Muscimol

5-(aminomethyl)-1,2-oxazol-3-one

Overview

Muscimol belongs to Depressants / GABAergic.

Key safety note: Muscimol is a genuine CNS depressant with a steep dose–response curve: the gap between a psychoactive dose (~6–15 mg) and a dangerous one is not large, and effects are unpredictable because Amanita muscaria potency varies enormously between mushrooms and preparations.[3][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • An atypical, sedating intoxication rather than a classic psychedelic: sedation, dizziness, incoordination, muscle relaxation and sleepiness, often with vivid, dream-like ('oneirogenic') states and rich dreaming.
  • Perceptual changes tend to be mild echo-like pseudo-hallucinations and distortions rather than the intense visuals of LSD or psilocybin. Early clinical reports explicitly note that 'intense hallucinations as with LSD were missing'.
  • Higher doses bring confusion, disorientation in time and space, difficulty speaking, agitation, dissociation and delirium, sometimes frightening or dysphoric, with painful muscular twitching.
  • Common physical effects include nausea, vomiting, abdominal discomfort, sweating or flushing and increased salivation. After-effects can include fatigue, headache and migraine.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral, Smoked (uncommon). Not a recommendation. The figures below are for isolated muscimol taken orally. Whole Amanita muscaria is far less predictable: muscimol content varies enormously between mushrooms and with preparation (drying and heat decarboxylate ibotenic acid to muscimol). Roughly 1 g of dried fly-agaric cap may contain a threshold dose, but this cannot be relied on. A dose of ~90 mg has been cited as potentially fatal: about 15× the threshold.

Dose ranges

Threshold

≈6 mg (isolated muscimol)

Common / psychoactive

≈8–15 mg

Strong

≈15–20 mg ('psychoptic' to 'visionary', per Ott)

Duration

onset

≈0.5–2 h

peak

≈1–3 h

total

≈4–10 h (occasionally up to 24 h)

Chemical & Physical Properties
FormulaC4H6N2O2
Molar mass114.1 g/mol
StateSolid
Melting point≈184–185 °C, PubChem lists ~175 °C (dec.)
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP−1.4 (XLogP3, predicted range −1.4 to −2.2)
SolubilityWater-soluble. A zwitterion at physiological pH (log P similar to GABA), Extractable from Amanita flesh with boiling water
Refractive indexNot reported
Identifiers & Synonyms
CAS2763-96-4
CAS (enantiomer)
PubChem CID4266
InChIKeyZJQHPWUVQPJPQT-UHFFFAOYSA-N
InChIInChI=1S/C4H6N2O2/c5-2-3-1-4(7)6-8-3/h1H,2,5H2,(H,6,7)
SMILESC1=C(ONC1=O)CN

Synonyms

  • Agarin
  • Pantherine
  • Pyroibotenic acid
  • 5-Aminomethylisoxazol-3-ol
  • 3-Hydroxy-5-aminomethylisoxazole
Pharmacodynamics & Biochemistry

Muscimol is a potent GABA-A receptor agonist and the principal psychoactive constituent of Amanita muscaria (fly agaric) and A. pantherina (panther cap). A conformationally restrained analogue of the inhibitory neurotransmitter GABA, it binds the same orthosteric site as GABA itself, unlike benzodiazepines, barbiturates and Z-drugs, which are allosteric modulators, and, unlike GABA, it crosses the blood–brain barrier (relatively poorly, via amino-acid transporters), so it is centrally active. It acts as a full agonist across the GABA-A α-subunit subtypes but is a preferential, supra-maximal ('super') agonist at extrasynaptic δ-subunit-containing receptors such as α4β3δ (Emax ≈120–140% of GABA), because it desensitises these receptors less than GABA does. This action on tonic inhibition is thought to drive much of its effect and further distinguishes it from benzodiazepines, which do not act at δ-containing receptors. Muscimol is additionally a potent partial agonist at GABA-A-ρ (formerly GABA-C) receptors, in fact more potent there than at the classical GABA-A receptor, is essentially inactive at GABA-B, and weakly inhibits GABA reuptake. It is a substrate of GABA transaminase but does not inhibit the enzyme. Receptor activation opens chloride channels, hyperpolarising neurons and lowering excitability across the cortex, hippocampus and cerebellum.

Biological targets

  • GABA-A

Binding & functional measurements

TargetMeasurementSpecies
GABA-AUnspecified Agonist across α1–α6 subunit-containing receptorsHuman
GABA-A-ρUnspecified More potent than at the classical GABA-A receptorHuman
Pharmacokinetics
BioavailabilityNot established (human)
Tmax≈1–3 h (peak effects)
Half-lifeNot established in humans, extensively metabolised (cf. gaboxadol ≈1.5–2 h)
VdNot reported
Protein bindingNot reported
MetabolismTransamination by GABA-T to an aldehyde metabolite. Interconverts with ibotenic acid (decarboxylation ↔ glutamate decarboxylase)
ExcretionRenal: partly excreted unchanged in urine (the basis of the Siberian urine-recycling practice)
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Muscimol is a genuine CNS depressant with a steep dose–response curve: the gap between a psychoactive dose (~6–15 mg) and a dangerous one is not large, and effects are unpredictable because Amanita muscaria potency varies enormously between mushrooms and preparations. Acute effects can include heavy sedation, confusion, delirium, dissociation, nausea and vomiting, muscle twitching and, at high doses, agitation, seizures and coma. Documented deaths are very rare, but the deeply sedated or delirious state is itself hazardous (injury, aspiration, exposure). The German Federal Institute for Risk Assessment (BfR) has specifically warned about muscimol-containing 'fly-agaric' fruit gummies, which children can mistake for sweets. The co-occurring prodrug ibotenic acid is additionally neurotoxic. Alcohol, benzodiazepines and other CNS depressants potentiate muscimol's effects. Limited human data must never be read as evidence of safety.[3][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Alcohol Additive sedation and cognitive or motor depression. Ethanol also selectively potentiates the same δ-subunit-containing GABA-A receptors muscimol prefers.[3]
Benzodiazepines Diazepam strongly potentiates muscimol's central depressant effects in animals, so expect additive sedation (the barbiturate phenobarbital, by contrast, did not potentiate it).[3]
Neurosteroids (allopregnanolone, pregnanolone) Neurosteroids such as allopregnanolone and pregnanolone may potentiate its effects.[3]

Contraindications

Combining with alcohol or other CNS depressants concurrent alcohol, benzodiazepines or other CNS depressants.[3]
Settings where impairment or dissociation risks injury (driving, water, heights) driving or operating machinery (marked sedation, incoordination and impaired attention).[3]
Children (age-restricted; respiratory-depression risk) products such as gummies are easily mistaken for sweets, and children are especially vulnerable.[4]
Pregnancy or breastfeeding no safety data.
Usage & Context
  • Traditional entheogenic and shamanic use of Amanita muscaria across Siberia and parts of northern Eurasia: including the well-documented practice of recycling muscimol excreted in urine to extend or share the effects.
  • Long a rare recreational drug, but from the mid-2020s Amanita muscaria and muscimol products (gummies, extracts and 'microdose' capsules) have become increasingly prominent, commonly marketed for sleep and claimed wellbeing benefits.
  • Widely used as a pharmacological tool, a standard GABA-A agonist for reversibly silencing brain regions in neuroscience, and as a scaffold for drugs such as gaboxadol (THIP) and tiagabine.
Sources & Evidence

Further Information