INTRODUCTION: Psilocybin, a member of the serotonergic psychedelic class, is currently attracting interest due to its suggested therapeutic effects on anxiety and mood disorders. An alternative to clinically effective single doses of psychedelics is the use of small doses (a one-tenth of the therapeutic one) administered over a longer period of time, so called "microdoses". Microdosing can provide therapeutic benefits, but with a low risk of adverse effects, such as hallucinations or perceptual distortions.

AIM(S): This study aimed to investigate the effectiveness of psilocybin microdosing on rat behaviour and oxidative DNA damage in the rat brain.

METHOD(S): Psilocybin at a dose of 0.06 mg/kg (sc) was administered to adult Wistar-Han rats for 2 weeks at 2-day intervals. Two days after drug termination several behavioral tests such as the Wet Dog Shakes test (WDS), the Elevated Plus Maze test (EPM) and the Light/Dark Box test (LDB), the Open Field Test (OF) and the Novel Object Recognition test (NOR) were performed. In addition, comet assay in the nuclear fraction obtained from the frontal cortex and hippocampus of rats was carried out.

RESULTS: Psilocybin induced a mild but significant hallucinogenic effect in the WDS test, demonstrated an anxiolytic effect in the EPM, but not in the LDB test. A small but statistically significant increase in motor activity and compulsive behavior in the OF test was observed. Furthermore, increased exploration of the illuminated central zone of the OF and no effect in the cognitive functions in the NOR test was obtained. Any oxidative damage of DNA was noted in the nuclear fractions of the frontal cortex and hippocampus of rats.

CONCLUSIONS: Results of our study indicate that psilocybin administered in a microdosing regimen may have a beneficial effect on the level of anxiety and exploratory activity of animals, does not cause the damage of genetic material, but induces psychotomimetic effect.

FINANCIAL SUPPORT: This research was funded by statutory funds of the Maj Institute of Pharmacology, Polish Academy of Sciences.