Norpsilocin, also known as 4-hydroxy-''N''-methyltryptamine (4-HO-NMT), is a

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

recently discovered in 2017 in the

psychedelic mushroom A mushroom or toadstool is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or another food source. ''Toadstool'' generally refers to a poisonous mushroom. The standard for the name "mushroom" is t ...

Psilocybe cubensis ''Psilocybe cubensis'', commonly known as the magic mushroom, shroom, golden halo, golden teacher, cube, or gold cap, is a species of psilocybin mushroom of moderate potency whose principal Psychoactive compound, active compounds are psilocybin ...

''. It is hypothesized to be a dephosphorylated metabolite of

baeocystin Baeocystin, also known as norpsilocybin or 4-phosphoryloxy-''N''-methyltryptamine (4-PO-NMT), is a zwitterionic alkaloid and analogue of psilocybin. It is found as a minor compound in most psilocybin mushrooms together with psilocybin, norbaeo ...

. Norpsilocin was found to be a near full

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the 5-HT_2A receptor and was found to be more potent than

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

. It also has

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for other

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s. Moreover, it has been found to cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

in animals and to have good

metabolic stability Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of ...

similarly to psilocin. Norpsilocin has shown psilocin-related

peripheral A peripheral device, or simply peripheral, is an auxiliary hardware device that a computer uses to transfer information externally. A peripheral is a hardware component that is accessible to and controlled by a computer but is not a core compo ...

effects in animals, including decreased

spinal reflex The stretch reflex (myotatic reflex), or more accurately ''muscle stretch reflex'', is a muscle contraction in response to stretching a muscle. The function of the reflex is generally thought to be maintaining the muscle at a constant length but t ...

es such as knee jerk response (opposite effect to psilocin),

antiserotonergic A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A receptor are sometimes used ...

activity (14% of that of psilocin), and

pressor An antihypotensive, also known as a vasopressor, is an agent that raises blood pressure by constricting blood vessels, thereby increasing systemic vascular resistance. This is different from inotropes which increase the force of cardiac contrac ...

activity (70% of that of psilocin). Surprisingly however, in spite of its serotonin 5-HT_2A receptor agonism and psilocin-like effects, norpsilocin failed to induce the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

, a behavioral proxy of

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

effects, in animals. Likewise,

norbaeocystin Norbaeocystin, also known as 4-phosphoryloxytryptamine (4-PO-T), is a psilocybin mushroom alkaloid and analog of psilocybin. It is found as a minor compound in most psilocybin mushrooms together with psilocin, psilocybin, aeruginascin, and baeoc ...

and

aeruginascin Aeruginascin, also known as 4-phosphoryloxy-''N'',''N'',''N''-trimethyltryptamine (4-PO-TMT), is an indoleamine derivative which occurs naturally within the mushrooms '' Inocybe aeruginascens'', ''Pholiotina cyanopus'', and ''Psilocybe cubensis' ...

failed to induce the head-twitch response. Only

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

was effective in this regard. In any case, norbaeocystin showed

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

-like activity (

forced swim test ''Forced'' is a single-player and co-op action role-playing game developed by BetaDwarf, released in October 2013 for Windows, OS X and Linux through the Steam platform as well as Wii U. It is about gladiators fighting for their freedom in a fant ...

) similarly to psilocybin and

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

in spite of its putative non-hallucinogenic nature. Norpsilocin itself was not tested in this assay. A 2025 animal study found that both baeocystin and norpsilocin are peripherally selective with very limited ability to cross the

. Norpsilocin is being evaluated under the developmental code name PLZ-1017 for the possible treatment of

pervasive developmental disorder The diagnostic category pervasive developmental disorders (PDD), as opposed to specific developmental disorders (SDD), was a group of disorders characterized by delays in the development of multiple basic functions including socialization and ...

s in children.

References

Experimental non-hallucinogens 4-Hydroxytryptamines N-Monoalkyltryptamines Non-hallucinogenic 5-HT2A receptor agonists Peripherally selective drugs Secondary amines Tryptamine alkaloids {{Alkaloid-stub

See also

References