Chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats.
Lucie Ladislavová, Viera Kútna, Kristýna Mazochová, Klára Šíchová, Hynek Danda, Eva Lhotková, Libor Uttl, Vojtěch Brejtr, Kateřina Syrová, Vladimír Mazoch, Rachel Horsley, Tomáš Páleníček
Pharmacology, biochemistry, and behavior June 30, 2026 DOI: 10.1016/j.pbb.2026.174231 via PubMed
Summary
AI-generated from the abstractChronic microdosing of psilocin (0.05 or 0.075 mg/kg) in adult male Wistar rats over five weeks did not alter locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase cell proliferation in the dentate gyrus of the hippocampus. A small anxiogenic effect was detected in the Elevated Plus Maze. The findings suggest that, under this dosing schedule, psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation.
Study at a glance
| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult male Wistar rats |
| Intervention | Psilocin |
| Dose | 0.05 or 0.075 mg/kg |
| Duration | Five weeks of microdosing on alternate days, with behavioral assessments starting after 18 days |
| Topics | Anxiety Depression |
| Keywords | Behavioral testing Hippocampal neurogenesis Psilocin microdosing |
| Key finding | Chronic psilocin microdosing did not affect locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase dentate gyrus cell proliferation, though a small anxiogenic effect was observed. |
Abstract
Psilocin (4-hydroxy-N, N-dimethyltryptamine) is a substituted tryptamine alkaloid and a nonselective serotonergic agonist acting predominantly at 5-HT2A/C receptors, with substantial binding to 5-HT1A and 5-HT2B receptors. Microdosing is the practice of taking a very small, sub-perceptual dose, typically 5% to 10% of a full recreational dose, to improve mood, creativity, and focus without hallucinogenic effects. However, rigorous preclinical evidence for its behavioral and neurobiological effects remains limited. We therefore examined whether chronic psilocin microdosing alters behavior and dentate gyrus (DG) cell proliferation in adult male Wistar rats. Psilocin was administered subcutaneously at 0.05 or 0.075 mg/kg. Animals received six doses of psilocin or saline on alternate days over 18 days prior to the first behavioral assessment, and microdosing on alternate days continued between behavioral tasks for five weeks. To minimize acute drug effects, all behavioral assessments were performed 48 h after the preceding dose. Animals were tested sequentially in the Elevated Plus Maze, Hole-Board, Open Field, Social Interaction, and modified Forced Swim Test, with six-day intervals between tests. DG cell proliferation was quantified by BrdU and Ki-67 immunohistochemistry. Across this regimen, psilocin microdosing did not measurably affect locomotor activity, depressive-like behavior, sociability, or novelty seeking, and it did not increase DG proliferation by either marker. A small anxiogenic effect was detected in the Elevated Plus Maze. These data indicate that, under the present dosing schedule and endpoints, chronic psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation in rats.