Psilocybin enhances conditioned place preference learning in planarians.
Bart A. Ellenbroek, Beth Naylor, Jiun Youn
Behavioural Pharmacology October 13, 2026 DOI: 10.1097/fbp.0000000000000903 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled laboratory experiment (animal model) Peer reviewed |
|---|---|
| Population | Planarians (flatworms) |
| Intervention | Psilocybin |
| Dose | 5 µM |
| Duration | Single exposure, 5 days of conditioning, effects assessed at least 6 days post-administration |
| Topics | Neuroplasticity Psilocybin Serotonin |
| Keywords | Conditioned place preference Learning Planaria |
| Key findings | A single 5 µM psilocybin exposure followed by five days of light-sucrose conditioning produced a significantly greater shift in light preference in treated planarians than in controls, persisting at least six days after administration. The authors argue this supports the hypothesis that psychedelic-induced neuroplasticity operates through evolutionarily conserved serotonergic mechanisms. |
Abstract
Psilocybin has emerged as a promising therapeutic agent, with clinical benefits attributed to enhanced neuroplasticity rather than acute pharmacological effects. However, the fundamental mechanisms underlying these effects remain poorly understood. Using planarians as a model system, we investigated whether psilocybin enhances associative learning using a conditioned place preference paradigm. Following a single exposure to 5 µM psilocybin, planarians underwent 5 days of conditioning in which light was paired with sucrose. Psilocybin-treated planarians showed a significantly greater shift in light preference compared to controls (time × group × drug interaction: F(2,38) = 3.3, P < 0.05), with effects persisting at least 6 days post-administration. These findings demonstrate that psilocybin enhances appetitive associative learning in an invertebrate model, supporting the hypothesis that psychedelic-induced neuroplasticity operates through evolutionarily conserved serotonergic mechanisms.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: Serotonin Supports
A single psilocybin exposure enhanced appetitive associative learning in planarians, with effects persisting at least 6 days.
Synthesized
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
Cites 17
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
and 12 more in the library