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
May 20, 2021
Rebeca Dı́ez-alarcia, Carolina Muguruza, Guadalupe Rivero et al.
27 citations
Serotonin 5-HT2A receptor density in the prefrontal cortex of people with schizophrenia depends on which radiotracer is used to measure it, because different tracers bind different receptor conformations. Using the inverse agonist [18F]altanserin, receptor density appeared decreased; using the agonist [3H]LSD, it appeared increased; and using the antagonist [3H]MDL100907, it was unchanged. These differences were more pronounced in schizophrenia subjects who were antipsychotic-free at death. The findings suggest a shift toward the active functional conformation of the 5-HT2A receptor in schizophrenia, consistent with increased cortical serotonin 2A receptor activity.
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.
Translational Psychiatry
July 16, 2026
Celia Martín-Cuevas, Víctor Darío Ramos‐Herrero, Álvaro Flores‐Martínez et al.
A dual-hit mouse model combining prenatal immune activation with adolescent THC exposure produces schizophrenia-relevant behavioral and brain changes, particularly in males. Social deficits and repetitive behaviors emerged, along with reduced cortical thickness and decreased dendritic spine density in the prefrontal cortex and hippocampus. Reelin signaling pathway alterations occurred in a sex-dependent manner: males showed reduced Reelin levels mainly after THC exposure alone, while females had general reductions across treatment groups. The number of Reelin-positive cells also decreased. Adolescent THC exposure appears to be a major driver of Reelin alterations, with prenatal immune activation potentially modulating this effect. The findings highlight complex, domain-specific interactions between environmental risk factors in schizophrenia-related processes.