Pharmacological and behavioural effects of tryptamines present in psilocybin‐containing mushrooms
Oscar Sandoval, Quynh Nguyen, Ryan J. Rakoczy, Grace N. Runge, Abhishek K. Sen, Hunter G. Wells, B. Roberts, Jon H. Sciortino, William E. Gibbons, Lucas M. Friedberg, J. Andrew Jones, Matthew S. Mcmurray
British Journal of Pharmacology June 2, 2024 DOI: 10.1111/bph.16466 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | baeocystin norbaeocystin aeruginascin psilocybin |
| Topics | Psilocybin |
| Keywords | Tryptamines Hallucinogen Pharmacology |
| Citations | 23 |
| Post-publication review | 1 comment on PubPeer (opens in new tab) · last active October 2024 |
| Key findings | Norbaeocystin shares overlapping therapeutic potential with psilocybin, improving forced swim test outcomes without inducing head twitch responses, suggesting potential antidepressant effects without hallucinations. |
Abstract
Background and Purpose Demand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing “magic” mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects. Experimental Approach We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood–brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound. Key Results In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood–brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5‐HT 2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5‐HT 2A ‐mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. Conclusions and Implications Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 21
- Pharmacokinetics of Psilocybin: A Systematic Review Pharmaceutics March 25, 2025
- Psilocybin Outside the Clinic JAMA Psychiatry November 5, 2025
- Psilocybin biosynthesis enhancement through gene source optimization. Metabolic Engineering April 16, 2025
- Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications Biotechnology Progress October 4, 2024
- Age- and estrous-dependent effects of psilocybin in rats. Neuropharmacology November 15, 2025
and 16 more in the library
Cites 32
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- The pharmacology of psilocybin Addiction Biology October 1, 2002
and 27 more in the library