Aeruginascin Explained

Aeruginascin, also known as 4-phosphoryloxy-N,N,N-trimethyltryptamine (4-PO-TMT), is an indoleamine derivative which occurs naturally within the mushrooms Inocybe aeruginascens,^{[1] [2] [3] [4] [5] [6]} Pholiotina cyanopus, and Psilocybe cubensis.^[7]

Aeruginascin is the N-trimethyl analogue of psilocybin. It is closely related to the frog skin toxin bufotenidine (5-HTQ), a potent serotonin 5-HT₃ receptor agonist, but the aeruginascin metabolite 4-HO-TMT (thought to be its active form) shows strong binding at the serotonin 5-HT₂ receptors similar to psilocin.^{[8] [9]} Aeruginascin itself has been found to have high affinity for the serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2B receptors, but does not bind to the 5-HT₃ receptor.^[10] Unlike psilocybin, but similarly to 4-HO-TMT, aeruginascin does not produce the head-twitch response in rodents.^{[11] [12]} It lacks affinity or activation of the mouse 5-HT_2A and 5-HT_1A receptors.

The first scientific literature about the pharmacological effects of aeruginascin is from a study published by Gartz in 1989.^[13] Across 23 analyzed cases of accidental hallucinogenic mushroom poisonings, people who had ingested the mushroom Inocybe aeruginascens reported only euphoric experiences.^{[14] [15]} This is in contrast to the slight and in some cases extremely dysphoric experiences reported from the accidental ingestion of non-aeruginascin-containing mushrooms (containing solely psilocybin and psilocin). However, these findings are anecdotal and preliminary.

See also

• 4-Hydroxytryptamine

Notes and References

1. Gartz J . Inocybe aeruginascens Babos. . Eleusis, Journal of Psychoactive Plants & Compounds. . 1995 . 3 . 31–4 . Museo Civico di Rovereto.
2. Jensen N, Gartz J, Laatsch H . Aeruginascin, a trimethylammonium analogue of psilocybin from the hallucinogenic mushroom Inocybe aeruginascens . Planta Medica . 72 . 7 . 665–666 . June 2006 . 16673333 . 10.1055/s-2006-931576 . 260281286 . dead . https://web.archive.org/web/20110524153555/http://wwwuser.gwdg.de/~ucoc/laatsch/168_Aeruginascin_col.pdf . 2011-05-24 .
3. Sherwood AM, Halberstadt AL, Klein AK, McCorvy JD, Kaylo KW, Kargbo RB, Meisenheimer P . Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin . Journal of Natural Products . 83 . 2 . 461–467 . February 2020 . 32077284 . 10.1021/acs.jnatprod.9b01061 . 211214973 .
4. Servillo L, Giovane A, Balestrieri ML, Cautela D, Castaldo D . N-methylated tryptamine derivatives in citrus genus plants: identification of N,N,N-trimethyltryptamine in bergamot . Journal of Agricultural and Food Chemistry . 60 . 37 . 9512–9518 . September 2012 . 22957740 . 10.1021/jf302767e . 2012JAFC...60.9512S .
5. de Carvalho Junior AR, Oliveira Ferreira R, de Souza Passos M, da Silva Boeno SI, Glória das Virgens LL, Ventura TL, Calixto SD, Lassounskaia E, de Carvalho MG, Braz-Filho R, Curcino Vieira IJ . 6 . Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Triterpenes and Alkaloids from Psychotria nuda (Cham. & Schltdl.) Wawra . Molecules . 24 . 6 . 1026 . March 2019 . 30875889 . 6471101 . 10.3390/molecules24061026 . free .
6. Gotvaldová K, Borovička J, Hájková K, Cihlářová P, Rockefeller A, Kuchař M . Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids . International Journal of Molecular Sciences . 23 . 22 . 14068 . November 2022 . 36430546 . 10.3390/ijms232214068 . 9693126 . free .
7. Web site: CaaMTech Publishes Fundamental Research on Aeruginascin Derivatives. 14 September 2022 .
8. Chadeayne AR, Pham DN, Reid BG, Golen JA, Manke DR . Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity . ACS Omega . 5 . 27 . 16940–16943 . July 2020 . 32685863 . 7365549 . 10.1021/acsomega.0c02208 .
9. Web site: Bauer BE . 2020-07-07. Study Finds Aeruginascin Metabolite 4-HO-TMT is Active at the Serotonin 5-HT2A Receptor. live. 2021-09-07. Psychedelic Science Review . en-US . https://web.archive.org/web/20200805013154/https://psychedelicreview.com/study-finds-aeruginascin-metabolite-4-ho-tmt-is-active-at-the-serotonin-5-ht2a-receptor/ . 2020-08-05 .
10. Chadeayne AR, Pham DN, Reid BG, Golen JA, Manke DR . Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity . ACS Omega . 5 . 27 . 16940–16943 . July 2020 . 32685863 . 7365549 . 10.1021/acsomega.0c02208 .
11. Rakoczy RJ, Runge GN, Sen AK, Sandoval O, Wells HG, Nguyen Q, Roberts BR, Sciortino JH, Gibbons WJ, Friedberg LM, Jones JA, McMurray MS . Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms . Br J Pharmacol . 181 . 19 . 3627–3641 . October 2024 . 38825326 . 10.1111/bph.16466 . free .
12. Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DN, Naeem M, Sammeta VR, DeBoer S, Golen JA, Hulley EB, Stove CP, Chadeayne AR, Manke DR, Baumann MH . Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice . ACS Pharmacol Transl Sci . 5 . 11 . 1181–1196 . November 2022 . 36407948 . 9667540 . 10.1021/acsptsci.2c00177 .
13. Gartz J . January 1989. Analysis of Aeruginascin in Fruit Bodies of the Mushroom Inocybe aeruginascens. International Journal of Crude Drug Research. en. 27. 3. 141–144. 10.3109/13880208909053954. 0167-7314.
14. Web site: 2018-11-19. Aeruginascin. 2021-09-07. Psychedelic Science Review. en-US.
15. Pepe M, Hesami M, de la Cerda KA, Perreault ML, Hsiang T, Jones AM . A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond . Biotechnol Adv . 69 . 108247 . December 2023 . 37659744 . 10.1016/j.biotechadv.2023.108247 .