Psilocibina: Explorando su potencial de reversión de las alteraciones neurofuncionais promovidas pelo Transtorno Depresivo Mayor

Autores/as

DOI:

https://doi.org/10.33448/rsd-v13i5.44891

Palabras clave:

Psilocibina; Uso terapéutico; Depresión.

Resumen

Introducción: El Trastorno Depresivo Mayor (TDM) afecta globalmente a alrededor del 5% de la población, con una etiología compleja que involucra interacciones entre el cerebro, la mente y el medio ambiente. Alrededor del 50% de los casos no responden al tratamiento farmacológico estándar, lo que pone de relieve la necesidad de enfoques terapéuticos innovadores. Objetivo: Este trabajo tiene como objetivo explorar el potencial terapéutico de la psilocibina en el trastorno depresivo mayor, analizando su interacción con los receptores serotoninérgicos e investigando los efectos de la sustancia sobre la conectividad cerebral. Metodología: Se trata de una revisión narrativa de la literatura, buscando artículos en la base de datos Pubmed. La selección consideró criterios de inclusión, resultando una muestra de artículos relevantes para el análisis. Resultados y Discusión: Los resultados revelan que el psilocibina, un agonista serotoninérgico, induce efectos terapéuticos rápidos y duraderos, modulando receptores como el 5-HT2AR. La sustancia promueve la neuroplasticidad, mejora la conectividad cerebral y reduce los síntomas depresivos. Conclusión: La eficacia de la psilocibina en el tratamiento de la depresión apunta a una comprensión innovadora de los mecanismos neurobiológicos. Su capacidad para inducir neuroplasticidad sugiere implicaciones prometedoras, destacando la seguridad de la combinación con terapias tradicionales.

Citas

Alonso, J. F., Romero, S., Mañanas, M. À., & Riba, J. (2015). Serotonergic psychedelics temporarily modify information transfer in humans. The International Journal of Neuropsychopharmacology, 18(8), pyv039. https://doi.org/10.1093/ijnp/pyv039

Andrade, M. C. R. (2021). O papel das revisões de literatura na produção e síntese do conhecimento científico em Psicologia. Gerais: Revista Interinstitucional de Psicologia, 14(SPE), 1–5. https://doi.org/10.36298/gerais202114e23310

Barnett, L., Muthukumaraswamy, S. D., Carhart-Harris, R. L., & Seth, A. K. (2020). Decreased directed functional connectivity in the psychedelic state. NeuroImage, 209, 116462. https://doi.org/10.1016/j.neuroimage.2019.116462

Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., & Griffiths, R. R. (2020). Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports, 10(1), 2214. https://doi.org/10.1038/s41598-020-59282-y

Becker, A. M., Holze, F., Grandinetti, T., Klaiber, A., Toedtli, V. E., Kolaczynska, K. E., Duthaler, U., Varghese, N., Eckert, A., Grünblatt, E., & Liechti, M. E. (2022). Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clinical Pharmacology and Therapeutics, 111(4), 886–895. https://doi.org/10.1002/cpt.2487

Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C. R., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology (Oxford, England), 29(3), 289–299. https://doi.org/10.1177/0269881114565144

Boulougouris, V., Glennon, J. C., & Robbins, T. W. (2008). Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 33(8), 2007–2019. https://doi.org/10.1038/sj.npp.1301584

Bouso, J. C., Palhano-Fontes, F., Rodríguez-Fornells, A., Ribeiro, S., Sanches, R., Crippa, J. A. S., Hallak, J. E. C., de Araujo, D. B., & Riba, J. (2015). Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 25(4), 483–492. https://doi.org/10.1016/j.euroneuro.2015.01.008

Brys, I., Barrientos, S. A., Ward, J. E., Wallander, J., Petersson, P., & Halje, P. (2023). 5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system. Communications Biology, 6(1), 737. https://doi.org/10.1038/s42003-023-05093-6

Buchborn, T., Schröder, H., Höllt, V., & Grecksch, G. (2014). Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling. Journal of Psychopharmacology (Oxford, England), 28(6), 545–552. https://doi.org/10.1177/0269881114531666

Cai, H., Zhu, J., & Yu, Y. (2020). Robust prediction of individual personality from brain functional connectome. Social Cognitive and Affective Neuroscience, 15(3), 359–369. https://doi.org/10.1093/scan/nsaa044

Calder, A. E., & Hasler, G. (2023). Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology, 48(1), Artigo 1. https://doi.org/10.1038/s41386-022-01389-z

Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., Tyacke, R. J., Leech, R., Malizia, A. L., Murphy, K., Hobden, P., Evans, J., Feilding, A., Wise, R. G., & Nutt, D. J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences of the United States of America, 109(6), 2138–2143. https://doi.org/10.1073/pnas.1119598109

Carhart-Harris, R. L., & Friston, K. J. (2010). The default-mode, ego-functions and free-energy: A neurobiological account of Freudian ideas. Brain: A Journal of Neurology, 133(Pt 4), 1265–1283. https://doi.org/10.1093/brain/awq010

Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.328

Doss, M. K., Považan, M., Rosenberg, M. D., Sepeda, N. D., Davis, A. K., Finan, P. H., Smith, G. S., Pekar, J. J., Barker, P. B., Griffiths, R. R., & Barrett, F. S. (2021). Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry, 11(1), 574. https://doi.org/10.1038/s41398-021-01706-y

Effinger, D. P., Quadir, S. G., Ramage, M. C., Cone, M. G., & Herman, M. A. (2023). Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding. Translational Psychiatry, 13(1), 119. https://doi.org/10.1038/s41398-023-02414-5

Ekins, T. G., Brooks, I., Kailasa, S., Rybicki-Kler, C., Jedrasiak-Cape, I., Donoho, E., Mashour, G. A., Rech, J., & Ahmed, O. J. (2023). Cellular rules underlying psychedelic control of prefrontal pyramidal neurons. bioRxiv: The Preprint Server for Biology, 2023.10.20.563334. https://doi.org/10.1101/2023.10.20.563334

Erkizia-Santamaría, I., Alles-Pascual, R., Horrillo, I., Meana, J. J., & Ortega, J. E. (2022). Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response. Biomedicine & Pharmacotherapy, 154, 113612. https://doi.org/10.1016/j.biopha.2022.113612

Fisher, P. M., & Hariri, A. R. (2012). Linking variability in brain chemistry and circuit function through multimodal human neuroimaging. Genes, Brain, and Behavior, 11(6), 633–642. https://doi.org/10.1111/j.1601-183X.2012.00786.x

Fullana, M. N., Ruiz-Bronchal, E., Ferrés-Coy, A., Juárez-Escoto, E., Artigas, F., & Bortolozzi, A. (2019). Regionally selective knockdown of astroglial glutamate transporters in infralimbic cortex induces a depressive phenotype in mice. Glia, 67(6), 1122–1137. https://doi.org/10.1002/glia.23593

González-Arias, C., Sánchez-Ruiz, A., Esparza, J., Sánchez-Puelles, C., Arancibia, L., Ramírez-Franco, J., Gobbo, D., Kirchhoff, F., & Perea, G. (2023). Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states. Molecular Psychiatry, 28(9), 3856–3873. https://doi.org/10.1038/s41380-023-02269-8

González-Maeso, J., Weisstaub, N. V., Zhou, M., Chan, P., Ivic, L., Ang, R., Lira, A., Bradley-Moore, M., Ge, Y., Zhou, Q., Sealfon, S. C., & Gingrich, J. A. (2007). Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior. Neuron, 53(3), 439–452. https://doi.org/10.1016/j.neuron.2007.01.008

Goodwin, G. M., Aaronson, S. T., Alvarez, O., Atli, M., Bennett, J. C., Croal, M., DeBattista, C., Dunlop, B. W., Feifel, D., Hellerstein, D. J., Husain, M. I., Kelly, J. R., Lennard-Jones, M. R., Licht, R. W., Marwood, L., Mistry, S., Páleníček, T., Redjep, O., Repantis, D., & Malievskaia, E. (2023). Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life. Journal of Affective Disorders, 327, 120–127. https://doi.org/10.1016/j.jad.2023.01.108

Goodwin, G. M., Croal, M., Feifel, D., Kelly, J. R., Marwood, L., Mistry, S., O’Keane, V., Peck, S. K., Simmons, H., Sisa, C., Stansfield, S. C., Tsai, J., Williams, S., & Malievskaia, E. (2023). Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 48(10), 1492–1499. https://doi.org/10.1038/s41386-023-01648-7

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology (Oxford, England), 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513

Grimm, O., Kraehenmann, R., Preller, K. H., Seifritz, E., & Vollenweider, F. X. (2018). Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 28(6), 691–700. https://doi.org/10.1016/j.euroneuro.2018.03.016

Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology (Oxford, England), 36(2), 151–158. https://doi.org/10.1177/02698811211073759

Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. The American Journal of Drug and Alcohol Abuse, 43(1), 55–60. https://doi.org/10.3109/00952990.2016.1170135

Kaare, M., Jayaram, M., Jagomäe, T., Singh, K., Kilk, K., Leevik, M., Varul, J., Leidmaa, E., Visnapuu, T., Nõmm, H., Rähn, K., Plaas, M., Lilleväli, K., Schäfer, M. K. E., Philips, M. A., & Vasar, E. (2022). Depression-associated Negr1 gene-deficiency induces alterations in the monoaminergic neurotransmission enhancing time-dependent sensitization to amphetamine in mice. Neuroscience Applied, 1, 100646. https://doi.org/10.1016/j.nsa.2022.100646

Karaki, S., Becamel, C., Murat, S., Mannoury la Cour, C., Millan, M. J., Prézeau, L., Bockaert, J., Marin, P., & Vandermoere, F. (2014). Quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2A receptor at Ser280 by hallucinogenic versus nonhallucinogenic agonists. Molecular & Cellular Proteomics: MCP, 13(5), 1273–1285. https://doi.org/10.1074/mcp.M113.036558

Kelly, J. R., Baker, A., Babiker, M., Burke, L., Brennan, C., & O’Keane, V. (2022). The psychedelic renaissance: The next trip for psychiatry? Irish Journal of Psychological Medicine, 39(4), 335–339. https://doi.org/10.1017/ipm.2019.39

Lebedev, A. V., Lövdén, M., Rosenthal, G., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2015). Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin. Human Brain Mapping, 36(8), 3137–3153. https://doi.org/10.1002/hbm.22833

Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Zarandi, S. S., Sood, A., Paddy, M. R., Duim, W. C., Dennis, M. Y., McAllister, A. K., Ori-McKenney, K. M., Gray, J. A., & Olson, D. E. (2018). Psychedelics Promote Structural and Functional Neural Plasticity. Cell reports, 23(11), 3170–3182. https://doi.org/10.1016/j.celrep.2018.05.022

Madsen, M. K., Stenbæk, D. S., Arvidsson, A., Armand, S., Marstrand-Joergensen, M. R., Johansen, S. S., Linnet, K., Ozenne, B., Knudsen, G. M., & Fisher, P. M. (2021). Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience. European Neuropsychopharmacology, 50, 121–132. https://doi.org/10.1016/j.euroneuro.2021.06.001

Mason, N. L., Kuypers, K. P. C., Müller, F., Reckweg, J., Tse, D. H. Y., Toennes, S. W., Hutten, N. R. P. W., Jansen, J. F. A., Stiers, P., Feilding, A., & Ramaekers, J. G. (2020). Me, myself, bye: Regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 45(12), 2003–2011. https://doi.org/10.1038/s41386-020-0718-8

Mertens, L. J., Wall, M. B., Roseman, L., Demetriou, L., Nutt, D. J., & Carhart-Harris, R. L. (2020). Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. Journal of Psychopharmacology (Oxford, England), 34(2), 167–180. https://doi.org/10.1177/0269881119895520

Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V., Biojone, C., Enkavi, G., Antenucci, L., Kot, E. F., Goncharuk, S. A., Kaurinkoski, K., Kuutti, M., Fred, S. M., Elsilä, L. V., Sakson, S., Cannarozzo, C., Diniz, C. R. A. F., Seiffert, N., Rubiolo, A., Haapaniemi, H., … Castrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature Neuroscience, 26(6), 1032–1041. https://doi.org/10.1038/s41593-023-01316-5

Nikolič, M., Viktorin, V., Zach, P., Tylš, F., Dudysová, D., Janků, K., Kopřivová, J., Kuchař, M., Brunovský, M., Horáček, J., & Páleníček, T. (2023). Psilocybin intoxication did not affect daytime or sleep-related declarative memory consolidation in a small sample exploratory analysis. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 74, 78–88. https://doi.org/10.1016/j.euroneuro.2023.04.019

Rizzolatti, G., Semi, A. A., & Fabbri-Destro, M. (2014). Linking psychoanalysis with neuroscience: The concept of ego. Neuropsychologia, 55, 143–148. https://doi.org/10.1016/j.neuropsychologia.2013.10.003

Rother, E. T. (2007). Revisão sistemática X revisão narrativa. Acta Paulista de Enfermagem, 20, v–vi. https://doi.org/10.1590/S0103-21002007000200001

Siegel, J. S., Subramanian, S., Perry, D., Kay, B., Gordon, E., Laumann, T., Reneau, R., Gratton, C., Horan, C., Metcalf, N., Chacko, R., Schweiger, J., Wong, D., Bender, D., Padawer-Curry, J., Raison, C., Raichle, M., Lenze, E. J., Snyder, A. Z., … Nicol, G. (2023). Psilocybin desynchronizes brain networks. medRxiv: The Preprint Server for Health Sciences, 2023.08.22.23294131. https://doi.org/10.1101/2023.08.22.23294131

Skosnik, P. D., Sloshower, J., Safi-Aghdam, H., Pathania, S., Syed, S., Pittman, B., & D’Souza, D. C. (2023). Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms. Journal of Psychopharmacology (Oxford, England), 37(7), 687–697. https://doi.org/10.1177/02698811231179800

Smigielski, L., Scheidegger, M., Kometer, M., & Vollenweider, F. X. (2019). Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. NeuroImage, 196, 207–215. https://doi.org/10.1016/j.neuroimage.2019.04.009

Sun, J., Ma, Y., Guo, C., Du, Z., Chen, L., Wang, Z., Li, X., Xu, K., Luo, Y., Hong, Y., Yu, X., Xiao, X., Fang, J., & Lu, J. (2023). Distinct patterns of functional brain network integration between treatment-resistant depression and non treatment-resistant depression: A resting-state functional magnetic resonance imaging study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 120, 110621. https://doi.org/10.1016/j.pnpbp.2022.110621

Thomas, P. J., Leow, A., Klumpp, H., Phan, K. L., & Ajilore, O. (2023). Default Mode Network Hypoalignment of Function to Structure Correlates With Depression and Rumination. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. https://doi.org/10.1016/j.bpsc.2023.06.008

Vancappel, A., Dansou, Y., Godin, O., Haffen, E., Yrondi, A., Stéphan, F., Richieri, R., Molière, F., Horn, M., Allauze, E., Genty, J., Bouvard, A., Dorey, J., Meyrel, M., Camus, V., Fond, G., Péran, B., Walter, M., Anguill, L., … El-Hage, W. (2021). Cognitive impairments in treatment-resistant depression: Results from the French cohort of outpatients (FACE-DR). Journal of Affective Disorders Reports, 6, 100272. https://doi.org/10.1016/j.jadr.2021.100272

Vosgerau, D. S. R., & Romanowski, J. P. (2014). Estudos de revisão: Implicações conceituais e metodológicas. Revista Diálogo Educacional, 14(41), 165–190.

Wang, Q.-S., Tian, J.-S., Cui, Y.-L., & Gao, S. (2014). Genipin is active via modulating monoaminergic transmission and levels of brain-derived neurotrophic factor (BDNF) in rat model of depression. Neuroscience, 275, 365–373. https://doi.org/10.1016/j.neuroscience.2014.06.032

World Health Organization. (2023, março 31). Depressive disorder (depression). https://www.who.int/news-room/fact-sheets/detail/depression

Descargas

Publicado

11/05/2024

Cómo citar

MENDES, L. F. da S. .; LEAL, A. K. M. P. .; BILIBIO, M. R. B. .; BRITO, S. R. S. .; NORONHA, M. Y. de C. .; MOURA, P. R. de S. e S. .; ARAÚJO JUNIOR, S. J. F. .; DIAS, J. O. R. . Psilocibina: Explorando su potencial de reversión de las alteraciones neurofuncionais promovidas pelo Transtorno Depresivo Mayor. Research, Society and Development, [S. l.], v. 13, n. 5, p. e4113544891, 2024. DOI: 10.33448/rsd-v13i5.44891. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/44891. Acesso em: 6 ene. 2025.

Número

Vol. 13 Núm. 5

Sección

Ciencias de la salud

Licencia

Derechos de autor 2024 Lucas Ferrari da Silva Mendes; Anne Kaline Marques Portela Leal; Mauro Ricardo Barros Bilibio; Silana Rosa Soares Brito; Maria Yasmin de Carvalho Noronha; Paulo Ricardo de Sousa e Silva Moura; Stanley Janary Ferreira Araújo Junior; João Otávio Rodrigues Dias

Creative Commons License

Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.

Los autores que publican en esta revista concuerdan con los siguientes términos:

1) Los autores mantienen los derechos de autor y conceden a la revista el derecho de primera publicación, con el trabajo simultáneamente licenciado bajo la Licencia Creative Commons Attribution que permite el compartir el trabajo con reconocimiento de la autoría y publicación inicial en esta revista.

2) Los autores tienen autorización para asumir contratos adicionales por separado, para distribución no exclusiva de la versión del trabajo publicada en esta revista (por ejemplo, publicar en repositorio institucional o como capítulo de libro), con reconocimiento de autoría y publicación inicial en esta revista.

3) Los autores tienen permiso y son estimulados a publicar y distribuir su trabajo en línea (por ejemplo, en repositorios institucionales o en su página personal) a cualquier punto antes o durante el proceso editorial, ya que esto puede generar cambios productivos, así como aumentar el impacto y la cita del trabajo publicado.