The effect of low-dose psilocybin on brain neurotransmission and rat behavior.
Agnieszka Bysiek, Adam Wojtas, Izabela Szpręgiel, Agnieszka Wawrzczak-Bargieła, Marzena Maćkowiak, Krystyna Gołembiowska
Progress in Neuro-Psychopharmacology and Biological Psychiatry April 2, 2025 DOI: 10.1016/j.pnpbp.2025.111347 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Freely moving rats |
| Intervention | Psilocybin |
| Dose | 0.1, 0.3 and 0.6 mg/kg |
| Topics | Psilocybin |
| Keywords | Behavior Dna damage Hpa axis Neurotransmitter release Neuroscience brain chemistry Psilocybin research psychedelics Hallucinogens Neurotransmitters Neural pathways Microdosing sub-per |
| Citations | 10 |
| Key points | Low doses of psilocybin (0.1–0.6 mg/kg) increased aminergic neurotransmitter release in the frontal cortex, had anxiolytic effects, and did not cause hallucinogenic behavior or DNA damage in rats. |
Abstract
Psilocybin has various therapeutic effects in mental and psychological disorders, including depression and mood disorders, obsessive-compulsive disorders, substance addiction and anxiety. Pharmacodynamic properties of psilocybin depend on doses used and time after administration. The psilocybin dose range varies depending on whether it is used therapeutically or for recreational purposes in humans, but most animal studies require larger doses to induce an effect on brain neurotransmission and animal behavior. The aim of this study was to investigate the effect of psilocybin on the release of cortical neurotransmitters and rat behavior when it was administered subcutaneously at doses of 0.1, 0.3 and 0.6 mg/kg. Psilocybin affected the release of dopamine, noradrenaline, serotonin and acetylcholine in the frontal cortex as measured by microdialysis in freely moving rats. Psilocybin increased the release of aminergic transmitters in a non-linear manner with the dose of 0.3 mg/kg being the weakest. Psilocybin also increased the release of γ-aminobutyric acid, but glutamate release was enhanced only for the first 2 h after drug injection and was followed by a decrease for the rest of the experimental period. In contrast to 25I-NBOMe, an agonist of 5-HT2A receptors, psilocybin did not produce hallucinogenic activity expressed as wet dog shakes and did not disrupt sensorimotor gating in the acoustic startle response test. Furthermore, psilocybin showed anxiolytic effect in the light dark box test 1 h after administration. It also modulated the hypothalamic-pituitary-adrenal axis activity as it transiently increased serum corticosterone level, decreased serotonin, but increased dopamine turnover rates in the hypothalamus and inhibited the content of noradrenaline and adrenaline in the adrenal glands. The changes in the neurotransmitter release seem to play a role in psilocybin behavioral effects. The lack of hallucinogenic activity and disruptive effect on sensorimotor gating by psilocybin lower doses indicates that psychotomimetic effects did not occur. Psilocybin in contrast to 25I-NBOMe, ketamine and MDMA did not produce oxidative damage of DNA in the frontal cortex and hippocampus. Thus, the single low doses of psilocybin may have some beneficial properties and fewer harmful effects.
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 11
- Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway Neuropsychopharmacology February 13, 2026
- The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior. Pharmacological Reports February 1, 2026
- Psilocybin, From Ancestral Use to Therapeutic Potential: A Multidimensional Review of Its Pharmacological Basis and Current Perspectives Human Psychopharmacology: Clinical and Experimental September 1, 2026
- Long- term administration of low doses of psilocybin causes epigenetic changes in the rat medial prefrontal cortex Psychopharmacology July 28, 2026
- Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms. Behavioural Pharmacology July 1, 2026
and 6 more in the library
Cites 48
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- The pharmacology of psilocybin Addiction Biology October 1, 2002
and 43 more in the library