Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms.

Razeen J. Akbar; Amy D. Stringer; Sonita Wiah; Meghana Dachepalli; Stephanie E. Daws; Saadet Inan; Scott M. Rawls

doi:10.1097/fbp.0000000000000879

Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms.

Razeen J. Akbar, Amy D. Stringer, Sonita Wiah, Meghana Dachepalli, Stephanie E. Daws, Saadet Inan, Scott M. Rawls

Behavioural Pharmacology July 1, 2026 DOI: 10.1097/fbp.0000000000000879 (opens in new tab)

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Study at a glance

AI-extracted from the abstract

Characteristics	Experimental animal study Peer reviewed
Population	Planarians (Dugesia dorotocephala)
Interventions	Psilocybin Volinanserin
Dose	Psilocybin: 0.01, 0.1, 1, and 10 nM; volinanserin: 1, 10, and 100 nM
Topics	Psilocybin Serotonin
Keywords	Animals Planarians Hallucinogens Stereotyped behavior Dose-response relationship, drug Phototaxis Invertebrate Anxiolytic Psychedelic
Key findings	Psilocybin increased stereotyped movements and reduced motility at higher concentrations, and at very low concentrations decreased defensive responding in planarians. The 5-HT2A antagonist volinanserin reduced psilocybin-evoked stereotypies and prevented the reduction in defensive responding, which the authors argue suggests conservation of certain aspects of psilocybin pharmacology via 5-HT2A receptor mechanisms.

Abstract

Psilocybin is a serotonergic 5-HT 2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [5-HT]) system. We quantified stereotyped movements (e.g. head bops, twists, scrunches, and C-shapes) and defensive responding (negative phototaxis) and probed a 5-HT 2A R mechanism for psilocybin using a selective 5-HT 2A R antagonist (volinanserin). Psilocybin (0.01, 0.1, 1, and 10 nM) increased all stereotyped movements and, at higher concentrations, reduced motility. Volinanserin (1, 10, and 100 nM) did not induce any stereotyped movements or reduce motility. For combination experiments, volinanserin reduced cumulative stereotyped movements produced by psilocybin (0.01 nM) and specifically reduced psilocybin-evoked twists and head bops. Concentrations (<0.01 nM) of psilocybin that did not significantly reduce motility decreased defensive responding (i.e. increased time spent in light side of Petri dish). The reduction in defensive responding by psilocybin (0.01 nM) was prevented by volinanserin (100 nM). Our results show that psilocybin induces stereotypies and anxiolytic-like effects in planarians, likely through mechanisms involving 5-HT 2A R, and suggest conservation of certain aspects of psilocybin pharmacology.

Comparable studies

Other preclinical and animal studies on psilocybin, most cited first.

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Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice	2021	Observational cohort
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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 1

Psilocybin enhances conditioned place preference learning in planarians. Behavioural Pharmacology October 13, 2026

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