Talk:Baclofen

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I have doubts that baclofen is a gabapentinoid. Although it blocks α2δ subunits, unlike other gabapentinoids (phenibut, gabapentin and pregabalin), the actions of baclofen on α2δ subunit-containing VGCCs are likely not clinically-relevant. What do you think about it? --Tracer (talk) 20 June 2019 (UTC)


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Death may result when gabapentinoids are combined with other depressants such as opiates, benzodiazepines, barbiturates, thienodiazepines, alcohol or other GABAergic substances.[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 GABAergic
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Bioavailability 74 %[2]
Threshold 5 - 10 mg
Light 10 - 20 mg
Common 20 - 50 mg
Strong 50 - 100 mg
Heavy 100 mg +
Duration
Total 3 - 6 hours
Onset 15 - 60 minutes









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Baclofen (also known as Lioresal, Gablofen, Kemstro, Liofen, Баклосан) is a depressant substance of the gabapentinoid 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 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

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).

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]

Subjective effects

In comparison to other commonly used GABAergic depressants such as alcohol or benzodiazepines, baclofen is reported to be longer lasting, more euphoric and more recreational at higher doses.

The effects listed below are based on the subjective effect index, which is based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy amount of skepticism. It is worth noting that these effects will rarely (if ever) occur all at once but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Visual effects
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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 such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it.
We also recommend that you conduct independent research and use harm reduction practices when using this substance.

Baclofen has a low toxicity relative to dose.[7] 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.

Tolerance and addiction 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 months) 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

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when taken with other substances. The following lists some known dangerous combinations, but cannot be guaranteed to include all of them. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed 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.

  • Russia: Baclofen is available through a prescription.

See also

External links

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. 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
  3. 3.0 3.1 3.2 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.
  4. Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23869179
  5. Enserink, M. (2011). "Anonymous Alcoholic Bankrolls Trial of Controversial Therapy". Science. 332 (6030): 653. doi:10.1126/science.332.6030.653. PMID 21551041.
  6. 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
  7. 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
  8. Delirium associated with baclofen withdrawal: a review of common presentations and management strategies. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16288128
  9. [Severe hyperthermia caused by sudden withdrawal of continuous intrathecal administration of baclofen]. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9033759
  10. Koski, A., Ojanperä, I., & Vuori, E. (2002). Alcohol and benzodiazepines in fatal poisonings. Alcoholism: Clinical and Experimental Research, 26(7), 956-959.