Muscimol in the context of "Psychoactive substances"

Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Hallucinogens are often categorized as either being psychedelics, dissociatives, or deliriants, but not all hallucinogens fall into these three classes.

Examples of hallucinogens include psychedelics or serotonin 5-HT_2A receptor agonists like LSD, psilocybin, mescaline, and DMT; dissociatives or NMDA receptor antagonists like ketamine, PCP, DXM, and nitrous oxide; deliriants or antimuscarinics like scopolamine and diphenhydramine; cannabinoids or cannabinoid CB₁ receptor agonists like THC, nabilone, and JWH-018; κ-opioid receptor agonists like salvinorin A and pentazocine; GABA_A receptor agonists like muscimol and gaboxadol; oneirogens like ibogaine and harmaline; and others like nutmeg, carbogen, glaucine, and hallucinogenic bolete mushrooms.

A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system (CNS) activity. Psychoactive and psychotropic drugs both affect the brain, with psychotropics sometimes referring to psychiatric drugs or high-abuse substances, while “drug” can have negative connotations. Novel psychoactive substances are designer drugs made to mimic illegal ones and bypass laws.

Psychoactive drug use dates back to prehistory for medicinal and consciousness-altering purposes, with evidence of widespread cultural use. Many animals intentionally consume psychoactive substances, and some traditional legends suggest animals first introduced humans to their use. Psychoactive substances are used across cultures for purposes ranging from medicinal and therapeutic treatment of mental disorders and pain, to performance enhancement. Their effects are influenced by the drug itself, the environment, and individual factors. Psychoactive drugs are categorized by their pharmacological effects into types such as anxiolytics (reduce anxiety), empathogen–entactogens (enhance empathy), stimulants (increase CNS activity), depressants (decrease CNS activity), and hallucinogens (alter perception and emotions). Psychoactive drugs are administered through various routes—including oral ingestion, injection, rectal use, and inhalation—with the method and efficiency differing by drug.

Amanita muscaria, commonly known as the fly agaric or fly amanita, is a basidiomycete fungus of the genus Amanita. Its common name derives from its traditional use as an insecticide. It is a distinctive, large white-gilled mushroom typically featuring a bright red cap covered with white warts. The complex genetic diversity of A. muscaria suggests that it is a species complex. It is a widely distributed mushroom native to temperate and boreal forests of the Northern Hemisphere, now also naturalised in the Southern Hemisphere, forming symbiotic relationships with various trees and spreading invasively in some regions.

Ingestion of the mushroom can cause poisoning, especially in children and those seeking its hallucinogenic effects, due to psychoactive compounds like muscimol and the ibotenic acid; however, fatal poisonings are extremely rare. Parboiling reduces toxicity, though drying converts ibotenic acid into muscimol, retaining psychoactive effects. Some cultures use it as food after preparation. Indigenous peoples of Siberia used A. muscaria as an inebriant and entheogen. It has been controversially linked to Santa Claus, Viking berserkers, Vedic soma, and early Christianity, though evidence is sparse and disputed. Its rise in the 2020s as a legal hallucinogen alternative has led to Food and Drug Administration scrutiny.

Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) and by its former developmental code names Lu-2-030, MK-0928, and OV101, is a GABA_A receptor agonist related to muscimol which was investigated for the treatment of insomnia and other conditions like Angelman syndrome but was never marketed. At lower doses, the drug has sedative and hypnotic effects, and at higher doses, it produces hallucinogenic effects. It is taken orally.

The drug acts as a potent and selective partial agonist of the GABA_A receptor, the major signaling receptor of the inhibitory endogenous neurotransmitter γ-aminobutyric acid (GABA). However, it acts as a preferential supra-maximal agonist at extrasynaptic δ subunit-containing GABA_A receptors. In contrast to GABA_A receptor positive allosteric modulators like benzodiazepines and Z drugs, gaboxadol is an orthosteric agonist of the GABA_A receptor, acting on the same site as GABA rather than at an allosteric regulatory site. As a result, gaboxadol has differing effects from benzodiazepines and related drugs. Gaboxadol is a conformationally constrained synthetic analogue of GABA and of muscimol, an alkaloid and hallucinogen found in Amanita muscaria (fly agaric) mushrooms. It has greatly improved drug-like properties compared to these compounds.