Norpsilocin
Norpsilocin, also known as 4-hydroxy-N-methyltryptamine, is a tryptamine alkaloid recently discovered in 2017 in the psychedelic mushroom Psilocybe cubensis. It is hypothesized to be a dephosphorylated metabolite of baeocystin.
Pharmacology
Norpsilocin was found to be a near full agonist of the 5-HT2A receptor and was found to be more potent than psilocin. It also has affinity for other serotonin receptors. Moreover, it has been found to cross the blood–brain barrier in animals and to have good metabolic stability similarly to psilocin.Norpsilocin has shown psilocin-related peripheral effects in animals, including decreased spinal reflexes such as knee jerk response, antiserotonergic activity, and pressor activity. Surprisingly however, in spite of its serotonin 5-HT2A receptor agonism and psilocin-like effects, norpsilocin failed to induce the head-twitch response, a behavioral proxy of psychedelic effects, in animals. Likewise, norbaeocystin and aeruginascin failed to induce the head-twitch response. Only psilocybin was effective in this regard. In any case, norbaeocystin showed antidepressant-like activity similarly to psilocybin and fluoxetine in spite of its putative non-hallucinogenic nature. Norpsilocin itself was not tested in this assay.
A 2025 animal study found that both baeocystin and norpsilocin are peripherally selective with very limited ability to cross the blood–brain barrier.