psilocybin; indocybin (magic mushroom)

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Introduction

  • 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

* used for spirituality & synesthesias (seeing music, hearing art)[4]

Clinical manifestations

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]

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

* misidentification of mushrooms gathered in the wild (& sold on the street) is common leading to potentially fatal outcome[9]

* Toxicity:

Laboratory

Mechanism of action

* connectivity & blood flow determined by fMRI[4]

Notes

  • psilocybin is illegal in the US
  • 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 & Colorado[18]

More general terms

References

  1. ↑ Stedman's Medical Dictionary 27th ed, Williams & Wilkins, Baltimore, 1999.
  2. ↑ Merck Index, I2th ed, Merck & Co, Rahway NJ, 1996 # 8111
  3. ↑ 3.0 3.1 3.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27909164 <Internet> http://jop.sagepub.com/content/30/12/1165.full
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 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: https://www.ncbi.nlm.nih.gov/pubmed/29030624 Free PMC Article
  5. ↑ 5.0 5.1 Brauser F FDA Permits Psilocybin to Be Tested for Refractory Depression. Medscape - Oct 30, 2018. https://www.medscape.com/viewarticle/904159
  6. ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/33146675 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2772628
  7. ↑ 7.0 7.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 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. ↑ 13.0 13.1 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. ↑ 14.0 14.1 Melville NA Psilocybin Effective Up to 12 Weeks in Severe Depression. Medscape. June 2, 2022 https://www.medscape.com/viewarticle/974935
  15. ↑ 15.0 15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36001306 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2795625
  16. ↑ 16.0 16.1 16.2 16.3 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: https://www.ncbi.nlm.nih.gov/pubmed/36322843 https://www.nejm.org/doi/full/10.1056/NEJMoa2206443
  17. ↑ 17.0 17.1 17.2 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: https://www.ncbi.nlm.nih.gov/pubmed/35166158 PMCID: PMC8864328 Free PMC article
  18. ↑ 18.0 18.1 18.2 Cornelius K Cancer Patients Struggle to Access Psilocybin Before They Die. Medscape. December 13, 2022 https://www.medscape.com/viewarticle/985501
  19. ↑ 19.0 19.1 Osorio L Psilocybin 'Rewires' the Brain to Alleviate Depression. Medscape. April 11, 2022 https://www.medscape.com/viewarticle/971965
  20. ↑ 20.0 20.1 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. ↑ 21.0 21.1 21.2 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: https://www.ncbi.nlm.nih.gov/pubmed/37052904 PMCID: PMC10102915 (available on 2024-04-13) https://jamanetwork.com/journals/jamaoncology/fullarticle/2803623
  22. ↑ 22.0 22.1 22.2 22.3 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/37651148 https://jamanetwork.com/journals/jama/fullarticle/2808951
  23. ↑ 23.0 23.1 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: https://www.ncbi.nlm.nih.gov/pubmed/38055270 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2812443

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