Psilocybin
3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate
Overview
Psilocybin belongs to Psychedelics / Tryptamines.
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.
- A classic serotonergic psychedelic experience: brightened colours, visual patterns and distortions, synaesthesia, time distortion, emotional amplification, ego dissolution and mystical-type or spiritual experiences.
- Effects are strongly dose-dependent and shaped by set and setting. Difficult, anxious or fearful experiences ('bad trips') and panic can occur, especially at higher doses.
- Onset ≈20–50 minutes, peak at ≈1–2 hours and total duration ≈4–6 hours (occasionally up to ~12 h). 'lemon tek' (soaking mushrooms in lemon juice) is claimed to speed onset and shorten duration by pre-converting psilocybin to psilocin.
- Common physical effects include nausea, dilated pupils, mild changes in heart rate and blood pressure, and headache.
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. Not a recommendation. Doses are for oral psilocybin. It is most often taken as dried Psilocybe mushrooms (~1% combined psilocybin+psilocin by dry weight, but highly variable), where roughly 1 g dried ≈ 10 mg psilocybin. Psilocin is ~1.4× as potent as psilocybin by weight. Controlled depression trials typically use a 25 mg dose.
Dose ranges
Microdose (sub-perceptual)
<2.5 mg (≈0.1–0.3 g dried mushroom)
Threshold
≈3 mg / 70 kg
Low
≈5–10 mg
Common ('good effect')
≈15–25 mg (≈1–3 g dried, 25 mg = typical trial dose)
Strong (ego-dissolution)
≈30–40 mg (≈3.5–5 g dried)
Duration
onset
≈20–50 min
peak
≈1–2 h
total
≈4–6 h (range 3–12 h)
Chemical & Physical Properties
| Formula | C12H17N2O4P |
| Molar mass | 284.25 g/mol |
| State | Solid |
| Melting point | 220–228 °C |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | Not reported |
| LogP | -1.6 (predicted, XLogP3) |
| Solubility | Soluble in 120 parts boiling methanol. Difficultly soluble in ethanol. Practically insoluble in chloroform, benzene., Soluble in 20 parts boiling water |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 520-52-5 |
| CAS (enantiomer) | |
| PubChem CID | 10624 |
| InChIKey | QVDSEJDULKLHCG-UHFFFAOYSA-N |
| InChI | 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) |
| SMILES | CN(C)CCC1=CNC2=C1C(=CC=C2)OP(=O)(O)O |
Synonyms
- O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine
- 4-PO-DMT
- Indocybin
- Psilocybine
Pharmacodynamics & Biochemistry
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, 4-PO-DMT) acts primarily as a prodrug. It is dephosphorylated by phosphatases to psilocin, the active metabolite responsible for most of its established psychedelic pharmacology. Psilocin is a non-selective serotonin-receptor agonist. The psychedelic effects are produced specifically through partial agonism at the 5-HT2A receptor (blocked by 5-HT2A antagonists such as ketanserin), with additional contributions from 5-HT2C (biased agonism), 5-HT1A and broad binding across the serotonin-receptor family: see the psilocin entry for the full receptor profile. It has essentially no meaningful activity at dopamine or adrenergic receptors or the monoamine transporters, and both dependence and addiction liability are low.
Biological targets
- 5-HT2A
- 5-HT2C
- 5-HT1A
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| 5-HT1A receptor | Ki 5,284 nM | Human |
| 5-HT1A receptor | Ki 197 nM | Mouse |
| 5-HT1B receptor | Ki 4,983 nM | Human |
| 5-HT1D receptor | Ki 186 nM | Human |
| 5-HT1E receptor | Ki 601 nM | Human |
| 5-HT2A receptor | EC50 1,242 nM Emax 74% | Human |
| 5-HT2A receptor | EC50 2,132 nM Emax 88% | Mouse |
| 5-HT2A receptor | Ki 2,096 nM | Mouse |
| 5-HT2B receptor | EC50 612 nM Emax 38% | Human |
| 5-HT2B receptor | Ki 259 nM | Human |
| 5-HT2C receptor | EC50 3,741 nM Emax 88% | Human |
| 5-HT2C receptor | Ki 808 nM | Human |
| 5-HT6 receptor | Ki 89 nM | Human |
| 5-HT7 receptor | Ki 138 nM | Human |
| Dopamine transporter | Ki 6,077 nM | Human |
| α2C-adrenoceptor | Ki 7,483 nM | Human |
Pharmacokinetics
| Bioavailability | ≈53% oral (as psilocin), plasma protein binding ≈66% |
| Tmax | Peak ≈1–2 h (onset 20–50 min oral) |
| Half-life | ≈2.1–4.7 h (as psilocin, oral), ≈1.2 h after IV |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Dephosphorylation to psilocin. Psilocin undergoes UGT-mediated glucuronidation and oxidative metabolism involving MAO and aldehyde dehydrogenase, including formation of 4-hydroxyindole-3-acetic acid (4-HIAA). |
| Excretion | Renal: mainly as psilocin-O-glucuronide. ~2–4% as unchanged psilocin |
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.
285 mg/kg (mouse, oral)
Psilocybin has low physiological toxicity, low dependence and addiction liability. There is no established lethal dose in humans. Its main risks are psychological: anxiety, panic or a frightening ('bad trip') experience and, rarely, prolonged perceptual disturbances (HPPD): together with accidents during intoxication and nausea/vomiting. As with other serotonergic psychedelics, people with a personal or family history of psychosis, schizophrenia or bipolar disorder, or significant cardiovascular disease, are at higher risk, and combining it with lithium has been linked to seizures. Since July 2023, authorised psychiatrists in Australia may access unapproved psilocybin products for treatment-resistant depression through the Authorised Prescriber pathway. This is restricted access to unapproved goods, not general marketing approval. Limited data must never be read as evidence of safety.[5][7][10]
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.
US: Schedule I. UK: Class A. DE: BtMG Anlage I
Interactions & Contraindications
Drug interactions
SSRIs, SNRIs May blunt the subjective effects through 5-HT2A downregulation.[5]
MAOIs Inhibit psilocin's metabolism and potentiate or prolong the experience.[5]
Other serotonergic drugs Additive serotonergic load carries a theoretical serotonin-toxicity risk.[5]
Lithium Associated with seizures and severe adverse reactions, avoid.[5]
Contraindications
Personal or family history of psychosis, schizophrenia or bipolar disorder[5]
Cardiovascular disease, hypertension or arrhythmia significant disease or uncontrolled hypertension.
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent lithium therapy (seizure risk).[5]
Pregnancy or breastfeeding
No interactions or contraindications listed.
Usage & Context
- Ritual and entheogenic use of psilocybin mushrooms in pre-Columbian Mesoamerica and, after their 1950s Western re-discovery, in modern spiritual and recreational contexts.
- One of the most widely used recreational psychedelics: almost always as dried or fresh Psilocybe mushrooms, or edibles such as chocolates and gummies.
- Psilocybin is investigated for several psychiatric indications, including depression. Since July 2023, specially authorised Australian psychiatrists may access unapproved psilocybin products for treatment-resistant depression. This restricted pathway is not general marketing approval.
Sources & Evidence
- PubChem: Psilocybin (CID 10624) — identifiers & experimental properties
- IUPHAR/BPS Guide to PHARMACOLOGY: psilocybin (ligand 14389) CC BY-SA 4.0
- Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, et al. (1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9:3897-902.
PMID 9875725 · doi:10.1097/00001756-199812010-00024
- McKenna DJ, Repke DB, Lo L, et al. (1990). Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. Neuropharmacology 29:193-8.
PMID 2139186 · doi:10.1016/0028-3908(90)90001-8
- Wikipedia: Psilocybin — prodrug pharmacology, effects, dosing, pharmacokinetics & clinical status CC BY-SA 4.0
- Dinis-Oliveira RJ (2017). Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Drug Metab Rev 49:84-91.
PMID 28074670 · doi:10.1080/03602532.2016.1278228
- Carhart-Harris R, Giribaldi B, Watts R, et al. (2021). Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med 384:1402-1411.
PMID 33852780 · doi:10.1056/NEJMoa2032994
- DEA Diversion Control Division: Controlled Substance Schedules (psilocybin — Schedule I, US)
- GOV.UK: Controlled drugs list — psilocybin is Class A (UK) OGL v3.0
- TGA: restricted access to unapproved MDMA and psilocybin products (2023)
- Glatfelter GC, Pottie E, Partilla JS, et al. (2022). Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. ACS Pharmacol Transl Sci 5:1181-1196.
PMID 36407948 · doi:10.1021/acsptsci.2c00177