British Journal of Pharmacology
June 2, 2024
Oscar Sandoval, Quynh Nguyen, Ryan J. Rakoczy et al.
23 citations
Several tryptamines found in psilocybin-containing mushrooms—baeocystin, norbaeocystin, and aeruginascin—were compared with psilocybin to assess their pharmacological and behavioral effects. All compounds showed nearly identical rates of dephosphorylation and metabolism by monoamine oxidase. Only dephosphorylated baeocystin and norbaeocystin crossed a blood–brain barrier mimetic as effectively as psilocin. Norbaeocystin's dephosphorylated form activated the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin. While only psilocybin induced head twitch responses in rats (a marker of hallucinogenic potential), norbaeocystin, like psilocybin, improved outcomes in the forced swim test. All compounds showed minimal changes to renal and hepatic health markers, suggesting safe profiles. Norbaeocystin may share therapeutic potential with psilocybin without causing hallucinations.
Metabolic Engineering Communications
March 11, 2022
Alexandra M. Adams, Nicholas A. Anas, Abhishek K. Sen et al.
21 citations
Psilocybin and other psychedelic compounds are being studied for therapeutic use, but little is known about norbaeocystin, a pathway intermediate, due to difficulties obtaining it. Researchers developed a new E. coli platform to produce gram-scale amounts of norbaeocystin, finding that even minor genetic changes required reoptimization of production. In vivo tests on Long-Evans rats showed a dose response to psilocybin, but norbaeocystin did not elicit any pharmacological response, suggesting it and its metabolites may not strongly bind to the serotonin 2A receptor. This work enables future studies of norbaeocystin in animal models and supports the safety of using cell broth as a drug delivery vehicle.
PeerJ
June 3, 2024
Mengyang Xu, Haifei Shi, Andor J. Kiss et al.
5 citations
Psilocybin and related tryptamines, currently studied as potential antidepressants, may work partly through the gut microbiome. In a preliminary experiment, male Long Evans rats received oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or a vehicle. Fecal samples collected 1 and 3 weeks later showed that neither drug significantly altered overall microbiome diversity, but both caused dose- and time-dependent shifts in bacterial abundance at the phylum level—increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria. These findings suggest a novel peripheral mechanism for tryptamine antidepressant activity and indicate norbaeocystin may warrant further investigation.
bioRxiv (Cold Spring Harbor Laboratory)
January 14, 2025
Alexia L. Zylko, Ryan J. Rakoczy, Brianna F Roberts et al.
preprint
Psilocybin, the psychedelic compound in magic mushrooms, produced head twitch responses in adult rats but not in adolescent rats. Adult female rats in diestrus showed more head twitches after psilocybin than those in proestrus, indicating that hormonal phase influences the response. Adolescent exposure to psilocybin did not cause lasting changes in anxiety-like behavior or behavioral flexibility. No age- or estrous-related differences were found in 5-HT2A receptor expression in the medial prefrontal cortex. These results show age- and sex-dependent differences in psychedelic effects and emphasize the need for inclusive research that accounts for age, sex, and hormonal status.
bioRxiv (Cold Spring Harbor Laboratory)
October 23, 2023
Ryan J. Rakoczy, Grace N. Runge, Abhishek K. Sen et al.
preprint
Naturally occurring tryptamines in psilocybin-containing mushrooms—baeocystin, norbaeocystin, and aeruginascin—were compared with psilocybin for pharmacological and behavioral effects. All compounds showed nearly identical rates of dephosphorylation and metabolism. Only dephosphorylated forms of baeocystin and norbaeocystin crossed a blood-brain barrier model similarly to psilocin (psilocybin's active form). In rats, only psilocybin triggered head twitch responses (a marker of hallucinogenic potential), but norbaeocystin, like psilocybin, improved outcomes in the forced swim test. All compounds showed minimal effects on renal and hepatic health markers. The findings suggest norbaeocystin may share psilocybin's therapeutic potential without causing hallucinations.