Fármacos enteógenos y la depresión resistente al tratamiento: Una revisión narrativa

• Autores: Andrea Herrera Solís, Jacqueline Cortés Morelos, Alejandra E. Ruiz Contreras, Mónica Méndez Díaz, Alette Ortega Gómez, Oscar E. Prospéro García
• Localización: PSICUMEX, ISSN-e 2007-5936, Nº. 14, 2024 (Ejemplar dedicado a: Psicumex Journal (January - December 2024)), págs. 1-34
• Idioma: español
• DOI: 10.36793/psicumex.v14i1.628
• Títulos paralelos:
  • Entheogenic Drugs and Treatment-Resistant Depression: A Narrative Review
• Enlaces
  • Texto completo
• Resumen
  • español

    Los enteógenos han surgido en la investigación clínica como un tratamiento alternativo para la Depresión Resistente al Tratamiento (DRT). Tienen efectos antidepresivos rápidos y duraderos, son ansiolíticos, y mitigan la ideación suicida. Además, inducen emociones positivas y provocan experiencias místicas o espirituales, atributos que pueden contribuir a su eficacia terapéutica, dada la influencia protectora del misticismo y la religiosidad contra la depresión. Esta revisión narrativa tiene como objetivo discutir la evidencia existente sobre la utilización de enteógenos en la DRT, proporcionar una comprensión actualizada del panorama de la investigación y discutir los mecanismos de acción de compuestos como la psilocibina, DMT, LSD, ketamina, esketamina y cannabinoides. La eficacia de los enteógenos en el manejo de la depresión ha sido validada consistentemente en los ensayos clínicos. No obstante, es imperativo reconocer nuestra limitada comprensión de los posibles efectos adversos, especialmente a largo plazo, a pesar de los datos que sustentan su tolerabilidad aguda.

  • English

    Entheogens have emerged in clinical research as an alternative pharmacological solution for Treatment-Resistant Depression (TRD) because they possess rapid and enduring antidepressant and anxiolytic effects and mitigate suicidal ideation. Furthermore, they induce positive emotions and elicit mystical or spiritual experiences, attributes that may contribute to their therapeutic efficacy, given the protective influence of mysticism and religiosity against depression. This narrative review aims to discuss the extant evidence concerning the utilization of entheogens in TRD, provide an up-to-date understanding of the research landscape and to elucidate the mechanisms of action of compounds such as psilocybin, DMT, LSD, ketamine, esketamine, and cannabinoids. The effectiveness of entheogens in the management of depression has been consistently validated in clinical trials. Nonetheless, it is imperative to recognize our limited understanding of potential adverse effects, particularly in the long term, despite data supporting its acute tolerability.

• Referencias bibliográficas
  • Aaronson, B. S., & Osmond, H. (1970). Psychedelics: the Uses and Implications of Hallucinogenic Drugs. (Vol. VII). Anchor Books.
  • Aghajanian, G. K., & Marek, G. J. (1999). Serotonin and Hallucinogens. Neuropsychopharmacology, 21(2 Suppl.), 16S-23S. https://doi.org/10.1016/S0893-133X(98)00135-3
  • American Psychiatric Association. (2013). DSM-5 : Diagnostic and Statistical Manual of Mental Disorders (5th ed.). American Psychiatric Publishing.
  • Andrews, C. N., Rehak, R., Woo, M., Walker, I., Ma, C., Forbes, N., Rittenbach, K., Hathaway, J., Wilsack, L., Liu, A., Nasser, Y., &...
  • Baca García, E. y Aroca, F. (2014). Factores de riesgo de la conducta suicida asociados a trastornos depresivos y ansiedad. Salud Mental,...
  • Barnby, J. M., Bailey, N. W., Chambers, R., & Fitzgerald, P. B. (2015). How Similar are the Changes in Neural Activity Resulting from...
  • Beal, J. E., Olson, R., Laubenstein, L., Morales, J. O., Bellman, P., Yangco, B., Lefkowitz, L., Plasse, T., & Shepard, K. V. (1995)....
  • Bell, A. D., MacCallum, C., Margolese, S., Walsh, Z., Wright, P., Daeninck, P. J., Lacasse, G., Kaur, J., de Freitas, L., St. Pierre, M.,...
  • Bhaskar, A., Bell, A., Boivin, M., Briques, W., Brown, M., Clarke, H., Cyr, C., Eisenberg, E., de Oliveira Silva, R., Frohlich, E., Georgius,...
  • Boyaji, S., Merkow, J., Elman, R. N. M., Kaye, A. D., Yong, R. J., & Urman, R. D. (2020). The Role of Cannabidiol (CBD) in Chronic Pain...
  • Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN...
  • Carbonaro, T. M., & Gatch, M. B. (2016). Neuropharmacology of N,N-dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74-88. https://doi.org/10.1016/j.brainresbull.2016.04.016
  • Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D., &...
  • Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., . . . & Nutt, D. J. (2016). Psilocybin with Psychological...
  • Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., . . . & Nutt, D. J. (2017). Psilocybin...
  • Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., . . . & Nutt, D. J. (2018). Psilocybin with...
  • Carod-Artal, F. J. (2015). Hallucinogenic Drugs in Pre-Columbian Mesoamerican Cultures. Neurología, 30(1), 42-49. https://doi.org/10.1016/j.nrl.2011.07.003
  • Cavenaghi, V. B., da Costa, L. P., Lacerda, A. L. T., Hirata, E. S., Miguel, E. C., & Fraguas, R. (2021). Subcutaneous Ketamine in Depression:...
  • Chen, C., & Nakagawa, S. (2023). Recent Advances in the Study of the Neurobiological Mechanisms Behind the Effects of Physical Activity...
  • https://doi.org/10.17219/acem/171565
  • Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., . . . & Geddes, J. R. (2018). Comparative Efficacy...
  • Comings, D. E. (2010). The Neurobiology, Genetics and Evolution of Human Spirituality: The Central Role of the Temporal Lobes. NeuroQuantology,...
  • Comings, D. E., Gonzales, N., Saucier, G., Johnson, J. P., & MacMurray, J. P. (2000). The DRD4 Gene and the Spiritual Transcendence Scale...
  • Daly, E. J., Turkoz, I., Salvadore, G., Fedgchin, M., Ionescu, D. F., Starr, H. L., . . . & Singh, J. B. (2021). The Effect of Esketamine...
  • Darquennes, G., Wacquier, B., Loas, G., & Hein, M. (2023). Suicidal Ideations in Major Depressed Subjects: Role of the Temporal Dynamics...
  • Dominguez-Clave, E., Soler, J., Elices, M., Pascual, J. C., Alvarez, E., de la Fuente Revenga, M., . . . & Riba, J. (2016). Ayahuasca:...
  • Dos Santos, R. G., Hallak, J. E., Baker, G., & Dursun, S. (2021). Hallucinogenic/Psychedelic 5HT2A Receptor Agonists as Rapid Antidepressant...
  • Duman, R. S., Li, N., Liu, R. J., Duric, V., & Aghajanian, G. (2012). Signaling Pathways Underlying the Rapid Antidepressant Actions of...
  • Fava, M. (2003). Diagnosis and Definition of Treatment-Resistant Depression. Biological Psychiatry, 53(8), 649-659. https://doi.org/10.1016/s0006-3223(03)00231-2
  • Food and Drug Administration. (2019, Sept). Depression Medicines. Food and Drug Administration US.
  • https://www.fda.gov/consumers/free-publications-women/depression-medicines
  • Forsythe, M. L., & Boileau, A. J. (2021). Use of Cannabinoids for the Treatment of Patients with Post-Traumatic Stress Disorder. Journal...
  • García-Frade Ruiz, L. F., Marín-Navarrete, R., Solís Ayala, E., & de la Fuente-Martín, A. (2017). Cannabinoid Hyperemesis Syndrome: A...
  • Ge, L., Zhu, M. M., Yang, J. Y., Wang, F., Zhang, R., Zhang, J. H., . . . Wu, C. F. (2015). Differential Proteomic Analysis of the Anti-Depressive...
  • Goncalves, J., Luis, A., Gallardo, E., & Duarte, A. P. (2021). Psychoactive Substances of Natural Origin: Toxicological Aspects, Therapeutic...
  • Gontijo Garcia, G. S., Meira, K. C., de Souza, A. H., & Guimaraes, N. S. (2023). Anxiety and depression disorders in oncological patients...
  • Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., . . . & Malievskaia, E. (2022). Single-Dose Psilocybin...
  • Greenberg, P. E., Fournier, A. A., Sisitsky, T., Simes, M., Berman, R., Koenigsberg, S. H., & Kessler, R. C. (2021). The Economic Burden...
  • Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin Can Occasion Mystical-Type Experiences Having Substantial...
  • Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., . . . Klinedinst, M. A. (2016). Psilocybin...
  • Blind Trial. Journal of Psychopharmacology, 30(12), 1181-1197. https://doi.org/10.1177/0269881116675513
  • Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot Study of Psilocybin...
  • Guzel, T., Mech, K., Iwanowska, M., Wronski, M., & Slodkowski, M. (2021). Brain Derived Neurotrophic Factor Declines After Complete Curative...
  • Hamill, J., Hallak, J., Dursun, S. M., & Baker, G. (2019). Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential...
  • Hasbi, A., Madras, B. K., & George, S. R. (2023). Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review....
  • Higginson, I. J., Finlay, I. G., Goodwin, D. M., Hood, K., Edwards, A. G., Cook, A., . . . & Normand, C. E. (2003). Is There Evidence...
  • Holze, F., Gasser, P., Muller, F., Dolder, P. C., & Liechti, M. E. (2022). Lysergic Acid Diethylamide-Assisted Therapy in Patients With...
  • Ji, Y., Liu, X., Zheng, S., Zhong, Q., Zheng, R., Huang, J., & Yin, H. (2023). Validation and Application of the Chinese Version of the...
  • Kirk, K. M., Eaves, L. J., & Martin, N. G. (1999). Self-Transcendence as a Measure of Spirituality in a Sample of Older Australian Twins....
  • Ley General de Salud. (2022, 16 de mayo). Diario Oficial de la Federación, Cámara de Diputados del H. Congreso de los Estados Unidos Mexicanos....
  • Liu, Y., Lin, D., Wu, B., & Zhou, W. (2016). Ketamine Abuse Potential and Use Disorder. Brain Research Bulletin, 126(Pt 1), 68-73. https://doi.org/10.1016/j.brainresbull.2016.05.016
  • Liu, Q., Ho, K. Y., Lam, K. K., Lam, W., Ma, P., Abu-Odah, H., . . . & Wong, F. K. (2023). The Associations Between Spiritual Well-Being,...
  • Madras, B. K. (2022). Psilocybin in Treatment-Resistant Depression. The New England Journal of Medicine, 387(18), 1708-1709. https://doi.org/10.1056/NEJMe2210975
  • Malleson, N. (1971). Acute Adverse Reactions to LSD in Clinical and Experimental Use in the United Kingdom. The British Journal of Psychiatry,...
  • Mathew, S. J. & Zarate, C. A. (2016). Ketamine for Treatment-Resistant Depression: the First Decade of Progress. Springer International.
  • Mato, S., Pilar-Cuellar, F., Valdizan, E. M., Gonzalez-Maeso, J., Rodriguez-Puertas, R., Meana, J., . . . & Pazos, A. (2018). Selective...
  • Matveychuk, D., Thomas, R. K., Swainson, J., Khullar, A., MacKay, M. A., Baker, G. B., & Dursun, S. M. (2020). Ketamine as an Antidepressant:...
  • McIntyre, R. S., Carvalho, I. P., Lui, L. M. W., Majeed, A., Masand, P. S., Gill, H., . . . & Rosenblat, J. D. (2020). The Effect of Intravenous,...
  • Miller, L., Wickramaratne, P., Gameroff, M. J., Sage, M., Tenke, C. E., & Weissman, M. M. (2012). Religiosity and Major Depression in...
  • Miller, L., Bansal, R., Wickramaratne, P., Hao, X., Tenke, C. E., Weissman, M. M., & Peterson, B. S. (2014). Neuroanatomical Correlates...
  • Mohandas, E. (2008). Neurobiology of Spirituality. Mens Sana Monographs, 6(1), 63-80. https://doi.org/10.4103/0973-1229.33001
  • Moltke, J., & Hindocha, C. (2021). Reasons for Cannabidiol Use: A Cross-Sectional Study of CBD Users, Focusing on Self-Perceived Stress,...
  • Nichols, D. E. (2004). Hallucinogens. Pharmacology & Therapeutics, 101(2), 131-181. https://doi.org/10.1016/j.pharmthera.2003.11.002
  • Nielsen, S. W., Ruhlmann, C. H., Eckhoff, L., Bronnum, D., Herrstedt, J., & Dalton, S. O. (2022). Cannabis Use Among Danish Patients with...
  • Organización Mundial de la Salud. (2021a, 13 de Septiembre, 2021). Depresión. Organización Mundial de la Salud. https://www.who.int/es/news-room/fact-sheets/detail/depression
  • Organización Mundial de la Salud. (2021b, 17 de Junio, 2021). Suicidio. Organización Mundial de la Salud. https://www.who.int/es/news-room/fact-sheets/detail/suicide
  • Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., . . . & Araujo, D. B. (2019). Rapid Antidepressant...
  • Pérez, A., Sandino, C. y Gómez O, V. (2005). Relación entre depresión y práctica religiosa: un estudio exploratorio. Suma Psicológica, 12(1),...
  • Pew Research Center. (2022). Religion. Pew Researcspanah Center. http://www.pewforum.org/
  • Pizzagalli, D. A. & Roberts, A. C. (2022). Prefrontal Cortex and Depression. Neuropsychopharmacology, 47(1), 225-246. https://doi.org/10.1038/s41386-021-01101-7
  • Poleszak, E., Wosko, S., Slawinska, K., Wyska, E., Szopa, A., Swiader, K., . . . & Serefko, A. (2020). Influence of the Endocannabinoid...
  • Prospéro-Garcia, O. (2021). Controversias sobre la marihuana, un análisis científico de sus propiedades (O. Prospero-Garcia, Ed. Primera ed.)....
  • Prospero-Garcia, O., Ruiz Contreras, A. E., Ortega Gomez, A., Herrera-Solis, A., Mendez-Diaz, M. y Grupo de Neurociencias de la Universidad...
  • Puig, M. V., & Gulledge, A. T. (2011). Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol Neurobiol, 44(3),...
  • Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodriguez, C. I., . . . & Novel Treatments, a. D. o. t....
  • Rosenstein, D. L. (2011). Depression and end-of-life care for patients with cancer. Dialogues Clin Neurosci, 13(1), 101-108. https://www.ncbi.nlm.nih.gov/pubmed/21485750
  • Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., . . . & Schmidt, B. L. (2016). Rapid and Sustained Symptom Reduction...
  • Rybak, Y. E., Lai, K. S. P., Ramasubbu, R., Vila-Rodriguez, F., Blumberger, D. M., Chan, P., . . . & Burhan, A. M. (2021). Treatment-Resistant...
  • Salgado, A. L. C. (2014). Revisión de estudios empíricos sobre el impacto de la religión, religiosidad y espiritualidad como factores protectores....
  • Salort, G., Hernandez-Hernandez, E., Garcia-Fuster, M. J., & Garcia-Sevilla, J. A. (2020). Regulation of Cannabinoid CB(1) and CB(2) Receptors,...
  • Sanches, R. F., de Lima Osorio, F., Dos Santos, R. G., Macedo, L. R., Maia-de-Oliveira, J. P., Wichert-Ana, L., . . . & Hallak, J. E....
  • Sapkota, A., Khurshid, H., Qureshi, I. A., Jahan, N., Went, T. R., Sultan, W., & Alfonso, M. (2021). Efficacy and Safety of Intranasal...
  • Schlag, A. K., Aday, J., Salam, I., Neill, J. C., & Nutt, D. J. (2022). Adverse Effects of Psychedelics: From Anecdotes and Misinformation...
  • Seak, Y. S., Nor, J., Tuan Kamauzaman, T. H., Arithra, A., & Islam, M. A. (2021). Efficacy and Safety of Intranasal Ketamine for Acute...
  • Shabani, M., Taheri-Kharameh, Z., Saghafipour, A., Ahmari-Tehran, H., Yoosefee, S., & Amini-Tehrani, M. (2023). Resilience and Spirituality...
  • https://doi.org/10.1186/s40359-023-01279-z
  • Shamabadi, A., Ahmadzade, A., Pirahesh, K., Hasanzadeh, A., & Asadigandomani, H. (2023). Suicidality Risk After Using Cannabis and Cannabinoids:...
  • Sinner, B. & Graf, B. M. (2008). Ketamine. Handbook of Experimental Pharmacology, (182), 313-333. https://doi.org/10.1007/978-3-540-74806-9_15
  • Spanagel, R., & Bilbao, A. (2021). Approved Cannabinoids for Medical Purposes - Comparative Systematic Review and Meta-Analysis for Sleep...
  • Stefanczyk-Sapieha, L., Oneschuk, D., & Demas, M. (2008). Intravenous Ketamine "Burst" for Refractory Depression in a Patient...
  • Timmermann, C., Roseman, L., Williams, L., Erritzoe, D., Martial, C., Cassol, H., . . . & Carhart-Harris, R. (2018). DMT Models the Near-Death...
  • van Elk, M., & Aleman, A. (2017). Brain Mechanisms in Religion and Spirituality: An Integrative Predictive Processing Framework. Neuroscience...
  • Walther, A., Kirschbaum, C., Wehrli, S., Rothe, N., Penz, M., Wekenborg, M., & Gao, W. (2023). Depressive Symptoms are Negatively Associated...
  • Wilkinson, S. T., Ballard, E. D., Bloch, M. H., Mathew, S. J., Murrough, J. W., Feder, A., . . . & Sanacora, G. (2018). The Effect of...
  • Yang, C., Zhou, Z. Q., & Yang, J. J. (2011). Be Prudent of Ketamine in Treating Resistant Depression in Patients with Cancer. Journal...
  • Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., . . . & Manji, H. K. (2006). A Randomized...