Chemistry:Muscimol

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Muscimol, also known as agarin, pantherine, or pyroibotenic acid, is a GABAA receptor agonist with sedative and hallucinogenic effects and the principal psychoactive constituent of Amanita mushrooms such as Amanita muscaria (fly agaric) and Amanita pantherina (panther cap).[1][2][3][4][5] It is a 3-hydroxyisoxazole alkaloid and is closely related structurally to the neurotransmitter γ-aminobutyric acid (GABA).[3][2][6] The compound is widely used as a ligand and agonist of the GABAA receptor in scientific research.[3][2] Muscimol is typically taken orally, but may also be smoked.[2][7][6][8] Peak effects occur after 1 to 3 hours orally[8][9][10] and its duration is 4 to 10 hours but up to 24 hours.[8][6][11][12]

The effects of muscimol in humans include central depression, sedation, sleep, cognitive and motor impairment, hallucinations, perceptual distortion, and muscle twitching, among others.[13][7][14][15][12] Muscimol acts as a potent GABAA receptor full agonist.[3][2][16] However, it acts as a preferential supra-maximal agonist at extrasynaptic δ subunit-containing GABAA receptors.[17][18][19][3][2] It is also a potent GABAA-ρ receptor partial agonist and a weak GABA reuptake inhibitor.[3][2][6] The drug is inactive at the GABAB receptor but is a substrate of GABA transaminase (GABA-T).[3][7][6] Muscimol mostly exerts its effects via GABAA receptor activation.[7] It is very different from drugs like benzodiazepines and barbiturates as it is an orthosteric agonist of the GABAA receptor rather than an allosteric modulator.[2][20] Unlike GABA, muscimol crosses the blood–brain barrier and hence is centrally active.[20][4][7] Muscimol is a conformationally restrained analogue of GABA.[3][6] The related compound and Amanita species constituent ibotenic acid is a prodrug of muscimol, but also has neurotoxic effects.[2][4][6]

Muscimol was first isolated from Amanita muscaria and hence was discovered in 1964.[3][2][5] It has been limitedly clinically studied as a potential pharmaceutical drug for a number of uses, such as treatment of epilepsy.[2][21][22][23] In addition, analogues and derivatives of muscimol, such as the selective GABAA receptor agonist gaboxadol (THIP; LU-2-030) and the selective GABA reuptake inhibitor tiagabine (Gabitril), have been developed as pharmaceutical drugs.[3][24][6][25] Muscimol and Amanita muscaria mushrooms have rarely been used as recreational drugs historically.[8] By the mid-2020s however, use of these substances, including recreational use for hallucinogenic effects and microdosing for claimed therapeutic benefits, has become increasingly prominent.[2][26][27][28][29] The most commonly cited therapeutic reason for their use is to improve sleep.[26] Muscimol is not a controlled substance and is unregulated in most of the world, including in most of the United States and Europe.[2][30][27]

Natural occurrence

Amanita muscaria (fly agaric) mushrooms, which contain muscimol.

The main natural sources of muscimol are fungi of the genus Amanita, such as Amanita muscaria (fly agaric) and Amanita pantherina (panther cap). It is produced in the mushrooms along with muscarine (which is present in trace amounts and it is not active), muscazone, and ibotenic acid.[31][4] In Amanita muscaria, the layer just below the skin of the cap contains the highest amount of muscimol, and is therefore the most psychoactive portion.[32]

Use and effects

The properties and effects of muscimol in humans have been limitedly assessed in clinical studies.[7][9][14][15] It has been assessed in these studies at doses of 5 to 15 mg orally.[7] The oral threshold dose of muscimol is approximately 6 mg,[7][33] while the psychoactive dose range has been said to range from approximately 8 to 15 mg.[2][6][11] As little as 1 g of dried Amanita muscaria button may contain this amount of muscimol, although the potency varies greatly among mushrooms.[34] According to Jonathan Ott, a 15 mg dose is "psychoptic" while a 20 mg dose is "visionary".[8] The onset of action of muscimol, via isolated muscimol or Amanita muscaria consumption orally, is between 30 minutes and 2 hours,[6][15][34][12] with peak effects occurring after 1 to 3 hours.[8][9][10] The duration is 4 to 10 hours, but some effects may persist for up to 24 hours.[8][6][35][11][9][10][12] In one publication, the effects of muscimol were described as follows:[14][15]

"Waser (1967) describes the effects of self-administration of 10–15 mg. of muscimol as '. . . intense hallucinations as with LSD were missing . . . there resulted considerable disturbances of psychic functions, such as orientation in space and time, visual perception, process of thinking, speech, and some new psychic phenomena of illusions and echo pictures'. Higher doses tended to produce severe intoxication in man, with painful muscular twitching, considerable agitation, and vivid hallucinations."[14][15]

The effects of muscimol in humans in different studies have been found to include sedation, central depression, dizziness, incoordination or clumsiness, relaxation, reduced anxiety, mood improvement or euphoria, sleep, rich dreaming, difficulty speaking, impaired attention, focus, and concentration, impaired learning, confusion, a glassy-eyed stare, loss of appetite, stimulation, agitation, hallucinogenic effects, echo-like pseudohallucinations (visual and auditory, vivid hallucinations, dissociation, psychosis, and delirium.[7][2][6][14][12] At higher doses, coma, seizures, and death can occur.[6][2] Physical effects of muscimol can include muscle twitching or tremors, flushing, slightly increased blood pressure, nausea, vomiting, abdominal pain, diarrhea, and increased salivation, among others.[7][6][2][13][12] After-effects have been reported to include fatigue, inactivity, and headache and migraine.[7] Some can find the hallucinogenic effects of muscimol to be highly unpleasant, for instance one person being "shaken and frightened" by the experience.[33]

Muscimol is said to have similar effects on sleep in rodents as the related experimental pharmaceutical drug gaboxadol (THIP).[24][3][36][37] In humans, gaboxadol decreases sleep onset latency, increases sleep duration, increases slow wave sleep (SWS) and slow wave activity (SWA), and does not suppress REM sleep.[36] The effects of muscimol and gaboxadol on sleep differ from those of widely used GABAA receptor positive allosteric modulators like benzodiazepines and Z-drugs, which can instead disrupt SWS and SWA despite improving sleep onset and duration.[24][3][36][38] Although muscimol and gaboxadol have similar effects on sleep, muscimol has additionally been found to increase REM sleep unlike gaboxadol.[37]

Ibotenic acid, a prodrug of muscimol, is active at doses of approximately 20 to 100 mg orally in humans.[8][7][6][2] About 10 to 20% of ibotenic acid is said to be converted into muscimol following decarboxylation.[26][8] Substantial amounts of ibotenic acid are also rapidly excreted unchanged.[8][33]

Overdose and toxicity

The German Federal Institute for Risk Assessment warns that muscimol and products containing it pose serious health risks, especially to children.[39]

The toxicity and safety profile of muscimol has been studied in various contexts, both experimental and clinical.[40][34][41] It is described as being a relatively toxic compound in animals.[42][21] The median lethal dose (LD50) in mice is 5.6 to 7 mg/kg intravenously, 3.8 mg/kg subcutaneously, 2.5 to 12 mg/kg intraperitoneally, and 22 mg orally.[40][41][34][43][44] The LD50 in rats is 4.5 mg/kg intravenously and 45 mg/kg orally.[40][34][45] Muscimol shows considerably greater lethal potency or toxicity than gaboxadol.[41][44][21]

A study on non-human primates indicated that muscimol, when administered in escalating doses, caused reversible hyperkinesia and dyskinesias at higher doses, but no long-term toxicity was observed on histological examination.[46] Muscimol has shown potential as an anticonvulsant, blocking seizures induced by various agents in animal models without causing significant toxicity at therapeutic doses.[47] Muscimol exhibits dose-dependent effects with higher doses leading to significant, but reversible, central nervous system symptoms.[48]

The dose of muscimol that is thought to be potentially fatal in humans has been reported to be approximately 90 mg,[34] which is 15 times the reported threshold hallucinogenic dose of 6 mg.[34][7][33] According to the North American Mycological Association (NAMA) however, "[i]n humans, no reliably documented cases of death from toxins in these mushrooms [mushrooms that contain isoxazole derivatives] in the past 100 years, though there is one case where a camper froze to death while in the comatose state".[49]

Interactions

The actions and effects of muscimol may be potentiated by benzodiazepines such as diazepam.[4][3][50] Diazepam has been found to strongly potentiate the central depressant effects of muscimol in rodents.[50] Conversely, the barbiturate phenobarbital did not potentiate the effects of muscimol in rodents.[50] Neurosteroids like allopregnanolone and pregnanolone may potentiate the effects of muscimol.[51][52][53][54]

Pharmacology

Pharmacodynamics

γ-Aminobutyric acid (GABA) and muscimol molecules can have similar 3D conformations which are shown superimposed in this image. Because of this similarity, muscimol binds to certain GABA receptors.[4]

Muscimol is a potent GABAA receptor full agonist, activating the receptor for the brain's principal inhibitory neurotransmitter, γ-aminobutyric acid (GABA).[3] Muscimol binds to the same site on the GABAA receptor complex as GABA itself, unlike other GABAergic drugs such as barbiturates, benzodiazepines, and Z-drugs, which interact with separate allosteric sites.[20][3] GABAA receptors are widely distributed in the brain, so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex, hippocampus, and cerebellum. By mimicking GABA, muscimol activates these receptors, leading to the opening of chloride channels and subsequent hyperpolarization of neurons. This results in decreased neuronal excitability, which is crucial for maintaining the balance between excitation and inhibition in the central nervous system.[55]

Muscimol was originally reported to show relatively uniform effects on GABAA receptors of differing subunit compositions.[3][2][19] However, it was found to act as a superagonist of extrasynaptic α4β3δ subunit-containing GABAA receptors (Emax = 120 to 140% relative to GABA).[3][2] This was found to be due to reduced receptor desensitization with muscimol compared to GABA.[3] Subsequent research has found that muscimol is a preferential agonist of the relatively small population of extrasynaptic and/or δ subunit-containing GABAA receptors and that these receptors have a substantial contribution to its effects.[17][18][56][19][2] Relatedly, muscimol, similarly to gaboxadol, has been described as being highly though incompletely selective for these GABAA receptors.[18][19] In contrast, benzodiazepines and Z-drugs do not activate δ subunit-containing GABAA receptors.[57] On the other hand, alcohol is known to selectively potentiate δ subunit-containing extrasynaptic GABAA receptors analogously to muscimol.[58][59][60]

While muscimol is often thought of as a selective GABAA agonist with exceptionally high affinity to δ subunit-containing GABAA receptors,[61][62][17] it is also a potent partial agonist of the GABAA-ρ receptor, and so its range of effects results from a combined action on more than one GABAA receptor subtype.[63] In fact, it is more potent as a partial agonist of the GABAA-ρ receptor than as a GABAA receptor agonist.[3][6] Muscimol has been said to be inactive at the GABAB receptor.[3][6] However, a subsequent study reported that muscimol may have GABAB receptor-mediated inhibitory activity, although more research is needed to further characterize this activity.[2][64] Muscimol is inactive in terms of affecting GABA transaminase (GABA-T).[6][65] There is little evidence that muscimol interacts with other biological targets besides the GABA receptors and the GABA transporters.[3]

Muscimol shows a very steep dose–response curve in rodents.[50][66] It produces effects in rodents including central depression, hypolocomotion, catalepsy, sedation, ataxia, analgesia, anxiolysis, anticonvulsant effects, neuroprotective effects, and anesthesia, among other effects.[7][67][50] In rodent drug discrimination studies, muscimol and gaboxadol fully generalize between each other, but generalization between benzodiazepines like diazepam does not occur.[36][37][68] These findings suggest that muscimol and gaboxadol have differing interoceptive effects from those of benzodiazepines.[36][68] During a test involving rabbits connected to an EEG, muscimol presented with a distinctly synchronized EEG tracing.[69] This is substantially different from serotonergic psychedelics like psilocybin, with which brainwave patterns generally show a desynchronization.[69] In higher doses (2 mg/kg via IV), the EEG will show characteristic spikes.[69] Muscimol can increase prolactin and growth hormone levels in humans.[70][71]

Pharmacokinetics

The pharmacokinetics of muscimol in humans have been very limitedly studied.[2] Pharmacokinetic parameters such as bioavailability, volume of distribution, plasma protein binding, and elimination half-life are unavailable.[2][72][12]

Absorption

Muscimol is readily absorbed in the gastrointestinal tract when taken orally.[6]

Distribution

The brain tissue distribution of muscimol in rats has been studied.[2][73] Muscimol rapidly enters and unevenly distributes in rat brain, especially in the substantia nigra, colliculi, and hypothalamus.[2][73] Muscimol crosses the blood–brain barrier and hence is centrally active.[20][4][7] This has been said to likely be mediated by active transport via the high-affinity GABA uptake system and other amino acid transporters.[2][4][7] Although muscimol crosses the blood–brain barrier, it does so relatively poorly and far less readily than gaboxadol.[36][74]

Metabolism

Muscimol is known to be metabolized via transamination by GABA transaminase (GABA-T) into an aldehyde metabolite.[2][7][73][75] Ibotenic acid is a prodrug of muscimol via decarboxylation.[2][4][6] However, it has been said that muscimol can also be converted back into ibotenic acid via glutamate decarboxylase.[6] The metabolites of muscimol have not been identified, but might contribute to the toxicity of muscimol.[5][74] In rodents, muscimol is rapidly and very extensively metabolized when given systemically, with only 0.02% reaching the brain unchanged and metabolites being present at far higher concentrations in comparison.[21][76][73][77][74]

Elimination

Muscimol is excreted by the kidneys into urine.[7] It is excreted partially unmetabolized.[7] This has been taken advantage of by Siberian practitioners of the traditional entheogenic use of Amanita muscaria via recycling of muscimol in urine.[78]

The elimination half-life of muscimol in humans is unknown.[2][72] The closely related drug gaboxadol (THIP), which is a cyclized derivative of muscimol, has an elimination half-life in humans of 1.5 to 2 hours.[79] In rodents, the half-life of gaboxadol was about twice as long as that of muscimol.[74] Gaboxadol is said to be more resistant to metabolism than muscimol, for instance not being a substrate for GABA-T.[20][5] Despite the preceding findings however, gaboxadol is shorter-lasting in its effects than muscimol in rats, with durations of up to 3 hours and more than 5 hours, respectively.[80]

Chemistry

Structure

Muscimol was first isolated from Amanita pantherina by Onda in 1964,[81] and thought to be an amino acid or peptide. Structure was then elucidated by Takemoto,[82] Eugster,[83] and Bowden.[84] Muscimol is a semi-rigid isoxazole containing both alcohol and aminomethyl substituents.[85] Muscimol is commonly portrayed as a tautomer, where it adopts an amide-like configuration.[40] It is also commonly shown as a zwitterion.[86]

Properties

Muscimol is a zwitterion at physiological pH.[2] Its predicted log P of –1.4 to –2.2.[72][40] The drug's log P is similar to that of γ-aminobutyric acid (GABA).[87]

Isolation

Muscimol can be extracted from the flesh of the Amanita muscaria by treatment with boiling water, followed by rapid cooling, and further treatment with a basic resin. This is washed with water, and eluted with acetic acid using column chromatography. The eluate is freeze dried, dissolved in water, and passed down a column of cellulose phosphate.[88] A subsequent elution with ammonium hydroxide and recrystallization from alcohol results in pure muscimol.[89]

In instances where pure muscimol is not required, such as recreational or spiritual use, a crude extract is often prepared by simmering dried Amanita muscaria in water for 30 minutes.[90]

Synthesis

Several chemical syntheses of muscimol have been published.[4][2][6][91][92][93][94][86]

Analogues

Analogues of muscimol include γ-aminobutyric acid (GABA), ibotenic acid, dihydromuscimol, thiomuscimol, piperidine-4-sulphonic acid (P4S), gaboxadol (THIP), 4-AHP, 4-PIOL, isonipecotic acid, guvacine, isoguvacine, THPO, nipecotic acid, and tiagabine, among others.[6][5][24][95] In contrast to the preceding compounds, certain other analogues, including isomuscimol and azamuscimol, are virtually inactive.[96][21][65][42] The structural requirements for GABAA receptor binding and activation are very strict, so relatively few high-efficacy GABAA receptor agonists are known.[97][98]

History

Amanita muscaria has been used by humans as a psychoactive drug since ancient times.[2][5][13] Muscimol was isolated from Amanita muscaria independently by three different research groups in 1964 and 1965.[3][2][5] It was synthesized by Gagneux and colleagues in 1965.[3][2][6][91] The chemical structure of muscimol, along with that of ibotenic acid, was published by Conrad Eugster at the University of Zurich in 1967.[3][99][100]

Its structural similarity to the neurotransmitter γ-aminobutyric acid (GABA) was quickly recognized and muscimol was shown to have GABA-like actions by Graham Johnston and colleagues in 1968.[3][101] Subsequently, its actions were shown to be reversed by the GABA receptor antagonist bicuculline in 1971.[3][102]

The effects of muscimol in humans were studied and described by Waser in 1967.[14][33][15] Later, ethnobotanist Jonathan Ott further described the effects of muscimol, via Amanita pantherina consumption, in 1976.[2][33]

Danish medicinal chemist Povl Krogsgaard-Larsen and colleagues studied muscimol and synthetic analogues over several decades starting in the 1970s.[3][2] Other GABAA receptor ligands, such as gaboxadol (THIP) and 4-PIOL, and GABA transporter modulators, such as nipecotic acid and tiagabine, have been derived from muscimol.[3][2][24] Many muscimol analogues were developed by Krogsgaard-Larsen and colleagues.[3][2][24]

Muscimol was encountered online as a novel designer drug in 2023.[103]

Society and culture

See also: Biology:Legal status of psychoactive Amanita mushrooms

Muscimol is not a controlled substance and is unregulated in most of the world.[2][30][27]

Australia

Muscimol is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). A Schedule 9 substance is a substance "which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities."[104]

Poland

Muscimol and ibotenic acid are both considered as novel psychoactive substances in Poland as of 2024.[105] Possessing or selling them is illegal.[105]

United States

Neither Amanita muscaria nor muscimol is considered a controlled substance by the Federal government of the United States. The United States Food and Drug Administration (FDA) has deemed Amanita muscaria and its constituents, including muscimol, unapproved for conventional foods and is also evaluating their use in dietary supplements.[106] Agriculture regulators in Florida actioned against one seller of Amanita products after the agency had determined such products were considered adulterated under state law.[107]

Muscimol may be regulated on a state level. Louisiana State Act 159 banned the possession and cultivation of the Amanita muscaria except for ornamental or aesthetic purposes. Except as a constituent of lawfully manufactured food or dietary supplements, the act outlaws preparations of the Amanita muscaria intended for human consumption, including muscimol.[108]

Research

Muscimol has been clinically studied for a number of potential medical uses.[2][21][22][23] It was assessed in small clinical studies in the treatment of Huntington's disease, tardive dyskinesia, and schizophrenia in the 1970s but was not found to be useful for these indications.[21][7][109][110][10][111][112][113] Another study evaluated muscimol in schizophrenics with tardive dyskinesia in 1992.[114] Studies also assessed the biochemical effects of muscimol in humans in the late 1970s and early 1980s.[70][115][71]

According to Povl Krogsgaard-Larsen, muscimol was too toxic and non-selective and as such was not developed for use as a pharmaceutical drug.[20][42][116][25][41] Instead, the synthetic analogue gaboxadol (THIP), which was more selective and much less toxic, was developed.[3][24][25][41]

In 2019, a phase 1 clinical trial of muscimol for drug-resistant epilepsy was published.[117][23] It has also been formally investigated for potential treatment of Alzheimer's disease and Parkinson's disease.[118][119] A 2023 systematic review and meta-analysis of 22 preclinical studies found that muscimol reduces neuropathic pain in animals, with effects beginning within 15 minutes and lasting up to 3 hours.[22][2]

Muscimol has never been approved as a pharmaceutical drug for any use anywhere in the world.[2][72]

See also

References

  1. ↑ The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA64. Retrieved 20 September 2025. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 2.34 2.35 2.36 2.37 2.38 2.39 2.40 2.41 2.42 "Classics in Chemical Neuroscience: Muscimol". ACS Chem Neurosci 15 (18): 3257–3269. September 2024. doi:10.1021/acschemneuro.4c00304. PMID 39254100. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 3.24 3.25 3.26 3.27 3.28 3.29 "Muscimol as an ionotropic GABA receptor agonist". Neurochem Res 39 (10): 1942–1947. October 2014. doi:10.1007/s11064-014-1245-y. PMID 24473816. https://core.ac.uk/download/pdf/357370693.pdf. "We now know that muscimol is a potent agonist at GABAA receptors, a potent partial agonist at GABAC receptors and inactive at GABAB receptors. Unlike bicuculline and TPMPA, it does not distinguish between GABAA and GABAC receptors. It is a weak inhibitor/substrate of GABA uptake and not a substrate for GABA transaminase [18–21].". 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 "Amanita muscaria: chemistry, biology, toxicology, and ethnomycology". Mycol Res 107 (Pt 2): 131–146. February 2003. doi:10.1017/s0953756203007305. PMID 12747324. Bibcode: 2003MycR..107..131M. https://www.davidmoore.org.uk/21st_Century_Guidebook_to_Fungi_PLATINUM/REPRINT_collection/Michelot_etal_A.muscaria_chemistry_biology_toxicology.pdf. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 "Muscimol, a psychoactive constituent of Amanita muscaria, as a medicinal chemical model structure". Acta Chem Scand B 35 (5): 311–324. 1981. doi:10.3891/acta.chem.scand.35b-0311. PMID 6274117. https://ia600800.us.archive.org/5/items/krogsgaard-larsen-et-al.-1981-muscimol-a-psychoactive-constituent-of-amanita-mus/Krogsgaard-Larsen%20et%20al.%20%281981%29%20-%20Muscimol%2C%20a%20Psychoactive%20Constituent%20of%20Amanita%20Muscaria%2C%20as%20a%20Medicinal%20Chemical%20Model%20Structure.pdf. 
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 "Psychoactive Isoxazoles, Muscimol, and Isoxazole Derivatives from the Amanita (Agaricomycetes) Species: Review of New Trends in Synthesis, Dosage, and Biological Properties". Int J Med Mushrooms 25 (9): 1–10. 2023. doi:10.1615/IntJMedMushrooms.2023049458. PMID 37824402. 
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 "Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities". Ther Drug Monit 35 (4): 420–442. August 2013. doi:10.1097/FTD.0b013e31828741a5. PMID 23851905. 
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 "Ibotenic Acid–Muscimol: The Primordial Pangk and Amrta". Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History (2 ed.). Natural Products Company. 1996. pp. 323–358, 446. ISBN 978-0-9614234-8-3. https://anthrome.wordpress.com/wp-content/uploads/2010/06/pharmacotheon.pdf#page=161. "[...] 34. Muscimol [...] Pharmacology: 15 mg psychoptic (Waser, Ethnopharm. Search Psychoactive Drugs, U.S. Government Print. Office, 1967); 20 mg visionary (Ott, unpublished). [...]" 
  9. ↑ 9.0 9.1 9.2 9.3 "New class of hallucinogens: GABA-enhancing agents". Drug Development Research 21 (3): 253–256. 1990. doi:10.1002/ddr.430210311. ISSN 0272-4391. https://onlinelibrary.wiley.com/doi/10.1002/ddr.430210311. Retrieved 22 September 2025. 
  10. ↑ 10.0 10.1 10.2 10.3 "Muscimol: GABA agonist therapy in schizophrenia". Am J Psychiatry 135 (6): 746–747. June 1978. doi:10.1176/ajp.135.6.746. PMID 350058. 
  11. ↑ 11.0 11.1 11.2 Cite error: Invalid <ref> tag; no text was provided for refs named Trachsel_2000
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 "NCATS Inxight Drugs". 19 October 2001. https://drugs.ncats.io/drug/D5M179TY2E. "Muscimol is one of the principal psychoactive constituents of Amanita muscaria and related species of mushroom. Muscimol is a potent, selective agonist for the GABAA receptors and displays sedative-hypnotic, depressant and hallucinogenic psychoactivity. The effects of the Amanita mushrooms begin 30–120 minutes after consumption and the effects last for 5–10 hours. Some of the desired effects include euphoria, dream-like (lucid) state of mind, out-of-body experiences, and synesthesia. Neutral effects include dizziness, clumsiness, the feeling of increased physical strength, loss of equilibrium, and a glassy-eyed stare. Calming effects may be felt, but completely opposite effects such as extreme energy bursts have been described. Negative effects include mild to moderate nausea, stomach discomfort, increased salivation, and muscle twitching or tremors. In large doses, strong dissociation or delirium may be felt." 
  13. ↑ 13.0 13.1 13.2 Hall, A. H., & Hall, P. K. (1994). Ibotenic acid/muscimol-containing mushrooms. In Handbook of Mushroom Poisoning—Diagnosis and Treatment (pp. 265-278). CRC Press, Boca Raton. https://books.google.com/books?id=WPWsZNvOqVAC&pg=PA265
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 "Miscellaneous Hallucinogens". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 196–216. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. "Waser (1967) describes the effects of self-administration of 10-15 mg. of muscimol as '. . . intense hallucinations as with LSD were missing . . . there resulted considerable disturbances of psychic functions, such as orientation in space and time, visual perception, process of thinking, speech, and some new psychic phenomena of illusions and echo pictures'. Higher doses tended to produce severe intoxication in man, with painful muscular twitching, considerable agitation, and vivid hallucinations. Similar doses of ibotenic acid or muscazone were virtually without hallucinogenic activity but showed only some unpleasant effects on the peripheral circulation. [...] WASER, P. G. (1967), in Ethnopharmacologic Search for Psychoactive Drugs (see BREKHMAN and SAM), pp. 419--439." 
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 "The Pharmacology of Amanita Muscaria". Ethnopharmacologic Search for Psychoactive Drugs. Raven Press. 1967. pp. 419–439. ISBN 978-0-89004-047-8. https://ia600800.us.archive.org/22/items/the-pharmacology-of-amanita-muscaria-waser-1967/the-pharmacology-of-amanita-muscaria-waser-1967.pdf. 
  16. ↑ "GABAA and GABAB receptor agonists, partial agonists, antagonists and modulators: design and therapeutic prospects". European Journal of Pharmaceutical Sciences 5 (6): 355–384. 1997. doi:10.1016/S0928-0987(97)10009-4. https://linkinghub.elsevier.com/retrieve/pii/S0928098797100094. Retrieved 21 September 2025. "Curiously, the full GABA A agonist muscimol, the very efficacious partial GABA A agonist THIP, as well as the GABA A antagonist bicuculline show potent antinociceptive effects.". 
  17. ↑ 17.0 17.1 17.2 "Extrasynaptic δ-GABAA receptors are high-affinity muscimol receptors". J Neurochem 149 (1): 41–53. April 2019. doi:10.1111/jnc.14646. PMID 30565258. 
  18. ↑ 18.0 18.1 18.2 "Guanidino compounds with native GABA(A) δ receptor selectivity: a tale of homeostatic compensation in δ-KO mice". BMC Neurosci 27 (1). December 2025. doi:10.1186/s12868-025-00987-z. PMID 41372746. "Muscimol and THIP are conformationally restricted high affinity orthosteric GABA ligands, with particularly high affinity for extrasynaptic δ subunit-containing GABARs. [...] Both muscimol and THIP are reported to be highly selective for δ-GABARs [34, 36] and their high potency for δ-GABARs provides the molecular basis for the pronounced behavioral insensitivity of δ-KO and α4-KO mice to THIP [46, 47] and muscimol [47]. [...] autoradiography studies showed an essentially complete loss of high-affinity (6 nM) [3H] muscimol binding in the δ-KO forebrain [44], [...]". 
  19. ↑ 19.0 19.1 19.2 19.3 "Prototypic GABA(A) receptor agonist muscimol acts preferentially through forebrain high-affinity binding sites". Neuropsychopharmacology 35 (4): 999–1007. March 2010. doi:10.1038/npp.2009.203. PMID 20032968. "Muscimol has been regarded as a universal agonist for all [GABAA-R] subtypes. However, brain regional distribution of muscimol’s high-affinity binding sites greatly differs from those of other binding sites of the GABAA-R. [...] δ-KO mice also had reduced binding to forebrain regions and a lower behavioral sensitivity to muscimol than their wild-type controls. In contrast, α1-KO mice had unaltered behavioral sensitivity to muscimol and unaltered [3H]muscimol binding, [...] These data suggest that a small special population of GABAA-Rs, most likely extrasynaptic non-α1-containing receptors, strongly contributes to the in vivo pharmacological effects of muscimol. [...] Our finding is striking particularly if we consider that the α1-KO mice with unchanged high-affinity [3H]muscimol binding in brain sections have dramatic overall changes in their GABAA-Rs: (1) a 55% reduction in total GABAA-Rs, [...] α1-subunit-containing GABAARs are widely expressed throughout the brain, in far greater number than GABAA-Rs containing α4- or δ-subunits [...] It is important to notice that changes in sensitivity to muscimol of transgenic mouse lines resemble closely the changes seen in sensitivity to gaboxadol, which mediates its action mainly directly on GABA sites of extrasynaptic receptors (Belelli et al, 2005; Jia et al, 2005). α4 and δ-KO mice are significantly less sensitive to gaboxadol (Boehm et al, 2006; Chandra et al, 2006), α1-KO mice have unaltered response to it (Herd et al, 2009) [...] Interestingly, the present findings suggest that at least some of the gaboxadol-induced behavioral effects may not be specific for that compound, but may be general properties of directly acting GABAA-R agonists. [...] In conclusion, the present results point to a correlation between high-affinity agonist binding sites of the GABAA-R in the forebrain and behavioral sensitivity to muscimol, and thus suggest that the behavioral effects of muscimol are preferentially mediated through high-affinity agonist binding sites of the forebrain GABAA-Rs. Most likely these receptors are non-α1 extrasynaptic GABAA-Rs containing δ and α4-subunits.". 
  20. ↑ 20.0 20.1 20.2 20.3 20.4 20.5 "GABA(A) receptor ligands and their therapeutic potentials". Curr Top Med Chem 2 (8): 817–832. August 2002. doi:10.2174/1568026023393525. PMID 12171573. "The fact that muscimol is a non-specific GABAA receptor agonist [38, 39], a substrate for the GABA-metabolizing enzyme, GABA transaminase [40], and moreover a neurotoxin, makes the compound therapeutically less valuable. [...] Further conformational restriction of the GABA structural element in muscimol has been achieved by incorporating the amino group into a piperidine ring leading to the bicyclic analogue, THIP, a specific GABAA agonist [11]. THIP has been shown to be devoid of the neurotoxic properties of muscimol and, in contrast to muscimol, is metabolically stable.". 
  21. ↑ 21.0 21.1 21.2 21.3 21.4 21.5 21.6 "Physiological and behavioral studies with muscimol". Neurochem Res 5 (10): 1047–1068. October 1980. doi:10.1007/BF00966163. PMID 6258091. "Even though muscimol is a relatively toxic compound (6, 54, 105) which does not appear to be useful in human therapy, certain muscimol analogs such as THIP (which is relatively nontoxic) might prove to be useful therapeutic agents (94; P. Krogsgaard-Larsen, personal communication, 1979). [...] Muscimol will likely not be very useful in human therapy (e.g., as an anticonvulsant or antiparkinson agent). Clinical trials have already revealed that muscimol is of no practical value for treatment of Huntington's chorea, tardive dyskinesia, or schizophrenia (14, 103).". 
  22. ↑ 22.0 22.1 22.2 "Muscimol as a treatment for nerve injury-related neuropathic pain: A systematic review and meta-analysis of preclinical studies". The Korean Journal of Pain 36 (4): 425–440. 2023. doi:10.3344/kjp.23161. PMID 37732408. 
  23. ↑ 23.0 23.1 23.2 "Convection-Enhanced Delivery of Muscimol in Patients with Drug-Resistant Epilepsy". Neurosurgery 85 (1): E4–E15. July 2019. doi:10.1093/neuros/nyy480. PMID 30407567. 
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 "GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic". Biochem Pharmacol 68 (8): 1573–1580. October 2004. doi:10.1016/j.bcp.2004.06.040. PMID 15451401. 
  25. ↑ 25.0 25.1 25.2 "Gaboxadol, by Hamilton Morris". Harper's Magazine. August 2013. https://harpers.org/archive/2013/08/gaboxadol/. Retrieved 21 September 2025. 
  26. ↑ 26.0 26.1 26.2 "Exploring User Experiences with Amanita muscaria: A Thematic Analysis of Reddit Online Forum Discussions". Subst Use Misuse 60 (7): 952–961. 2025. doi:10.1080/10826084.2025.2476141. PMID 40057818. "The commonly reported reason for Amanita muscaria use was to improve sleep.". 
  27. ↑ 27.0 27.1 27.2 "Emerging Risks of Amanita Muscaria: Case Reports on Increasing Consumption and Health Risks". Acta Med Litu 32 (1): 182–189. 2025. doi:10.15388/Amed.2025.32.1.23. PMID 40641545. 
  28. ↑ "Reasons, Form of Ingestion and Side Effects Associated with Consumption of Amanita muscaria". Toxics 11 (4): 383. April 2023. doi:10.3390/toxics11040383. PMID 37112610. Bibcode: 2023Toxic..11..383O. 
  29. ↑ Ordak, Michal (12 May 2026). "toxicological risks and clinical implications: a narrative review". Frontiers in Pharmacology (Frontiers) 17. doi:10.3389/fphar.2026.1838212. ISSN 1663-9812. 
  30. ↑ 30.0 30.1 "Need for a Public Health Response to the Unregulated Sales of Amanita muscaria Mushrooms". Am J Prev Med 67 (3): 458–463. September 2024. doi:10.1016/j.amepre.2024.05.006. PMID 38864780. 
  31. ↑ "Toxic metabolites of Amanita pantherina, A. cothurnata, A. muscaria and other Amanita species". Lloydia 39 (2–3): 150–157. 1976. PMID 985999. 
  32. ↑ "Chemistry and Mode of Action of Mushroom Toxins". Mushroom Poisoning: Diagnosis and Treatment. CRC Press. 1978. pp. 87–124. ISBN 978-0-8493-5185-3. 
  33. ↑ 33.0 33.1 33.2 33.3 33.4 33.5 "Psycho-Mycological Studies Of Amanita – From Ancient Sacrament To Modern Phobia". Journal of Psychedelic Drugs 8 (1): 27–35. 1976. doi:10.1080/02791072.1976.10472005. ISSN 0022-393X. https://www.tandfonline.com/doi/full/10.1080/02791072.1976.10472005. Retrieved 21 September 2025. 
  34. ↑ 34.0 34.1 34.2 34.3 34.4 34.5 34.6 "Mushrooms, Ibotenic Acid". Encyclopedia of Toxicology. 2014. pp. 412–413. doi:10.1016/B978-0-12-386454-3.00756-9. ISBN 978-0-12-386455-0. "The doses of ibotenic acid and muscimol likely to cause symptoms are 60 mg and 6 mg, respectively, or approximately the amount found in one A. muscaria cap. Fifteen times these doses are thought to be potentially fatal. [...] A psychoactive dose of muscimol is reported to be between 8 and 15 mg. As little as a gram of dried A. muscaria may contain this amount of muscimol; however, the potency varies greatly among mushrooms. The LD50 of muscimol is 3.8 mg kg–1 subcutaneously and 2.5 mg kg–1 intraperitoneally and the LD50 in rats is 4.5 mg kg–1 orally." 
  35. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Satora_2005
  36. ↑ 36.0 36.1 36.2 36.3 36.4 36.5 "Gaboxadol--a new awakening in sleep". Curr Opin Pharmacol 6 (1): 30–36. February 2006. doi:10.1016/j.coph.2005.10.004. PMID 16368265. 
  37. ↑ 37.0 37.1 37.2 "Gaboxadol, a selective extrasynaptic GABA(A) agonist, does not generalise to other sleep-enhancing drugs: a rat drug discrimination study". Neuropharmacology 52 (3): 844–853. March 2007. doi:10.1016/j.neuropharm.2006.10.009. PMID 17196996. "For example, zolpidem, indiplon, RS-zopiclone and S-zopiclone were all reported to enhance sleep onset and increase the total duration of sleep (Nakajima et al., 2000; Zammit et al., 2004; Swainston Harrison and Keating, 2005; Thomson Scientific, 2006). Gaboxadol did not affect sleep onset and had no effect on rapid eye movement (REM) sleep, but increased the total duration of slow-wave sleep in rats (Lancel and Faulhaber, 1996), which resembled the changes it induces in human sleep (Faulhaber et al., 1997). Muscimol had similar effects to gaboxadol on sleep in rats, although it also increased REM sleep (Lancel et al., 1996).". 
  38. ↑ "Slow-wave sleep deficiency and enhancement: implications for insomnia and its management". World J Biol Psychiatry 11 (Suppl 1): 22–28. June 2010. doi:10.3109/15622971003637645. PMID 20509829. 
  39. ↑ "Fly agaric poison: Health risks of "fruit gummies" containing muscimol – children are particularly at risk" (in en). 2025-06-27. https://www.bfr.bund.de/en/notification/fly-agaric-poison-health-risks-of-fruit-gummies-containing-muscimol-children-are-particularly-at-risk/. 
  40. ↑ 40.0 40.1 40.2 40.3 40.4 "Muscimol". https://pubchem.ncbi.nlm.nih.gov/compound/4266. 
  41. ↑ 41.0 41.1 41.2 41.3 41.4 Povl Krogsgaard-Larsen, "Heterocyclic compounds", US patent 4278676, published 14 July 1981, issued 14 July 1981, assigned to H Lundbeck AS
  42. ↑ 42.0 42.1 42.2 "GABA receptor agonists: relationship between structure and biological activity in vivo and in vitro". GABA—Biochemistry and CNS Functions. Advances in Experimental Medicine and Biology. 123. Boston, MA: Springer US. 1979. pp. 303–321. doi:10.1007/978-1-4899-5199-1. ISBN 978-1-4899-5201-1. "It has been suggested that muscimol might be useful for the treatment of diseases caused by loss of GABA-ergic neurones (32). However, muscimol apparently is excessively metabolized after systemic administration to mice (33) and rats (S. J. Enna, unpublished results), and only a small proportion of peripherally administered muscimol appears to enter the brain (34). In addition, muscimol is a relatively toxic compound (35,36); this property is either inherent to muscimol, or due to its conversion to toxic metabolites in vivo. Therefore, muscimol does not appear to be a potentially useful drug. [...] THIP is a relatively non-toxic compound in mice and dogs, and it seems to penetrate easily into the brain after peripheral administration (V. Christensen, unpublished results). [...]" 
  43. ↑ "Pharmakologische und experimentalpsychologische Untersuchungen mit 2 Inhalsstoffen des Fliegenpilzes (Amanita Muscaria)" (in German). Arzneimittelforschung 18 (3): 311–315. March 1968. PMID 5696006. https://scholar.google.com/scholar?cluster=7165244348805609044. 
  44. ↑ 44.0 44.1 "Comparative assay of anticonvulsant and toxic potencies of sixteen GABAmimetic drugs". Neuropharmacology 21 (8): 803–810. August 1982. doi:10.1016/0028-3908(82)90068-5. PMID 7121752. 
  45. ↑ "Psychoactive Amanitas Chemistry". https://www.erowid.org/plants/amanitas/amanitas_chemistry.shtml. [unreliable source?]
  46. ↑ "Image-guided convection-enhanced delivery of muscimol to the primate brain: Laboratory investigation". Journal of Neurosurgery 112 (4): 790–795. April 2010. doi:10.3171/2009.7.JNS09652. PMID 19715424. 
  47. ↑ "Anticonvulsant effects of muscimol". Neurology 30 (6): 575–581. June 1980. doi:10.1212/wnl.30.6.575. PMID 7189834. 
  48. ↑ "Muscimol prevents NMDA antagonist neurotoxicity by activating GABAA receptors in several brain regions". Brain Research 993 (1–2): 90–100. December 2003. doi:10.1016/j.brainres.2003.09.002. PMID 14642834. 
  49. ↑ "Mushroom poisoning syndromes". North American Mycological Association (NAMA) website. NAMA. http://www.namyco.org/toxicology/poison_syndromes.html. 
  50. ↑ 50.0 50.1 50.2 50.3 50.4 "Effect of muscimol, a GABA-mimetic agent, on dopamine metabolism in the mouse brain". Life Sci 21 (4): 525–531. August 1977. doi:10.1016/0024-3205(77)90092-3. PMID 904431. 
  51. ↑ "Neurosteroid regulation of GABA(A) receptors: Focus on the alpha4 and delta subunits". Pharmacol Ther 116 (1): 58–76. October 2007. doi:10.1016/j.pharmthera.2007.03.008. PMID 17512983. 
  52. ↑ "Brain allopregnanolone regulates the potency of the GABA(A) receptor agonist muscimol". Neuropharmacology 39 (3): 440–448. January 2000. doi:10.1016/s0028-3908(99)00149-5. PMID 10698010. 
  53. ↑ "Enhancement of Muscimol Binding and Gating by Allosteric Modulators of the GABAA Receptor: Relating Occupancy to State Functions". Mol Pharmacol 98 (4): 303–313. October 2020. doi:10.1124/molpharm.120.000066. PMID 32873746. 
  54. ↑ "Neuroactive steroid modulation of [3H]muscimol binding to the GABAA receptor complex in rat cortex". Eur J Pharmacol 288 (2): 157–162. January 1995. doi:10.1016/0922-4106(95)90190-6. PMID 7720777. 
  55. ↑ Heldman, Dennis R., ed (1999). "Muscimol". Encyclopedia of Agricultural, Food, and Biological Engineering. CRC Press. pp. 1234–1238. 
  56. ↑ "Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice". Proc Natl Acad Sci U S A 96 (22): 12905–12910. October 1999. doi:10.1073/pnas.96.22.12905. PMID 10536021. Bibcode: 1999PNAS...9612905M. "[...] the maximal binding for muscimol was markedly decreased in δ–/– homogenates (Table 1). [...] Using in situ autoradiography to examine the abundance and distribution of GABA and benzodiazepine sites, it was observed that [3H]muscimol binding was drastically reduced in most regions of δ–/– brains (Fig. 2).". 
  57. ↑ "Effect of short-term treatment with gaboxadol on sleep maintenance and initiation in patients with primary insomnia". Sleep 30 (3): 281–287. March 2007. doi:10.1093/sleep/30.3.281. PMID 17425224. "When given orally in healthy subjects, gaboxadol is rapidly absorbed (tmax of 30-60 min) and eliminated (t½ of 1.5 h). More than 95% of the dose is excreted in the urine, mostly unchanged. A glucoronide conjugate is the only metabolite formed in significant amounts. Hence the CYP450 system does not have significant involvement in the metabolism of gaboxadol.". 
  58. ↑ "GABA(A) receptors and alcohol". Pharmacology, Biochemistry, and Behavior 90 (1): 90–94. July 2008. doi:10.1016/j.pbb.2008.03.006. PMID 18423561. 
  59. ↑ "Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition". Alcohol 41 (3): 211–221. May 2007. doi:10.1016/j.alcohol.2007.04.011. PMID 17591544. 
  60. ↑ "Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development?". British Journal of Pharmacology 154 (2): 288–298. May 2008. doi:10.1038/bjp.2008.32. PMID 18278063. 
  61. ↑ "Characterisation of delta-subunit containing GABAA receptors from rat brain". European Journal of Pharmacology 290 (3): 175–181. August 1995. doi:10.1016/0922-4106(95)00061-5. PMID 7589211. 
  62. ↑ "GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol". Proceedings of the National Academy of Sciences of the United States of America 103 (41): 15230–15235. October 2006. doi:10.1073/pnas.0604304103. PMID 17005728. Bibcode: 2006PNAS..10315230C. 
  63. ↑ "Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists". Molecular Pharmacology 43 (4): 609–625. April 1993. doi:10.1016/S0026-895X(25)13444-5. PMID 8386310. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8386310. 
  64. ↑ "Presynaptic inhibition by muscimol through GABAB receptors". Eur J Neurosci 12 (9): 3433–3436. September 2000. doi:10.1046/j.1460-9568.2000.00248.x. PMID 10998126. 
  65. ↑ 65.0 65.1 "Dihydromuscimol, thiomuscimol and related heterocyclic compounds as GABA analogues". J Neurochem 32 (6): 1717–1724. June 1979. doi:10.1111/j.1471-4159.1979.tb02284.x. PMID 448364. 
  66. ↑ "Low doses of muscimol produce anticonflict actions in the lateral septum of the rat". Neuropharmacology 25 (2): 203–205. February 1986. doi:10.1016/0028-3908(86)90042-0. PMID 3703171. 
  67. ↑ "Pharmacology of GABA and Its Receptors". Frontiers in Pharmacology of Neurotransmitters. 2020. pp. 241–292. doi:10.1007/978-981-15-3556-7_8. ISBN 978-981-15-3555-0. 
  68. ↑ 68.0 68.1 "GABA and the behavioral effects of anxiolytic drugs". Life Sci 36 (16): 1503–1513. April 1985. doi:10.1016/0024-3205(85)90374-1. PMID 2858804. 
  69. ↑ 69.0 69.1 69.2 "Neuropharmacological investigations on muscimol, a psychotropic drug extracted from Amanita muscaria". Psychopharmacologia 15 (3): 186–195. January 1969. doi:10.1007/BF00411168. PMID 5389124. 
  70. ↑ 70.0 70.1 "Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist". J Clin Endocrinol Metab 47 (6): 1348–1351. December 1978. doi:10.1210/jcem-47-6-1348. PMID 162520. 
  71. ↑ 71.0 71.1 "Plasma growth hormone and prolactin response to dopaminergic GABAmimetic and cholinergic stimulation in Huntington's disease". Neurology 33 (9): 1229–1232. September 1983. doi:10.1212/wnl.33.9.1299. PMID 6225034. 
  72. ↑ 72.0 72.1 72.2 72.3 Cite error: Invalid <ref> tag; no text was provided for refs named DrugBank
  73. ↑ 73.0 73.1 73.2 73.3 "Distribution and metabolism of muscimol in the brain and other tissues of the rat" (in en). Neuropharmacology 18 (1): 57–62. 1979. doi:10.1016/0028-3908(79)90009-1. PMID 418955. https://colab.ws/articles/10.1016/0028-3908(79)90009-1?utm_. Retrieved 2025-05-24. 
  74. ↑ 74.0 74.1 74.2 74.3 "Relative disposition of the GABA agonists THIP and muscimol in the brain of the rat". J Pharm Pharmacol 34 (10): 676–678. October 1982. doi:10.1111/j.2042-7158.1982.tb04702.x. PMID 6128395. 
  75. ↑ "Reaction of muscimol with 4-aminobutyrate aminotransferase". J Neurochem 41 (6): 1751–1754. December 1983. doi:10.1111/j.1471-4159.1983.tb00889.x. PMID 6644308. 
  76. ↑ Greig, Nigel H. (1989). "Drug Delivery to the Brain by Blood-Brain Barrier Circumvention and Drug Modification". Implications of the Blood-Brain Barrier and Its Manipulation. Boston, MA: Springer US. p. 311–367. doi:10.1007/978-1-4613-0701-3_12. ISBN 978-1-4612-8039-2. http://link.springer.com/10.1007/978-1-4613-0701-3_12. Retrieved 18 May 2026. 
  77. ↑ "Characteristics of muscimol accumulation in mouse brain after systemic administration". Neuropharmacology 18 (4): 361–366. April 1979. doi:10.1016/0028-3908(79)90143-6. PMID 450201. 
  78. ↑ "Another Magic Mushroom" p. 228 in: "Hallucinogens". Addiction. 2001. pp. 219–232. doi:10.1093/oso/9780195146639.003.0014. ISBN 978-0-19-514663-9. 
  79. ↑ "Effects of THIP on chronic anxiety". Psychopharmacology (Berl) 80 (4): 338–341. 1983. doi:10.1007/BF00432116. PMID 6414002. "THIP, a 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridin-3-ol, is a muscimol analog which exhibits specific GABA-agonists properties without affecting enzymes involved in the synthesis or the catabolism of the neurotransmitter. It is 5–15-times weaker than muscimol and substantially less toxic. THIP penetrates the blood–brain barrier and has a half-life of 1.5–2 h (H Lundbeck and Company 1981).". 
  80. ↑ "Pharmacodynamic effects and possible therapeutic uses of THIP, a specific GABA-agonist". Pharmaceutisch Weekblad. Scientific Edition 4 (5): 145–153. October 1982. doi:10.1007/BF01959034. PMID 6292818. "Compared to muscimol, THIP is generally less potent in the rat. Figure 7 indicates the dose-response-effect of THIP in rats. THIP is active for up to 3 h whereas comparable doses of morphine and muscimol have an effect over 5 h. However, in the rhesus monkey (HILL et al. 1981), the duration of action of THIP is between 4 and 5 h with a maximal effect being reached within 60-90 min.". 
  81. ↑ "A Flycidal Constituent of Amanita pantherina (DC.) FR". Chemical & Pharmaceutical Bulletin 12 (6): 751. June 1964. doi:10.1248/cpb.12.751. PMID 14199180. 
  82. ↑ (in ja) イボテン酸の構造 (none). pp. 1232–1233.  in: "寄書" (in ja). Yakugaku Zasshi 84 (12): 1230–1236. 1964. doi:10.1248/yakushi1947.84.12_1230. 
  83. ↑ "Wirkstoffe aus amanita muscaria: ibotensaeure und muscazon" (in de). Tetrahedron Letters 6 (23): 1813–1815. January 1965. doi:10.1016/s0040-4039(00)90133-3. PMID 5891631. 
  84. ↑ "Constituents of Amanita muscaria". Nature 206 (991): 1359–1360. June 1965. doi:10.1038/2061359a0. PMID 5891274. Bibcode: 1965Natur.206.1359B. 
  85. ↑ "Structural features of muscimol, a potent GABAA receptor agonist, crystal structure and quantum chemicalab initio calculations". Structural Chemistry 8 (6): 443–451. December 1997. doi:10.1007/BF02311703. Bibcode: 1997StrCh...8..443B. 
  86. ↑ 86.0 86.1 "An Improved Synthesis of Muscimol". Synthetic Communications 22 (13): 1939–1948. July 1992. doi:10.1080/00397919208021324. 
  87. ↑ "The role of the blood-brain barrier in movement disorders". Clin Neuropharmacol 13 (2): 129–146. April 1990. doi:10.1097/00002826-199004000-00003. PMID 2183934. 
  88. ↑ "Cellulose Phosphate: Product Information". https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/c2258pis.pdf. 
  89. ↑ "A novel constituent of Amanita muscaria". Tetrahedron Letters 6 (12): 727–728. 1965. doi:10.1016/s0040-4039(01)83973-3. PMID 14291871. 
  90. ↑ "Amanita muscaria Preparation for Beginners". Erowid. 23 November 2008. https://erowid.org/plants/amanitas/amanitas_info8.shtml. [self-published source?]
  91. ↑ 91.0 91.1 "Synthesis of pantherine (agarin)". Tetrahedron Letters 6 (25): 2077–2079. January 1965. doi:10.1016/S0040-4039(00)90157-6. 
  92. ↑ "A convenient synthesis of muscimol by a 1,3-dipolar cycloaddition reaction". Tetrahedron Letters 27 (27): 3181–3182. 1986. doi:10.1016/S0040-4039(00)84748-6. 
  93. ↑ "The synthesis of pantherine and related compounds". Journal of the Chemical Society C: Organic: 172. 1968. doi:10.1039/j39680000172. 
  94. ↑ "A facile synthesis of muscimol". Tetrahedron Letters 22 (51): 5153–5156. January 1981. doi:10.1016/S0040-4039(01)92445-1. 
  95. ↑ "Synthesis and Pharmacological Evaluation of Amidine Containing GABAA Receptor Agonists". EFMC International Symposium on Medicinal Chemistry Manchester, UK Aug. 28 - Sept. 1, 2016. 2016. pp. P278. https://istina.msu.ru/media/publications/article/6f5/7ea/31004876/ISMC-Book-web-1209.pdf#page=231. 
  96. ↑ "Ligands for the GABAA receptor complex". Glutamate and GABA Receptors and Transporters. CRC Press. 4 October 2001. p. 248–286. doi:10.1201/9780203299388-15. ISBN 978-0-429-09545-0. 
  97. ↑ "GABAA Agonists and Partial Agonists: THIP (Gaboxadol) as a Non-Opioid Analgesic and a Novel Type of Hypnotic1". GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic. Adv Pharmacol. 54. 2006. pp. 53–71. doi:10.1016/s1054-3589(06)54003-7. ISBN 978-0-12-032957-1. 
  98. ↑ Krogsgaard-Larsen, Povl (2018). "THIP/Gaboxadol, a Unique GABA Agonist". Reference Module in Biomedical Sciences. Elsevier. doi:10.1016/b978-0-12-801238-3.97290-8. ISBN 978-0-12-801238-3. https://linkinghub.elsevier.com/retrieve/pii/B9780128012383972908. Retrieved 7 October 2025. 
  99. ↑ "Zur Nomenklatur der neuen Verbindungen aus Amanita -Arten". Helvetica Chimica Acta 50 (1): 126–127. 1967. doi:10.1002/hlca.19670500119. ISSN 0018-019X. PMID 5593205. Bibcode: 1967HChAc..50..126E. https://onlinelibrary.wiley.com/doi/10.1002/hlca.19670500119. Retrieved 20 September 2025. 
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  108. ↑ "Louisiana Act No 159". http://legis.la.gov/Legis/Law.aspx?d=321523. 
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  119. ↑ "Pharmacology of GABA and Its Receptors". Frontiers in Pharmacology of Neurotransmitters. Singapore: Springer Singapore. 2020. pp. 241–292. doi:10.1007/978-981-15-3556-7_8. ISBN 978-981-15-3555-0. http://link.springer.com/10.1007/978-981-15-3556-7_8. Retrieved 29 September 2025. 

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See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators

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