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| {{headerpanel|{{DepressantOD|gabapentinoids}}}}
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| {{SummarySheet}}
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| {{SubstanceBox/Baclofen}}
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| '''Baclofen''' (also known as '''Lioresal''', '''Gablofen''', '''Kemstro''', '''Liofen''', '''Баклосан''') is a [[psychoactive class::depressant]] substance of the [[chemical class::gabapentinoid]] class. It is a derivative of [[GABA]] and is chemically related to [[phenibut]], [[pregabalin]], and [[gabapentin]]. It primarily acts as a [[GABA]]<sub>B</sub> [[receptor]] [[agonist]].
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| Baclofen was synthesized in 1962 at Ciba-Geigy, a Swiss pharmaceutical company.<ref name="Froestl">Froestl, Wolfgang (2010). "Chemistry and Pharmacology of GABAb Receptor Ligands". In Blackburn, Thomas P. (ed.). GABAb Receptor Pharmacology – A Tribute to Norman Bowery. Advances in Pharmacology. 58. pp. 19–62. doi:10.1016/S1054-3589(10)58002-5. ISBN 978-0-12-378647-0. PMID 20655477.</ref> Today, it is used clinically to treat muscle spasticity, and holds promise as a treatment for [[alcoholism]].<ref>Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23869179</ref>
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| [[Subjective effects]] include [[sedation]], [[anxiety suppression]], [[muscle relaxation]], and moderate [[euphoria]]. It is usually described as somewhat similar to [[phenibut]] in its effects.
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| It is highly advised to use [[harm reduction practices]] if using this substance.
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| ==History and culture==
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| Baclofen was synthesized in 1962 by Heinrich Keberle at Ciba (pharmaceutical company) in Basel, Switzerland, based on the idea of enhancing the lipophilicity of GABA in order to achieve penetration of the blood-brain barrier.<ref name="Froestl" /> It was marketed as '''Lioresal''' in 1972.<ref name="Froestl" />
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| In his 2008 book, ''Le Dernier Verre'' (translated literally as "The Last Glass" and published in English as "The End of my Addiction"), French-American cardiologist Olivier Ameisen described how he treated his alcoholism with baclofen. Inspired by this book, an anonymous donor gave $750,000 to the University of Amsterdam to initiate a clinical trial of high-dose baclofen, which Ameisen had called for since 2004.<ref>Enserink, M. (2011). "Anonymous Alcoholic Bankrolls Trial of Controversial Therapy". Science. 332 (6030): 653. doi:10.1126/science.332.6030.653. PMID 21551041.</ref>
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| ==Chemistry==
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| As with [[phenibut]], baclofen is a derivative of γ-aminobutyric acid ([[GABA]]), except with a chlorine-substituted phenyl group in the β-position of the molecule. It is a chiral molecule and thus has two potential configurations as (R)- and (S)-enantiomers. It has an almost identical chemical structure to [[F-phenibut]] (only replacing a fluorine with a chlorine atom in the para-position of the phenyl group).
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| ==Pharmacology==
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| Baclofen produces its effects by activating the [[GABA]]<sub>B</sub> [[receptor]], similar to the drug [[phenibut]] which also activates this [[receptor]] and shares some of its effects. Baclofen is postulated to block mono-and-polysynaptic reflexes by acting as an inhibitory ligand, inhibiting the release of excitatory [[neurotransmitter]]s.
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| Similarly to [[phenibut]] (β-phenyl-GABA), as well as [[pregabalin]] (β-isobutyl-GABA), which are close analogues of baclofen, baclofen (β-(4-chlorophenyl)-GABA) has been found to block α2δ subunit-containing voltage-gated calcium channels (VGCCs). However, it is weaker relative to phenibut in this action (Ki = 23 and 39 μM for R- and S-phenibut and 156 μM for baclofen). Moreover, baclofen is in the range of 100-fold more potent by weight as an agonist of the [[GABA]]<sub>B</sub> receptor in comparison to [[phenibut]], and in accordance, is used at far lower relative dosages. As such, the actions of baclofen on α2δ subunit-containing VGCCs are likely not clinically-relevant.<ref>R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/26234470</ref>
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| ==Subjective effects==
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| In comparison to other commonly used [[GABA|GABAergic]] depressants such as [[alcohol]] or [[benzodiazepines]], baclofen is reported to be longer lasting, more euphoric and more recreational at higher doses.
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| {{Preamble/SubjectiveEffects}}
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| {{effects/base
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| |{{effects/physical|
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| *'''[[Effect::Stimulation]]''' and '''[[Effect::Sedation]]'''
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| *'''[[Effect::Physical euphoria]]'''
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| *'''[[Effect::Muscle relaxation]]'''
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| *'''[[Effect::Respiratory depression]]'''
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| *'''[[Effect::Nausea]]'''
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| *'''[[Effect::Orgasm suppression]]'''
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| *'''[[Effect::Pain relief]]'''
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| *'''[[Effect::Motor control loss]]'''
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| *'''[[Effect::Diarrhea]]'''
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| *'''[[Effect::Dizziness]]'''
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| *'''[[Effect::Dehydration]]'''
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| *'''[[Effect::Headaches]]'''
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| *'''[[Effect::Muscle cramps]]'''
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| *'''[[Effect::Pupil dilation]]'''
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| *'''[[Effect::Appetite enhancement]]'''
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| *'''[[Effect::Frequent urination]]'''
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| *'''[[Effect::Pain relief]]'''
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| *'''[[Effect::Difficulty urinating]]'''
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| }}
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| {{effects/visual|
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| *'''[[Effect::Internal hallucination]]'''
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| }}
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| |{{effects/cognitive|
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| *'''[[Effect::Anxiety suppression]]'''
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| *'''[[Effect::Disinhibition]]''' -
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| *'''[[Effect::Cognitive euphoria]]'''
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| *'''[[Effect::Empathy, affection, and sociability enhancement]]'''
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| *'''[[Effect::Motivation enhancement]]'''
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| *'''[[Effect::Analysis suppression]]'''
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| *'''[[Effect::Thought deceleration]]'''
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| *'''[[Effect::Increased music appreciation]]'''
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| *'''[[Effect::Amnesia]]'''
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| *'''[[Compulsive redosing]]'''
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| }}
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| {{effects/aftereffects|
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| *'''[[Effect::Anxiety|Rebound anxiety]]'''
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| *'''[[Effect::Sleepiness|Residual sleepiness]]'''
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| *'''[[Effect::Depression]]'''
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| *'''[[Effect::Depersonalization]]'''
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| *'''[[Effect::Dream potentiation]]'''
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| }}
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| }}
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| ===Experience reports===
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| There are currently {{#ask:[[Category:Baclofen]][[Category:Experience]] | format=count}} experience reports which describe the effects of this compound in our [[experience index]].
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| {{#ask: [[Category:SUBSTANCE]][[Category:Experience]]|format=ul|Columns=1}}
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| Additional experience reports can be found here:
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| * [https://www.erowid.org/experiences/subs/exp_Pharms_Baclofen.shtml Erowid Experience Vaults: Baclofen]
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| ==Toxicity and harm potential==
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| Baclofen has a [[Toxicity::low toxicity]] relative to dose.<ref>A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25028414</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]], [[benzodiazepines]] or [[opioids]]]].
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| It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance.
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| ===Tolerance and addiction potential===
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| Baclofen is [[Addiction potential::moderately physically and psychologically addictive]], although this usually only occurs with heavy abuse of the substance.
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| Discontinuation of baclofen can be associated with a withdrawal syndrome which resembles benzodiazepine withdrawal and alcohol withdrawal. Withdrawal symptoms are more likely if baclofen is used for long periods of time (more than a couple of months) and can occur from low or high doses. The severity of baclofen withdrawal depends on the rate at which it is discontinued. Thus to minimise withdrawal symptoms, the dose should be tapered down slowly when discontinuing baclofen therapy. Abrupt withdrawal is more likely to result in severe withdrawal symptoms. Acute withdrawal symptoms can be stopped by recommencing baclofen.<ref>Delirium associated with baclofen withdrawal: a review of common presentations and management strategies. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16288128</ref>
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| Withdrawal symptoms may include auditory hallucinations, visual hallucinations, tactile hallucinations, delusions, confusion, agitation, delirium, disorientation, fluctuation of consciousness, insomnia, dizziness, nausea, inattention, memory impairments, perceptual disturbances, itching, anxiety, depersonalization, hypertonia, hyperthermia (higher than normal temperature without infection), formal thought disorder, psychosis, mania, mood disturbances, restlessness, and behavioral disturbances, tachycardia, seizures, tremors, autonomic dysfunction, hyperpyrexia (fever), extreme muscle rigidity resembling neuroleptic malignant syndrome and rebound spasticity.<ref>[Severe hyperthermia caused by sudden withdrawal of continuous intrathecal administration of baclofen]. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9033759</ref>
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| Baclofen produces cross-tolerance with [[Cross-tolerance::all [[GABA]]genic depressants]], meaning that after its consumption, depressants will have a reduced effect.
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| ===Dangerous interactions===
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| {{DangerousInteractions/Intro}}
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| *'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2M2B]], [[alcohol]],<ref>Koski, A., Ojanperä, I., & Vuori, E. (2002). Alcohol and benzodiazepines in fatal poisonings. Alcoholism: Clinical and Experimental Research, 26(7), 956-959.</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.
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| *'''[[Dissociatives]]''' - This combination can result in an increased risk of vomiting during unconsciousness and dying 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.
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| *'''[[Stimulants]]''' - It is dangerous to combine phenibut with [[stimulant]]s due to the risk of excessive intoxication. Stimulants mask the [[sedation|sedative]] effect of phenibut, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the 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 only dosing a certain amount of phenibut per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
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| ==Legal status==
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| {{legalStub}}
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| *'''Russia:''' Baclofen is available through a prescription.
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| ==See also==
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| *[[Responsible use]]
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| *[[Depressant]]
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| *[[Gabapentinoid]]
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| *[[GABA]]
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| *[[Phenibut]]
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| *[[F-Phenibut]]
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| *[[Gabapentin]]
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| *[[Pregabalin]]
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| ==External links==
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| *[https://en.wikipedia.org/wiki/Baclofen Baclofen (Wikipedia)]
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| *[https://www.erowid.org/pharms/baclofen/ Baclofen (Erowid Vault)]
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| *[https://isomerdesign.com/PiHKAL/explore.php?id=2379 Baclofen (TiHKAL / Isomer Design)]
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| ==References==
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| <references/>
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| [[Category:Anxiolytic]]
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| [[Category:Psychoactive substance]]
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| [[Category:Depressant]]
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| [[Category:Gabapentinoid]]
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| [[Category:Approval]]
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| {{#set:Featured=true}}
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