Psilocybin

Psilocybin
INN: Psilocybine
Kekulé, skeletal formula of canonical psilocybin
Ball-and-stick model of canonical psilocybin
Clinical data
Pronunciation/ˌsləˈsbɪn/ sy-lə-SY-bin, /ˌsɪl-/
Other namesPsilocybine; Psilocibin; Psylocybin; Psilotsibin; Psilocin phosphate; Psilocin phosphate ester; O-Phosphoryl-4-hydroxy-N,N-dimethyltryptamine; 4-Phosphoryloxy-N,N-dimethyltryptamine; 4-Phosphoryl-N,N-dimethyltryptamine; 4-PO-DMT; COMP360; COMP-360; CY-39; CY39; PSOP, Psilocybin (USAN US)
Dependence
liability
Low
Addiction
liability
Low
Routes of
administration
Drug classSerotonergic psychedelic; Hallucinogen; Serotonin receptor agonist; Serotonin 5-HT2A receptor agonist
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: 52.7 ± 20.4% (as psilocin) (n=3)
Protein binding66%
MetabolismLiver, other tissues:
Dephosphorylation (ALPTooltip alkaline phosphatase)
Demethylation and deamination (MAOTooltip monoamine oxidase)
Oxidation (ALDHTooltip aldehyde dehydrogenase)
Glucuronidation (UGTs)
MetabolitesPsilocin
• Psilocin-O-glucuronide
• 4-Hydroxyindole-3-acetaldehyde
• 4-Hydroxyindole-3-acetic acid (4-HIAA)
• 4-Hydroxytryptophol
Onset of actionOral: 0.5–0.8 (range 0.1–1.5) h
IVTooltip Intravenous injection: immediate
Elimination half-lifeOral (as psilocin): 2.1–4.7 h (range 1.2–18.6 h)
IVTooltip Intravenous administration (as psilocin): 1.2 h (range 1.8–4.5 h)
Duration of actionOral: 4–6 h (range 3–12 h)
IVTooltip Intravenous injection: 15–60 min (1–2 mg)
ExcretionUrine (mainly as psilocin-O-glucuronide, 2–4% as unchanged psilocin)
Identifiers
  • [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.007.542
Chemical and physical data
FormulaC12H17N2O4P
Molar mass284.252 g·mol−1
3D model (JSmol)
Melting point220–228 °C (428–442 °F)
  • CN(C)CCC1=CNC2=C1C(=CC=C2)OP(=O)(O)O
  • InChI=1S/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17) Y
  • Key:QVDSEJDULKLHCG-UHFFFAOYSA-N Y
  (verify)

Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in more than 200 species of mushrooms, with hallucinogenic and serotonergic effects. Effects include euphoria, changes in perception, a distorted sense of time (via brain desynchronization), and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks. Its effects depend on set and setting and one's expectations.

Psilocybin is a prodrug of psilocin. That is, the compound itself is biologically inactive but quickly converted by the body to psilocin. Psilocybin is transformed into psilocin by dephosphorylation mediated via phosphatase enzymes. Psilocin is chemically related to the neurotransmitter serotonin and acts as a non-selective agonist of the serotonin receptors. Activation of one serotonin receptor, the serotonin 5-HT2A receptor, is specifically responsible for the hallucinogenic effects of psilocin and other serotonergic psychedelics. Psilocybin is usually taken orally. By this route, its onset is about 20 to 50 minutes, peak effects occur after around 60 to 90 minutes, and its duration is about 4 to 6 hours.

Imagery in cave paintings and rock art of modern-day Algeria and Spain suggests that human use of psilocybin mushrooms predates recorded history. In Mesoamerica, the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in the 16th century. In 1958, the Swiss chemist Albert Hofmann isolated psilocybin and psilocin from the mushroom Psilocybe mexicana. His employer, Sandoz, marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic therapy. Increasingly restrictive drug laws of the 1960s and the 1970s curbed scientific research into the effects of psilocybin and other hallucinogens, but its popularity as an entheogen grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms.

Possession of psilocybin-containing mushrooms has been outlawed in most countries, and psilocybin has been classified as a Schedule I controlled substance under the 1971 United Nations Convention on Psychotropic Substances. Psilocybin is being studied as a possible medicine in the treatment of psychiatric disorders such as depression, substance use disorders, obsessive–compulsive disorder, and other conditions such as cluster headaches. It is in late-stage clinical trials for treatment-resistant depression.