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

📖 Top 20% JournalJan 6, 2026Journal of neuroscience research

Magic Mushroom's effects on social behavior, anxiety, and depression in male rats linked to brain inflammation, stress, and growth factors

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Abstract

Oral consumption of Psilocybe azurescens at high doses significantly increased anxiety- and depressive-like behaviors in rats.

Increased doses of P. azurescens (10, 100, and 250 mg/kg) were administered every other day for 14 days.
Social interaction, anxiety- and depressive-like behaviors were measured using established behavioral tests.
The findings indicated that high doses disrupted social behavior and increased anxiety and depressive-like behaviors.
Increased levels of neuroinflammation and oxidative stress were observed alongside decreased neurotrophic factors in brain regions measured.
These results suggest that high doses of P. azurescens may be associated with mood disorders due to inflammatory responses and oxidative stress.

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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.

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