may necessitate a gradual dose reduction. | ||
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===Interactions=== | ===Interactions=== | ||
One report of a patient entering serotonin syndrome following perioperative | One report of a patient entering serotonin syndrome following perioperative | ||
[[UncertainInteraction::Oxycodone]] and pregabalin exists.<ref>Song, H.-K. | [[UncertainInteraction::Oxycodone]] and pregabalin exists.<ref>{{cite journal | vauthors=((Song, H.-K.)) | journal=Pain Physician | title=Serotonin syndrome with perioperative oxycodone and pregabalin | volume=16 | issue=5 | pages=E632-633 | date= October 2013 | issn=2150-1149}}</ref> However, several studies have failed to find any serotonergic effect whatsoever from pregabalin. One paper states, "Although pregabalin is a structural analog of GABA, it has no clinically significant effects at GABA-A or GABA-B receptors, and it is not converted metabolically into GABA or a GABA agonist. Pregabalin is not a serotonin reuptake inhibitor and does not act as a glutamate receptor antagonist."<ref>{{cite journal | vauthors=((Kavoussi, R.)) | journal=European Neuropsychopharmacology | title=Pregabalin: From molecule to medicine | volume=16 | pages=S128–S133 | date= July 2006 | url=https://linkinghub.elsevier.com/retrieve/pii/S0924977X06000733 | issn=0924977X | doi=10.1016/j.euroneuro.2006.04.005}}</ref> A more recent study writes that "Pregabalin has no involvement with serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake."<ref>{{cite journal | vauthors=((Marks, D. M.)), ((Patkar, A. A.)), ((Masand, P. S.)), ((Pae, C.-U.)) | journal=Psychiatry Investigation | title=Does Pregabalin Have Neuropsychotropic Effects?: A Short Perspective | volume=6 | issue=2 | pages=55–58 | date= June 2009 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796047/ | issn=1738-3684 | doi=10.4306/pi.2009.6.2.55}}</ref> Pregabalin's main mechanism of action is binding and blocking sub receptor on Voltage-Gated Calcium Channels, leading to a downstream reduction of overactive neurons. | ||
If pregabalin has [[serotonin|serotonergic]] effects, it could interact negatively with other serotonergic substances, including [[UncertainInteraction::SSRI]]s, [[UncertainInteraction::MDMA]], various analgesics, and possibly other recreational and medical substances. Given the total lack of evidence for any serotonergic activity in multiple studies, it seems possible that the one reported adverse event was a freak accident, caused by unknown factors. | If pregabalin has [[serotonin|serotonergic]] effects, it could interact negatively with other serotonergic substances, including [[UncertainInteraction::SSRI]]s, [[UncertainInteraction::MDMA]], various analgesics, and possibly other recreational and medical substances. Given the total lack of evidence for any serotonergic activity in multiple studies, it seems possible that the one reported adverse event was a freak accident, caused by unknown factors. | ||
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Pregabalin is regulated as a prescription drug in most countries. | Pregabalin is regulated as a prescription drug in most countries. | ||
*'''Germany:''' Pregabalin is a prescription medicine, according to Anlage 1 AMVV.<ref>https://www.gesetze-im-internet.de/amvv/BJNR363210005.html</ref> | *'''Germany:''' Pregabalin is a prescription medicine, according to Anlage 1 AMVV.<ref>{{Citation | title=AMVV - Verordnung über die Verschreibungspflicht von Arzneimitteln | url=https://www.gesetze-im-internet.de/amvv/BJNR363210005.html}}</ref> | ||
*'''Norway:''' Pregabalin is in prescription schedule B alongside most benzodiazepines and painkillers. It was rescheduled to schedule B from the less restrictive schedule C because of reported recreational use, tolerance development and addiction.<ref>https://nhi.no/for-helsepersonell/nytt-om-legemidler/pregabalin-lyrica-flyttes-til-reseptgruppe-b/</ref> | *'''Norway:''' Pregabalin is in prescription schedule B alongside most benzodiazepines and painkillers. It was rescheduled to schedule B from the less restrictive schedule C because of reported recreational use, tolerance development and addiction.<ref>https://nhi.no/for-helsepersonell/nytt-om-legemidler/pregabalin-lyrica-flyttes-til-reseptgruppe-b/</ref> | ||
*'''Sweden:''' Pregabalin is a prescription drug. classified as a controlled substance, as a schedule V drug, since 24 july 2018 <ref>https://lakemedelsverket.se/Alla-nyheter/NYHETER---2018/Pregabalin-narkotikaklassas/</ref> | *'''Sweden:''' Pregabalin is a prescription drug. classified as a controlled substance, as a schedule V drug, since 24 july 2018 <ref>https://lakemedelsverket.se/Alla-nyheter/NYHETER---2018/Pregabalin-narkotikaklassas/</ref> | ||
*'''Switzerland:''' Pregabalin is listed as a "Abgabekategorie B" pharmaceutical, which requires a prescription.{{citation needed}} | *'''Switzerland:''' Pregabalin is listed as a "Abgabekategorie B" pharmaceutical, which requires a prescription.{{citation needed}} | ||
*'''Turkey''': Pregabalin is a 'green prescription' only substance<ref>YEŞİL REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/01.04.2019%20SKRS%20Ye%C5%9Fil%20Re%C3%A7eteli%20%C4%B0la%C3%A7lar%20Aktif%20SON%20-%20G%C3%9CNCEL_58b1ff4a-2e1c-4867-bad7-eec855d6162a.pdf</ref> | *'''Turkey''': Pregabalin is a 'green prescription' only substance and illegal when sold or possessed without a prescription.<ref>YEŞİL REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/01.04.2019%20SKRS%20Ye%C5%9Fil%20Re%C3%A7eteli%20%C4%B0la%C3%A7lar%20Aktif%20SON%20-%20G%C3%9CNCEL_58b1ff4a-2e1c-4867-bad7-eec855d6162a.pdf</ref>{{citation needed}} | ||
*'''United Kingdom:''' The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription and, for such purposes, it is classified as a Class C drug.<ref> | *'''United Kingdom:''' The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription and, for such purposes, it is classified as a Class C drug.<ref>{{Citation | title=The Misuse of Drugs Act 1971 (Amendment) Order 2018 | url=https://www.legislation.gov.uk/uksi/2018/1356/article/2/made}}</ref> | ||
*'''United States:''' Pregabalin is in Schedule V, indicating "low potential for abuse." For comparison, benzodiazepines are in Schedule IV.<ref>http://web.archive.org/web/20161017105621/https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_15.htm</ref> | *'''United States:''' Pregabalin is in Schedule V, indicating "low potential for abuse." For comparison, benzodiazepines are in Schedule IV.<ref>{{Citation | year=2016 | title=Title 21 CFR - PART 1308 - Section 1308.15 Schedule V | url=http://web.archive.org/web/20161017105621/https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_15.htm}}</ref> | ||
<br /> | |||
== Combinations == | |||
with [[Memantine]] (anecdotal, N=1)<blockquote>Add-on of 20mg to 30mg Memantine per day to 75mg Pregabalin is equivalent to 300mg Pregabalin (I had tolerance of that much at the time. I have chronic anxiety)</blockquote> | |||
==See also== | ==See also== | ||