Acute anxiogenic effects of psilocybin and the related tryptamine, norbaeocystin, in male and female rats
Marisa J. Savini, Kylie M. King, Lillianna P. Puppel, Aleece K. Al-Olimat, Noelle M. Molnar, Evelynn J. Schneider, Savannah E. Straub, Joe Parker, Colin J. Gottron, Allison M. Bach, Solomon M. Lambdin, Stephanie M. Regan, Kaitlyn E. Williams, Troy R. Welker, J. Andrew Jones, Phillip R. Zoladz
Psychopharmacology October 13, 2026 DOI: 10.1007/s00213-026-07188-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (three experiments) Peer reviewed |
|---|---|
| Population | Rats (male and female) |
| Interventions | Psilocybin Norbaeocystin |
| Dose | 0.3-1 mg/kg; 1 mg/kg |
| Duration | Acute testing 30 min after treatment; delayed testing 24 h later |
| Measures | Elevated plus maze (EPM), open field, acoustic startle response (ASR) |
| Topics | Psilocybin |
| Key findings | Psilocybin and norbaeocystin produced acute, dose- and sex-specific increases in anxiety-like behavior in rats: both compounds were anxiogenic in males at 0.3–1 mg/kg, while only the highest psilocybin dose increased anxiety-like behavior in females. Neither compound affected elevated plus maze behavior 24 hours later. Psilocybin's acute anxiogenic effect was independent of estrous stage, and females treated during diestrus showed some signs of greater acoustic startle habituation. |
Abstract
Abstract:
Rationale: Psychedelics are considered to be promising therapeutic agents that could effectively treat several psychological disorders. However, these compounds can exert acute adverse effects that limit their practicality.
Objectives: Across three experiments, the present study examined the acute and delayed effects of psilocybin (PSIL) and its putatively non-hallucinogenic analog, norbaeocystin (NOR), on anxiety-like behavior and the influence of the female estrous cycle on acute response to the compounds.
Methods: In Experiment 1, rats were treated with PSIL or NOR (0.3-1 mg/kg) and tested on the elevated plus maze (EPM) or open field 30 min later. In Experiment 2, male and female rats were treated with 1 mg/kg PSIL or NOR and tested on the EPM 24 h later. In Experiment 3, we tracked the female estrous cycle to determine whether it was associated with the acute effects of PSIL or NOR on EPM behavior and the acoustic startle response (ASR).
Results: In Experiment 1, both PSIL and NOR exerted acute anxiogenic effects in males, while only the highest dose of PSIL increased anxiety-like behavior in females. In Experiment 2, neither PSIL nor NOR impacted EPM behavior the next day. In Experiment 3, PSIL, but not NOR, had acute anxiogenic effects on EPM behavior, effects that were independent of estrous stage. Females treated with PSIL during diestrus exhibited some signs of greater ASR habituation.
Conclusions: PSIL and NOR exerted transient dose- and sex-specific effects on anxiety-like behavior, which may inform their use as novel therapeutics.
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 |