Fly Agaric

Fly agaric held sacred status in Siberia and was central to shamanic rites, where dried caps were eaten to produce a trance ^{17,24Reference 17Rivera-Illanes et al. · 2024ReviewClassics in chemical neuroscience: muscimol — reviewView study →Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

Ibotenic acid and muscimol pass into the urine largely unchanged. This allowed a practice of “secondary intoxication”, in which the urine of people, or of reindeer, that had eaten the mushroom was drunk to extend the effect ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

In some regions the mushroom is eaten as food after treatment to remove its toxins. In Japan the caps are dried, brined for about twelve weeks and rinsed repeatedly. In Mexico and Italy they are boiled and the toxin-rich water discarded ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

Some hypotheses propose that fly agaric was Soma, the divine drink of the Hindu Rigveda ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}. The best known is the ethnomycologist R. Gordon Wasson’s. The identity of Soma remains contested, and psilocybin mushrooms, Syrian rue (Peganum harmala) and ephedra have all been suggested instead.

The mushroom has also been linked, more speculatively, to Viking “berserker” rage and to the imagery of Christmas: red-and-white dress, reindeer that “fly”, and a gift-bringer from the frozen north.

The mushroom’s defining effect is heavy sedation and a dream-like haze. It is driven by muscimol, a close structural relative of GABA and a potent agonist at GABA-A receptors ^{6,17Reference 6Johnston · 2014ReviewMuscimol as an ionotropic GABA receptor agonist — reviewView study →Reference 17Rivera-Illanes et al. · 2024ReviewClassics in chemical neuroscience: muscimol — reviewView study →}.

Early pharmacological and psychological studies in people identified muscimol and ibotenic acid as the components responsible for the intoxication ^{1Reference 1Theobald et al. · 1968Pharmacological and experimental-psychological studies with two components of fly agaric (Amanita muscaria) — early human pharmacological characterisation of muscimol and ibotenic acidView study →}.

In a typical course, an excited phase with warmth, restlessness, unsteadiness and visual and auditory hallucinations is followed by deep sleep ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

In a social-media survey of 684 users, men most often took the mushroom for stress, low mood and insomnia ^{21Reference 21Ordak et al. · 2023ObservationalReasons, form of ingestion and side effects associated with consumption of Amanita muscaria — observational surveyView study →}.

Gap: No controlled human trial of the dried mushroom for sleep or sedation exists; potency varies widely between specimens, so effect and dose are not reproducible without lab testing ^{3,24Reference 3Michelot et al. · 2003ReviewAmanita muscaria: chemistry, biology, toxicology, and ethnomycology — reviewView study →Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

Given systemically to rats, muscimol blocked seizures from penicillin applied to the brain and delayed metrazol convulsions. It had no effect on seizures from picrotoxin or strychnine. Applied directly to the cortex, it blocked focal seizure discharges in a dose-related way ^{7Reference 7Collins · 1980AnimalAnticonvulsant effects of muscimol — rat/animal modelView study →}.

Continuous delivery of muscimol into the subthalamic nucleus of rats for three weeks raised seizure thresholds, with dose-dependent responder rates ^{9Reference 9Gernert et al. · 2023AnimalAcute and chronic convection-enhanced muscimol delivery into the rat subthalamic nucleus induces antiseizure effects — animal modelView study →}.

In a Phase 1 crossover trial, three adults with drug-resistant epilepsy received muscimol infused directly into the seizure focus. Seizure frequency fell in one of the three during muscimol and in none during the vehicle infusion, and there was no infusion-related brain injury. The authors concluded that the study did not confirm that muscimol infusion suppressed seizures ^{8Reference 8Heiss et al. · 2019Clinical trialConvection-enhanced delivery of muscimol in patients with drug-resistant epilepsy — Phase 1 clinical trial (n=3)View study →}. The registered trial was terminated.

Muscimol was infused into the brain rather than taken by mouth, so none of this applies to eating the mushroom.

Gap: The only human trial was Phase 1, terminated, n=3, and used direct intracerebral infusion of pure muscimol — not an achievable or safe route for the mushroom as consumed ^{8Reference 8Heiss et al. · 2019Clinical trialConvection-enhanced delivery of muscimol in patients with drug-resistant epilepsy — Phase 1 clinical trial (n=3)View study →}.

In mice given bacterial endotoxin, isolated muscimol lowered TNF-α, IL-1β, IL-12 and nitric oxide, raised IL-10, suppressed NF-κB activity and improved survival. The protection was at least partly independent of GABA and cholinergic receptors ^{10Reference 10Li et al. · 2022AnimalThe protective effect of muscimol against systemic inflammatory response in endotoxemic mice is independent of GABAergic and cholinergic receptors — mouse modelView study →}.

Muscimol also blocked cell rupture during pyroptosis, an inflammatory form of cell death, by preventing ninjurin-1 from clustering. This too did not run through GABA-A receptors, and muscimol reduced deaths from septic shock in mice ^{11Reference 11den Hartigh et al. · 2023In vitroMuscimol inhibits plasma-membrane rupture and ninjurin-1 oligomerization during pyroptosis — in vitro and mouse septic-shock modelView study →}.

A commercially sourced A. muscaria extract behaved differently. It increased IL-8 production by human microglial cells stimulated with a viral-mimicking signal, possibly because of its trehalose content ^{13Reference 13Wagner et al. · 2023In vitroAmanita muscaria extract potentiates production of proinflammatory cytokines by dsRNA-activated human microglia — in vitroView study →}.

Gap: All positive data are single-molecule and animal/in-vitro; the whole extract showed the opposite direction in human microglia, and there is no in-vivo work on the mushroom itself ^{10,11,13Reference 10Li et al. · 2022AnimalThe protective effect of muscimol against systemic inflammatory response in endotoxemic mice is independent of GABAergic and cholinergic receptors — mouse modelView study →Reference 11den Hartigh et al. · 2023In vitroMuscimol inhibits plasma-membrane rupture and ninjurin-1 oligomerization during pyroptosis — in vitro and mouse septic-shock modelView study →Reference 13Wagner et al. · 2023In vitroAmanita muscaria extract potentiates production of proinflammatory cytokines by dsRNA-activated human microglia — in vitroView study →}.

Injected into the abdomen of mice, muscimol (0.12–0.25 mg/kg) raised the pain threshold in the tail-flick test and shortened immobility in the forced-swim test, an antidepressant-like signal. The GABA-A blocker bicuculline did the opposite ^{14Reference 14Baghani et al. · 2024AnimalAdditive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice — animal modelView study →}.

Injected into the spinal fluid, muscimol reduced bicuculline-induced touch sensitivity and heat sensitivity in mice ^{15Reference 15Lee et al. · 2010AnimalIntracisternal or intrathecal glycine, taurine, or muscimol inhibit bicuculline-induced allodynia and thermal hyperalgesia in mice — animal modelView study →}.

A 2024 review names neuropathic pain as an active direction for muscimol research ^{17Reference 17Rivera-Illanes et al. · 2024ReviewClassics in chemical neuroscience: muscimol — reviewView study →}.

In a social-media survey of users, pain relief was the most common reason women gave for taking the mushroom, most often as a tincture ^{21Reference 21Ordak et al. · 2023ObservationalReasons, form of ingestion and side effects associated with consumption of Amanita muscaria — observational surveyView study →}.

The animal data use injected pure muscimol, not the dried mushroom by mouth, and human use for pain is self-reported only, with no controlled trial ^{14,15,21Reference 14Baghani et al. · 2024AnimalAdditive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice — animal modelView study →Reference 15Lee et al. · 2010AnimalIntracisternal or intrathecal glycine, taurine, or muscimol inhibit bicuculline-induced allodynia and thermal hyperalgesia in mice — animal modelView study →Reference 21Ordak et al. · 2023ObservationalReasons, form of ingestion and side effects associated with consumption of Amanita muscaria — observational surveyView study →}.

A standardised, muscimol-rich A. muscaria extract protected against several laboratory models of nerve-cell damage: rat brain microsomes, mitochondria and synaptosomes, and the SH-SY5Y neuroblastoma cell line. It did not inhibit human monoamine oxidase-B ^{12Reference 12Kondeva-Burdina et al. · 2019In vitroEffects of Amanita muscaria extract on different in vitro neurotoxicity models at sub-cellular and cellular levels — in vitroView study →}.

The extract’s free-radical-scavenging and antioxidant activity is the proposed basis for the effect ^{12Reference 12Kondeva-Burdina et al. · 2019In vitroEffects of Amanita muscaria extract on different in vitro neurotoxicity models at sub-cellular and cellular levels — in vitroView study →}.

There is no whole-animal or human work. Ibotenic acid from the same mushroom is used experimentally to destroy nerve cells, so a protective effect in a living animal has not been shown ^{4,12Reference 4Jørgensen et al. · 2007Novel 5-substituted 1-pyrazolol analogues of ibotenic acid: synthesis and pharmacology at glutamate receptorsView study →Reference 12Kondeva-Burdina et al. · 2019In vitroEffects of Amanita muscaria extract on different in vitro neurotoxicity models at sub-cellular and cellular levels — in vitroView study →}.

Gap: Entirely in-vitro; the same species contains an excitotoxin used to destroy neurons, so a net protective effect in vivo is unproven ^{4,12Reference 4Jørgensen et al. · 2007Novel 5-substituted 1-pyrazolol analogues of ibotenic acid: synthesis and pharmacology at glutamate receptorsView study →Reference 12Kondeva-Burdina et al. · 2019In vitroEffects of Amanita muscaria extract on different in vitro neurotoxicity models at sub-cellular and cellular levels — in vitroView study →}.

A standardised water–ethanol extract of A. muscaria was cytotoxic to a small panel of lung cell lines. When analysed, it contained no significant amount of muscimol, ibotenic acid or ergosterol, so the effect came from something else ^{2Reference 2Dushkov et al. · 2023In vitroAnalysis of the ibotenic acid, muscimol, and ergosterol content of an Amanita muscaria hydroalcoholic extract and evaluation of its cytotoxic effect against lung cell lines — in vitroView study →}.

Separately, A. muscaria extract was used to coat silver and iron-oxide nanoparticles in a hyaluronic-acid gel. The mushroom compounds formed the particle surface, and the gel was cytotoxic to HeLa cervical cancer cells ^{16Reference 16Ivashchenko et al. · 2018In vitroGel with silver and ultrasmall iron oxide nanoparticles produced with Amanita muscaria extract: physicochemical characterization, microstructure analysis and anticancer properties — in vitroView study →}.

Neither study shows selectivity for cancer cells over healthy cells, and there is no animal or human evidence.

Gap: In-vitro cytotoxicity only, no demonstrated tumour selectivity, and the nanoparticle gel also contains silver ^{2,16Reference 2Dushkov et al. · 2023In vitroAnalysis of the ibotenic acid, muscimol, and ergosterol content of an Amanita muscaria hydroalcoholic extract and evaluation of its cytotoxic effect against lung cell lines — in vitroView study →Reference 16Ivashchenko et al. · 2018In vitroGel with silver and ultrasmall iron oxide nanoparticles produced with Amanita muscaria extract: physicochemical characterization, microstructure analysis and anticancer properties — in vitroView study →}.

Poisoning. Fly agaric and the panther cap cause a poisoning syndrome of the central nervous system ^{3Reference 3Michelot et al. · 2003ReviewAmanita muscaria: chemistry, biology, toxicology, and ethnomycology — reviewView study →}. Among 34 cases of fly agaric and panther cap poisoning reported to a US poison centre over 15 years, symptoms included stomach upset, excitement and drowsiness, alone or together. Most began within 6 hours and settled within 24; five patients needed a breathing tube, and there were no seizures, kidney or liver injury, or deaths ^{19Reference 19Moss et al. · 2019Case reportToxicity of muscimol and ibotenic acid containing mushrooms reported to a regional poison control center from 2002–2016 — case seriesView study →}.

The two species differ. Fly agaric contains more ibotenic acid and less muscimol than the panther cap. In a case series, people poisoned by fly agaric were more often confused (26 of 32) and agitated (20 of 32), while those poisoned by the panther cap were more often in a coma ^{20Reference 20Vendramin et al. · 2014Case reportAmanita muscaria and Amanita pantherina poisoning: two syndromes — clinical case seriesView study →}.

Cholinergic signs. Drooling, sweating, a slow heart rate and diarrhoea can occur. They are usually mild and reversible, but at high doses can become a severe cholinergic crisis ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}. Severe poisoning can also bring tremor, seizures, loss of consciousness, and failing breathing or circulation ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}. Deaths from fly agaric itself are very rare ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

Lethal-dose data. In rats the oral lethal dose (LD50) is about 129 mg/kg for ibotenic acid and 45 mg/kg for muscimol ^{24Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

Deadly lookalikes. The Amanita genus contains some of the deadliest fungi known — the death cap (Amanita phalloides) and the destroying angels (A. virosa, A. bisporigera, A. ocreata and others) — which can cause fatal liver and kidney failure from a single meal. They grow in the same habitats as fly agaric and can resemble it at various life stages; a young, unopened A. muscaria button is especially easy to confuse. Never wild-harvest this or any Amanita unless you are 100% certain of the identification. A mistake here is not a bad trip but potentially fatal organ failure.

Metals. The mushroom concentrates vanadium and other metals from the soil, so its content depends on where it grew ^{5,24Reference 5Garner et al. · 2000Investigations of amavadin — the vanadium compound accumulated by A. muscariaView study →Reference 24Stoeva-Grigorova et al. · 2025Case reportAcute Amanita muscaria toxicity: a literature review and two case reports in elderly spouses following home preparation — review and case reportsView study →}.

Sedatives. Do not combine it with alcohol, benzodiazepines, sleep aids or other central nervous system depressants, as muscimol is itself a strong sedative. Driving or operating machinery is out of the question given the sedation and confusion.

Contemporary use. In a 2025 analysis of Reddit discussions, users reported more positive than negative effects, and most adverse effects were mild and passed on their own ^{23Reference 23Hartwig et al. · 2025ObservationalExploring user experiences with Amanita muscaria: a thematic analysis of Reddit online forum discussions — observationalView study →}. In a survey of social-media users, men most often reported nausea, vomiting, abdominal pain and drowsiness, and women most often reported headaches ^{21Reference 21Ordak et al. · 2023ObservationalReasons, form of ingestion and side effects associated with consumption of Amanita muscaria — observational surveyView study →}.

Legal status. The mushroom is unregulated in much of the world, including the United States, Canada and the UK, but is banned or restricted in some places — for example Australia, where muscimol is scheduled, some European countries, and the US state of Louisiana. Check local law before handling or possessing it.