Psilocybin
Naturally occurring psychedelic compound found in certain mushroom species. Psilocybin is converted to psilocin in the body, which produces psychedelic effects.
Important information
This information is for educational purposes only. Always research thoroughly, test your substances, understand legal implications, and consult healthcare professionals. Never use substances alone or in unsafe environments.
Dosage information
Psilocybin · Oral · non-clinical reference ranges · dried mushrooms
Tier labels reproduce reported amount and intensity terminology; they do not indicate safety or a recommendation.
| Tier | Amount | Note |
|---|---|---|
| Threshold | 0.25 grams | |
| Light | 0.5 to 1 grams | |
| Common | 1 to 2.5 grams | |
| Strong | 2.5 to 5 grams | |
| Heavy | Reported lower bound: 5 grams; no upper bound is established. |
Dosage ranges are reference values from published literature, not recommendations. Potency varies by source, body weight, and individual sensitivity — harm-reduction practice starts well below the ranges listed.
Limitations: Figures are transcribed from a reference compilation, not measured in a controlled study; the potency of any given material is unknown until tested.
Evidence: Review or reference work
Before any number: set, setting, purity, dose · LD50 · microdosing
On this page: known interactions · harm reduction
Duration
Total: 4-6 hours | Onset: 20-40 minutes | Peak: 2-3 hours
Total: 4-6 hours. Effects vary significantly with dose, set, and setting.
Known interactions
Dangerous Psilocybin + Lithium
Lithium combined with psychedelics has caused seizures and other severe adverse events. This applies to all serotonergic psychedelics.
Risks: Seizures · Serotonin toxicity · Psychotic episodes · Medical emergency
Mechanism: Lithium alters serotonin signaling. Combined with 5-HT2A agonists, it may produce serotonin toxicity and lower seizure threshold.
What reduces the risk
- NEVER combine lithium with any psychedelic
- This includes psilocybin, LSD, DMT, mescaline, 2C-B
- Do not discontinue lithium without medical guidance
Sources: PsychonautWiki: Lithium Interactions · Multiple case reports on Erowid · Bonson KR et al. Hallucinogens and lithium: reports on psychedelic users. Drug Alcohol Depend. 1996
Caution Psilocybin + THC (Tetrahydrocannabinol)
Cannabis can dramatically intensify and alter psychedelic experiences, sometimes triggering anxiety, paranoia, or thought loops.
Risks: Intensified trip (potentially overwhelming) · Anxiety and paranoia · Thought loops · Disorientation
Mechanism: CB1 receptor activation modulates serotonergic signaling, potentially amplifying 5-HT2A-mediated effects unpredictably.
What reduces the risk
- Experienced users only
- Use very small amounts of cannabis if at all
- Avoid during the peak of psychedelic experience
- Cannabis on the comedown is less risky
Sources: TripSit Interaction Chart · PsychonautWiki: Psilocybin Interactions · Erowid: Combination Reports
Caution Psilocybin + MDMA (Ecstasy/Molly)
Known as 'hippy flipping.' MDMA adds euphoria and empathy to psilocybin's psychedelic effects, but increases physiological risks.
Risks: Increased neurotoxicity · Hyperthermia · Serotonin depletion · Dehydration · Overwhelming experience
Mechanism: Dual serotonergic activity — MDMA releases serotonin while psilocin agonizes 5-HT2A receptors.
What reduces the risk
- Experienced users only
- Reduce doses of both
- Stay hydrated and cool
- Have a sitter present
Sources: TripSit Interaction Chart · PsychonautWiki: MDMA Combinations
Caution Psilocybin + LSD (Lysergic Acid Diethylamide)
Both act on 5-HT2A receptors. Combining amplifies effects unpredictably and dramatically increases intensity.
Risks: Extremely intense experience · Prolonged duration · Difficult to predict effects · Psychological overwhelm
Mechanism: Both are 5-HT2A agonists. Cross-tolerance exists but combining increases total receptor activation.
What reduces the risk
- Not recommended for most users
- If combining, reduce doses of both significantly
- Have a sitter present
- Prepare for a long experience
Sources: TripSit Interaction Chart · PsychonautWiki: LSD Interactions
Caution Psilocybin + Salvia divinorum
Salvia acts on kappa-opioid receptors (unique mechanism). Combining with serotonergic psychedelics creates unpredictable and potentially overwhelming effects.
Risks: Extremely intense and unpredictable experience · Physical danger from disorientation · Severe dysphoria · Psychological overwhelm
Mechanism: Kappa-opioid agonism (salvia) + 5-HT2A agonism (psilocybin) = dual psychedelic mechanisms with unpredictable interaction.
What reduces the risk
- Not recommended
- If combining, use very low doses of both
- Sitter absolutely essential
- Safe physical environment critical
Sources: PsychonautWiki: Salvia Interactions · Erowid: Combination Reports
Caution Psilocybin + Ketamine
Both produce altered states through different mechanisms. The combination can be intensely disorienting but is not typically physiologically dangerous.
Risks: Extreme disorientation · Loss of motor control · Nausea · Overwhelming psychological effects
Mechanism: Psilocybin's 5-HT2A agonism + ketamine's NMDA antagonism = dual dissociative-psychedelic state.
What reduces the risk
- Only for very experienced users
- Reduce doses of both significantly
- Sitter essential
- Safe physical environment mandatory
Sources: TripSit Interaction Chart · PsychonautWiki: Ketamine Combinations
Absence of a listed interaction never implies safety. Check any combination in the app's 23×23 interaction matrix.
Harm reduction
- Test your substance
- Start with low dose
- Safe, comfortable setting
- Trusted trip sitter
- Avoid mixing with other substances
- Research contraindications
Risks & side effects
- Challenging experiences
- Anxiety or panic
- HPPD (rare)
- Psychological distress in vulnerable individuals
Effects
- Visual hallucinations
- Altered perception of time
- Euphoria
- Spiritual experiences
- Enhanced creativity
- Emotional insights
Legal status
Schedule I in most countries. Decriminalized in some US cities and legal for therapeutic use in some jurisdictions.
Pharmacology
5-HT2A receptor agonist. Psilocybin is dephosphorylated to psilocin, which crosses the blood-brain barrier.
Therapeutic research
- Johns Hopkins: Psilocybin for major depressive disorder — 71% response rate at 4 weeks (Davis et al., 2021)
- NYU/Johns Hopkins: End-of-life anxiety in cancer patients — sustained reductions in existential distress (Griffiths et al., 2016)
- FDA Breakthrough Therapy designation for treatment-resistant depression (Compass Pathways, 2018)
- Imperial College London: Psilocybin vs. escitalopram for depression — comparable efficacy with faster onset (Carhart-Harris et al., 2021)
- Johns Hopkins: Smoking cessation — 80% abstinence at 6 months (Johnson et al., 2014)
- Ongoing trials for OCD, anorexia nervosa, alcohol use disorder, and cluster headaches
Clinical studies 85
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning
Landmark Griffiths et al. 2006 study showing psilocybin produces mystical experiences with lasting personal and spiritual significance. One of the foundational modern psilocybin studies. Published in Psychopharmacology.
Psychedelics promote neuroplasticity through activation of intracellular 5-HT2A receptors
Vargas et al. 2023 Science paper discovering that psychedelics promote neuroplasticity via intracellular (not cell-surface) 5-HT2A receptors, explaining why serotonin doesn't trigger comparable effects.
Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis
Irizarry et al. 2022 meta-analysis of 9 studies showing psilocybin improves symptoms in anxiety, depression, OCD, PTSD, and substance abuse. Published in Cureus.
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
Roseman et al. 2018 Neuropharmacology. fMRI study showing psilocybin increased (not decreased) amygdala responses to emotional faces in treatment-resistant depression, suggesting enhanced emotional processing rather than blunting.
Serotonin receptor involvement in acute effects of psilocybin in mice
Erkizia-Santamaría et al. 2022 study examining psilocybin's interaction with 5-HT2A, 5-HT2C, and 5-HT1A receptors and effects on thermoregulation. Published in Biomedicine & Pharmacotherapy.
Madsen et al. 2019 Neuropsychopharmacology. PET imaging study (n=15) showing psilocybin's subjective effects correlate with 5-HT2A receptor occupancy in the brain and plasma psilocin levels. Key pharmacokinetic data.
Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in Healthy Subjects
Becker, Liechti et al. 2022 Clin Pharmacol Ther. RCT showing 14-day escitalopram pretreatment reduces psilocybin's subjective effects by 30-40%. Key safety data for SSRI interactions.
Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids
Gotvaldová et al. 2022 study quantifying psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin in 226 mushroom samples. Key finding: tryptamine concentrations are extremely variable. Published in IJMS.
The neural basis of psychedelic action
Kwan et al. 2022 Nature Neuroscience review on how psilocybin, LSD, and mescaline produce effects via 5-HT2A receptor signaling, neuroplasticity, and brain network alterations.
Comparison of psychedelic and near-death experiences in changing attitudes about death
Sweeney/Griffiths et al. 2022 Johns Hopkins study of 3,192 participants comparing psychedelics (LSD, psilocybin, DMT, ayahuasca) with NDEs. ~90% reported decreased fear of death. Published in PLOS ONE.
Griffiths et al. 2016 landmark Johns Hopkins RCT showing psilocybin produced sustained decreases in depression/anxiety in cancer patients. Published in Journal of Psychopharmacology.
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial
Landmark Johns Hopkins RCT (Davis et al., 2021) showing psilocybin-assisted therapy produced large, rapid, and sustained antidepressant effects in patients with major depressive disorder. Published in JAMA Psychiatry.
Acute Physiological and Psychological Moderators of Psychedelic-induced Personality Change
Explores physiological and psychological moderators during psilocybin administration in healthy volunteers.
Effects of psychoplastogens on blood levels of BDNF in humans
Systematic review of psychoplastogens, including psilocybin, and their effects on brain-derived neurotrophic factor levels.
Psilocybin as a novel treatment for chronic pain
Investigates the potential of psilocybin as an anti-nociceptive agent for chronic pain treatment.
Neuroplasticity and Psychedelics
Comprehensive review of neuroplastic effects of classic psychedelics like psilocybin.
Synergistic Behavioral and Neuroplastic Effects of Psilocybin-NMDAR Modulator Administration
Study analyzing the synergistic effects of psilocybin combined with NMDA receptor modulators.
Carhart-Harris et al. 2016 landmark Lancet Psychiatry study - first modern clinical trial of psilocybin for depression. All 12 patients showed reduced depression symptoms at 1 week, with 67% in remission at 3 months.
Psychedelics Promote Structural and Functional Neural Plasticity
Ly, Olson et al. 2018 Cell Reports landmark paper showing DMT, LSD, and psilocin promote dendritic arbor complexity, spinogenesis, and synaptogenesis. Foundational evidence for psychedelic neuroplasticity.
Single-Dose Psilocybin Treatment for Major Depressive Disorder
Raison et al. 2023 JAMA Phase 2 RCT. Single 25mg synthetic psilocybin dose produced significantly reduced depression ratings vs placebo through 43 days in 104 participants.
Johnson, Griffiths et al. 2018 Neuropharmacology analysis. Systematic evaluation concluding psilocybin has low abuse potential, supporting rescheduling. Key policy paper.
Serotonin toxicity of serotonergic psychedelics
Malcolm & Thomas 2022 Psychopharmacology review examining serotonin syndrome risk with psychedelics. Key harm reduction paper on drug interactions with MAOIs, SSRIs, and other serotonergics.
Psychedelics not linked to mental health problems or suicidal behavior: A population study
Johansen & Krebs 2015 J Psychopharmacology landmark population study (N=135,000+). Found no associations between lifetime psychedelic use and mental health problems. Key safety evidence.
Pilot study of psilocybin in the treatment of tobacco addiction
Johnson, Griffiths et al. 2014 Johns Hopkins pilot study. 15 participants achieved 80% smoking abstinence at 6 months - far exceeding typical cessation rates. Published in J Psychopharmacology.
Long-term follow-up of psilocybin-assisted psychotherapy for cancer-related distress
Agin-Liebes et al. 2020 NYU long-term follow-up (4.5 years) of cancer patients. ~60-80% showed clinically significant reductions in anxiety/depression. Published in J Psychopharmacology.
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
Carhart-Harris et al. 2017 Scientific Reports. fMRI study showing psilocybin decreased amygdala blood flow and altered default mode network connectivity in treatment-resistant depression.
Ross et al. 2016 NYU RCT (companion to Griffiths study). Single psilocybin dose with psychotherapy reduced cancer-related anxiety/depression with 60-80% maintaining benefits at 6.5 months. Published in J Psychopharmacology.
Doss et al. 2021 Johns Hopkins Translational Psychiatry study. Psilocybin increased cognitive flexibility and reduced neural rigidity in depression, suggesting mechanism for therapeutic effects.
Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study Protocol
Spriggs, Carhart-Harris et al. 2021 Frontiers in Psychiatry. First study protocol for psilocybin treatment of anorexia nervosa, addressing rigid thought patterns and self-perception in eating disorders.
Hendricks et al. 2017 J Psychopharmacology population study. Classic psychedelic use associated with reduced odds of criminal behavior including theft, assault, and property crime.
Emotions and brain function are altered up to one month after a single high dose of psilocybin
Barrett, Griffiths et al. 2020 Scientific Reports. Single psilocybin dose produced sustained improvements in positive affect and reduced anxiety lasting at least one month.
Effects of psilocybin on cognitive and emotional functions in healthy participants: Phase 1 RCT
Rucker et al. 2022 J Psychopharmacology Phase 1 trial in healthy volunteers. Established safety profile and showed psilocybin effects on cognition and emotion without lasting impairment.
Subjective features of psilocybin experience: Double-blind comparison with dextromethorphan
Carbonaro, Griffiths et al. 2020 Psychopharmacology. Compared psilocybin to active placebo (DXM). Psilocybin produced unique mystical-type experiences not seen with DXM.
Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing
Kaertner, Carhart-Harris et al. 2021 Scientific Reports. Showed microdosing benefits may be significantly influenced by expectation/placebo effects. Important for interpreting microdosing research.
Kuypers et al. 2019 J Psychopharmacol systematic review of microdosing research. Found mostly anecdotal evidence; called for rigorous RCTs examining potential risks of repeated low doses.
Petranker et al. 2020 J Psychopharmacol. Global Drug Survey (n=6,753) showing microdosers report benefits (mood, creativity) and challenges (illegal status, dosing uncertainty). Intention predicts outcomes.
Mason, Kuypers, Ramaekers et al. 2020 Neuropsychopharmacology. MRS neuroimaging showing psilocybin reduces glutamate in hippocampus and prefrontal cortex, correlating with ego dissolution experience.
Ross, Bossis et al. 2016 J Psychopharmacol NYU RCT. Single-dose psilocybin with psychotherapy produced immediate and sustained decreases in anxiety and depression in cancer patients.
Gukasyan, Davis et al. 2022 J Psychopharmacol. 12-month follow-up showing sustained antidepressant effects: 75% showing significant improvement, 58% achieving remission at 12 months.
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up
Carhart-Harris et al. 2018 Psychopharmacology. Six-month follow-up to 2016 Lancet study showing sustained depression remission in treatment-resistant patients.
Carhart-Harris 2019 Current Opinion in Psychiatry review examining mechanisms of action underlying psychedelic effects: 5-HT2A activation, entropic brain theory, and therapeutic implications.
Psychedelics reopen the social reward learning critical period
Nardou, Dölen et al. 2023 Nature. Landmark study showing MDMA, LSD, psilocybin, ibogaine, and ketamine reopen critical period for social reward learning in mice. Duration of effect correlated with therapeutic potential.
Singleton, Carhart-Harris et al. 2022 Nature Communications. Shows LSD and psilocybin reduce brain control energy needed for state transitions using network control theory and 5-HT2A mapping.
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, Gobbi et al. 2021 Pharmacological Reviews comprehensive review. Examines mechanisms underlying psychedelic psychiatric applications including neuroplasticity, immunomodulation, and neurotransmitter effects.
Griffiths, Johnson et al. 2018 J Psychopharmacology. Psilocybin combined with meditation/spiritual practices produced lasting improvements in psychological functioning and prosocial behaviors at 6-month follow-up.
Emotions and brain function are altered up to one month after a single high dose of psilocybin
Barrett, Doss et al. 2020 Scientific Reports. Single high-dose psilocybin produces enduring changes in affect and neural correlates in healthy volunteers persisting 1 month post-dose.
McCulloch et al. 2022 J Psychopharmacology. Single psilocybin dose produced lasting changes in brain resting-state connectivity associated with positive clinical and wellbeing outcomes.
Madsen et al. 2019 Neuropsychopharmacology. PET imaging study showing psilocybin's subjective effects correlate with 5-HT2A receptor occupancy and plasma psilocin concentrations.
Stenbaek et al. 2020 J Psychopharmacology. PET study showing individual differences in 5-HT2A receptor binding predict mystical-type experience intensity from psilocybin.
The hidden therapist: evidence for a central role of music in psychedelic therapy
Kaelen et al. 2018 Psychopharmacology. Shows music plays a central therapeutic role during psilocybin/LSD sessions, influencing emotional breakthroughs and treatment outcomes.
Peill, Carhart-Harris et al. 2022 J Psychopharmacology. Validated a new psychometric tool measuring psychological insight from psychedelic experiences. Insight predicted therapeutic outcomes.
Lyons & Carhart-Harris 2018 J Psychopharmacology. Found psilocybin therapy significantly increased nature connectedness and decreased authoritarian political views in depression patients at 7-12 month follow-up.
Psilocybin: From Serendipity to Credibility?
Rucker & Young 2021 Frontiers in Psychiatry. Reviews psilocybin's therapeutic potential based on early-phase clinical trials and discusses ethical concerns about commercial psychedelic retreat centers.
Psychedelics, Meditation, and Self-Consciousness
Millière, Carhart-Harris et al. 2018 Frontiers in Psychology. Reviews how psychedelics and meditation alter self-consciousness through shared neurobiological mechanisms affecting sense of self and ego dissolution.
Serotonin and brain function: a tale of two receptors
Carhart-Harris & Nutt 2017 J Psychopharmacology. Landmark theory paper proposing psychedelics (5-HT2A agonists) enhance plasticity and active coping, contrasting with SSRIs (5-HT1A). Key framework for understanding psychedelic mechanisms.
Psychiatry & the psychedelic drugs. Past, present & future
Rucker, Iliff & Nutt 2018 Neuropharmacology. Comprehensive review of psychedelics in psychiatry covering history, current research on psilocybin/LSD/mescaline, and future therapeutic potential.
Increased global integration in the brain after psilocybin therapy for depression
Daws, Carhart-Harris et al. 2022 Nature Medicine. fMRI study showing psilocybin therapy increases brain network integration in depression, with changes correlating with symptom improvement.
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
Goodwin et al. 2022 NEJM. Large Phase 2b RCT (n=233) showing 25mg psilocybin produced significant depression reduction vs 1mg control at 3 weeks. First NEJM psilocybin trial.
A potential role for psilocybin in the treatment of obsessive-compulsive disorder
Jacobs 2020 J Psychedelic Studies. Review examining psilocybin's potential for OCD treatment based on serotonin 2A receptor agonism and preliminary clinical evidence.
Clinical treatment of cluster headache with psilocybin, LSD, and ketamine: A case series
Leighton et al. 2025 Cephalalgia Reports. Case series documenting successful treatment of cluster headache with serotonergic psychedelics and ketamine.
Sharifan 2025 Cochrane Clinical Answers. Cochrane systematic review examining evidence for psilocybin and LSD in treating psychological distress in terminal illness.
Bogenschutz, Ross et al. 2022 JAMA Psychiatry. Landmark RCT (n=93) showing psilocybin-assisted therapy significantly reduced heavy drinking days compared to placebo. First major trial for psilocybin in alcohol use disorder.
Acute change in functional brain entropy following psilocybin administration in healthy volunteers
McCulloch et al. 2022 Neuroscience Applied. Neuroimaging study showing psilocybin acutely increases brain entropy, providing mechanistic insights into psychedelic state.
Safety pharmacology of acute psilocybin administration in healthy participants
Straumann, Holze et al. 2024 Neuroscience Applied. Comprehensive safety/toxicity assessment of acute psilocybin showing favorable safety profile in healthy volunteers.
Wiegand 2024 Encyclopedia of Toxicology. Comprehensive toxicology reference entry covering psilocybin mushroom identification, toxicity profile, clinical presentation, and treatment guidelines.
Rahbarnia et al. 2025 Psychopharmacology. Study examining how psilocybin's 5-HT2A receptor binding affects visual attention using selective agonists and antagonists.
Drewko et al. 2025 Molecular Psychiatry. Review exploring how 5-HT2A receptor activation drives neuroplasticity and antidepressant effects of psychedelics.
Pottie & Stove 2022 J Neurochemistry. Methodological paper on in vitro assays for characterizing psychedelic binding and functional activity at 5-HT2A receptors.
Chemistry/structural biology of psychedelic drugs and their receptor(s)
Gumpper & Nichols 2024 Br J Pharmacology. Comprehensive review of psychedelic drug chemistry and structural biology of serotonin receptor binding.
Madsen et al. 2023 Neuroscience Applied. PET imaging study comparing 5-HT2A receptor occupancy of psychedelic vs non-psychedelic compounds in vivo.
5-HT2A Receptor Heterodimerization
Łukasiewicz et al. 2018 5-HT2A Receptors in the CNS. Chapter on 5-HT2A receptor heterodimerization and implications for psychedelic signaling.
Smigielski et al. 2019 NeuroImage. fMRI study showing psilocybin combined with mindfulness meditation produces lasting changes in DMN connectivity and self-consciousness.
From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS)
Zeifman et al. 2025 Scientific Reports. Empirical test of REBUS model showing psilocybin enables belief revision through relaxed high-level priors in brain hierarchy.
How psilocybin affects the brain
O'Leary 2024 Nature Medicine. News feature summarizing neuroimaging findings on psilocybin's effects on brain connectivity and neural networks.
Future directions for clinical psilocybin research: The relaxed symptom network
Lewis-Healey et al. 2022 Psychology & Neuroscience. Framework proposing psilocybin's therapeutic effects work through relaxing pathological symptom networks in the brain.
An introduction to psychedelic neuroscience
Calvey & Howells 2018 Progress in Brain Research. Foundational chapter introducing neuroimaging methods for studying psychedelic effects on brain function.
Weiss et al. 2025 Brain Sciences. Comprehensive review of neuroimaging evidence for psychedelic-induced neural plasticity and clinical applications.
Scanning the new frontier of mental health: psychedelic brain imaging
Ertl & Wall 2024 The Biochemist. Overview of neuroimaging techniques used to study psychedelic effects on brain activity and connectivity.
Jang et al. 2024 Brain Sciences. Neuroimaging analysis using graph theory to classify and compare brain states under psychedelics vs other altered states.
Mapping the claustrum to elucidate consciousness
Calarco 2024 Nature Reviews Psychology. Review of neuroimaging studies examining claustrum's role in consciousness, relevant to psychedelic mechanisms.
Hemispheric annealing and lateralization under psychedelics (HEALS): A novel hypothesis
Levin 2025 J Psychopharmacology. Novel neuroimaging-based hypothesis that psychedelics promote interhemispheric connectivity and reduce lateralization.
Schindler et al. 2025 Headache. Exploratory RCT comparing single and repeat psilocybin doses versus active placebo for migraine prevention.
Psilocybin for End-of-Life Anxiety Symptoms: A Systematic Review and Meta-Analysis
Yu et al. 2021 Psychiatry Investigation. Systematic review and meta-analysis of psilocybin trials for anxiety in terminal illness patients.
Psilocybin-assisted psychotherapy for cancer-related anxiety and depression
Yaniv et al. 2023 Int J Gynecological Cancer. Review of psilocybin-assisted psychotherapy trials for anxiety and depression in cancer patients.
Dino 2025 Cureus. Comprehensive overview of psilocybin clinical trials for depression, TRD, and end-of-life distress.
Sources 3
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. Journal of Psychopharmacology, 30(12), pp. 1181-1197 (2016) doi:10.1177/0269881116675513
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports, 7, Article 13282 (2017) doi:10.1038/s41598-017-13282-7
- Erowid Psilocybin Mushroom Vault
History & culture
Psilocybin mushrooms have been used ceremonially for thousands of years. Aztec priests called them teonanácatl ('flesh of the gods') and used them in divination rituals documented by Spanish friar Bernardino de Sahagún in the 16th century. Stone mushroom sculptures dating to 1000 BCE have been found in Guatemala and Mexico. Western science rediscovered psilocybin through R. Gordon Wasson's 1957 Life magazine article about Mazatec healer María Sabina's velada ceremonies. Albert Hofmann isolated and synthesized psilocybin at Sandoz Laboratories in 1958. The longer history matters: Spanish colonial authorities suppressed ceremonial mushroom use for centuries — Indigenous practice survived underground and continues today — and enforcement of the prohibition era that began in 1968 fell hardest on communities of color, not on the researchers and counterculture figures who popularized psilocybin.
Natural origins
Found in over 200 mushroom species, primarily in the genus Psilocybe. Key species include Psilocybe cubensis (pantropical, most commonly cultivated), Psilocybe semilanceata ('liberty cap,' widespread in temperate grasslands), and Psilocybe azurescens (Pacific Northwest, among the most potent). The blue bruising reaction characteristic of psilocybin-containing mushrooms results from oxidation of psilocin. Caution: deadly look-alikes exist, including Galerina marginata — proper identification is critical.
Molecular family: Tryptamines
Tryptamines are a class of indole-based compounds derived from tryptophan, an amino acid. This family includes some of the most powerful and well-studied psychedelics. The indole nucleus is conserved across all members, with variations in alkyl side chains and ring substitutions determining pharmacological effects. Tryptamines are found naturally in plants and fungi, with psilocybin being the most famous. Key characteristics: - Based on indole (benzene fused with pyrrole) - Often possess dimethylamino side chains - Range from mild (5-MeO-DMT) to extremely potent (DMT) - Found in nature: psilocybin mushrooms, ayahuasca, certain toads - Tend toward serotonergic mechanisms Members demonstrate remarkable diversity in intensity and duration despite similar core structure. Their indole foundation provides stability while allowing nature to create compounds spanning from gentle to overwhelming in effect.
Structurally related to Serotonin (5-HT)
