Baclofen
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Fatal overdose may occur when GABAergic substances are combined with other depressants such as opiates, benzodiazepines, barbiturates, gabapentinoids, thienodiazepines or alcohol.[1]
It is strongly discouraged to combine these substances, particularly in common to heavy doses.
| Summary sheet: Baclofen |
| Baclofen | |||||||||||||||||||||||||||||||
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| Chemical Nomenclature | |||||||||||||||||||||||||||||||
| Common names | Baclofen, Lioresal | ||||||||||||||||||||||||||||||
| Substitutive name | β-(4-chlorophenyl)-GABA | ||||||||||||||||||||||||||||||
| Systematic name | 5-amino-4-(4-chlorophenyl)-1-hydroxypentan-2-one | ||||||||||||||||||||||||||||||
| Class Membership | |||||||||||||||||||||||||||||||
| Psychoactive class | Depressant | ||||||||||||||||||||||||||||||
| Chemical class | Butyric acid | ||||||||||||||||||||||||||||||
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Baclofen (also known as Lioresal, Gablofen, Kemstro, Liofen) is a depressant substance of the butyric acid class. It is a derivative of GABA and is chemically related to phenibut, pregabalin, and gabapentin. It primarily acts as a GABAB receptor agonist.
Baclofen was synthesized in 1962 at Ciba-Geigy, a Swiss pharmaceutical company.[3] Today, it is used clinically to treat muscle spasticity, and holds promise as a treatment for alcoholism.[4]
Subjective effects include sedation, anxiety suppression, muscle relaxation, and moderate euphoria. It is usually described as somewhat similar to phenibut in its effects. It is reported to have lower recreational effects such as euphoria compared to depressants like alprazolam.
Baclofen has moderate abuse potential and produces physical dependence with chronic use. Once physical dependence to a GABAergic substance occurs, the user cannot stop use abruptly without risking withdrawal symptoms such as anxiety, muscle tremors, and in severe cases, seizures.
It is highly advised to use harm reduction practices if using this substance.
History and culture
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.[3] It was marketed as Lioresal in 1972.[3]
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.[5]
Chemistry
Baclofen is a derivative of γ-aminobutyric acid (GABA), except with a chlorine-substituted phenyl group in the β-position of the molecule.
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).
It is a chiral molecule and thus has two potential configurations as (R)- and (S)-enantiomers.
Baclofen is a white (or sometimes off-white) mostly odorless crystalline powder, with a molecular weight of 213.66 g/mol and it is somewhat soluble in water.
Pharmacology
Baclofen produces its effects by activating the GABAB 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 neurotransmitters.
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 GABAB 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.[6]
The drug is rapidly absorbed after oral administration and is widely distributed throughout the body. Biotransformation is low: the drug is predominantly excreted unchanged by the kidneys.[7]
Subjective effects
Baclofen is often compared to phenibut, but more "messy", less euphoric, anxiolytic, and causing a stronger dizziness.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects 
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- Stimulation and Sedation - Baclofen has different effects on physical energy levels depending on the dosage used. At lower doses, baclofen has a mild physical and mental stimulation effect, encouraging movement, wakefulness, and productivity. At common doses and higher, baclofen is physically sedating, encouraging sleep and lethargy.
- Physical euphoria - Compared to gabapentinoids (such as phenibut) and benzodiazepines, baclofen is considered less euphoric.
- Muscle relaxation
- Respiratory depression
- Nausea - Compared to gabapentinoids (such as phenibut) and alcohol, baclofen has stronger and longer lasting nausea.
- Orgasm suppression
- Increased libido - This effect is more pronounced at lower doses.
- Pain relief
- Motor control loss
- Diarrhea
- Dizziness - Compared to gabapentinoids (such as phenibut), baclofen has stronger dizziness.
- Dehydration[citation needed]
- Headaches
- Pupil dilation
- Appetite enhancement
- Frequent urination
- Difficulty urinating
Cognitive effects 
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- Anxiety suppression - This effect is less pronounced compared to gabapentinoids or benzodiazepines.
- Disinhibition
- Compulsive redosing - This effect is generally caused by the anxiety the user experiences during the comedown.
- Cognitive euphoria - Compared to gabapentinoids (such as phenibut) and benzodiazepines, this effect is pronounced less.
- Empathy, affection, and sociability enhancement
- Motivation enhancement
- Analysis suppression
- Thought deceleration
- Increased music appreciation
- Amnesia
- Addiction suppression - Baclofen is also used for alcoholism treatment.
- Confusion
After effects 
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- Rebound anxiety
- Residual sleepiness -This effect is mostly caused by decreased blood pressure.
- Cognitive fatigue - This effect is mostly caused by decreased blood pressure.
- Compulsive redosing
- Low Blood Pressure
- Low Heart Rate
- Depression
- Depersonalization
Experience reports
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
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This toxicity and harm potential section is a stub. As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. |
Baclofen has a low toxicity relative to dose.[2] However, it is potentially lethal when mixed with depressants like alcohol, benzodiazepines or opioids.
It is strongly recommended that one use harm reduction practices when using this substance.
Dependence and abuse potential
Baclofen is moderately physically and psychologically addictive. 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 weeks) and can occur from low or high doses.
The severity of baclofen withdrawal depends on the rate at which it is discontinued. Abrupt withdrawal is more likely to result in severe withdrawal symptoms. Acute withdrawal symptoms can be stopped by recommencing baclofen.[8]
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction. Withdrawal symptoms may include auditory hallucinations, visual hallucinations, tactile hallucinations, delusions, confusion, delirium, disorientation, fluctuation of consciousness, insomnia, dizziness, nausea, inattention, memory impairments, perceptual disturbances, itchiness, anxiety, depersonalization, hypertonia, hyperthermia, psychosis, mania, mood disturbances, tachycardia, seizures, tremors, autonomic dysfunction, hyperpyrexia (fever), extreme muscle rigidity resembling neuroleptic malignant syndrome and rebound spasticity.[9]
Baclofen produces cross-tolerance with all GABAgenic depressants, meaning that after its consumption, depressants will have a reduced effect.
Dangerous interactions
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- Depressants (1,4-Butanediol, 2M2B, Alcohol, [10] 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 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.
- Stimulants - It is dangerous to combine baclofen with stimulants due to the risk of excessive intoxication. Stimulants mask the sedative effect of baclofen, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of baclofen will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of baclofen per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
Legal status
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This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it. |
- Germany: Baclofen is a prescription medicine, according to Anlage 1 AMVV.[11]
- Russia: Baclofen is available through a prescription.[citation needed]
- Sweden: Baclofen is available through a prescription.[12]
- Turkey: Baclofen is available at pharmacies without prescription.[citation needed]
- United States: Baclofen is not a scheduled substance, but may only be sold with a prescription.[13]
See also
External links
References
- ↑ Risks of Combining Depressants - TripSit
- ↑ 2.0 2.1 Agarwal, S. K., Kriel, R. L., Cloyd, J. C., Coles, L. D., Scherkenbach, L. A., Tobin, M. H., Krach, L. E. (January 2015). "A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers". Journal of Child Neurology. 30 (1): 37–41. doi:10.1177/0883073814535504. ISSN 1708-8283.
- ↑ 3.0 3.1 3.2 Froestl, W. (2010). "Advances in Pharmacology". Chemistry and Pharmacology of GABAB Receptor Ligands. 58. Elsevier. pp. 19–62. doi:10.1016/S1054-3589(10)58002-5. ISBN 9780123786470.
- ↑ Brennan, J. L., Leung, J. G., Gagliardi, J. P., Rivelli, S. K., Muzyk, A. J. (2013). "Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review". Clinical Pharmacology: Advances and Applications. 5: 99–107. doi:10.2147/CPAA.S32434. ISSN 1179-1438.
- ↑ Enserink, M. (6 May 2011). "Anonymous Alcoholic Bankrolls Trial of Controversial Therapy". Science. 332 (6030): 653–653. doi:10.1126/science.332.6030.653. ISSN 0036-8075.
- ↑ Zvejniece, L., Vavers, E., Svalbe, B., Veinberg, G., Rizhanova, K., Liepins, V., Kalvinsh, I., Dambrova, M. (October 2015). "R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects". Pharmacology, Biochemistry, and Behavior. 137: 23–29. doi:10.1016/j.pbb.2015.07.014. ISSN 1873-5177.
- ↑ Wuis, E. W., Dirks, M. J. M., Termond, E. F. S., Vree, T. B., Van der Kleijn, E. (1 March 1989). "Plasma and urinary excretion kinetics of oral baclofen in healthy subjects". European Journal of Clinical Pharmacology. 37 (2): 181–184. doi:10.1007/BF00558228. ISSN 1432-1041.
- ↑ Leo, R. J., Baer, D. (December 2005). "Delirium associated with baclofen withdrawal: a review of common presentations and management strategies". Psychosomatics. 46 (6): 503–507. doi:10.1176/appi.psy.46.6.503. ISSN 0033-3182.
- ↑ Grenier, B., Mesli, A., Cales, J., Castel, J. P., Maurette, P. (1996). "[Severe hyperthermia caused by sudden withdrawal of continuous intrathecal administration of baclofen]". Annales Francaises D’anesthesie Et De Reanimation. 15 (5): 659–662. doi:10.1016/0750-7658(96)82130-7. ISSN 0750-7658.
- ↑ Koski, A., Ojanpera, I., Vuori, E. (July 2002). "Alcohol and Benzodiazepines in Fatal Poisonings". Alcoholism: Clinical and Experimental Research. 26 (7): 956–959. doi:10.1111/j.1530-0277.2002.tb02627.x. ISSN 0145-6008.
- ↑ "Anlage 1 AMVV" (in German). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. Retrieved November 13, 2020.
- ↑ Baklofen Mylan - FASS Allmänhet
- ↑ Baclofen: MedlinePlus Drug Information