Surprisingly however, the compound, similarly tobaeocystin,norbaeocystin, andnorpsilocin, does not produce thehead-twitch response, a behavioral proxy of psychedelic effects, in animals, and hence is putatively non-hallucinogenic.[4][7] In older literature, thepsychoactive effects of 4-hydroxylated tryptamines have been said to increase in the series of 4-hydroxytryptamine,4-hydroxy-N-methyltryptamine (norpsilocin], and 4-hydroxy-N,N-dimethyltryptamine (psilocin).[3]
The reason for the lack of hallucinogenic effects with 4-HT and related compounds is unknown, but may be due tobiased agonism of the serotonin 5-HT2A receptor; or, more specifically, biased agonism for theβ-arrestin2 signaling pathway.[4]
Norbaeocystin is thought to be aprodrug of 4-HT, analogously to how psilocybin is a prodrug of psilocin and how baeocystin is thought to be a prodrug of norpsilocin.[6][4]
^abcWurst M, Kysilka R, Flieger M (2002). "Psychoactive tryptamines from basidiomycetes".Folia Microbiologica.47 (1):3–27.doi:10.1007/BF02818560.PMID11980266.
^abcdefghijRakoczy 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".British Journal of Pharmacology.181 (19):3627–3641.doi:10.1111/bph.16466.PMID38825326.Norpsilocin, 4-hydroxytryptamine and 4-hydroxy-N,N,Ntrimethyltryptamine have similar stability, metabolism and blood brain barrier penetration to psilocin. [...] As norpsilocin and 4-HT (active forms of baeocystin and norbaeocystin, respectively) are evidenced to be capable of crossing the BBB and bind with 5-HT2A receptors, it was surprising that neither induced significant head twitch responses at any concentration tested. However, these results concur with previous studies demonstrating these compounds do not significantly induce head twitch responses in rodents (Glatfelter et al., 2022; Sherwood et al., 2020).
^abSherwood 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.Bibcode:2020JNAtP..83..461S.doi:10.1021/acs.jnatprod.9b01061.PMID32077284.
^Repke DB, Leslie DT, Guzmán G (1977). "Baeocystin in psilocybe, conocybe and panaeolus".Lloydia.40 (6):566–578.PMID600026.
^Irvine W, Tyler M, Delgoda R (June 2023). "In silico characterization of the psilocybin biosynthesis pathway".Computational Biology and Chemistry.104: 107854.doi:10.1016/j.compbiolchem.2023.107854.PMID36990027.
^Erspamer V, Glasser A, Mantegazzini P (November 1960). "Pharmacological actions of 4-hydroxytryptamine and 4-hydroxytryptophan".Experientia.16 (11):505–506.doi:10.1007/BF02158367.PMID13697285.
