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Baeocystin

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Baeocystin
Skeletal formula of baeocystin as a zwitterion
Space-filling model of the baeocystin molecule as a zwitterion
Clinical data
Other namesNorpsilocybin; N-Desmethylpsilocybin; 4-Phosphoryloxy-N-methyltryptamine; 4-PO-NMT; 4-Hydroxy-N-methyltryptamine 4-phosphate; PLZ-1019
Routes of
administration		Oral
ATC code
  • None
Legal status
Legal status
Identifiers
  • 3-[2-(Methylammonio)ethyl]-1H-indol-4-yl hydrogenphosphate
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H15N2O4P
Molar mass270.225 g·mol−1
3D model (JSmol)
  • CNCCc1c[nH]c2cccc(OP(=O)(O)O)c12
  • InChI=1S/C11H15N2O4P/c1-12-6-5-8-7-13-9-3-2-4-10(11(8)9)17-18(14,15)16/h2-4,7,12-13H,5-6H2,1H3,(H2,14,15,16) checkY
  • Key:WTPBXXCVZZZXKR-UHFFFAOYSA-N checkY
  (verify)

Baeocystin, also known as norpsilocybin or 4-phosphoryloxy-N-methyltryptamine (4-PO-NMT), is a zwitterionic alkaloid and analogue of psilocybin. It is found as a minor compound in most psilocybin mushrooms together with psilocybin, norbaeocystin, aeruginascin, and psilocin.[1] Baeocystin is the N-demethylated derivative of psilocybin and the 4-phosphorylated derivative of 4-HO-NMT (4-hydroxy-N-methyltryptamine). The structures at right illustrate baeocystin in its zwitterionic form.

History

[edit]

Baeocystin was first isolated from the mushroom Psilocybe baeocystis,[2] and later from P. semilanceata,[3] Panaeolus renenosus, Panaeolus subbalteatus, and Copelandia chlorocystis.[4] It was first synthesized by Troxler et al. in 1959.[5]

Pharmacology

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Baeocystin is thought to be a prodrug of norpsilocin, analogously to how psilocybin is a prodrug of psilocin.[6] Norpsilocin is a potent and centrally penetrant agonist of the serotonin 5-HT2A receptor and also interacts with other serotonin receptors.[6]

Baeocystin and norpsilocin have been found to be inactive in terms of hallucinogen-like effects in rodents in multiple studies published in the 2020s.[7][8][6] More specifically, they were unable to produce the head-twitch response (HTR), a well-established behavioral proxy of psychedelic effects, and this was in contrast to psilocybin.[7][8][6] In one of the papers, the researchers concluded that "...baeocystin alone would likely not induce hallucinogenic effects in vivo".[7] As with baeocystin and norpsilocin, norbaeocystin, aeruginascin, 4-hydroxytryptamine (4-HT), and 4-HO-TMT also all failed to induce the HTR in rodents.[7][8][6] However, these compounds have not necessarily been inactive in terms of behavioral effects in general.[8][6]

Chemist and mycologist Jochen Gartz reported in the 1990s that baeocystin is active as a psychedelic in humans.[9][10][11][12][13][14] He has stated that 4 mg produced a "threshold" or "gentle hallucinogenic experience" with "mild hallucinations for three hours" and that "10 mg of baeocystin [was] found to be about as psychoactive as a similar amount of psilocybin".[9][10][11][12][13] Gartz also personally communicated these findings to Jonathan Ott, who has reproduced the claims.[12][13][14] Hamilton Morris has expressed surprise and skepticism about the reported psychoactivity of baeocystin however.[14]

Gartz has also claimed that mushrooms with high baeocystin content, such as Psilocybe semilanceata, are more frequently associated with dysphoric experiences.[15][16] Conversely, he has claimed that accidental ingestions of Inocybe aeruginascens, which contains high levels of both aeruginascin and baeocystin, is usually associated with euphoric experiences, in contrast to the dysphoric experiences that can occur with mushrooms containing only high levels of psilocybin.[15][16] However, more research is needed on the effects of baeocystin and aeruginascin in humans.[15][16]

In contrast to Gartz, mycologist Paul Stamets has reported that he tried 10 mg pure baeocystin and it didn't produce hallucinogenic effects but did produce pupil dilation and apparent anxiolysis.[17][18][19]

The reasons for the apparently non-hallucinogenic nature of norpsilocin, baeocystin, and related compounds in animals (and possibly in humans), in spite of norpsilocin and others being potent serotonin 5-HT2A receptor agonists and producing other centrally mediated behavioral effects in animals, remain unknown.[6][8] One possibility however is that these compounds may be biased agonists of the serotonin 5-HT2A receptor and may not sufficiently activate the intracellular signaling cascades responsible for psychedelic effects.[6][8]

Development

[edit]

Baeocystin is being evaluated by Pilz Bioscience ("pilz" being German for "mushroom") under the developmental code name PLZ-1019 for the possible treatment of pervasive developmental disorders like autism in children.[20]

References

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  1. ^ Gotvaldová K, Borovička J, Hájková K, Cihlářová P, Rockefeller A, Kuchař M (November 2022). "Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids". International Journal of Molecular Sciences. 23 (22): 14068. doi:10.3390/ijms232214068. PMC 9693126. PMID 36430546.
  2. ^ Leung AY, Paul AG (October 1968). "Baeocystin and norbaeocystin: new analogs of psilocybin from Psilocybe baeocystis". Journal of Pharmaceutical Sciences. 57 (10): 1667–1671. doi:10.1002/jps.2600571007. PMID 5684732.
  3. ^ Repke DB, Leslie DT, Guzmán G (1977). "Baeocystin in psilocybe, conocybe and panaeolus". Lloydia. 40 (6): 566–578. PMID 600026.
  4. ^ Brossi A (1988). The Alkaloids: Chemistry and Pharmacology V32: Chemistry and Pharmacology. Academic Press. p. 46. ISBN 978-0-08-086556-0.
  5. ^ Troxler F, Seeman F, Hofmann A (1959). "Abwandlungsprodukte von Psilocybin und Psilocin. 2. Mitteilung über synthetische Indolverbindungen". Helvetica Chimica Acta (in German). 42 (6): 2073–2103. doi:10.1002/hlca.19590420638.
  6. ^ a b c d e f g h Rakoczy RJ, Runge GN, Sen AK, Sandoval O, Wells HG, Nguyen Q, et al. (October 2024). "Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms". Br J Pharmacol. 181 (19): 3627–3641. doi:10.1111/bph.16466. PMID 38825326.
  7. ^ a b c d Sherwood AM, Halberstadt AL, Klein AK, McCorvy JD, Kaylo KW, Kargbo RB, et al. (February 2020). "Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin". Journal of Natural Products. 83 (2): 461–467. doi:10.1021/acs.jnatprod.9b01061. PMID 32077284.
  8. ^ a b c d e f Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DN, et al. (November 2022). "Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice". ACS Pharmacol Transl Sci. 5 (11): 1181–1196. doi:10.1021/acsptsci.2c00177. PMC 9667540. PMID 36407948.
  9. ^ a b Gartz J, Appelius C, Taake C, Falk B (1996). "The Current State of Knowledge About European Species: Psilocybe Semilanceata: The Classic Species Among European Psychotropic Mushrooms" (PDF). Magic Mushrooms Around the World: A Scientific Journey Across Cultures and Time : the Case for Challenging Research and Value Systems. Los Angeles, California: LIS Publications. pp. 16–28 (27). ISBN 978-0-9653399-0-2. Retrieved 25 January 2025. Early controlled studies of the psychoactivity of various species in the former Czechoslovakia concluded that Psilocybe semilanceata is a more potently psychoactive species than Psilocybe bohemica, even though both species were found to contain the same amounts of psilocybin. Thus, researchers hypothesized that the mushrooms are likely to contain additional substances that contribute to the overall psychotropic effect. This hypothesis is supported by the fact that considerable amounts of baeocystin are consistently found in samples of Psilocybe semilanceata. I am also aware of an experiment whose results showed that 4 mg of baeocystin caused mild hallucinations for three hours, while 10 mg of baeocystin were found to be about as psychoactive as a similar amount of psilocybin.
  10. ^ a b Gartz J (1999). Narrenschwämme: Psychoaktive Pilze rund um die Welt [Magic Mushrooms: Psychoactive Mushrooms Around the World] (in German). Nachtschatten Verlag. p. 55. ISBN 978-3-03788-494-2. Retrieved 25 January 2025. [Translated: In earlier controlled studies on the psychoactivity of various species in the former Czechoslovakia, it was already possible to prove that, with the same psilocybin content, Psilocybe semilanceata was more potent than Psilocybe bohemica (Chapter 2.3). The hypothesis put forward that other substances in the mushrooms must also contribute to the psychotropic effect is confirmed by the regular detection of baeocystin in considerable quantities in Psilocybe semilanceata. I know of one experiment in which 4 mg of baeocystin produced a mild hallucinosis lasting three hours, and 10 mg was approximately identical to the effect of the same amount of psilocybin.]
  11. ^ a b Gartz J (1992). "Further Investigations on Psychoactive Mushrooms of the Genera Psylocibe, Gymnopilus and Conocybe" (PDF). Annali del Museo Civico di Rovereto. 7: 265–274. Psilocybe semilanceata is a species that blues inconsistently. The high levels of psilocybin and baeocystin making it one of the most potent species as well as one of the most constant in amount in comparison with other species (GARTZ & MÜLLER, 1989; Semerdzieva et al., 1986). In a self experiment a small sample of baeocystin from Psilocybe semilanceata (GARTZ, 1989b) (4 mg) has caused a gentle hallucinogenic experience. [...] GARTZ J., 1989b - Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe. Journal of Basic Microbiology, 29: 347-352. [Note: There was, strangely, no actual information in the cited paper (Gartz, 1989b) about the psychoactivity of baeocystin.]
  12. ^ a b c Ott J (1996). Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History. Natural Products Company. p. 431. ISBN 978-0-9614234-9-0. Retrieved 25 January 2025. Baeocystin [...] Pharmacology: psychoptic in 10 mg oral dose; 4 mg threshold (Gartz, pers. com.); active in animals (Cerletti, Advances in Pharmacology 6B: 233, 1968)
  13. ^ a b c Keeper of the Trout and Friends (2007). "Baeocystin". Some Simple Tryptamines (2 ed.). Austin, Texas: Mydriatric Productions. p. 59. ASIN B0041OLXM0. ISBN 978-0977087655. OCLC 948674100. Baeocystin [...] Activity: Psychoactive in animals. Ott 1996 cited Cerletti 1968 [Cerletti et al. 1968 evaluated 4-HO-MMT rather than Baeocystine. See comments under its entry] Dose: Psychoptic in human with a 10 mg oral dose (4 mg threshold) (Ott 1996 cited Gartz, pers. comm.) See: Ott 1996: Entry #3, page 431 [...] Ott, Jonathan (1996) Pharmacotheon. Entheogenic Drugs, their Plant Sources and History. Second Edition Densified. Natural Products Co., Kennewick, WA 639 pp. ISBN 0-9614234-8-x (Hardcover)/ 0-9614234-9-8 (paperback)
  14. ^ a b c Hamilton Morris (1 September 2021). "PODCAST 28: A talk with Jonathan Ott". The Hamilton Morris Podcast (Podcast). Patreon. Event occurs at 1:06:15–1:07:21. Retrieved 20 January 2025. [Morris:] Do you have any thoughts about some of the remaining uncharacterized tryptamines or lesser-characterized tryptamines like baeocystin or lespedamine? [Ott:] Sorry, what was the question? [Morris:] Baeocystin? Do you have any—seems like nobody has done an authoritative bioassay of the isolated material. [Ott:] Yeah, not authoritative but it is active. Jochen Gartz bioassayed it. [Morris:] I know I saw that you wrote that but he— [Ott:] But not norbaeocystin. He just told me that probably, maybe he hasn't published it. [Morris:] It's such a bizarre—I've heard that as well but it seems so unlikely and weird. [Ott:] And also the mono—I mean I would say there's potentially six active tryptamines there. I mean, we have the 4-phosphoryloxy-DMT, 4-hydroxy-DMT, monomethyl analogues and the tryptamine analogues. They're all potentially active and could well explain the subtle differences that many people experience between different Psilocybe species.
  15. ^ a b c Pepe M, Hesami M, de la Cerda KA, Perreault ML, Hsiang T, Jones AM (December 2023). "A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond". Biotechnol Adv. 69: 108247. doi:10.1016/j.biotechadv.2023.108247. PMID 37659744. Anecdotal and preliminary research suggests that the biological outcome experi enced by humans following ingestion of psychedelic mushrooms is not strictly a result of psilocybin or psilocin and that there are other com pounds that interact to alter the psychoactive and/or medicinal expe rience. Gartz (1989a, 1989b) evaluated data from 24 cases of accidental ingestion of Inocybe aeruginascens, a species of mushroom with high concentrations of aeruginascin and baeocystin (Gartz, 1989a, 1989b). Of particular note, Gartz (1989a, 1989b) reported that in all cases of accidental ingestion, patients only experienced euphoric responses, in contrast to frequent reports of slight, and sometimes deep, dysphoric outcomes from people who ingested mushrooms with high levels of psilocybin and psilocin without aeruginascin. The author concluded that aeruginascin can modify the pharmacological action of psilocybin. In contrast, they also reported that use of mushrooms with high levels of baeocystin, such as P. semilanceata, lead to higher rates of dysphoric experiences (Gartz, 1989a, 1989b).
  16. ^ a b c Gartz J (1989). "Analysis of Aeruginascin in Fruit Bodies of the Mushroom Inocybe aeruginascens". International Journal of Crude Drug Research. 27 (3): 141–144. doi:10.3109/13880208909053954. ISSN 0167-7314. Because of some similarities with edible mushrooms like Marasmius oreades (Bolt.: Fr.) Fr., I. aeruginascens has caused 20 accidental hallucinogenic poisonings in the GDR and also one case in Hungary (3, 6, 7, 8) as well as 3 further unpublished psychoses with visual hallucinations. In all of these cases only euphoric experiences were reported. This is in contrast to the often slight and in some cases deep dysphoric mood observed in people who used mushrooms with a content of psilocybin and psilocin for hallucinogenic purposes(1, 11, 13, 14, 17). It is well known that one's experience with hallucinogens depends upon a host of environmental, cultural and psychological factors (setting and set) (12) as well as the amounts and potency of the used psilocybian species. But in a similar context, accidental ingestion of these mushrooms or other hallucinogens produced in known cases psychosis with anxiety, panic and physical symptoms while a variety of perceptual disorders may also be present (4,12). It seems that the significant amounts of the indole derivative aeruginascin can modify the pharmacological action of psilocybin to give an euphoric mood during psychosis with hallucinations due to ingestion of I. aeruginascens. Additionally, baeocystin was often found in psilocybian mushrooms and pharmacological or clinical studies are lacking. But by use of mushrooms with a high content of baeocystin like R semilanceuta (2, 10, 16) a lot of dysphoric experiences were also described (1 1, 13, 14, 17). In order to establish the specific action of aeruginascin, investigations of human ingestion of aeruginascin with and without additional application of psilocybin should be done.
  17. ^ K. Mandrake (1 March 2021). "Psilocybin Isn't the Only Compound in Magic Mushrooms—Here's What Else There Is". doubleblindmag.com. Retrieved 27 January 2025. Although little is known about the effects of baeocystin in isolation, Jochen Gartz, a chemist and mycologist at the Institute for Biotechnology in Germany, made anecdotal references to its psychoactivity being comparable to psilocybin in his book, "Magic Mushrooms Around the World" published in the 1997. In somewhat of a contradiction, famous mycologist Paul Stamets recently reported on The Joe Rogan podcast in 2019 that a pure baeocystin experience during a high state of anxiety didn't cause psilocybin-like hallucinations, but did dilate his pupils and cause his anxiety to disappear.
  18. ^ "Joe Rogan Experience #1385: Paul Stamets". YouTube (Podcast). 15 November 2019. Event occurs at 37:45–41:27. Retrieved 27 January 2025. I obtained some pure baeocystin from a laboratory. [...] Since there were no reports in the scientific literature [...] with a doctor friend of mine who measured my vitals [...] we did an n of 1 study. [...] I could find no one who had ever ingested this, so I decided I would ingest it. [...] So I had super high anxiety. [...] I did 10 milligrams of baeocystin. She measured my heart beat, blood pressure, all those metrics. My eyes did dilate. She said that was good, so had a drug-like effect. [...] I didn't get high. No, not at all. She goes "how do you feel?" And I said "I feel great. I have no anxiety." [...] So here we found an analogue of psilocybin that does not get you high, that's legal, that reduced anxiety.
  19. ^ Bauer BE (5 March 2020). "Scientists Synthesize and Test the Magic Mushroom Compounds Baeocystin, Norbaeocystin, Norpsilocin, and Aeruginascin". Psychedelic Science Review. Retrieved 27 January 2025. Notably, mushroom expert Paul Stamets recently described a similar lack of psychoactive activity upon ingesting pure baeocystin. In an interview with Joe Rogan, Stamets says he took 10 mg of baeocystin but did not feel high. He said, I was ready for liftoff. I was hoping for liftoff, I know what liftoff feels like, and I didn't get it.
  20. ^ "Baeocystin - Pilz Bioscience". AdisInsight. 19 January 2021. Retrieved 27 October 2024.
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