Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice

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dc.contributor.affiliationLaboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Colonia Huipulco, Alcaldía Tlalpan, C.P. 14370, Ciudad de México, Mexico
dc.contributor.emailalbertoh-leon@hotmail.com (A. Hernandez-Leon), rescam01@gmail.com (R.I. Escamilla-Orozco), ta260266@uaeh.edu.mx (A.R. Tabal-Robles), davmv2@gmail.com (D. Martínez-Vargas), romerob@uaeh.edu.mx (L. Romero-Bautista), gerson.escamilla.soto@gmail.com (G. Escamilla-Soto), osirissinuheg@gmail.com (O.S. González-Romero), jmartin@uaeh.edu.mx (M. Torres-Valencia), evagontru@yahoo.com.mx (M.E. González-Trujano)
dc.creatorHernandez-Leon, Alberto
dc.creatorEscamilla-Orozco, Raúl Iván
dc.creatorTabal-Robles, Aylín R.
dc.creatorMartínez-Vargas, David
dc.creatorRomero-Bautista, Leticia
dc.creatorEscamilla-Soto, Gerson
dc.creatorGonzález-Romero, Osiris S.
dc.creatorTorres-Valencia, Martín
dc.creatorGonzález-Trujano, María Eva
dc.date2024
dc.date.accessioned2026-06-22T19:24:48Z
dc.date.issued2024
dc.date.published2024
dc.descriptionEthnopharmacology relevance: Central nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits. Aim of the study: To evaluate the anxiolytic- and antidepressant-like effects, as well as the acute toxicity of P. cubensis mushroom. Material and methods: First, the acute toxicity (LD50) of P. cubensis (2000 mg/kg) was determined after the esophageal (p.o.) and intraperitoneal (i.p.) route of administration. The rota-rod test and electroencephalogram (EEG) were included to assess CNS toxicity in free moving mice. Anxiolytic (ambulatory or exploratory and rearing behaviors) and antidepressant behavioral responses were assayed in the open-field, plus-maze, and forced swimming test, respectively, after administration of 1000 mg/kg, p.o., of the whole P. cubensis mushroom or the polar aqueous (AQ) or methanolic (MeOH) extractions (1, 10, and/or 100 mg/kg, i.p.) in comparison to the reference drugs buspirone (4 mg/kg, i.p.), fluoxetine and/or imipramine (10 mg/kg, s.c. and i.p., respectively). A chemical analysis of the AQ and MeOH extractions was performed to detect psilocybin and/or psilocin by using UHPLC. Results: Neurotoxic effects of P. cubensis mushroom administered at high doses were absent in mice assessed in the rota-rod test or for EEG activity. A LD50 > 2000 mg/kg was calculated by p.o. or i.p. administration. While significant and/or dose-response antidepressant-like effects were produced with the whole P. cubensis mushroom, p.o., and after parenteral administration of the AQ or MeOH extractions resembling the effects of the reference drugs. Behavioral responses were associated with an anxiolytic-like effect in the open-field as corroborated in the plus-maze tests. The presence of psilocybin and psilocin was mainly characterized in the AQ extraction. Conclusion: Our results provide preclinical evidence of the anxiolytic- and antidepressant-like effects of the P. cubensis mushroom without producing neurotoxicity after enteral or parenteral administration, where psilocybin and psilocin were identified mainly after AQ extraction. This study reinforces the benefits of the P. cubensis mushroom in mental health and therapy for anxiety and depression.
dc.formatPDF
dc.identifierJC24NC24
dc.identifier.doi10.1016/j.jep.2023.117415
dc.identifier.eissn1872-7573
dc.identifier.issn0378-8741
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñiz
dc.identifier.placeIrlanda
dc.identifier.urihttps://repositorio.inprf.gob.mx/handle/123456789/129
dc.identifier.urihttps://doi.org/10.1016/j.jep.2023.117415
dc.language.isoeng
dc.publisherElsevier
dc.relation320:117415
dc.relation.jnabreviadoJ ETHNOPHARMACOL
dc.relation.journalJournal of Ethnopharmacology
dc.rightsAcceso Cerrado
dc.subject.kwAnxiety
dc.subject.kwDepression
dc.subject.kwMexican traditional medicine
dc.subject.kwP. cubensis mushroom
dc.subject.kwPsychedelics
dc.titleAntidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice
dc.typeArtículo

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