The Effect of Magic Mushroom ( Psilocybe azurescens ) on Social Interaction, Anxiety‐ and Depressive‐Like Behaviors in Male Rats; the Role of Neuroinflammation, Oxidative Stress, and Neurotrophic Factors
Hediye Moghadam, Parisa Akbari, Elmira Beirami, Samaneh Nabavifard, Akram Ameli, Neda Valian
Journal of Neuroscience Research 2026 DOI: 10.1002/jnr.70107 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Intervention | Psilocybe azurescens |
| Dose | 10, 100, and 250 mg/kg |
| Duration | 14 days |
| Topics | Psilocybin Anxiety |
| Keywords | Oxidative stress Neurotrophic factors Brain-derived neurotrophic factor Neurotrophin Endocrinology Amygdala Prefrontal cortex Social behavior Adverse effect Neuroinflammation Mood disorders Pharmacology Ginseng |
| Key findings | High doses of Psilocybe azurescens increased anxiety- and depressive-like behaviors and disrupted social interaction in rats, linked to increased neuroinflammation and oxidative stress and decreased neurotrophic factors. |
Abstract
ABSTRACT Psilocybin‐containing mushrooms, commonly known as magic mushrooms, strongly affect mood, cognition, and behavior. Psilocybe azurescens is a species of psilocybin mushrooms that contains the main active compounds psilocybin and psilocin. Psilocybin mushrooms have been used since ancient times to improve the quality of life. However, their adverse effects have been less studied. This study aimed to investigate, for the first time, the effect of oral consumption of P. azurescens on social behavior, anxiety‐ and depressive‐like behaviors in rats. The underlying mechanisms of these behaviors were also studied. Male Wistar rats received three doses of P. azurescens (10, 100, and 250 mg/kg) by gavage every other day for 14 days. Social interaction, anxiety‐ and depressive‐like behaviors were assessed using the three‐chamber, elevated plus maze, and forced swimming tests, respectively. Protein levels of neurotrophic (BDNF and GDNF), neuroinflammatory (IL‐6 and TNFα), and oxidative stress (ROS and SOD) factors were measured in the hippocampus, prefrontal cortex (PFC), and amygdala by ELISA technique. The results showed that P. azurescens significantly increased anxiety‐ and depressive‐like behaviors and disrupted social interaction behavior in rats. These effects were accompanied by increased neuroinflammation and oxidative stress and decreased neurotrophic factors in the hippocampus, PFC, and amygdala. This study suggests that the high doses of P. azurescens can cause mood disorders by increasing inflammatory responses and oxidative stress and decreasing the expression of neurotrophic factors.
Comparable studies
Other preclinical and animal studies on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming SAPAP3 knockout mice | 2024 | Randomized controlled trial | n = 50 |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study | |
| Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor Mice | 2024 | Experimental study |