Biomedicine & Pharmacotherapy
August 29, 2022
Ines Erkizia-Santamaría, R. Alles-Pascual, Igor Horrillo et al.
108 citations
Psilocybin, a psychedelic drug that activates the 5-HT2A receptor, shows potential for treating neuropsychiatric diseases. In mice, psilocin (the active metabolite) binds with similar affinity to 5-HT2A, 5-HT2C, and 5-HT1A receptors. Psilocybin causes a dose-dependent head-twitch response, a sign of psychosis-like effects, which is blocked by a 5-HT2A antagonist but increased by a 5-HT2C antagonist. Body temperature rises at low doses but falls at higher doses; a 5-HT1A antagonist reverses this drop, causing hyperthermia. These findings clarify the roles of specific serotonin receptors in psilocybin's acute effects, aiding understanding of its therapeutic and side effects.
Translational Psychiatry
June 14, 2025
Ines Erkizia-Santamaría, Igor Horrillo, Nerea Martínez-Álvarez et al.
16 citations
In a mouse model of chronic unpredictable mild stress, two doses of psilocybin (1 mg/kg, given 7 days apart) reversed stress-induced anhedonia and behavioral despair, but not apathy-related behavior. Psilocybin also produced an anxiolytic-like effect. However, it did not reverse stress-induced physiological signs of a hyperactive HPA axis or restore decreased brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Psilocybin increased expression and function of serotonin-2A receptors in the cortex of both control and stressed mice, and selectively increased glucocorticoid receptor expression in the cortex of stressed mice. These findings suggest psilocybin can rescue certain depressive and anxiety-like behaviors without normalizing all stress-related physiological or neuroplasticity impairments.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
January 1, 2025
Ines Erkizia-Santamaría, Igor Horrillo, J. Javier Meana et al.
10 citations
Psilocybin, along with its active metabolite psilocin, shows promise as a treatment for neuropsychiatric disorders. Clinical trials report that psilocybin produces a large, rapid, and lasting improvement in symptoms of depression and anxiety, with a favorable safety profile of low toxicity and good tolerance. Preclinical studies in naïve animals and animal models of disease have yielded somewhat discrepant results in standard tests for depression- and anxiety-like behavior, but overall suggest positive outcomes. This review provides an overview of clinical trials of psilocybin-assisted psychotherapy and surveys up-to-date preclinical research, including rodent models used to study the neurobiological and behavioral actions of psilocybin and its primary molecular target, the serotonin 2A receptor.
The International Journal of Neuropsychopharmacology
May 25, 2025
Ines Erkizia-Santamaría, Nerea Martínez-Álvarez, Leyre Salinas-Novoa et al.
7 citations
The intensity of acute psychedelic effects from psilocybin is inversely related to cortical serotonin levels. In mice, the head-twitch response—a behavioral measure of psychedelic-like effects—was lower in animals lacking the serotonin 2A receptor and was dose-dependently reduced by the antidepressant citalopram, which increases synaptic serotonin. Conversely, depleting serotonin with p-chlorophenylalanine potentiated the response. A serotonin 1A receptor agonist also decreased the response, indicating functional interaction between receptor types. These findings suggest that prior antidepressant treatment may influence individual variability in acute responses to psilocybin, with implications for optimizing psychedelic-based therapies.