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psilocybin; indocybin (magic mushroom)

- the major of 2 hallucinogenic components of Teonanaacatl, the sacred mushroom of Mexico - obtained from the fruiting bodies of Psilocyne mexicana & other species of Psylocybe & Stropharia - Psilocin is the minor component. DEA schedule 1 drug. Indications: - treatment of anxiety & depression in patients with terminal cancer [3] - helps overcome fear, anxiety, & despair about death & to experience an inner peace [18] - treatment of major depression (47% response) [4,5,6,13] - not inferior to escitalopram for treatment of major depression [7] - superior to escitalopram for treatment of major depression [27] - treatment-resistant depression, rapid improvement with benefits sustained for up to 12 weeks [14] - single dose of 25 mg reduced depression scores - with 8 days [22] - over a period of 3-6 weeks [16,22] - treatment of major depression in cancer patients [21] - treatment of major depression associated with bipolar type II disorder [23] - robust & stable antidpressant effects for 12 months after 2 doses [17] - effective treatment of secondary depression [24] - treatment of alcoholism [15] * used for spirituality & synesthesias (seeing music, hearing art) [4] Dosage: - 0.3 mg/kg, or ~ 21 mg/70 kg, 25 mg 3 weeks apart [4] - 0.215 mg/kg is effective [20] - 20 mg/70 kg & 30 mg/70 kg about 2 weeks apart [17] - single dose 25 mg [16,22] Clinical manifestations: - visual & religious hallucinations - perceived motion of objects or surfaces that do not move [9] - feeling closer to nature [9] Pharmacokinetics: - alterations in perception generally begin within 30 minutes, but may be delayed up to 2 hours [9] - effects generally last 4-6 hours but may last up to 12 hours [9] - a single dose of 25 mg is associated with sustained improvement in symptoms of major depression in cancer patients over 8 weeks [21] Adverse effects: - feelings of mystic experience (adverse ?) [4] - schizophrenia-like syndromes - fear, agitation, confusion, delirium, psychosis [9] - anxiety, panic attacks - nausea - sympathomimetic activity: mydriasis, tachycardia [9] - hyperthermia, seizures especially in children [9] - coma [9] - headache, dizziness [16] * misidentification of mushrooms gathered in the wild (& sold on the street) is common leading to potentially fatal outcome [9] * Toxicity: - gastric lavage or oral administration of activated charcoal if presentation within 1 hour of ingestion - suggestion not evidence-based - avoid ipecac - avoid antipyretics for treatment of hyperthermia - not true fever, most likely from agitation & increased motor activity - benzodiazepines may be used for treatment of panick attacks, hallucinations, seizures Laboratory: - if mushrooms consumed - complete blood count (CBC) - gyromitrin (mushroom toxin) can cause hemolytic anemia - liver function tests - cyclopeptides (mushroom toxins) are hepatotoxic - renal function tests - some mushrooms contain nephrotoxins - serum creatine kinase, basic metabolic panel, serum phosphate, urinalysis - some mushrooms may cause rhabdomyolysis [9] Mechanism of action: - 5-HT2A receptor inhibition [19] - immediate & ongoing anxiolytic & antidepressant response [3] - decreases blood flow in temporal lobe including amygdala & parietal lobe [4]* - increased connectivity between ventromedial prefrontal cortex & inferior parietal cortex* - decreased parahippocampal-prefrontal connectivity* * connectivity & blood flow determined by fMRI [4] Notes: - patients argue they have a legal right to take psilocybin through the Right to Try Act - in 2023, facilitated use of psilocybin will become legal in Oregon, Missouri & Colorado & several cities in the US [18,25]

Interactions

drug adverse effects of psychotropic agents

General

hallucinogen; psychodysleptic phosphomonoester psilocin; psilotsin; 4-hydroxy N,N-dimethyltryptamine

Database Correlations

PUBCHEM cid=10624

References

  1. Stedman's Medical Dictionary 27th ed, Williams & Wilkins, Baltimore, 1999.
  2. Merck Index, I2th ed, Merck & Co, Rahway NJ, 1996 # 8111
  3. Anderson P Psilocybin May Be a Psychiatry Game Changer Medscape. Dec 01, 2016. http://www.medscape.com/viewarticle/872504 - Ross S, Bossis A, Guss J et al Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life- threatening cancer: a randomized controlled trial. J Psychopharmacol December 2016 vol. 30 no. 12 1165-1180 PMID: 27909164 http://jop.sagepub.com/content/30/12/1165.full
  4. Carhart-Harris RL, Roseman L, Bolstridge M et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep 2017 Oct 13; 7:13187. PMID: 29030624 Free PMC Article
  5. Brauser F FDA Permits Psilocybin to Be Tested for Refractory Depression. Medscape - Oct 30, 2018. https://www.medscape.com/viewarticle/904159
  6. Davis AK, Barrett FS, May BG et al Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder. A Randomized Clinical Trial. JAMA Psychiatry. Published online November 4, 2020 PMID: 33146667 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2772630 - Reynolds III CF Psilocybin-Assisted Supportive Psychotherapy in the Treatment of Major Depression- Quo Vadis? JAMA Psychiatry. Published online November 4, 2020 PMID: 33146675 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2772628
  7. Carhart-Harris R, Giribaldi B, Watts R et al Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med 2021; 384:1402-1411. April 15. PMID: 33852780 https://www.nejm.org/doi/full/10.1056/NEJMoa2032994 - Lieberman JA Back to the Future - The Therapeutic Potential of Psychedelic Drugs. N Engl J Med 2021; 384:1460-1461. April 15. PMID: 33852784 https://www.nejm.org/doi/full/10.1056/NEJMe2102835
  8. Lange R (Texas Tech), Tracey E (Johns Hopkins Medicine) Face Masks and Exercise; Dosing Psilocybin: It's TTHealthWatch! Also this week: COVID and inactivity, and inflammatory diets. Medpage Today April 17, 2021 https://www.medpagetoday.com/podcasts/healthwatch/92141
  9. Sinert RO Fast Five Quiz: Psilocybin and Other Hallucinogenic Drugs. Medscape. September 07, 2021 https://reference.medscape.com/viewarticle/957547
  10. Rolston-Cregler L, Wiener SW Hallucinogenic Mushroom Toxicity Medscape. Jan 23, 2021 https://emedicine.medscape.com/article/817848-overview#showall
  11. Rolston-Cregler L, Wiener SW Hallucinogenic Mushroom Toxicity Workup Medscape. Jan 23, 2021 https://emedicine.medscape.com/article/817848-workup#showall
  12. Rolston-Cregler L, Wiener SW Hallucinogenic Mushroom Toxicity Treatment & Management. Medscape. Jan 23, 2021 https://emedicine.medscape.com/article/817848-treatment#showall
  13. Grant K 'Magic Mushrooms' Get a Win for Depression in Early Trial, Drugmaker Says. Psilocybin reduced depressive symptoms in largest trial of psychedelic drug to date. MedPage Today November 10, 2021 https://www.medpagetoday.com/psychiatry/depression/95579
  14. Melville NA Psilocybin Effective Up to 12 Weeks in Severe Depression. Medscape. June 2, 2022 https://www.medscape.com/viewarticle/974935
  15. AMA Morning Report. August 25, 2022 American Medican Association - Bogenschutz MP, Ross S, Bhatt S et al Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder. A Randomized Clinical Trial. JAMA Psychiatry. Published online August 24, 2022 PMID: 36001306 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2795625
  16. Goodwin GM, Aaronson ST, Alvarez O et al Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med 2022; 387:1637-1648. Nov 3. PMID: 36322843 https://www.nejm.org/doi/full/10.1056/NEJMoa2206443
  17. Brooks M Psilocybin's Antidepressant Effects Rapid, Durable. Medscape. Feb 17, 2022 https://www.medscape.com/viewarticle/968771 - Gukasyan N, Davis AK, Barrett FS et al Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. J Psychopharmacol. 2022 Feb;36(2):151-158. PMID: 35166158 PMCID: PMC8864328 Free PMC article
  18. Cornelius K Cancer Patients Struggle to Access Psilocybin Before They Die. Medscape. December 13, 2022 https://www.medscape.com/viewarticle/985501
  19. Osorio L Psilocybin 'Rewires' the Brain to Alleviate Depression. Medscape. April 11, 2022 https://www.medscape.com/viewarticle/971965
  20. von Rotz R, Schindowski EM, Jungwirth J et al Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. eClinicalMedicine 2023. 56:101809. Feb 1. ePub December 28, 2022 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00538-7/fulltext
  21. Agrawal M, Emanuel E, Richards B et al Assessment of Psilocybin Therapy for Patients With Cancer and Major Depression Disorder. JAMA Oncol. 2023;9(6):864-866. PMID: 37052904 PMCID: PMC10102915 (available on 2024-04-13) https://jamanetwork.com/journals/jamaoncology/fullarticle/2803623
  22. Raison CL, Sanacora G, Woolley J et al Single-Dose Psilocybin Treatment for Major Depressive Disorder. A Randomized Clinical Trial. JAMA. Published online August 31, 2023 PMID: 37651119 https://jamanetwork.com/journals/jama/fullarticle/2808950 - Yehuda R, Lehrner A Psychedelic Therapy - A New Paradigm of Care for Mental Health. JAMA. 2023;330(9):813-814 PMID: 37651148 https://jamanetwork.com/journals/jama/fullarticle/2808951
  23. Aaronson ST, van der Vaart A, Miller T et al Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes. A Nonrandomized Controlled Trial. JAMA Psychiatry. Published online December 6, 2023 PMID: 38055270 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2812443
  24. Metaxa AM, Clarke M Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ. 2024 May 1:385:e078084 PMID: 38692686 PMCID: PMC11062320 Free PMC article
  25. Brown NA The Promise of 'Magic Mushrooms' for Mental Health Is Real. But more research and careful regulation is necessary. MedPage Today, August 3, 2024 https://www.medpagetoday.com/opinion/prescriptionsforabrokensystem/111361
  26. Wikipedia: Psilocybin decriminalization in the United States https://en.wikipedia.org/wiki/Psilocybin_decriminalization_in_the_United_States
  27. Johnson K Psilocybin Bests SSRI for Major Depression in First Long-Term Comparison. Medscape. Sept 23, 2024 https://www.medscape.com/viewarticle/psilocybin-bests-ssri-major-depression-first-long-term-2024a1000h77