Psilocybin

from Wikipedia, the free encyclopedia
Structural formula
Structural formula psilocybin
General
Surname Psilocybin
other names
  • 4-phosphoryloxy- N , N -dimethyltryptamine
  • 3- [2- (dimethylamino) ethyl] -1H-indol-4-yl dihydrogen phosphate
  • CY-39
  • Indocybin
Molecular formula C 12 H 17 N 2 O 4 P
External identifiers / databases
CAS number 520-52-5
EC number 208-294-4
ECHA InfoCard 100.007.542
PubChem 10624
ChemSpider 10178
DrugBank DB11664
Wikidata Q208118
properties
Molar mass 284.25 g · mol -1
Physical state

firmly

Melting point
safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data

13 mg kg −1 ( LD 50 ,  rabbit ,  iv )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Psilocybin is an indole alkaloid from the tryptamine group . The consumption of psilocybin is usually in the form of mushrooms containing psilocybin and induces a psychedelic high with visual hallucinations . This state is similar to an LSD high, but is usually shorter. The hydrolysis product psilocin is largely responsible for the effect . Psilocybin is thus a prodrug of psilocin.

history

Maria Sabina in Oaxaca .

1955 took in Mexico the healing priestess led María Sabina bankers and Ethnomykologe R. Gordon Wasson and his wife, the doctor Valentina Pavlovna Wasson, actively participated in a sacred mushroom ceremony (a Velada , Spanish "Night Watch") of the Mazatec in Mixeteco -Bergen part . R. Gordon Wasson made psilocybin-containing mushrooms known in 1957 through the article " Magic Mushrooms " in the magazine " Life ". Valentina Pavlovna Wasson's report on the " I Ate the Sacred Mushroom " mushroom ceremony was published in This Week magazine on May 19, 1957 - six days after her husband's article was published. In this article, she was one of the first to suggest that psychedelic mushrooms could be used as a psychotherapeutic agent. The Swiss chemist Albert Hofmann isolated psilocybin and psilocin from naturally grown and cultivated fruit bodies and mycelia of the mushroom species Psilocybe mexicana and Psilocybe cubensis . The publication about it appeared in 1959; later he also succeeded in total synthesis. Wassons and Hofmann visited Sabina in the autumn of 1962 and she ran a Velada in which she first used synthetic psilocybin in the form of pills with 5 mg each. After the nightly ceremony, Sabina confirmed that the pills had the same effect as the mushrooms.

In the 1960s, studies and psycholytic therapy with psilocybin were carried out, especially in the psychiatric field , until these came to a standstill due to strict regulations. At the moment psilocybin-assisted psychotherapy is being researched again. a. treatment-resistant depression and end-stage cancer patients, in order to enable them to possibly better deal with death.

chemistry

After ingestion, psilocybin is converted into psilocin by splitting off a phosphate group , which is the actual psychoactive substance . As an indole alkaloid, psilocin is a tryptamine . The parent substance psilocybin is a zwitterion . It can be detected using Ehrlich's reagent in thin layer chromatography (TLC).

presentation

In August 2017, a work on the enzymatic synthesis of psilocybin from tryptophan via 4-hydroxy-L-tryptophan by isolating the four key enzymes (PsiD, PsiH, PsiK, PsiM) from P. cubensis and P. cyanescens was published for the first time. Other synthetic routes such as total synthesis and biosynthesis have been described.

Occurrence

The conical bald head ( Psilocybe semilanceata ) contains psilocybin.

Psilocybin occurs in some types of mushrooms, especially the genus of the bald heads ( Psilocybe azurescens , P. tampanensis , P. cubensis , P. cyanescens , P. mexicana , in Central Europe in P. semilanceata (pointed, conical bald head) and others); these are grouped under the term psilocybin-containing mushrooms . The amount of psilocybin in dried mushrooms is between around 0.1 and 2%.

Art % Psilocybin
P. azurescens 1.78
P. serbica 1.34
P. semilanceata 0.98
P. baeocystis 0.85
P. cyanescens 0.85
P. tampanensis 0.68
P. cubensis 0.63
P. weilii 0.61
P. hoogshagenii 0.60
P. stuntzii 0.36
P. cyanofibrillosa 0.21
P. liniformans 0.16
Documented maximum content of psilocybin in the genus Psilocybe (% of dry weight)

Effect in humans

Effect and side effects

Effect on the amount of psilocybin
amount effect
3-6 mg Threshold, slight intoxication
5-10 mg hallucinogenic, stimulating effect
~ 10 mg typical consumption dose
10+ mg enhanced hallucinogenic effects
~ 20 mg high consumption dose
20+ mg strong hallucinogenic effects
30+ mg Maximum dose
20,000 mg presumed lethal dose

The effects of psilocybin are characterized by physical lightness and energy, uncontrolled laughter, joy, euphoria and altered visual perception. Dizziness, nausea, vomiting, and panic attacks can all occur as side effects of psilocybin. No organic damage is known. The low dose of psilocybin in the threshold range below or within the effective dose is called microdosing or minidosing .

Mechanism of action

To nerve cells in the brain's psychoactive substance psilocin secondary docked mainly via serotonin - receptors of the type 5-HT 2A , and indeed as a partial agonist with a high affinity . There is now agreement that the effects of psychedelic drugs are mainly triggered by this type of receptor.

Localization of effects in the brain

Neuronal excitation via this serotonin receptor in turn leads to an increase in GABA -mediated, inhibitory signals in important switching centers in the brain. Investigations into the visible effects of psilocin in the brain by means of imaging tests then also showed several significant centers with reduced activity. The stronger the effect of the drug experienced by the test subjects, the more the neuronal activity of these centers was reduced. In contrast, brain regions of increased activity were not found. A possible explanation has been suggested that psilocin disrupts the normal balance of neural information flows.

In another study with imaging methods, decreased brain functions were also measured. Here they were linked to the effects of ego disorders ( depersonalization ) registered directly after the brain scans .

Risks

A Dutch government study (CAM study) came to the conclusion that the consumption of psilocybin was not significantly influenced by psychotic side effects. Flashbacks were observed; however, they are less common than when consuming LSD.

Like all psychoactive substances, psilocybin also carries the risk of triggering a latent psychosis . The medical literature describes a case in which psilocybin use (in combination with cannabis ) led to a hallucinogen persisting perception disorder . The set and setting must also be observed, as psilocybin, contrary to euphoric states, can also trigger temporary schizophrenia-like psychoses in healthy people. These psychotic disorders include the distortion of sensory perception and thought processes as well as impaired self-awareness . The psychotomimetic effects of psilocybin could be prevented with ketanserin or risperidone , but haloperidol increased the effect.

In the case of strong excitement (“ bad trip ”), medical treatment is indicated - “Goodman & Gilman's The Pharmacological Basis of Therapeutics” suggests 20 mg diazepam orally , but calming conversations have proven to be effective and are therefore indicated as the first measure.

Combination with monoamine oxidase inhibitors

Simultaneous use of monoamine oxidase inhibitors (MAOH) can prolong and intensify the psilocybin high, but also change it in a less predictable way, as this combination has a complex effect on brain chemistry (see also serotonin syndrome ). The MAO inhibitors block the enzyme monoamine oxidase , which breaks down monoamines , including psilocybin / psilocin and a number of neurotransmitters (via oxide-active deamination). Short-acting reversible inhibitors such as harmalin are not subject to the strict diet regulations that apply to irreversible MAOIs; the latter were introduced into psychiatry 40 years ago as antidepressants . For psilocybin, there are other breakdown pathways in the organism in addition to MAO.

Legal position

The United Nations Convention on Psychotropic Substances (1971) requires its members to ban psilocybin in the free movement of goods and to strictly regulate research applications. The psilocybin-containing mushrooms are not affected by the regulation, largely due to demands from the Mexican government.

With the fourth Narcotics Equality Ordinance (4th BtMGlV) of February 21, 1967, which came into force on February 25, 1967, psilocybin and psilocin in the Federal Republic of Germany were made subject to the narcotics regulations of the Opium Act . Today psilocybin and psilocin are listed in Appendix I to § 1 BtMG (non-marketable and non-prescription substances), i.e. any handling of these substances (with the exception of consumption) is generally prohibited for the general public.

In the United States, psilocybin (and psilocin) was banned by the Drug Abuse Control Amendments as an addition to the Food, Drug and Cosmetic Act (ratified July 1965, effective February 1966), based on a bill proposed by Thomas J. Dodd . However, psilocybin was not listed as a hallucinogen and various uses were exempt from the ban, including possession for personal use, for use by a member of the household, or for use on animals. On October 24, 1968, the regulation was tightened. On October 27, 1970, psilocybin and psilocin were classified as Schedule I drugs and hallucinogens under the Controlled Substances Act . In some states of the USA there is a selective implementation, especially with regard to the psilocybin-free spores. In May 2019, a referendum in the US city of Denver voted for the decriminalization of mushrooms containing psilocybin. In June 2019, Oakland became the second city ​​in the United States to decriminalize psilocybin-containing mushrooms and Santa Cruz became the third city in January 2020 .

In Great Britain the ban came in 1971 in the Misuse of Drugs Act , in Canada with the Controlled Drugs and Substances Act of 1996. In Japan psilocybin was banned in 2002, in Australia it was banned in the Standard for the Uniform Scheduling of Medicines and Poisons of October 2015. The spores do not contain psilocybin and are therefore only banned in some countries, e.g. B. in the USA in California, Georgia and Idaho.

In October 2018, the Food and Drug Administration (FDA) awarded Breakthrough Therapy status to a large study of psilocybin in the treatment of treatment-resistant depression .

literature

  • HA Geiger, MG Wurst, RN Daniels: DARK Classics in Chemical Neuroscience: Psilocybin. In: ACS chemical neuroscience. July 2018, doi : 10.1021 / acschemneuro.8b00186 , PMID 29956917 (Review).
  • F. Tylš, T. Páleníček, J. Horáček: Psilocybin - summary of knowledge and new perspectives. In: European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology. Volume 24, number 3, March 2014, pp. 342–356, doi: 10.1016 / j.euroneuro.2013.12.006 . PMID 24444771 (Review).
  • J. van Amsterdam, A. Opperhuizen, W. van den Brink: Harm potential of magic mushroom use: a review. In: Regulatory toxicology and pharmacology: RTP. Volume 59, Number 3, April 2011, pp. 423-429, doi: 10.1016 / j.yrtph.2011.01.006 . PMID 21256914 (Review).
  • T. Passie, J. Seifert, U. Schneider, HM Emrich: The pharmacology of psilocybin. In: Addiction biology. Volume 7, Number 4, October 2002, pp. 357-364, doi: 10.1080 / 1355621021000005937 . PMID 14578010 (Review).
  • A. Hofmann, R. Heim, A. Brack, H. Kobel, A. Frey, H. Ott, Th. Petrzilka, F. Troxler: Psilocybin and Psilocin, two psychotropic active ingredients from Mexican intoxicating mushrooms. In: Helvetica Chimica Acta. 42, 1959, pp. 1557-1572, doi: 10.1002 / hlca.19590420518 .

Web links

Wiktionary: Psilocybin  - explanations of meanings, word origins, synonyms, translations
Commons : Psilocybin  - Collection of Images, Videos, and Audio Files

Individual evidence

  1. ^ The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 1363.
  2. ↑ David E. Nichols: Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin. In: Synthesis. 1999, pp. 935-938, doi: 10.1055 / s-1999-3490 .
  3. ↑ SWGDRUG Monographs: PSILOCIN & PSILOCYBIN Monograph (PDF; 364 kB), accessed on June 11, 2014.
  4. ^ Royal Pharmaceutical Society (Ed.): Clarke's Analysis of Drugs and Poisons FOURTH EDITION. Pharmaceutical Press, London / Chicago 2011, ISBN 978-0-85369-711-4 .
  5. ↑ a b Psilocybin data sheet from Sigma-Aldrich , accessed on June 15, 2011 ( PDF ).
  6. ↑ Entry on psilocybin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  7. ^ Wasson, Valentina Pavlovna; Wasson, R. Gordon (1957). Mushrooms: Russia and History. Pantheon Books.
  8. ^ Valentina Pavlovna Wasson: I Ate the Sacred Mushroom. This Week Magazine, May 19, 1957.
  9. ↑ Erowid Valentina Wasson Vault . Retrieved November 25, 2018.
  10. ↑ A. Hofmann, R. Heim, A. Brack, H. Kobel, A. Frey, H. Ott, Th. Petrzilka, F. Troxler: Psilocybin and Psilocin, two psychotropic active ingredients from Mexican intoxicating mushrooms. In: Helvetica Chimica Acta. 42, 1959, pp. 1557-1572, doi: 10.1002 / hlca.19590420518 .
  11. ↑ A. Hofmann, A. Frey, H. Ott, Th. Petrzilka, F. Troxler: Constitution clarification and synthesis of psilocybin. In: Experientia. 14, 1958, pp. 397-399, doi: 10.1007 / bf02160424 .
  12. ↑ http://www.huh.harvard.edu/libraries/wasson/BIOG.html http://www.huh.harvard.edu/libraries/wasson/BIOG.html
  13. ↑ Deutscher Ärzteverlag GmbH, editor of the Deutsches Ärzteblatt: Cancer: Fungal hallucinogen relieves depression and takes away fear of ... ( aerzteblatt.de [accessed on September 22, 2018]).
  14. ^ Robin L Carhart-Harris, Leor Roseman, Mark Bolstridge, Lysia Demetriou, J Nienke Pannekoek: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms . In: Scientific Reports . tape 7 , no. 1 , October 13, 2017, doi : 10.1038 / s41598-017-13282-7 .
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  18. Jump up ↑ Janis Fricke, Claudius Lenz, Jonas Wick, Felix Blei, Dirk Hoffmeister: Production Options for Psilocybin: Making of the Magic. In: Chemistry - A European Journal. 25, 2019, p. 897, doi : 10.1002 / chem.201802758 (Review).
  19. ↑ P. Stamets: Psilocybin Mushrooms of the World: An Identification Guide. Ten Speed ​​Press, Berkeley, California 1996, ISBN 0-89815-839-7 .
  20. ↑ Psilocybin & Psilocin Dosage by Erowid
  21. ↑ a b European Monitoring Center for Drugs and Drug Addiction : “Hallucinogenic Mushrooms: An Emerging Trend Case Study” PDF .
  22. ↑ Felix Hasler, Ulrike Grimberg, Marco A. Benz, Theo Huber, Franz X. Vollenweider: Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose – effect study. In: Psychopharmacology. 172, 2004, pp. 145-156, doi: 10.1007 / s00213-003-1640-6 .
  23. ↑ Kim PC Kuypers, Livia Ng, David Erritzoe, Gitte M Knudsen, Charles D Nichols, David E Nichols, Luca Pani, Anaïs Soula, David Nutt: Microdosing psychedelics: More questions than answers? An overview and suggestions for future research. In: Journal of Psychopharmacology. 33, 2019, p. 1039, doi : 10.1177 / 0269881119857204 .
  24. ^ T. Passie, J. Seifert, U. Schneider, HM Emrich: The pharmacology of psilocybin. In: Addiction Biology. 7, 2002, pp. 357-364. PMID 14578010 .
  25. ^ DE Nichols: Hallucinogens. In: Pharmacology & therapeutics. Volume 101, Number 2, February 2004, pp. 131-181, doi: 10.1016 / j.pharmthera.2003.11.002 . PMID 14761703 . (Review).
  26. ↑ RL Carhart-Harris, D. Erritzoe u. a .: Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. In: Proceedings of the National Academy of Sciences . Volume 109, Number 6, February 2012, pp. 2138-2143, doi: 10.1073 / pnas.1119598109 . PMID 22308440 . PMC 3277566 (free full text).
  27. ↑ Alexander V. Lebedev, Martin Lövdén, Gidon Rosenthal, Amanda Feilding, David J. Nutt, Robin L. Carhart-Harris: Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin. In: Human Brain Mapping. 2015, p. N / a, doi: 10.1002 / hbm.22833 .
  28. ↑ Coordinatiepunt Assessment en Monitoring nieuwe drugs (CAM) p / a Inspection des Gesundheitsamt (IGZ) -CAM, The Hague, 2000 (study on the legal classification and the dangers of psychoactive fungi). (PDF)
  29. ↑ ML Espiard et al .: Hallucinogen persisting perception disorder after psilocybin consumption: a case study. In: Eur. Psychiatry. 20 (5-6), 2005, pp. 458-446. PMID 15963699 .
  30. ↑ FX Vollenweider, MF Vollenweider-Scherpenhuyzen, A. Bäbler, H. Vogel, D. Hell: Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. In: Neuroreport. Volume 9, Number 17, December 1998, pp. 3897-3902. PMID 9875725 .
  31. ↑ "Severe agitation may respond to diazepam (20 mg orally). "Talking down" by reassurance is also effective and is the management of first choice. Antipsychotic medications may intensify the experience and thus are not indicated. "In: Laurence Brunton, Bruce A. Chabner, Bjorn Knollman: Goodman and Gilman's Manual of Pharmacology and Therapeutics. 12th edition. McGraw-Hill, 2011, ISBN 978-0-07-176939-6 , p. 1537.
  32. ↑ E. Bone: Mycophilia: Revelations from the Weird World of Mushrooms. Rodale, New York, 2011. pp. 257-258. ISBN 978-1-60529-407-0 .
  33. ↑ 4th BtMGlV of February 21, 1967 .
  34. ↑ a b c d e R. G. Boire: Sacred Mushrooms and the Law. Ronin Publishing, Berkeley, 2002. ISBN 978-1-57951-061-9 . Pp. 25-48.
  35. ↑ International Narcotics Control Board: List of psychotropic substances under international control , 23rd edition, Vienna, 2003.
  36. ↑ Michaela Haas: Psilocybin Mushrooms: Legalization of Magic Mushrooms in Denver. Süddeutsche Zeitung Magazin, May 10, 2019, accessed on May 29, 2019 .
  37. ↑ Tom Angell: Denver Voters Approve Measure To Decriminalize Psychedelic Mushrooms. Forbes, accessed May 29, 2019 .
  38. ↑ Colleen Shalby: Oakland becomes 2nd US city to decriminalize magic mushrooms. Retrieved June 5, 2019 .
  39. ↑ Kelly McCarthy: Santa Cruz decriminalizes psychedelic mushrooms. In: ABC News. January 29, 2020, accessed on January 31, 2020 .
  40. ↑ Harmeet Kaur: Santa Cruz decriminalizes magic mushrooms and other natural psychedelics, making it the third US city to take such a step. In: CNN. January 30, 2020, accessed February 2, 2020 .
  41. ↑ a b S. Ballesteros, MF Ramon, MJ Iturralde, R. Martinez-Arrieta: Natural sources of drugs of abuse: magic mushrooms. In: Cole SM. New Research on Street Drugs. Nova Publishers, New York, 2006. ISBN 978-1-59454-961-8 . Pp. 167-88.
  42. ↑ Standard for the Uniform Scheduling of Medicines and Poisons ( Memento of the original dated December 22, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . @1@ 2Template: Webachiv / IABot / www.slp.wa.gov.au
  43. ↑ COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression. Retrieved December 6, 2018 .