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More than 200 species of fungi have been reported with hallucinogenic properties belonging to more than 10 genera, both Basidiomycota (the majority) and Ascomycota. Psilocybe, Amanita muscaria and Claviceps purpurea are true hallucinogens. Of these, the more important are the psilocybes for their great global distribution, traditional ceremonial uses, and numerous potential clinical applications.

 

Psilocybe has more than 150 hallucinogenic species throughout the world which have long been used in ceremonial and traditional medicinal ways.

 

Amanita muscaria seems to be the oldest hallucinogenic mushroom used by humans, although the first hallucinogenic substance, LSD, was isolated from ergot, Claviceps purpurea.

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of profound efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing anti-inflammatory agents.

Psilocybin, the most clinically researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. Psilocybin is the prodrug of psilocin (4-OH-dimethyltryptamine), a non-selective serotonin 2A receptor (5-HT2AR) agonist and classic ‘psychedelic’ drug. Both compounds occur naturally in the psilocybe genus of mushrooms and are structurally related to the endogenous neurotransmitter serotonin (5-OH-tryptamine, 5-HT). Psilocybin has an ancient and more recent history of medicinal use. Efficacy of psilocybin in the treatment of clinical depression has been demonstrated in the electrophysiologic and neuroimaging findings and in neuropsychological assessments.

Additionally, in recent years, there has been a growing awareness that the psychological, spiritual, and existential crises often encountered by patients with advanced cancer and their families need to be addressed more vigorously. From the late 1950s to the present, research has been conducted exploring the use of psilocybes to treat the existential anxiety, despair, and isolation often associated with advanced-stage cancer. Those studies have described critically ill individuals undergoing psychospiritual epiphanies, often with powerful and sustained improvement in mood and anxiety as well as diminished need for narcotic pain medication.

Hallucinogenic mushrooms constitute part of humanity’s ethnobotanical knowledge of substances of great medicinal and therapeutic importance cross-culturally and throughout history. Where used, these substances generally have been viewed as central sources of spiritual experience and religious participation, providing inspiration for the institutionalization of religious sentiments and activity.

Though there are numerous hallucinogenic plants that have been used traditionally throughout the world as sources of spiritual experience and inspiration and hold promise for clinical use, the following selected articles are confined to mushrooms only (particularly the psilocybes).

Bogenschutz MP, Forcehimes AA, Pommy JA, et al. (2015) Psilocybin assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol 29: 289–299.

Bogenschutz, Michael P., and Jessica M. Pommy. "Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses." Drug testing and analysis 4, no. 7-8 (2012): 543-555. (Abstract)

Carhart-Harris, Robin L., Leor Roseman, Mark Bolstridge, Lysia Demetriou, J. Nienke Pannekoek, Matthew B. Wall, Mark Tanner et al. "Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms." Scientific reports 7, no. 1 (2017): 1-11.

Carhart-Harris, Robin L., Mark Bolstridge, James Rucker, Camilla MJ Day, David Erritzoe, Mendel Kaelen, Michael Bloomfield et al. "Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study." The Lancet Psychiatry 3, no. 7 (2016): 619-627.

Carhart-Harris RL, Erritzoe D, Williams TM, et al. (2012a) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A 109: 2138–2143.

Carhart-Harris RL, Leech R, Williams TM, et al. (2012b) Implications for psychedelic-assisted psychotherapy: a functional magnetic resonance imaging study with psilocybin. Br J Psychiatry 200: 238–244.

Crundwell, E. "The unnatural history of the fly agaric." Mycologist 1, no. 4 (1987): 178-181.

Drewnowska, Małgorzata, Krzysztof Lipka, Grażyna Jarzyńska, Dorota Danisiewicz-Czupryńska, and Jerzy Falandysz. "Investigation on metallic elements in fungus Amanita muscaria (fly agaric) and the forest soils from the Mazurian lakes district of Poland." Fresenius Environ Bull 22 (2013): 455-460.

Grimm, O., R. Kraehenmann, K. H. Preller, E. Seifritz, and F. X. Vollenweider. "Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination." European Neuropsychopharmacology 28, no. 6 (2018): 691-700. (Abstract)

Griffiths, Roland R., Matthew W. Johnson, Michael A. Carducci, Annie Umbricht, William A. Richards, Brian D. Richards, Mary P. Cosimano, and Margaret A. Klinedinst. "Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial." Journal of psychopharmacology 30, no. 12 (2016): 1181-1197.

Griffiths RR, Johnson MW, Richards WA, et al. (2011) Psilocybin occasioned mystical-type experiences: immediate and persisting dose related effects. Psychopharmacology (Berl) 218: 649–665.

Griffiths RR, Richards WA, Johnson MW, et al. (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol 22: 621–632.

Griffiths RR, Richards WA, McCann U, et al. (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl) 187: 268–283; discussion 284–292.

Grob, Charles S. "The use of psilocybin in patients with advanced cancer and existential anxiety." Psychedelic medicine: New evidence for hallucinogenic substances as treatments 1 (2007): 205-216.

Grob CS, Danforth AL, Chopra GS, et al. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 68: 71–78.

Guzmán, Gastón. "The hallucinogenic mushrooms: diversity, traditions, use and abuse with special reference to the genus Psilocybe." Fungi from different environments (2009): 256-277.

Johnson MW, Garcia-Romeu A, Cosimano MP, et al. (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 28: 983–992.

Kometer M, Schmidt A, Bachmann R, et al. (2012) Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biol Psychiatry 72: 898–906.

Garcia-Romeu, Albert, Roland R Griffiths, and Matthew W Johnson. "Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction." Current drug abuse reviews 7, no. 3 (2014): 157-164.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342293/

Guzmán, Gastón. "New studies on hallucinogenic mushrooms: history, diversity, and applications in psychiatry." International journal of medicinal mushrooms 17, no. 11 (2015).

Hajicek-Dobberstein, Scott. "Soma siddhas and alchemical enlightenment: psychedelic mushrooms in Buddhist tradition." Journal of Ethnopharmacology 48, no. 2 (1995): 99-118.

Johnson, Matthew W., Albert Garcia-Romeu, Mary P. Cosimano, and Roland R. Griffiths. "Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction." Journal of psychopharmacology 28, no. 11 (2014): 983-992.

Johnston, Peter, and Peter K. Buchanan. "The genus Psilocybe (Agaricales) in New Zealand." New Zealand Journal of Botany 33, no. 3 (1995): 379-388.

Kelmendi, Benjamin, Philip Corlett, Mohini Ranganathan, Cyril D’Souza, and John H. Krystal. "The role of psychedelics in palliative care reconsidered: A case for psilocybin." Journal of Psychopharmacology 30, no. 12 (2016): 1212-1214.

Kraehenmann, Rainer, Katrin H. Preller, Milan Scheidegger, Thomas Pokorny, Oliver G. Bosch, Erich Seifritz, and Franz X. Vollenweider. "Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers." Biological psychiatry 78, no. 8 (2015): 572-581.

Krogsgaard-Larsen, P. O. V. L., L. Brehm, and K. Schaumburg. "Muscimol, a psychoactive constituent of Amanita muscaria, as a medicinal chemical model structure." Acta Chem. Scand. B 35, no. 5 (1981).

Kuypers, K. P. C. "Out of the box: A psychedelic model to study the creative mind." Medical hypotheses 115 (2018): 13-16.

Moreno, Francisco A., Christopher B. Wiegand, E. Keolani Taitano, and Pedro L. Delgado. "Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder." Journal of Clinical Psychiatry 67, no. 11 (2006): 1735-1740.

Musshoff, F., B. Madea, and J. Beike. "Hallucinogenic mushrooms on the German market—simple instructions for examination and identification." Forensic science international 113, no. 1-3 (2000): 389-395.

 Mason, Natasha L., Elisabeth Mischler, Malin V. Uthaug, and Kim PC Kuypers. "Sub-acute effects of psilocybin on empathy, creative thinking, and subjective well-being." Journal of psychoactive drugs 51, no. 2 (2019): 123-134.

Michelot, Didier, and Leda Maria Melendez-Howell. "Amanita muscaria: chemistry, biology, toxicology, and ethnomycology." Mycological research 107, no. 2 (2003): 131-146.

Nutt, David. "Psilocybin for anxiety and depression in cancer care? Lessons from the past and prospects for the future." J Psychopharmacol 30 (2016): 1163-1164.

Nyberg, H. A. R. R. I. "Religious use of hallucinogenic fungi: A comparison between Siberian and Mesoamerican Cultures." Karstenia 32, no. 2 (1992): 71-80.

Oss, O. T., and O. N. Oeric. Psilocybin: Magic Mushroom Grower's Guide: A Handbook for Psilocybin Enthusiasts. Ed Rosenthal, 1992.

Passie, Torsten, Juergen Seifert, Udo Schneider, and Hinderk M. Emrich. "The pharmacology of psilocybin." Addiction biology 7, no. 4 (2002): 357-364.

Patocka, Jiri, and Barbora Kocandrlova. "Pharmacologically and Toxicologically Relevant Components of Amanita muscaria."

Patra, Suravi. "Return of the psychedelics: Psilocybin for treatment resistant depression." Asian journal of psychiatry 24 (2016): 51-52. (Abstract)

Pokorny, Thomas, Katrin H. Preller, Michael Kometer, Isabel Dziobek, and Franz X. Vollenweider. "Effect of psilocybin on empathy and moral decision-making." International Journal of Neuropsychopharmacology 20, no. 9 (2017): 747-757.

Ross, Stephen, Anthony Bossis, Jeffrey Guss, Gabrielle Agin-Liebes, Tara Malone, Barry Cohen, Sarah E. Mennenga et al. "Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial." Journal of psychopharmacology 30, no. 12 (2016): 1165-1180.

Sewell, R. Andrew, John H. Halpern, and Harrison G. Pope. "Response of cluster headache to psilocybin and LSD." Neurology 66, no. 12 (2006): 1920-1922. (Abstract)

 

Shelton, Richard C., and Peter S. Hendricks. "Psilocybin and palliative end-of-life care." Journal of Psychopharmacology 30, no. 12 (2016): 1207-1208.

Singer, Rolf, and Alexander H. Smith. "Mycological investigations on teonanácatl, the Mexican hallucinogenic mushroom. Part II. A taxonomic monograph of Psilocybe, section Caerulescentes." Mycologia 50, no. 2 (1958): 262-303.

Stintzing, Florian, and Willibald Schliemann. "Pigments of fly agaric (Amanita muscaria)." Zeitschrift für Naturforschung C 62, no. 11-12 (2007): 779-785.

Stroud, J. B., T. P. Freeman, R. Leech, C. Hindocha, W. Lawn, D. J. Nutt, H. V. Curran, and R. L. Carhart-Harris. "Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression." Psychopharmacology 235, no. 2 (2018): 459-466.

Thomas, Kelan, Benjamin Malcolm, and Dan Lastra. "Psilocybin-assisted therapy: a review of a novel treatment for psychiatric disorders." Journal of psychoactive drugs 49, no. 5 (2017): 446-455.

Tylš, Filip, Tomáš Páleníček, and Jiří Horáček. "Psilocybin–summary of knowledge and new perspectives." European Neuropsychopharmacology 24, no. 3 (2014): 342-356.

Vollenweider, Franz X., and Michael Kometer. "The neurobiology of psychedelic drugs: implications for the treatment of mood disorders." Nature Reviews Neuroscience 11, no. 9 (2010): 642.

Wilcox, James Allen. "Psilocybin and obsessive compulsive disorder." Journal of psychoactive drugs 46, no. 5 (2014): 393-395.

Winkelman, Michael J. "Therapeutic bases of psychedelic medicines: psychointegrative effects." Psychedelic medicine 1 (2007): 1-19.

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