View source for Muscimol

{{Short description|Naturally occurring sedative and hallucinogen}}
{{Redirect|Pantherine|the cat subfamily|Pantherinae}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 410573320
| drug_name = 
| image = Muscimol chemical structure.svg
| image_class = skin-invert-image
| width = 200px
| caption = 
| image2 = Muscimol structure ball and stick.png
| image_class2 = bg-transparent
| width2 = 185px
| caption2 = 

<!-- Clinical data -->
| pronounce = 
| tradename = 
| Drugs.com = 
| MedlinePlus = 
| licence_CA = 
| licence_EU = 
| DailyMedID = 
| licence_US = 
| pregnancy_AU = 
| pregnancy_category = 
| dependency_liability = 
| addiction_liability = 
| routes_of_administration = [[Oral administration|Oral]], [[smoking]]<ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023" /><ref name="Ott_1996" />
| class = [[GABAA receptor agonist|GABA<sub>A</sub> receptor agonist]]; [[Sedative]]; [[Hypnotic]]; [[Hallucinogen]]
| ATC_prefix = None
| ATC_suffix = 

<!-- Legal status -->
| legal_AU = S9
| legal_status = Uncontrolled, in general<ref name="RiveraIllanes_2024" /><ref name="Leas_2024" /><ref name="Savickaite_2025" />

<!-- Pharmacokinetic data -->
| bioavailability = Unknown<ref name="RiveraIllanes_2024" /><ref name="DrugBank">{{cite web | title = Muscimol: Uses, Interactions, Mechanism of Action | date = 20 October 2016 | website = DrugBank Online | url = https://go.drugbank.com/drugs/DB12458 | access-date = 21 September 2025 }}</ref>
| protein_bound = Unknown<ref name="RiveraIllanes_2024" /><ref name="DrugBank" />
| metabolism = [[Transamination]] (via [[GABA transaminase|GABA-T]])<ref name="RiveraIllanes_2024" /><ref name="Stebelska_2013" />
| metabolites = 
| onset = 0.5–2 hours (peak 1–3 hours)<ref name="Okhovat_2023" /><ref name="Ott_1996" /><ref name="Hollister_1990" /><ref name="Waser_1967" /><ref name="Tamminga_1978" />
| elimination_half-life = Unknown<ref name="RiveraIllanes_2024" /><ref name="DrugBank" />
| duration_of_action = 4–8 hours (but up to 24 hours)<ref name="Okhovat_2023" /><ref name="Satora_2005">{{cite journal | vauthors = Satora L, Pach D, Butryn B, Hydzik P, Balicka-Slusarczyk B | title = Fly agaric (Amanita muscaria) poisoning, case report and review | journal = Toxicon | volume = 45 | issue = 7 | pages = 941–943 | date = June 2005 | pmid = 15904689 | doi = 10.1016/j.toxicon.2005.01.005 | bibcode = 2005Txcn...45..941S }}</ref><ref name="Trachsel_2000">{{cite book | vauthors = Trachsel D, Richard N | chapter = Muscimol | title = Psychedelische Chemie Aspekte Psychoaktiver Moleküle | pages = 321–329 | year = 2000 | trans-title = Psychedelic Chemistry: Aspects of Psychoactive Molecules | edition = 1 | publisher = Nachtschatten-Verlag | isbn = 978-3-907080-53-5 | oclc = 247657972 | url = https://books.google.com/books?id=xPAiAAAACAAJ | language = de | archive-url = https://archive.org/details/psychedelische-chemie-trachsel-richard-2000 | archive-date = 18 October 2025 }}</ref><ref name="Tamminga_1978" />
| excretion = [[Urine]] (partially unchanged)<ref name="Stebelska_2013" />

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 2763-96-4
| CAS_supplemental = 
| PubChem = 4266
| PubChemSubstance = 
| IUPHAR_ligand = 4259
| DrugBank = DB12458
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4116
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = D5M179TY2E
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C08311
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 7035
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 273481
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = Agarin; Agarine; Pantherine; Pantherin; Pyroibotenic acid; β-Toxin; 5-Aminomethylisoxazol-3-ol; 3-Hydroxy-5-aminomethylisoxazole

<!-- Chemical data -->
| IUPAC_name = 5-(aminomethyl)-1,2-oxazol-3-one
| C=4 | H=6 | N=2 | O=2
| SMILES = NCc1cc(no1)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C4H6N2O2/c5-2-3-1-4(7)6-8-3/h1H,2,5H2,(H,6,7)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZJQHPWUVQPJPQT-UHFFFAOYSA-N

<!-- Physical data -->
| melting_point = 184
| melting_high = 185
}}
<!-- Definition and uses -->
'''Muscimol''', also known as '''agarin''', '''pantherine''', or '''pyroibotenic acid''', is a [[GABAA receptor agonist|GABA<sub>A</sub> receptor agonist]] with [[sedative]] and [[hallucinogen]]ic effects and the principal [[psychoactive]] constituent of ''[[Amanita]]'' [[mushroom]]s such as ''[[Amanita muscaria]]'' (fly agaric) and ''[[Amanita pantherina]]'' (panther cap).<ref name="Elks_2014">{{cite book | vauthors = Elks J | title = The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | date = 14 November 2014 | publisher = Springer | isbn = 978-1-4757-2085-3 | url = https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA64 | access-date = 20 September 2025 }}</ref><ref name="RiveraIllanes_2024">{{cite journal | vauthors = Rivera-Illanes D, Recabarren-Gajardo G | title = Classics in Chemical Neuroscience: Muscimol | journal = ACS Chem Neurosci | volume = 15 | issue = 18 | pages = 3257–3269 | date = September 2024 | pmid = 39254100 | doi = 10.1021/acschemneuro.4c00304 }}</ref><ref name="Johnston_2014">{{cite journal | vauthors = Johnston GA | title = Muscimol as an ionotropic GABA receptor agonist | journal = Neurochem Res | volume = 39 | issue = 10 | pages = 1942–1947 | date = October 2014 | pmid = 24473816 | doi = 10.1007/s11064-014-1245-y | url = https://core.ac.uk/download/pdf/357370693.pdf | quote = 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]. }}</ref><ref name="Michelot_2003">{{cite journal | vauthors = Michelot D, Melendez-Howell LM | title = Amanita muscaria: chemistry, biology, toxicology, and ethnomycology | journal = Mycol Res | volume = 107 | issue = Pt 2 | pages = 131–146 | date = February 2003 | pmid = 12747324 | doi = 10.1017/s0953756203007305 | url = https://www.davidmoore.org.uk/21st_Century_Guidebook_to_Fungi_PLATINUM/REPRINT_collection/Michelot_etal_A.muscaria_chemistry_biology_toxicology.pdf }}</ref><ref name="KrogsgaardLarsen_1981">{{cite journal | vauthors = Krogsgaard-Larsen P, Brehm L, Schaumburg K | title = Muscimol, a psychoactive constituent of Amanita muscaria, as a medicinal chemical model structure | journal = Acta Chem Scand B | volume = 35 | issue = 5 | pages = 311–324 | date = 1981 | pmid = 6274117 | doi = 10.3891/acta.chem.scand.35b-0311 | url = 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 }}</ref> It is a 3-hydroxy[[isoxazole]] [[alkaloid]] and is closely related [[chemical structure|structurally]] to the [[neurotransmitter]] [[γ-aminobutyric acid]] (GABA).<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023" /> The compound is widely used as a [[ligand (biochemistry)|ligand]] and agonist of the GABA<sub>A</sub> receptor in [[scientific research]].<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /> Muscimol is typically taken [[oral administration|orally]], but may also be [[smoking|smoked]].<ref name="RiveraIllanes_2024" /><ref name="Stebelska_2013" /><ref name="Okhovat_2023" /><ref name="Ott_1996" /> Peak effects occur after 1 to 3{{nbsp}}hours orally<ref name="Ott_1996" /><ref name="Hollister_1990" /><ref name="Tamminga_1978" /> and its [[duration of action|duration]] is 4 to 8{{nbsp}}hours but up to 24{{nbsp}}hours.<ref name="Ott_1996" /><ref name="Okhovat_2023" /><ref name="Trachsel_2000" />

<!-- Effects, pharmacology, and chemistry -->
The effects of muscimol in humans include [[central depressant|central depression]], [[sedation]], [[sleep]], [[cognitive impairment|cognitive]] and [[motor impairment]], [[hallucination]]s, [[sensory processing disorder|perceptual distortion]], and [[muscle twitching]], among others.<ref name="HallHall1994" /><ref name="Stebelska_2013" /><ref name="Brimblecombe_1975" /><ref name="Waser_1967" /> Muscimol acts as a [[potency (pharmacology)|potent]] [[GABAA receptor|GABA<sub>A</sub> receptor]] [[full agonist]].<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="KrogsgaardLarsen_1997">{{cite journal | vauthors = Krogsgaard-Larsen P, Frølund B, Kristiansen U, Frydenvang K, Ebert B | title = GABAA and GABAB receptor agonists, partial agonists, antagonists and modulators: design and therapeutic prospects | journal = European Journal of Pharmaceutical Sciences | volume = 5 | issue = 6 | pages = 355–384 | date = 1997 | doi = 10.1016/S0928-0987(97)10009-4 | url = https://linkinghub.elsevier.com/retrieve/pii/S0928098797100094 | access-date = 21 September 2025 | quote = 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. | url-access = subscription }}</ref> It is also a potent [[GABAA-rho|GABA<sub>A</sub>-ρ receptor]] [[partial agonist]] and a weak [[GABA reuptake inhibitor]].<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023" /> The drug is inactive at the [[GABA-B receptor|GABA<sub>B</sub> receptor]] but is a [[substrate (biochemistry)|substrate]] of [[GABA transaminase]] (GABA-T).<ref name="Johnston_2014" /><ref name="Stebelska_2013" /><ref name="Okhovat_2023" /> Muscimol mostly exerts its effects via GABA<sub>A</sub> receptor activation.<ref name="Stebelska_2013" /> It is very different from drugs like [[benzodiazepine]]s and [[barbiturate]]s as it is an [[orthosteric]] agonist of the GABA<sub>A</sub> receptor rather than an [[allosteric modulator]].<ref name="RiveraIllanes_2024" /><ref name="Frlund_2002" /> Unlike GABA, muscimol crosses the [[blood–brain barrier]] and hence is [[central nervous system|centrally active]].<ref name="Frlund_2002">{{cite journal | vauthors = Frølund B, Ebert B, Kristiansen U, Liljefors T, Krogsgaard-Larsen P | title = GABA(A) receptor ligands and their therapeutic potentials | journal = Curr Top Med Chem | volume = 2 | issue = 8 | pages = 817–832 | date = August 2002 | pmid = 12171573 | doi = 10.2174/1568026023393525 | quote = 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. }}</ref><ref name="Michelot_2003" /><ref name="Stebelska_2013" /> Muscimol, which is also known chemically as 5-aminomethylisoxazol-3-ol, is a [[conformational restriction|conformationally restrained]] [[structural analog|analogue]] of GABA.<ref name="Johnston_2014" /><ref name="Okhovat_2023" /> The related compound and ''Amanita'' spp. constituent [[ibotenic acid]] is a [[prodrug]] of muscimol.<ref name="RiveraIllanes_2024" /><ref name="Michelot_2003" /><ref name="Okhovat_2023" />

<!-- History, society, and culture -->
Muscimol was first isolated from ''Amanita muscaria'' and hence was discovered in 1964.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="KrogsgaardLarsen_1981" /> It has been limitedly clinically studied as a potential [[pharmaceutical drug]] for a number of uses, such as treatment of [[epilepsy]].<ref name="RiveraIllanes_2024" /><ref name="DeFeudis_1980" /><ref name="Ramawad_2023" /><ref name="Heiss_2019" /> In addition, [[structural analog|analogue]]s and [[chemical derivative|derivative]]s of muscimol, such as the [[binding selectivity|selective]] GABA<sub>A</sub> receptor agonist [[gaboxadol]] (THIP; LU-2-030) and the selective GABA reuptake inhibitor [[tiagabine]] (Gabitril), have been developed as pharmaceutical drugs.<ref name="Johnston_2014" /><ref name="KrogsgaardLarsen_2004">{{cite journal | vauthors = Krogsgaard-Larsen P, Frølund B, Liljefors T, Ebert B | title = GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic | journal = Biochem Pharmacol | volume = 68 | issue = 8 | pages = 1573–1580 | date = October 2004 | pmid = 15451401 | doi = 10.1016/j.bcp.2004.06.040 }}</ref><ref name="Okhovat_2023" /><ref name="Morris_2013">{{cite magazine | vauthors = Morris H | title = Gaboxadol, by Hamilton Morris | date = August 2013 | magazine = Harper's Magazine | url = https://harpers.org/archive/2013/08/gaboxadol/ | access-date = 21 September 2025 }}</ref> Muscimol and ''Amanita muscaria'' mushrooms have rarely been used as [[recreational drug]]s historically.<ref name="Ott_1996" /> 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.<ref name="RiveraIllanes_2024" /><ref name="Hartwig_2025" /><ref name="Savickaite_2025">{{cite journal | vauthors = Savickaitė E, Laubner-Sakalauskienė G | title = Emerging Risks of Amanita Muscaria: Case Reports on Increasing Consumption and Health Risks | journal = Acta Med Litu | volume = 32 | issue = 1 | pages = 182–189 | date = 2025 | pmid = 40641545 | pmc = 12239171 | doi = 10.15388/Amed.2025.32.1.23 }}</ref><ref name="Ordak_2023">{{cite journal | vauthors = Ordak M, Galazka A, Nasierowski T, Muszynska E, Bujalska-Zadrozny M | title = Reasons, Form of Ingestion and Side Effects Associated with Consumption of Amanita muscaria | journal = Toxics | volume = 11 | issue = 4 | pages = 383 | date = April 2023 | pmid = 37112610 | pmc = 10142736 | doi = 10.3390/toxics11040383 | bibcode = 2023Toxic..11..383O | doi-access = free }}</ref> The most commonly cited therapeutic reason for their use is to improve sleep.<ref name="Hartwig_2025" /> Muscimol is not a [[controlled substance]] and is unregulated in most of the world, including in most of the [[United States]] and [[Europe]].<ref name="RiveraIllanes_2024" /><ref name="Leas_2024">{{cite journal | vauthors = Leas EC, Satybaldiyeva N, Kepner W, Yang KH, Harati RM, Corroon J, Rouffet M | title = Need for a Public Health Response to the Unregulated Sales of Amanita muscaria Mushrooms | journal = Am J Prev Med | volume = 67 | issue = 3 | pages = 458–463 | date = September 2024 | pmid = 38864780 | pmc = 11832274 | doi = 10.1016/j.amepre.2024.05.006 }}</ref><ref name="Savickaite_2025" />

==Natural occurrence==
[[Image:Amanita muscaria 3 vliegenzwammen op rij.jpg|left|thumb|''[[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]].<ref name="Chilton_1976">{{cite journal | vauthors = Chilton WS, Ott J | title = Toxic metabolites of Amanita pantherina, A. cothurnata, A. muscaria and other Amanita species | journal = Lloydia | volume = 39 | issue = 2–3 | pages = 150–157 | year = 1976 | pmid = 985999 }}</ref><ref name="Michelot_2003" /> 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.<ref name="Chilton_1978">{{cite book | vauthors = Chilton WS | chapter = Chemistry and Mode of Action of Mushroom Toxins | title = Mushroom Poisoning: Diagnosis and Treatment | pages = 87–124 | date = 1978 | veditors = Rumack BH, Salzman E | publisher = CRC Press | isbn = 978-0-8493-5185-3 }}</ref>

==Use and effects==
The properties and effects of muscimol in humans have been limitedly assessed in [[clinical study|clinical studies]].<ref name="Stebelska_2013" /><ref name="Hollister_1990" /><ref name="Brimblecombe_1975">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Miscellaneous Hallucinogens | title = Hallucinogenic Agents | location = Bristol | pages = 196–216 | date = 1975 | publisher = Wright-Scientechnica | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1 | quote = 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. }}</ref><ref name="Waser_1967">{{cite book | vauthors = Waser PG | chapter = The Pharmacology of Amanita Muscaria | title = Ethnopharmacologic Search for Psychoactive Drugs | pages = 419–439 | date = 1967 | publisher = Raven Press | isbn = 978-0-89004-047-8 | url = https://books.google.com/books?id=IvfBDethZkYC | chapter-url = https://ia600800.us.archive.org/22/items/the-pharmacology-of-amanita-muscaria-waser-1967/the-pharmacology-of-amanita-muscaria-waser-1967.pdf }}</ref> It has been assessed in these studies at doses of 5 to 15{{nbsp}}mg orally.<ref name="Stebelska_2013" /> The [[oral administration|oral]] threshold dose of muscimol is approximately 6{{nbsp}}mg,<ref name="Stebelska_2013">{{cite journal | vauthors = Stebelska K | title = Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities | journal = Ther Drug Monit | volume = 35 | issue = 4 | pages = 420–442 | date = August 2013 | pmid = 23851905 | doi = 10.1097/FTD.0b013e31828741a5 }}</ref><ref name="Ott_1976" /> while the [[psychoactive drug|psychoactive]] dose range has been said to range from approximately 8 to 15{{nbsp}}mg.<ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023">{{cite journal | vauthors = Okhovat A, Cruces W, Docampo-Palacios ML, Ray KP, Ramirez GA | title = Psychoactive Isoxazoles, Muscimol, and Isoxazole Derivatives from the Amanita (Agaricomycetes) Species: Review of New Trends in Synthesis, Dosage, and Biological Properties | journal = Int J Med Mushrooms | volume = 25 | issue = 9 | pages = 1–10 | date = 2023 | pmid = 37824402 | doi = 10.1615/IntJMedMushrooms.2023049458 }}</ref><ref name="Trachsel_2000" /> As little as 1{{nbsp}}g of dried ''Amanita muscaria'' button may contain this amount of muscimol, although the [[potency (pharmacology)|potency]] varies greatly among mushrooms.<ref name="Peredy_2014">{{cite book | vauthors = Peredy T, Bruce R | chapter = Mushrooms, Ibotenic Acid | title = Encyclopedia of Toxicology | pages = 412–413 | date = 2014 | doi = 10.1016/B978-0-12-386454-3.00756-9 | isbn = 978-0-12-386455-0 }}</ref> According to [[Jonathan Ott]], a 15{{nbsp}}mg dose is "psychoptic" while a 20{{nbsp}}mg dose is "visionary".<ref name="Ott_1996" /> The [[onset of action]] of muscimol, via isolated muscimol or ''[[Amanita muscaria]]'' consumption orally, is between 30{{nbsp}}minutes and 2{{nbsp}}hours,<ref name="Okhovat_2023" /><ref name="Waser_1967" /> with peak effects occurring after 1 to 3{{nbsp}}hours.<ref name="Ott_1996" /><ref name="Hollister_1990">{{cite journal | vauthors = Hollister LE | title = New class of hallucinogens: GABA-enhancing agents | journal = Drug Development Research | volume = 21 | issue = 3 | pages = 253–256 | date = 1990 | doi = 10.1002/ddr.430210311 | issn = 0272-4391 | url = https://onlinelibrary.wiley.com/doi/10.1002/ddr.430210311 | access-date = 22 September 2025 | url-access = subscription }}</ref><ref name="Tamminga_1978" /> The [[duration of action|duration]] is 4 to 8{{nbsp}}hours, but some effects may persist for up to 24{{nbsp}}hours.<ref name="Ott_1996" /><ref name="Okhovat_2023" /><ref name="Satora_2005" /><ref name="Trachsel_2000" /><ref name="Hollister_1990" /><ref name="Tamminga_1978" /> In one publication, the effects of muscimol were described as follows:<ref name="Brimblecombe_1975" /><ref name="Waser_1967" />

: "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."<ref name="Brimblecombe_1975" /><ref name="Waser_1967" />

The effects of muscimol in humans in different studies have been found to include [[sedation]], [[dizziness]], [[ataxia|incoordination]], [[relaxation (psychology)|relaxation]], [[anxiolysis|reduced anxiety]], [[mood improvement]], [[sleep]], rich [[dream|dreaming]], [[difficulty speaking]], impaired attention, focus, and concentration, [[learning impairment|impaired learning]], [[mental confusion|confusion]], [[anorexia (symptom)|loss of appetite]], [[psychostimulant|stimulation]], [[psychomotor agitation|agitation]], [[hallucinogen]]ic effects, [[echo]]-like [[pseudohallucination]]s ([[visual hallucination|visual]] and [[auditory hallucination|auditory]], vivid [[hallucination]]s, [[psychosis]], and [[delirium]].<ref name="Stebelska_2013" /><ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023" /><ref name="Brimblecombe_1975" /> At higher doses, [[coma]], [[seizure]]s, and [[death]] can occur.<ref name="Okhovat_2023" /><ref name="RiveraIllanes_2024" /> Physical effects of muscimol can include [[muscle twitching]], [[flushing (physiology)|flushing]], slightly increased [[blood pressure]], [[nausea]], [[vomiting]], [[abdominal pain]], and [[diarrhea]], among others.<ref name="Stebelska_2013" /><ref name="Okhovat_2023" /><ref name="RiveraIllanes_2024" /><ref name="HallHall1994" /> [[After-effect]]s have been reported to include [[fatigue]], inactivity, and [[headache]] and [[migraine]].<ref name="Stebelska_2013" /> Muscimol can increase [[prolactin]] and [[growth hormone]] levels.<ref name="Tamminga_1978a" /><ref name="Durso_1983" />

Muscimol is said to have similar effects on sleep in rodents as the related experimental [[pharmaceutical drug]] [[gaboxadol]] (THIP).<ref name="KrogsgaardLarsen_2004" /><ref name="Johnston_2014" /><ref name="Wafford_2006">{{cite journal | vauthors = Wafford KA, Ebert B | title = Gaboxadol--a new awakening in sleep | journal = Curr Opin Pharmacol | volume = 6 | issue = 1 | pages = 30–36 | date = February 2006 | pmid = 16368265 | doi = 10.1016/j.coph.2005.10.004 }}</ref><ref name="McDonaldSheppardStaveley2007">{{cite journal | vauthors = McDonald LM, Sheppard WF, Staveley SM, Sohal B, Tattersall FD, Hutson PH | title = Gaboxadol, a selective extrasynaptic GABA(A) agonist, does not generalise to other sleep-enhancing drugs: a rat drug discrimination study | journal = Neuropharmacology | volume = 52 | issue = 3 | pages = 844–853 | date = March 2007 | pmid = 17196996 | doi = 10.1016/j.neuropharm.2006.10.009 | url = | quote = 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).}}</ref> In humans, gaboxadol decreases [[sleep onset latency]], increases [[total sleep time|sleep duration]], increases [[slow wave sleep]] (SWS) and [[slow wave activity]] (SWA), and does not suppress [[REM sleep]].<ref name="Wafford_2006" /> The effects of muscimol and gaboxadol on sleep differ from those of widely used [[GABAA receptor positive allosteric modulator|GABA<sub>A</sub> receptor positive allosteric modulator]]s like [[benzodiazepine]]s and [[Z-drug]]s, which can instead disrupt SWS and SWA despite improving sleep onset and duration.<ref name="KrogsgaardLarsen_2004" /><ref name="Johnston_2014" /><ref name="Wafford_2006" /><ref name="Dijk_2010">{{cite journal | vauthors = Dijk DJ | title = Slow-wave sleep deficiency and enhancement: implications for insomnia and its management | journal = World J Biol Psychiatry | volume = 11 | issue = Suppl 1 | pages = 22–28 | date = June 2010 | pmid = 20509829 | doi = 10.3109/15622971003637645 }}</ref> Although muscimol and gaboxadol have similar effects on sleep, muscimol has additionally been found to increase [[REM sleep]] unlike gaboxadol.<ref name="McDonaldSheppardStaveley2007" />

[[Ibotenic acid]], a [[prodrug]] of muscimol, is active at doses of approximately 20 to 100{{nbsp}}mg orally in humans.<ref name="Ott_1996">{{cite book | vauthors = Ott J | chapter = Ibotenic Acid–Muscimol: The Primordial Pangk and Amrta | title = Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History | pages = 323–358,446 | date = 1996 | edition = 2 | publisher = Natural Products Company | isbn = 978-0-9614234-8-3 | url = https://books.google.com/books?id=VMjwAAAAMAAJ&pg=PA323 | chapter-url = https://anthrome.wordpress.com/wp-content/uploads/2010/06/pharmacotheon.pdf#page=161 }}</ref><ref name="Stebelska_2013" /><ref name="Okhovat_2023" /><ref name="RiveraIllanes_2024" /> About 10 to 20% of ibotenic acid is said to be converted into muscimol following [[decarboxylation]].<ref name="Hartwig_2025">{{cite journal | vauthors = Hartwig J, Kendrick J, Ahmad G, Cook J, Matthews DB, Sharma P | title = Exploring User Experiences with Amanita muscaria: A Thematic Analysis of Reddit Online Forum Discussions | journal = Subst Use Misuse | volume = 60 | issue = 7 | pages = 952–961 | date = 2025 | pmid = 40057818 | doi = 10.1080/10826084.2025.2476141 | quote = The commonly reported reason for Amanita muscaria use was to improve sleep. }}</ref><ref name="Ott_1996" />

==Toxicity and overdose==
The [[toxicity]] and [[drug safety|safety]] profile of muscimol has been studied in various contexts, both experimental and clinical. The [[median lethal dose]] (LD<sub>50</sub>) in mice is 3.8{{nbsp}}mg/kg s.c, 2.5{{nbsp}}mg/kg i.p. The LD<sub>50</sub> in rats is 4.5{{nbsp}}mg/kg i.v, 45&nbsp;mg/kg orally.<ref name="Erowid">{{Cite web | title = Psychoactive Amanitas Chemistry | url = https://www.erowid.org/plants/amanitas/amanitas_chemistry.shtml | website = Erowid }}{{rs|date=July 2024}}</ref> A study on non-human primates indicated that muscimol, when administered in escalating doses, caused reversible [[hyperkinesia]] and [[dyskinesias]] at higher doses (up to 88.8 mM), but no long-term toxicity was observed on histological examination.<ref>{{cite journal | vauthors = Heiss JD, Walbridge S, Asthagiri AR, Lonser RR | title = Image-guided convection-enhanced delivery of muscimol to the primate brain: Laboratory investigation | journal = Journal of Neurosurgery | volume = 112 | issue = 4 | pages = 790–795 | date = April 2010 | pmid = 19715424 | pmc = 2853729 | doi = 10.3171/2009.7.JNS09652 }}</ref> Muscimol has shown potential as an [[anticonvulsant]], blocking [[seizure]]s induced by various agents in [[animal model]]s without causing significant toxicity at [[therapeutic]] doses.<ref>{{cite journal | vauthors = Collins RC | title = Anticonvulsant effects of muscimol | journal = Neurology | volume = 30 | issue = 6 | pages = 575–581 | date = June 1980 | pmid = 7189834 | doi = 10.1212/wnl.30.6.575 }}</ref> Muscimol exhibits [[dose dependence|dose-dependent]] [[efficacy|effects]] with higher doses leading to significant, but reversible, central nervous system [[symptom]]s.<ref>{{cite journal | vauthors = Farber NB, Jiang X, Dikranian K, Nemmers B | title = Muscimol prevents NMDA antagonist neurotoxicity by activating GABAA receptors in several brain regions | journal = Brain Research | volume = 993 | issue = 1–2 | pages = 90–100 | date = December 2003 | pmid = 14642834 | doi = 10.1016/j.brainres.2003.09.002 }}</ref> The dose of muscimol that is thought to be potentially fatal in humans is 90{{nbsp}}mg, which is 15{{nbsp}}times its threshold active dose of 6{{nbsp}}mg.<ref name="Peredy_2014" />

==Interactions==
The actions and effects of muscimol may be potentiated by [[benzodiazepine]]s such as [[diazepam]].<ref name="Michelot_2003" /><ref name="Johnston_2014" />

==Pharmacology==
===Pharmacodynamics===
[[File:Muscimol vs GABA 3D.png|thumb|right|275px|[[γ-Aminobutyric acid]] (GABA) and muscimol molecules can have similar 3D [[conformational isomerism|conformations]] which are shown superimposed in this image. Because of this similarity, muscimol binds to certain GABA receptors.<ref name="Michelot_2003" />]]

Muscimol is a [[potency (pharmacology)|potent]] [[GABAA receptor|GABA<sub>A</sub> receptor]] [[full agonist]], activating the [[receptor (biochemistry)|receptor]] for the brain's principal [[Inhibitory postsynaptic potential|inhibitory]] [[neurotransmitter]], [[γ-aminobutyric acid]] (GABA).<ref name="Johnston_2014" /> Muscimol binds to the same site on the GABA<sub>A</sub> receptor complex as GABA itself, unlike other GABAergic drugs such as [[barbiturate]]s, [[benzodiazepine]]s, and [[Z-drug]]s, which interact with separate [[allosteric site]]s.<ref name="Frlund_2002" /><ref name="Johnston_2014" /> GABA<sub>A</sub> 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 (biology)|hyperpolarization]] of [[neuron]]s. This results in decreased neuronal excitability, which is crucial for maintaining the balance between excitation and inhibition in the [[central nervous system]].<ref name="Chebib_1999">{{cite encyclopedia | vauthors = Chebib M, Johnston GA | title = Muscimol | pages = 1234–1238 | year = 1999 | editor = Heldman, Dennis R. | encyclopedia = Encyclopedia of Agricultural, Food, and Biological Engineering | publisher = CRC Press }}</ref>

Muscimol shows relatively uniform effects on GABA<sub>A</sub> receptors of differing [[protein subunit|subunit]] compositions.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /> However, it was found to act as a [[superagonist]] of [[extrasynaptic]] α<sub>4</sub>β<sub>3</sub>δ subunit-containing GABA<sub>A</sub> receptors ({{Abbrlink|E<sub>max</sub>|maximal efficacy}} = 120 to 140% relative to GABA).<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /> This was found to be due to reduced [[receptor desensitization]] with muscimol compared to GABA.<ref name="Johnston_2014" /> Subsequent research has found that muscimol is a preferential agonist of the relatively small population of δ subunit-containing GABA<sub>A</sub> receptors and that these receptors have a substantial contribution to its effects.<ref name="Benkherouf_2019">{{cite journal | vauthors = Benkherouf AY, Taina KR, Meera P, Aalto AJ, Li XG, Soini SL, Wallner M, Uusi-Oukari M | title = Extrasynaptic δ-GABAA receptors are high-affinity muscimol receptors | journal = J Neurochem | volume = 149 | issue = 1 | pages = 41–53 | date = April 2019 | pmid = 30565258 | pmc = 6438731 | doi = 10.1111/jnc.14646 }}</ref><ref name="RiveraIllanes_2024" /> In contrast to muscimol, benzodiazepines and Z-drugs do not activate δ subunit-containing GABA<sub>A</sub> receptors.<ref name="DeaconStanerStaner2007">{{cite journal | vauthors = Deacon S, Staner L, Staner C, Legters A, Loft H, Lundahl J | title = Effect of short-term treatment with gaboxadol on sleep maintenance and initiation in patients with primary insomnia | journal = Sleep | volume = 30 | issue = 3 | pages = 281–287 | date = March 2007 | pmid = 17425224 | doi = 10.1093/sleep/30.3.281 | url = | quote = 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.}}</ref> On the other hand, [[alcohol (drug)|alcohol]] is known to selectively potentiate δ subunit-containing extrasynaptic GABA<sub>A</sub> receptors analogously to muscimol.<ref name="LoboHarris2008">{{cite journal | vauthors = Lobo IA, Harris RA | title = GABA(A) receptors and alcohol | journal = Pharmacology, Biochemistry, and Behavior | volume = 90 | issue = 1 | pages = 90–94 | date = July 2008 | pmid = 18423561 | pmc = 2574824 | doi = 10.1016/j.pbb.2008.03.006 }}</ref><ref name="SanthakumarWallnerOtis2007">{{cite journal | vauthors = Santhakumar V, Wallner M, Otis TS | title = Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition | journal = Alcohol | volume = 41 | issue = 3 | pages = 211–221 | date = May 2007 | pmid = 17591544 | pmc = 2040048 | doi = 10.1016/j.alcohol.2007.04.011 }}</ref><ref name="WallnerOlsen2008">{{cite journal | vauthors = Wallner M, Olsen RW | title = Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development? | journal = British Journal of Pharmacology | volume = 154 | issue = 2 | pages = 288–298 | date = May 2008 | pmid = 18278063 | pmc = 2442438 | doi = 10.1038/bjp.2008.32 }}</ref>

While muscimol is often thought of as a [[binding selectivity|selective]] GABA<sub>A</sub> agonist with exceptionally high [[affinity (pharmacology)|affinity]] to δ subunit-containing GABA<sub>A</sub> receptors,<ref>{{cite journal | vauthors = Quirk K, Whiting PJ, Ragan CI, McKernan RM | title = Characterisation of delta-subunit containing GABAA receptors from rat brain | journal = European Journal of Pharmacology | volume = 290 | issue = 3 | pages = 175–181 | date = August 1995 | pmid = 7589211 | doi = 10.1016/0922-4106(95)00061-5 }}</ref><ref>{{cite journal | vauthors = Chandra D, Jia F, Liang J, Peng Z, Suryanarayanan A, Werner DF, Spigelman I, Houser CR, Olsen RW, Harrison NL, Homanics GE  | title = GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 41 | pages = 15230–15235 | date = October 2006 | pmid = 17005728 | pmc = 1578762 | doi = 10.1073/pnas.0604304103 | doi-access = free | bibcode = 2006PNAS..10315230C }}</ref><ref name="Benkherouf_2019" /> it is also a potent[[partial agonist]] of the [[GABAA-rho receptor|GABA<sub>A</sub>-ρ receptor]], and so its range of effects results from a combined action on more than one GABA<sub>A</sub> receptor subtype.<ref>{{cite journal | vauthors = Woodward RM, Polenzani L, Miledi R | title = 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 | journal = Molecular Pharmacology | volume = 43 | issue = 4 | pages = 609–625 | date = April 1993 | pmid = 8386310 | doi = 10.1016/S0026-895X(25)13444-5 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8386310 | url-access = subscription }}</ref> In fact, it is more potent as a partial agonist of the GABA<sub>A</sub>-ρ receptor than as a GABA<sub>A</sub> receptor agonist.<ref name="Johnston_2014" /><ref name="Okhovat_2023" /> Muscimol has been said to be inactive at the [[GABA-B receptor|GABA<sub>B</sub> receptor]].<ref name="Johnston_2014" /><ref name="Okhovat_2023" /> However, a subsequent study reported that muscimol may have GABA<sub>B</sub> receptor-mediated inhibitory activity, although more research is needed to further characterize this activity.<ref name="RiveraIllanes_2024" /><ref name="Yamauchi_2000">{{cite journal | vauthors = Yamauchi T, Hori T, Takahashi T | title = Presynaptic inhibition by muscimol through GABAB receptors | journal = Eur J Neurosci | volume = 12 | issue = 9 | pages = 3433–3436 | date = September 2000 | pmid = 10998126 | doi = 10.1046/j.1460-9568.2000.00248.x }}</ref> Muscimol is inactive in terms of affecting [[GABA transaminase]] (GABA-T).<ref name="Okhovat_2023" /> There is little evidence that muscimol interacts with other [[biological target]]s besides the [[GABA receptor]]s and the [[GABA transporter]]s.<ref name="Johnston_2014" />

In animals, muscimol produces [[central depressant|central depression]], [[sedation]], [[analgesia]], [[anxiolysis]], [[anticonvulsant]] effects, [[neuroprotection|neuroprotective]] effects, and [[anesthesia]], among other effects.<ref name="Stebelska_2013" /><ref name="KaurSinghArora2020">{{cite book | vauthors = Kaur S, Singh S, Arora A, Ram P, Kumar S, Kumar P, Abed SN | chapter = Pharmacology of GABA and Its Receptors | title = Frontiers in Pharmacology of Neurotransmitters | pages = 241–292 | date = 2020 | doi = 10.1007/978-981-15-3556-7_8 | isbn = 978-981-15-3555-0 }}</ref> In rodent [[drug discrimination]] studies, muscimol and [[gaboxadol]] fully generalize between each other, but generalization between benzodiazepines like [[diazepam]] does not occur.<ref name="Wafford_2006" /><ref name="McDonaldSheppardStaveley2007" /><ref name="Sanger_1985">{{cite journal | vauthors = Sanger DJ | title = GABA and the behavioral effects of anxiolytic drugs | journal = Life Sci | volume = 36 | issue = 16 | pages = 1503–1513 | date = April 1985 | pmid = 2858804 | doi = 10.1016/0024-3205(85)90374-1 }}</ref> These findings suggest that muscimol and gaboxadol have differing [[interoceptive]] effects from those of benzodiazepines.<ref name="Wafford_2006" /><ref name="Sanger_1985" /> During a test involving rabbits connected to an [[Electroencephalography|EEG]], muscimol presented with a distinctly [[Neural oscillation|synchronized]] [[Electroencephalography|EEG]] tracing.<ref name="De_Carolis_1969" /> This is substantially different from [[serotonergic psychedelic]]s like [[psilocybin]], with which brainwave patterns generally show a desynchronization.<ref name="De_Carolis_1969" /> In higher doses (2{{nbsp}}mg/kg via [[Intravenous therapy|IV]]), the EEG will show characteristic spikes.<ref name="De_Carolis_1969">{{cite journal | vauthors = De Carolis AS, Lipparini F, Longo VG | title = Neuropharmacological investigations on muscimol, a psychotropic drug extracted from Amanita muscaria | journal = Psychopharmacologia | volume = 15 | issue = 3 | pages = 186–195 | date = January 1969 | pmid = 5389124 | doi = 10.1007/BF00411168 | s2cid = 26824149 }}</ref>

===Pharmacokinetics===
The [[pharmacokinetics]] of muscimol in humans have been very limitedly studied.<ref name="RiveraIllanes_2024" /> Pharmacokinetic parameters such as [[bioavailability]], [[volume of distribution]], [[plasma protein binding]], and [[elimination half-life]] are unavailable.<ref name="RiveraIllanes_2024" /><ref name="DrugBank" />

====Absorption====
Muscimol is readily [[absorption (pharmacokinetics)|absorbed]] in the [[gastrointestinal tract]] when taken [[oral administration|orally]].<ref name="Okhovat_2023" />

====Distribution====
The [[brain]] [[tissue (biology)|tissue]] [[distribution (pharmacology)|distribution]] of muscimol in rats has been studied.<ref name="RiveraIllanes_2024" /><ref name="Baraldi_1979" /> Muscimol rapidly enters and unevenly distributes in rat brain, especially in the [[substantia nigra]], colliculi, and [[hypothalamus]].<ref name="RiveraIllanes_2024" /><ref name="Baraldi_1979">{{Cite journal | vauthors = Baraldi M, Grandison L, Guidotti A | title = Distribution and metabolism of muscimol in the brain and other tissues of the rat | journal = Neuropharmacology | volume = 18 | issue = 1 | pages = 57–62 | date = 1979 | pmid = 418955 | doi = 10.1016/0028-3908(79)90009-1 | url = https://colab.ws/articles/10.1016/0028-3908(79)90009-1?utm_ | access-date = 2025-05-24 | language = en }}</ref> Muscimol crosses the [[blood–brain barrier]] and hence is [[central nervous system|centrally active]].<ref name="Frlund_2002" /><ref name="Michelot_2003" /><ref name="Stebelska_2013" /> This has been said to likely be mediated by [[active transport]] via the high-[[affinity (pharmacology)|affinity]] GABA uptake system and other [[amino acid transporter]]s.<ref name="RiveraIllanes_2024" /><ref name="Michelot_2003" /><ref name="Stebelska_2013" /> Although muscimol crosses the blood–brain barrier, it does so relatively poorly and far less readily than [[gaboxadol]].<ref name="Wafford_2006" /><ref name="MoroniForchettiKrogsgaard-Larsen1982" />

====Metabolism====
Muscimol is known to be [[drug metabolism|metabolized]] via [[transamination]] by [[GABA transaminase]] (GABA-T).<ref name="RiveraIllanes_2024" /><ref name="Stebelska_2013" /><ref name="Baraldi_1979" /> [[Ibotenic acid]] is a [[prodrug]] of muscimol via [[decarboxylation]].<ref name="RiveraIllanes_2024" /><ref name="Michelot_2003" /><ref name="Okhovat_2023" /> However, it has been said that muscimol can also be converted back into ibotenic acid via [[glutamate decarboxylase]].<ref name="Okhovat_2023" /> The [[metabolite]]s of muscimol have not been identified, but might contribute to the [[toxicity]] of muscimol.<ref name="KrogsgaardLarsen_1981" />

====Elimination====
Muscimol is [[excretion|excreted]] by the [[kidney]]s into [[urine]].<ref name="Stebelska_2013" /> It is excreted partially unmetabolized.<ref name="Stebelska_2013" /> This has been taken advantage of by [[Siberian people|Siberian]] practitioners of the traditional [[entheogen]]ic use of ''[[Amanita muscaria]]'' via recycling of muscimol in urine.<ref>"[{{GBurl|g51AJv8UETgC|p=228}} Another Magic Mushroom]" p. 228 in: {{cite book | vauthors = Goldstein A | chapter = Hallucinogens | title = Addiction | pages = 219–232 | date = 2001 | doi = 10.1093/oso/9780195146639.003.0014 | isbn = 978-0-19-514663-9 }}</ref>

The [[elimination half-life]] of muscimol in humans is unknown.<ref name="RiveraIllanes_2024" /><ref name="DrugBank" /> The closely related drug [[gaboxadol]] (THIP), which is a [[cyclic compound|cyclized]] [[chemical derivative|derivative]] of muscimol, has an elimination half-life in humans of 1.5 to 2{{nbsp}}hours.<ref name="HoehnSaric_1983">{{cite journal | vauthors = Hoehn-Saric R | title = Effects of THIP on chronic anxiety | journal = Psychopharmacology (Berl) | volume = 80 | issue = 4 | pages = 338–341 | date = 1983 | pmid = 6414002 | doi = 10.1007/BF00432116 | quote = 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). }}</ref> In rodents, the half-life of gaboxadol was about twice as long as that of muscimol.<ref name="MoroniForchettiKrogsgaard-Larsen1982">{{cite journal | vauthors = Moroni F, Forchetti MC, Krogsgaard-Larsen P, Guidotti A | title = Relative disposition of the GABA agonists THIP and muscimol in the brain of the rat | journal = J Pharm Pharmacol | volume = 34 | issue = 10 | pages = 676–678 | date = October 1982 | pmid = 6128395 | doi = 10.1111/j.2042-7158.1982.tb04702.x | url = }}</ref> The drug is said to be more resistant to [[drug metabolism|metabolism]] than muscimol, for instance not being a [[substrate (biochemistry)|substrate]] for GABA-T.<ref name="Frlund_2002" /><ref name="KrogsgaardLarsen_1981" />

==Chemistry==
===Structure===
Muscimol was first isolated from ''[[Amanita pantherina]]'' by Onda in 1964,<ref>{{cite journal | vauthors = Onda M, Fukushima H, Akagawa M | title = A Flycidal Constituent of Amanita pantherina (DC.) F<SUB>R</SUB> | journal = Chemical & Pharmaceutical Bulletin | volume = 12 | issue = 6 | pages = 751 | date = June 1964 | pmid = 14199180 | doi = 10.1248/cpb.12.751 | doi-access = free }}</ref> and thought to be an [[amino acid]] or [[peptide]]. Structure was then elucidated by Takemoto,<ref>{{cite report | title = イボテン酸の構造 | pages = 1232–1233 | type = none | trans-title = Structure of Ibotenic Acid | language = ja }} in: {{cite journal | vauthors = Takemoto T, Nakajima T, Yokobe T, Sakuma R, Fujitani K, Aoyagi Y, Masaki Y | title = 寄書 | journal = Yakugaku Zasshi | volume = 84 | issue = 12 | pages = 1230–1236 | date = 1964 | doi = 10.1248/yakushi1947.84.12_1230 | trans-title = Communication to the Editor | language = ja | doi-access = free }}</ref> Eugster,<ref>{{cite journal | vauthors = Eugster C, Müller G, Good R | title = Wirkstoffe aus amanita muscaria: ibotensaeure und muscazon | journal = Tetrahedron Letters | volume = 6 | issue = 23 | pages = 1813–1815 | date = January 1965 | pmid = 5891631 | doi = 10.1016/s0040-4039(00)90133-3 | trans-title = The active ingredients from Amanita muscaria: ibotenic acid and muscazone | language = de }}</ref> and Bowden.<ref>{{cite journal | vauthors = Bowden K, Drysdale AC, Mogey GA | title = Constituents of Amanita muscaria | journal = Nature | volume = 206 | issue = 991 | pages = 1359–1360 | date = June 1965 | pmid = 5891274 | doi = 10.1038/2061359a0 | s2cid = 4178793 | bibcode = 1965Natur.206.1359B }}</ref> Muscimol is a semi-rigid [[isoxazole]] containing both [[Alcohol (chemistry)|alcohol]] and [[Aminomethyl group|aminomethyl]] substituents.<ref>{{cite journal | vauthors = Brehm L, Frydenvang K, Hansen LM, Norrby PO, Krogsgaard-Larsen P, Liljefors T | title = Structural features of muscimol, a potent GABAA receptor agonist, crystal structure and quantum chemicalab initio calculations | journal = Structural Chemistry | volume = 8 | issue = 6 | pages = 443–451 | date = December 1997 | doi = 10.1007/BF02311703 | bibcode = 1997StrCh...8..443B | s2cid = 93397543 }}</ref> Muscimol is commonly portrayed as a [[tautomer]], where it adopts an [[amide]]-like configuration.<ref name="PubChem" /> It is also commonly shown as a [[zwitterion]].<ref name="Pevarello_1992">{{cite journal | title = An Improved Synthesis of Muscimol | journal = Synthetic Communications | volume = 22 | issue = 13 | pages = 1939–1948 | date = July 1992 | doi = 10.1080/00397919208021324 }}</ref>

===Properties===
Muscimol is a [[zwitterion]] at physiological [[pH]].<ref name="RiveraIllanes_2024" /> Its predicted [[partition coefficient|log P]] of –1.4 to –2.2.<ref name="DrugBank" /><ref name="PubChem">{{cite web | title = Muscimol | website = PubChem | url = https://pubchem.ncbi.nlm.nih.gov/compound/4266 | access-date = 21 September 2025 }}</ref> The drug's log P is similar to that of [[γ-aminobutyric acid]] (GABA).<ref name="Paleologos_1990">{{cite journal | vauthors = Paleologos NA, Groothuis DR | title = The role of the blood-brain barrier in movement disorders | journal = Clin Neuropharmacol | volume = 13 | issue = 2 | pages = 129–146 | date = April 1990 | pmid = 2183934 | doi = 10.1097/00002826-199004000-00003 }}</ref>

===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 (chemistry)|basic]] [[resin]]. This is washed with water, and [[Elution|eluted]] with [[acetic acid]] using [[column chromatography]]. The [[Elution|eluate]] is freeze dried, dissolved in water, and passed down a column of [[Ion exchange|cellulose phosphate]].<ref>{{cite web | title = Cellulose Phosphate: Product Information | url = https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/c2258pis.pdf | website = Sigma Aldrich | access-date = 23 April 2020 }}</ref> A subsequent elution with [[ammonium hydroxide]] and [[Recrystallization (chemistry)|recrystallization]] from alcohol results in pure muscimol.<ref>{{cite journal | vauthors = Bowden K, Drysdale A | title = A novel constituent of Amanita muscaria | journal = Tetrahedron Letters | volume = 6 | issue = 12 | pages = 727–728 | date = 1965 | pmid = 14291871 | doi = 10.1016/s0040-4039(01)83973-3 }}</ref>

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{{nbsp}}minutes.<ref>{{cite web | vauthors = Heinrich C | title = Amanita muscaria Preparation for Beginners | date = 23 November 2008 | url = https://erowid.org/plants/amanitas/amanitas_info8.shtml | work = Erowid }}{{self-published inline|date=July 2024}}</ref>

===Synthesis===
Several [[chemical synthesis|chemical syntheses]] of muscimol have been published.<ref name="Michelot_2003" /><ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023" /><ref name="Gagneux_1965">{{cite journal | vauthors = Gagneux AR, Häfliger F, Eugster CH, Good R | title = Synthesis of pantherine (agarin) | journal = Tetrahedron Letters | volume = 6 | issue = 25 | pages = 2077–2079 | date = January 1965 | doi = 10.1016/S0040-4039(00)90157-6 }}</ref><ref name="ChiarinoNapoletanoSala1986">{{cite journal | vauthors = Chiarino D, Napoletano M, Sala A | title = A convenient synthesis of muscimol by a 1,3-dipolar cycloaddition reaction | journal = Tetrahedron Letters | volume = 27 | issue = 27 | pages = 3181–3182 | year = 1986 | doi = 10.1016/S0040-4039(00)84748-6 }}</ref><ref name="BowdenCrankRoss1968">{{cite journal | vauthors = Bowden K, Crank G, Ross WJ | title = The synthesis of pantherine and related compounds | journal = Journal of the Chemical Society C: Organic | pages = 172 | year = 1968 | doi = 10.1039/j39680000172 }}</ref><ref name="McCarrySavard1981">{{cite journal | vauthors = McCarry BE, Savard M | title = A facile synthesis of muscimol | journal = Tetrahedron Letters | volume = 22 | issue = 51 | pages = 5153–5156 | date = January 1981 | doi = 10.1016/S0040-4039(01)92445-1 }}</ref><ref name="Pevarello_1992" />

===Analogues===
[[Structural analog|Analogue]]s 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 (drug)|THPO]], [[nipecotic acid]], and [[tiagabine]], among others.<ref name="Okhovat_2023" /><ref name="KrogsgaardLarsen_1981" /><ref name="KrogsgaardLarsen_2004" /><ref name="GrinbergaDamgaardAndersen2016">{{cite conference | vauthors = Grinberga S, Damgaard M, Andersen V, Jensen AA, Krogsgaard-Larsen P, Nielsen B, Waagepetersen HS, Schousboe A, Frølund B | title = Synthesis and Pharmacological Evaluation of Amidine Containing GABA<sub>A</sub> Receptor Agonists | conference = EFMC International Symposium on Medicinal Chemistry Manchester, UK Aug. 28 - Sept. 1, 2016 | date = 2016 | pages = P278 | url = https://istina.msu.ru/media/publications/article/6f5/7ea/31004876/ISMC-Book-web-1209.pdf#page=231}}</ref> The structural requirements for GABA<sub>A</sub> receptor binding and activation are very strict, so relatively few high-[[intrinsic activity|efficacy]] GABA<sub>A</sub> receptor agonists are known.<ref name="Krogsgaard-LarsenFrølundLiljefors2006">{{cite book | vauthors = Krogsgaard-Larsen P, Frølund B, Liljefors T | chapter = GABAA Agonists and Partial Agonists: THIP (Gaboxadol) as a Non-Opioid Analgesic and a Novel Type of Hypnotic1 | title = GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic | volume = 54 | pages = 53–71 | date = 2006 | pmid = 17175810 | doi = 10.1016/s1054-3589(06)54003-7 | series = Adv Pharmacol | isbn = 978-0-12-032957-1}}</ref><ref name="Krogsgaard-Larsen2018">{{cite book | last=Krogsgaard-Larsen | first=Povl | title=Reference Module in Biomedical Sciences | chapter=THIP/Gaboxadol, a Unique GABA Agonist | publisher=Elsevier | date=2018 | isbn=978-0-12-801238-3 | doi=10.1016/b978-0-12-801238-3.97290-8 | url=https://linkinghub.elsevier.com/retrieve/pii/B9780128012383972908 | access-date=7 October 2025 | page=}}</ref>

==History==
''[[Amanita muscaria]]'' has been used by humans as a [[psychoactive drug]] since ancient times.<ref name="RiveraIllanes_2024" /><ref name="KrogsgaardLarsen_1981" /><ref name="HallHall1994">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</ref> Muscimol was isolated from ''Amanita muscaria'' independently by three different research groups in 1964 and 1965.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="KrogsgaardLarsen_1981" /> It was [[chemical synthesis|synthesized]] by Gagneux and colleagues in 1965.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="Okhovat_2023" /><ref name="Gagneux_1965" /> The [[chemical structure]] of muscimol, along with that of [[ibotenic acid]], was published by Conrad Eugster at the [[University of Zurich]] in 1967.<ref name="Johnston_2014" /><ref name="Eugster_1967">{{cite journal | vauthors = Eugster CH, Takemoto T | title = Zur Nomenklatur der neuen Verbindungen aus Amanita -Arten | journal = Helvetica Chimica Acta | volume = 50 | issue = 1 | pages = 126–127 | date = 1967 | pmid = 5593205 | doi = 10.1002/hlca.19670500119 | issn = 0018-019X | bibcode = 1967HChAc..50..126E | url = https://onlinelibrary.wiley.com/doi/10.1002/hlca.19670500119 | access-date = 20 September 2025 | url-access = subscription }}</ref><ref name="UZH-Eugster">{{cite web | title = Conrad Eugster | website = UZH | url = https://www.chem.uzh.ch/en/research/groups/emeriti/eugster.html | access-date = 20 September 2025 }}</ref>

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.<ref name="Johnston_2014" /><ref name="Johnston_1968">{{cite journal | vauthors = Johnston GA, Curtis DR, De Groat WC, Duggan AW | title = Central actions of ibotenic acid and muscimol | journal = Biochem Pharmacol | volume = 17 | issue = 12 | pages = 2488–2489 | date = December 1968 | pmid = 5752907 | doi = 10.1016/0006-2952(68)90141-x }}</ref> Subsequently, its actions were shown to be reversed by the [[GABA receptor antagonist]] [[bicuculline]] in 1971.<ref name="Johnston_2014" /><ref name="Curtis_1971">{{cite journal | vauthors = Curtis DR, Duggan AW, Felix D, Johnston GA | title = Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat | journal = Brain Res | volume = 32 | issue = 1 | pages = 69–96 | date = September 1971 | pmid = 4398801 | doi = 10.1016/0006-8993(71)90156-9 }}</ref>

The effects of muscimol in humans were studied and described by Waser in 1967.<ref name="Brimblecombe_1975" /><ref name="Ott_1976">{{cite journal | vauthors = Ott J | title = Psycho-Mycological Studies Of Amanita – From Ancient Sacrament To Modern Phobia | journal = Journal of Psychedelic Drugs | volume = 8 | issue = 1 | pages = 27–35 | date = 1976 | doi = 10.1080/02791072.1976.10472005 | issn = 0022-393X | url = https://www.tandfonline.com/doi/full/10.1080/02791072.1976.10472005 | access-date = 21 September 2025 | url-access = subscription }}</ref><ref name="Waser_1967" /> Later, [[ethnobotanist]] [[Jonathan Ott]] further described the effects of muscimol, via ''[[Amanita pantherina]]'' consumption, in 1976.<ref name="RiveraIllanes_2024" /><ref name="Ott_1976" />

[[Danish people|Danish]] [[medicinal chemist]] [[Povl Krogsgaard-Larsen]] and colleagues studied muscimol and [[synthetic compound|synthetic]] [[structural analog|analogue]]s over several decades starting in the 1970s.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /> Other GABA<sub>A</sub> receptor [[ligand (biochemistry)|ligand]]s, such as [[gaboxadol]] (THIP) and [[4-PIOL]], and [[GABA transporter]] [[transporter modulator|modulator]]s, such as [[nipecotic acid]] and [[tiagabine]], have been [[chemical derivative|derived]] from muscimol.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="KrogsgaardLarsen_2004" /> Many muscimol analogues were developed by Krogsgaard-Larsen and colleagues.<ref name="Johnston_2014" /><ref name="RiveraIllanes_2024" /><ref name="KrogsgaardLarsen_2004" />

==Society and culture==
===Legal status===
{{See also|Legal status of psychoactive Amanita mushrooms}}

Muscimol is not a [[controlled substance]] and is unregulated in most of the world.<ref name="RiveraIllanes_2024" /><ref name="Leas_2024" /><ref name="Savickaite_2025" />

====Australia====
Muscimol is considered a [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 9: Prohibited Substance|Schedule 9]] [[controlled substance|prohibited substance]] in Australia under the [[Standard for the Uniform Scheduling of Medicines and Poisons|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."<ref name="Poisons Standard">{{cite web | title = Poisons Standard | date = October 2015 | work = The Government of Australia | url = https://www.comlaw.gov.au/Details/F2015L01534 }}</ref>

====Poland====
Muscimol and [[ibotenic acid]] are both considered as [[designer drug|novel psychoactive substances]] in [[Poland]] as of 2024.<ref name="SEJM" /> Possessing or selling them is illegal.<ref name="SEJM">{{cite web | title = Rozporządzenie Ministra Zdrowia z dnia 30 kwietnia 2025 r. zmieniające rozporządzenie w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych | url = https://isap.sejm.gov.pl/isap.nsf/DocDetails.xsp?id=WDU20250000598 | website = isap.sejm.gov.pl }}</ref>

====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.<ref>{{cite web | title = FDA Alerts Industry and Consumers About Use of Amanita muscaria or Its Constituents in Food | date = December 18, 2024 | url = https://www.fda.gov/food/hfp-constituent-updates/fda-alerts-industry-and-consumers-about-use-amanita-muscaria-or-its-constituents-food | website = U.S. Food and Drug Administration | publisher = FDA | access-date = April 2, 2025 }}</ref> [[Florida Department of Agriculture and Consumer Services|Agriculture regulators]] in [[Florida]] actioned against one seller of ''Amanita'' products after the agency had determined such products were considered adulterated under state law.<ref>{{Cite web | vauthors = Sam O | title = Mood-altering mushroom sales bloom despite safety concerns | date = May 31, 2023 | url = https://health.wusf.usf.edu/health-news-florida/2023-05-31/mood-altering-mushroom-sales-bloom-despite-safety-concerns | access-date = June 6, 2023 | website = Health News Florida }}</ref>

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.<ref>{{cite web | title = Louisiana Act No 159 | url = http://legis.la.gov/Legis/Law.aspx?d=321523 | website = Louisiana State Legislature | access-date = 6 May 2020 | archive-date = 25 January 2024 | archive-url = https://web.archive.org/web/20240125224246/https://legis.la.gov/legis/Law.aspx?d=321523 }}</ref>

==Research==
Muscimol has been clinically studied for a number of potential medical uses.<ref name="RiveraIllanes_2024" /><ref name="DeFeudis_1980" /><ref name="Ramawad_2023" /><ref name="Heiss_2019" /> It was assessed in small [[clinical study|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.<ref name="DeFeudis_1980">{{cite journal | vauthors = DeFeudis FV | title = Physiological and behavioral studies with muscimol | journal = Neurochem Res | volume = 5 | issue = 10 | pages = 1047–1068 | date = October 1980 | pmid = 6258091 | doi = 10.1007/BF00966163 | quote = 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). }}</ref><ref name="Stebelska_2013" /><ref name="Shoulson_1977">{{cite journal | vauthors = Shoulson I, Goldblatt D, Charlton M, Joynt RJ | title = Huntington's disease: treatment with muscimol, a GABA-mimetic drug | journal = Trans Am Neurol Assoc | volume = 102 | issue = 3 | pages = 124–125 | date = 1977 | pmid = 150672 | doi = 10.1002/ana.410040316 }}</ref><ref name="Shoulson_1978">{{cite journal | vauthors = Shoulson I, Goldblatt D, Charlton M, Joynt RJ | title = Huntington's disease: treatment with muscimol, a GABA-mimetic drug | journal = Ann Neurol | volume = 4 | issue = 3 | pages = 279–284 | date = September 1978 | pmid = 152602 | doi = 10.1002/ana.410040316 }}</ref><ref name="Tamminga_1978">{{cite journal | vauthors = Tamminga CA, Crayton JW, Chase TN | title = Muscimol: GABA agonist therapy in schizophrenia | journal = Am J Psychiatry | volume = 135 | issue = 6 | pages = 746–747 | date = June 1978 | pmid = 350058 | doi = 10.1176/ajp.135.6.746 }}</ref><ref name="Tamminga_1979">{{cite journal | vauthors = Tamminga CA, Crayton JW, Chase TN | title = Improvement in tardive dyskinesia after muscimol therapy | journal = Arch Gen Psychiatry | volume = 36 | issue = 5 | pages = 595–598 | date = May 1979 | pmid = 35117 | doi = 10.1001/archpsyc.1979.01780050105013 }}</ref><ref name="ChaseTamminga1979">Chase, N., & Tamminga, C. A. (1979). Muscimol therapy of hyperkinetic extpapyramidal disorders Thomas. ''Brain Research Bulletin'', ''4''(5), 700. https://scholar.google.com/scholar?cluster=11103420926788228270</ref><ref name="TammingaChase1979">Tamminga, C. A., & Chase, T. N. (1979). GABA agonist effect on cognitive dysfunction in schizophrenic subjects. ''Brain Research Bulletin'', ''4''(5), 708. https://scholar.google.com/scholar?cluster=12333477908462637709</ref> Another study evaluated muscimol in schizophrenics with tardive dyskinesia in 1992.<ref name="Cassady_1992">{{cite journal | vauthors = Cassady SL, Thaker GK, Moran M, Birt A, Tamminga CA | title = GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia | journal = Biol Psychiatry | volume = 32 | issue = 4 | pages = 302–311 | date = August 1992 | pmid = 1358231 | doi = 10.1016/0006-3223(92)90035-x }}</ref> Studies also assessed the [[biochemistry|biochemical]] effects of muscimol in humans in the late 1970s and early 1980s.<ref name="Tamminga_1978a">{{cite journal | vauthors = Tamminga CA, Neophytides A, Chase TN, Frohman LA | title = Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist | journal = J Clin Endocrinol Metab | volume = 47 | issue = 6 | pages = 1348–1351 | date = December 1978 | pmid = 162520 | doi = 10.1210/jcem-47-6-1348 }}</ref><ref name="Cavagnini_1982">{{cite journal | vauthors = Cavagnini F, Pinto M, Dubini A, Invitti C, Cappelletti G, Polli EE | title = Effects of gamma aminobutyric acid (GABA) and muscimol on endocrine pancreatic function in man | journal = Metabolism | volume = 31 | issue = 1 | pages = 73–77 | date = January 1982 | pmid = 7043162 | doi = 10.1016/0026-0495(82)90029-4 }}</ref><ref name="Durso_1983">{{cite journal | vauthors = Durso R, Tamminga CA, Denaro A, Ruggeri S, Chase TN | title = Plasma growth hormone and prolactin response to dopaminergic GABAmimetic and cholinergic stimulation in Huntington's disease | journal = Neurology | volume = 33 | issue = 9 | pages = 1229–1232 | date = September 1983 | pmid = 6225034 | doi = 10.1212/wnl.33.9.1299 }}</ref>

According to [[Povl Krogsgaard-Larsen]], muscimol was too [[toxicity|toxic]] and [[binding selectivity|non-selective]] and as such was not developed for use as a [[pharmaceutical drug]].<ref name="Frlund_2002" /><ref name="Morris2018-S02E07">{{cite episode | title = A Fungal Fairy Tale | issue = 7 | date = 9 January 2018 | credits = [[Hamilton Morris | Morris H]] | series = [[Hamilton's Pharmacopeia]] | season = 2 | url = https://www.youtube.com/watch?v=snM7RsUZtaE | publisher = [[Vice Media]] | network = [[Viceland]] }}</ref><ref name="Morris_2013" /> Instead, the [[synthetic compound|synthetic]] [[structural analog|analogue]] [[gaboxadol]] (THIP), which was more selective and less toxic, was developed.<ref name="Johnston_2014" /><ref name="KrogsgaardLarsen_2004" /><ref name="Morris_2013" />

In 2019, a [[Phases of clinical research#Phase I|phase 1]] [[clinical trial]] of muscimol for drug-resistant [[epilepsy]] was published.<ref name="Kaur_2016">{{cite journal | vauthors = Kaur H, Kumar B, Medhi B | title = Antiepileptic drugs in development pipeline: A recent update | journal = eNeurologicalSci | volume = 4 | pages = 42–51 | date = September 2016 | pmid = 29430548 | pmc = 5803110 | doi = 10.1016/j.ensci.2016.06.003 }}</ref><ref name="Heiss_2019">{{cite journal | vauthors = Heiss JD, Argersinger DP, Theodore WH, Butman JA, Sato S, Khan OI | title = Convection-Enhanced Delivery of Muscimol in Patients with Drug-Resistant Epilepsy | journal = Neurosurgery | volume = 85 | issue = 1 | pages = E4–E15 | date = July 2019 | pmid = 30407567 | pmc = 6704347 | doi = 10.1093/neuros/nyy480 }}</ref> It has also been formally investigated for potential treatment of [[Alzheimer's disease]] and [[Parkinson's disease]].<ref name="Synapse">{{cite web | title=Delving into the Latest Updates on Muscimol with Synapse | website=Synapse | date=27 September 2025 | url=https://synapse.patsnap.com/drug/ff05dd3e15a049f494d559b491308f30 | access-date=29 September 2025}}</ref><ref name="Kaur_2020">{{cite book | vauthors = Kaur S, Singh S, Arora A, Ram P, Kumar S, Kumar P, Abed SN | chapter = Pharmacology of GABA and Its Receptors | title = Frontiers in Pharmacology of Neurotransmitters | pages = 241–292 | date = 2020 | doi = 10.1007/978-981-15-3556-7_8 | publisher = Springer Singapore | publication-place = Singapore | isbn = 978-981-15-3555-0 | chapter-url = http://link.springer.com/10.1007/978-981-15-3556-7_8 | access-date = 29 September 2025 }}</ref> A 2023 [[systematic review]] and [[meta-analysis]] of 22{{nbsp}}[[preclinical research|preclinical studies]] found that muscimol reduces [[neuropathic pain]] in animals, with effects beginning within 15{{nbsp}}minutes and lasting up to 3{{nbsp}}hours.<ref name="Ramawad_2023">{{cite journal | vauthors = Ramawad HA, Paridari P, Jabermoradi S, Gharin P, Toloui A, Safari S, Yousefifard M | title = Muscimol as a treatment for nerve injury-related neuropathic pain: A systematic review and meta-analysis of preclinical studies | journal = The Korean Journal of Pain | volume = 36 | issue = 4 | pages = 425–440 | date = 2023 | pmid = 37732408 | pmc = 10551397 | doi = 10.3344/kjp.23161 }}</ref><ref name="RiveraIllanes_2024" />

Muscimol has never been approved as a pharmaceutical drug for any use anywhere in the world.<ref name="RiveraIllanes_2024" /><ref name="DrugBank" />

==See also==
* [[List of hallucinogens]]
* [[Mushroom edible]]

==References==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/626 Muscimol - Isomer Design]
* [http://www.erowid.org/plants/amanitas Psychoactive Amanitas - Erowid]
* [https://psychonautwiki.org/wiki/Amanita_muscaria Amanita muscaria - PsychonautWiki]
* [https://www.reddit.com/r/AmanitaMuscaria/ r/AmanitaMuscaria - Reddit]

{{Hallucinogens}}
{{Hypnotics and sedatives}}
{{GABA receptor modulators}}
{{GABA metabolism and transport modulators}}

[[Category:Alkaloids]]
[[Category:Aminomethyl compounds]]
[[Category:Anticonvulsants]]
[[Category:Enols]]
[[Category:Entheogens]]
[[Category:GABA analogues]]
[[Category:GABAA receptor agonists]]
[[Category:GABAA-rho receptor agonists]]
[[Category:GABA reuptake inhibitors]]
[[Category:Hallucinogens]]
[[Category:Human drug metabolites]]
[[Category:Hypnotics]]
[[Category:Isoxazoles]]
[[Category:Mycotoxins]]
[[Category:Mycotoxins found in Basidiomycota]]
[[Category:Peripherally selective drugs]]<!-- Partially -->
[[Category:Recreational drug metabolites]]
[[Category:Sedatives]]