Psilocybin as a potential novel treatment for treatment-resistant depression (TRD)
Paula Alconchel
Introduction
Depression and treatment-resistant depression (TRD)
Depression is a treatable mood or affective disorder characterized by persistent feelings of sadness and loss of interest. It affects how a person feels, thinks, and behaves, leading to emotional (eg. increased irritability and impulsivity) and physical problems (eg. sleep disturbances, changes in appetite) that can cause difficulty in functioning at work and at home. As it is a complex disorder, it has multiple etiologies including genetic, environmental, and neurobiological factors. Even though there is still a lot to discover, advances in research in disciplines such as genetics, cellular and molecular biology, and neuroscience strive to discover the underlying causes of the disorder and develop more precise treatment options and diagnostic tests. There are various treatment options available depending on the severity of the disorder [26,2,20.] Current options include prescription medications (antidepressants), psychotherapy, somatic treatments, lifestyle changes, and social support [10]. Medications such as Tetracyclic Antidepressants (TeCAs), Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are commonly used but can have minor side effects such as weight gain, xerostomia, psychomotor agitation, dizziness, insomnia and headaches [8]. There also exist psychotherapy options like cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) that focus on changing patients' thoughts and opinions [16]. Additionally, somatic treatments such as electroconvulsive therapy and transcranial magnetic stimulation (TMS) are used for severe cases [7]. Apart from these, lifestyle changes and social support are also important in managing depression [11]. Although several treatment options are available, it is not always the case that the patient responds positively to the applied treatment. This is the case of treatment-resistant depression (TRD) which refers to a lack of significant improvement in depressive symptoms after multiple attempts of antidepressant therapy. The criteria for defining TRD vary among studies, leading to a lack of consensus in the psychiatric community [10]; though some researchers state that TRD is highly associated with the use of psychotropic medications but also with the increase of healthcare costs and hospitalizations [28]. Treatment strategies for TRD include optimizing antidepressant dosage, augmentation/combination therapies, switching therapies, and neuromodulation in severe cases. However, the optimal strategy for treating TRD remains uncertain, and further controlled clinical trials are needed to identify the most effective treatment approaches.
Psilocybin and other psychedelic drugs
Emerging treatments such as ketamine, psychedelics, or new psychoactive substances (NPS) including synthetic cathinones, have potential utility in treating mental illnesses and show promise in rapidly improving depressive symptoms[17]. Psychedelics are chemical compounds that induce mystical experiences and altered states of consciousness. They may mediate their therapeutic effects through various mechanisms, including the modulation of brain network activity, neuronal plasticity, neuroendocrine function, glial cell regulation, epigenetic processes, and the gut-brain axis [1]. Psychedelic drugs induce temporary physiological changes and distortions in cognition, emotion, and perception. Their principal activity is mediated by the activation of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR). Hallucinogenic/psychedelic 5HT2A receptor agonists such as LSD, psilocybin, and ayahuasca have shown evidence of fast-acting antidepressant effects. These compounds have been found to modulate brain networks underlying various psychiatric disorders as well promoting neurogenesis and neuroplasticity [25] and produce their effects primarily through agonism at the serotonin (5-HT) receptors, particularly the 5-HT 2A receptor. Studies have reported the antidepressant and anxiolytic effects of these drugs, and modern trials have confirmed their efficacy in treating major depressive disorder (MDD). As previously stated, psilocybin has shown therapeutic benefits for psychiatric conditions, but concerns about its long duration of psychedelic effects limit its therapeutic application. Also, the fact that it is a drug raises concerns and is highly controversial. Therefore, the objective of this systematic review is to analyze the effects of psychedelic therapies, specifically psilocybin, on treatment-resistant depression.
Material and Methods
For this systematic review, the widely known database Pubmed was used. The booleans and search terms used for this article were “((((clinical) AND (effect OR effects)) AND (psilocybin)) AND (treatment-resistant depression OR TRD))”. A total of 124 results appeared, ranging from the year 2016 to 2024. This led to a selection of the literature relevant to psilocybin as a novel treatment for TRD over the past years. A total of 31 papers were chosen based on the content of the title and the abstract. It is important to highlight that a distinction between depression and depressive symptoms and treatment-resistant depression was considered, as only the latter was taken into account. Subsequently, a further selection was carried out to account for the content of the rest of the paper that specifically adjusted to the studied topic. Therefore, out of those 31, just 13 papers were included in this review, including mostly randomized controlled trials.
Results
Clinical symptomatology approach
Psychedelics have shown significant reductions in depression symptoms at follow-ups compared to placebo, and they have been well-tolerated by patients [12] with no persisting adverse effects, though the most common ones reported were transient anxiety, short-lived headaches, nausea, and mild increases in heart rate and blood pressure[19]. Roseman, et al. found that the occurrence and magnitude of Oceanic Boundlessness (OBN) and Dread of Ego Dissolution (DED) during treatment would predict long-term positive outcomes for patients with treatment-resistant depression (TRD)[23]. Carhart-Harris performed a study and a follow-up on severe unipolar treatment-resistant major depression. Patients received two oral doses of psilocybin (10 mg and 25 mg) in a supportive setting, with psychological support provided throughout the sessions. Depressive symptoms were assessed using standard assessments such as thorough physical health check, a psychiatric interview (Mini-International Neuropsychiatric Interview), the 21-item Hamilton Depression Rating scale (HAM-D), Global Assessment of Functioning (GAF), the Montgomery-Åsberg Depression Rating Scale (MADRS), 16-item Quick Inventory of Depressive Symptoms (QIDS), Beck Depression Inventory (BDI—original version), Spielberger's State-Trait Anxiety Inventory (form 2, STAI-T), and the Snaith-Hamilton Pleasure Scale (SHAPS). From 1 week to 3 months after treatment, they found a reduction in depressive symptoms over time. [4] In the six-month follow-up, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment, with nine and four patients meeting the criteria for response and remission at week 5. The results remained positive at 3 and 6 months post-treatment.[3] Finally, Rosenblat et al. found that Psilocybin-assisted psychotherapy (PAP) was feasible in complex populations including individuals with treatment-resistant depression, bipolar disorder, baseline suicidality, and significant comorbidity, with participants reporting improvements in depressive symptoms and quality of life [24.] Jefsen et. al found that psilocybin does not show an antidepressant-like effect in the Flinders Sensitive Line (FSL) rat model of depression, as there were no significant changes were observed in immobility, struggling, swimming behavior, or locomotor activity in the FSL rats during the forced swim test (FST). [15]
Neurobiological approach
Carhart-Harris et al. measured cerebral blood flow (CBF) and blood-oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) using functional magnetic resonance imaging (fMRI) before and after psilocybin treatment. Decreased depressive symptoms were observed in all patients at 1 week post-treatment, and 47 patients met response criteria at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala; and decreased amygdala CBF correlated with reduced depressive symptoms. Increased RSFC was observed within the default-mode network (DMN) post-treatment; and increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5 weeks, as was decreased parahippocampal-prefrontal cortex RSFC. [5] However, Mertens et al. focused on amygdala responsiveness to fearful faces and its correlations with treatment efficacy. Results showed decreased amygdala-ventromedial prefrontal cortex functional connectivity during face processing after treatment, which was associated with levels of rumination. Psilocybin therapy may revive emotional responsiveness on a neural and psychological level, which could be a key treatment mechanism for psychedelic therapy. [18]
Conclusion
Taking into account the current literature, we can conclude that even while there is still much to uncover regarding psilocybin and its effectiveness and safety in treatment-resistant depression, some studies reveal that apart from some adverse effects like headaches and nausea, psilocybin seems to be a suitable alternative treatment for cases where patients do not respond positively to the conventional treatments. However, it remains unclear whether psilocybin therapy for depression is associated with an increased risk of psychosis or mania, and whether there is any direct effect of the drug contributing to an increased risk of suicidal behavior. Phase 3 trials are starting to make an appearance recently, indicating further exploration of the substance´s potential, as well as dose-response studies in placebo-controlled settings with real-world clinical populations. Such extensions of pre-existing research on psilocybin hint allow for a deepened understanding of the drug’s effects and additional potential uses.
About the Author
Paula Alconchel (‘26) is a junior at the University of California - San Diego concentrating in Neuroscience.
References
Depression and treatment-resistant depression (TRD)
Depression is a treatable mood or affective disorder characterized by persistent feelings of sadness and loss of interest. It affects how a person feels, thinks, and behaves, leading to emotional (eg. increased irritability and impulsivity) and physical problems (eg. sleep disturbances, changes in appetite) that can cause difficulty in functioning at work and at home. As it is a complex disorder, it has multiple etiologies including genetic, environmental, and neurobiological factors. Even though there is still a lot to discover, advances in research in disciplines such as genetics, cellular and molecular biology, and neuroscience strive to discover the underlying causes of the disorder and develop more precise treatment options and diagnostic tests. There are various treatment options available depending on the severity of the disorder [26,2,20.] Current options include prescription medications (antidepressants), psychotherapy, somatic treatments, lifestyle changes, and social support [10]. Medications such as Tetracyclic Antidepressants (TeCAs), Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are commonly used but can have minor side effects such as weight gain, xerostomia, psychomotor agitation, dizziness, insomnia and headaches [8]. There also exist psychotherapy options like cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) that focus on changing patients' thoughts and opinions [16]. Additionally, somatic treatments such as electroconvulsive therapy and transcranial magnetic stimulation (TMS) are used for severe cases [7]. Apart from these, lifestyle changes and social support are also important in managing depression [11]. Although several treatment options are available, it is not always the case that the patient responds positively to the applied treatment. This is the case of treatment-resistant depression (TRD) which refers to a lack of significant improvement in depressive symptoms after multiple attempts of antidepressant therapy. The criteria for defining TRD vary among studies, leading to a lack of consensus in the psychiatric community [10]; though some researchers state that TRD is highly associated with the use of psychotropic medications but also with the increase of healthcare costs and hospitalizations [28]. Treatment strategies for TRD include optimizing antidepressant dosage, augmentation/combination therapies, switching therapies, and neuromodulation in severe cases. However, the optimal strategy for treating TRD remains uncertain, and further controlled clinical trials are needed to identify the most effective treatment approaches.
Psilocybin and other psychedelic drugs
Emerging treatments such as ketamine, psychedelics, or new psychoactive substances (NPS) including synthetic cathinones, have potential utility in treating mental illnesses and show promise in rapidly improving depressive symptoms[17]. Psychedelics are chemical compounds that induce mystical experiences and altered states of consciousness. They may mediate their therapeutic effects through various mechanisms, including the modulation of brain network activity, neuronal plasticity, neuroendocrine function, glial cell regulation, epigenetic processes, and the gut-brain axis [1]. Psychedelic drugs induce temporary physiological changes and distortions in cognition, emotion, and perception. Their principal activity is mediated by the activation of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR). Hallucinogenic/psychedelic 5HT2A receptor agonists such as LSD, psilocybin, and ayahuasca have shown evidence of fast-acting antidepressant effects. These compounds have been found to modulate brain networks underlying various psychiatric disorders as well promoting neurogenesis and neuroplasticity [25] and produce their effects primarily through agonism at the serotonin (5-HT) receptors, particularly the 5-HT 2A receptor. Studies have reported the antidepressant and anxiolytic effects of these drugs, and modern trials have confirmed their efficacy in treating major depressive disorder (MDD). As previously stated, psilocybin has shown therapeutic benefits for psychiatric conditions, but concerns about its long duration of psychedelic effects limit its therapeutic application. Also, the fact that it is a drug raises concerns and is highly controversial. Therefore, the objective of this systematic review is to analyze the effects of psychedelic therapies, specifically psilocybin, on treatment-resistant depression.
Material and Methods
For this systematic review, the widely known database Pubmed was used. The booleans and search terms used for this article were “((((clinical) AND (effect OR effects)) AND (psilocybin)) AND (treatment-resistant depression OR TRD))”. A total of 124 results appeared, ranging from the year 2016 to 2024. This led to a selection of the literature relevant to psilocybin as a novel treatment for TRD over the past years. A total of 31 papers were chosen based on the content of the title and the abstract. It is important to highlight that a distinction between depression and depressive symptoms and treatment-resistant depression was considered, as only the latter was taken into account. Subsequently, a further selection was carried out to account for the content of the rest of the paper that specifically adjusted to the studied topic. Therefore, out of those 31, just 13 papers were included in this review, including mostly randomized controlled trials.
Results
Clinical symptomatology approach
Psychedelics have shown significant reductions in depression symptoms at follow-ups compared to placebo, and they have been well-tolerated by patients [12] with no persisting adverse effects, though the most common ones reported were transient anxiety, short-lived headaches, nausea, and mild increases in heart rate and blood pressure[19]. Roseman, et al. found that the occurrence and magnitude of Oceanic Boundlessness (OBN) and Dread of Ego Dissolution (DED) during treatment would predict long-term positive outcomes for patients with treatment-resistant depression (TRD)[23]. Carhart-Harris performed a study and a follow-up on severe unipolar treatment-resistant major depression. Patients received two oral doses of psilocybin (10 mg and 25 mg) in a supportive setting, with psychological support provided throughout the sessions. Depressive symptoms were assessed using standard assessments such as thorough physical health check, a psychiatric interview (Mini-International Neuropsychiatric Interview), the 21-item Hamilton Depression Rating scale (HAM-D), Global Assessment of Functioning (GAF), the Montgomery-Åsberg Depression Rating Scale (MADRS), 16-item Quick Inventory of Depressive Symptoms (QIDS), Beck Depression Inventory (BDI—original version), Spielberger's State-Trait Anxiety Inventory (form 2, STAI-T), and the Snaith-Hamilton Pleasure Scale (SHAPS). From 1 week to 3 months after treatment, they found a reduction in depressive symptoms over time. [4] In the six-month follow-up, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment, with nine and four patients meeting the criteria for response and remission at week 5. The results remained positive at 3 and 6 months post-treatment.[3] Finally, Rosenblat et al. found that Psilocybin-assisted psychotherapy (PAP) was feasible in complex populations including individuals with treatment-resistant depression, bipolar disorder, baseline suicidality, and significant comorbidity, with participants reporting improvements in depressive symptoms and quality of life [24.] Jefsen et. al found that psilocybin does not show an antidepressant-like effect in the Flinders Sensitive Line (FSL) rat model of depression, as there were no significant changes were observed in immobility, struggling, swimming behavior, or locomotor activity in the FSL rats during the forced swim test (FST). [15]
Neurobiological approach
Carhart-Harris et al. measured cerebral blood flow (CBF) and blood-oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) using functional magnetic resonance imaging (fMRI) before and after psilocybin treatment. Decreased depressive symptoms were observed in all patients at 1 week post-treatment, and 47 patients met response criteria at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala; and decreased amygdala CBF correlated with reduced depressive symptoms. Increased RSFC was observed within the default-mode network (DMN) post-treatment; and increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5 weeks, as was decreased parahippocampal-prefrontal cortex RSFC. [5] However, Mertens et al. focused on amygdala responsiveness to fearful faces and its correlations with treatment efficacy. Results showed decreased amygdala-ventromedial prefrontal cortex functional connectivity during face processing after treatment, which was associated with levels of rumination. Psilocybin therapy may revive emotional responsiveness on a neural and psychological level, which could be a key treatment mechanism for psychedelic therapy. [18]
Conclusion
Taking into account the current literature, we can conclude that even while there is still much to uncover regarding psilocybin and its effectiveness and safety in treatment-resistant depression, some studies reveal that apart from some adverse effects like headaches and nausea, psilocybin seems to be a suitable alternative treatment for cases where patients do not respond positively to the conventional treatments. However, it remains unclear whether psilocybin therapy for depression is associated with an increased risk of psychosis or mania, and whether there is any direct effect of the drug contributing to an increased risk of suicidal behavior. Phase 3 trials are starting to make an appearance recently, indicating further exploration of the substance´s potential, as well as dose-response studies in placebo-controlled settings with real-world clinical populations. Such extensions of pre-existing research on psilocybin hint allow for a deepened understanding of the drug’s effects and additional potential uses.
About the Author
Paula Alconchel (‘26) is a junior at the University of California - San Diego concentrating in Neuroscience.
References
- Acero, V. P., Cribas, E. S., Browne, K. D., Rivellini, O., Burrell, J. C., O'Donnell, J. C., Das, S., & Cullen, D. K. (2023). Bedside to bench: the outlook for psychedelic research. Frontiers in pharmacology, 14, 1240295. https://doi.org/10.3389/fphar.2023.1240295
- Arya, A., & Kumar, T. (2011). Depression: a review. Journal of chemical and pharmaceutical research, 3(2), 444-453.
- Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V., & Nutt, D. J. (2017). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, 235(2), 399–408. https://doi.org/10.1007/s00213-017-4771-x
- Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H., & Nutt, D. J. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The lancet. Psychiatry, 3(7), 619–627. https://doi.org/10.1016/S2215-0366(16)30065-7
- Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., Tanner, M., Kaelen, M., McGonigle, J., Murphy, K., Leech, R., Curran, H. V., & Nutt, D. J. (2017). Psilocybin for treatment-resistant depression: fMRI-measure brain mechanisms. Scientific reports, 7(1), 13187. https://doi.org/10.1038/s41598-017-13282-7
- Carrillo, F., Sigman, M., Fernández Slezak, D., Ashton, P., Fitzgerald, L., Stroud, J., Nutt, D. J., & Carhart-Harris, R. L. (2018). Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. Journal of affective disorders, 230, 84–86. https://doi.org/10.1016/j.jad.2018.01.006
- Charles, Yan., Katherine, Rittenbach., Sepideh, Souri., Peter, H., Silverstone. (2019). Cost-effectiveness analysis of a randomized study of depression treatment options in primary care suggests stepped-care treatment may have economic benefits. BMC Psychiatry, doi: 10.1186/S12888-019-2223-3
- Cristian, Daniel, Marineci. (2022). Drugs for mood disorders. Farmacist.ro, doi: 10.26416/farm.208.5.2022.7143
- Daniel, R., Strunk. (2023). Impact of messaging on views of depression treatment options: Examining credibility and expectations.. Journal of Clinical Psychology, doi: 10.1002/jclp.23548
- Daniel, Souery., George, I., Papakostas., Madhukar, H., Trivedi. (2006). Treatment-resistant depression. The Journal of Clinical Psychiatry] [Amy, Werremeyer. (2014). Treatment-resistant depression. Mental Health Clinician, doi: 10.9740/MHC.N207177
- Dawei, Li. (2022). Treatment of depression from both biological and psychological aspects. doi: 10.1117/12.2660405
- Dos Santos, R. G., Hallak, J. E., Baker, G., & Dursun, S. (2021). Hallucinogenic/psychedelic 5HT2A receptor agonists as rapid antidepressant therapeutics: Evidence and mechanisms of action. Journal of psychopharmacology (Oxford, England), 35(4), 453–458. https://doi.org/10.1177/0269881120986422
- Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., Bird, C., Blom, R. E., Brennan, C., Brusch, D., Burke, L., Campbell-Coker, K., Carhart-Harris, R., Cattell, J., Daniel, A., DeBattista, C., Dunlop, B. W., Eisen, K., Feifel, D., Forbes, M., … Malievskaia, E. (2022). Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. The New England journal of medicine, 387(18), 1637–1648. https://doi.org/10.1056/NEJMoa2206443
- 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., Schoevers, R. A., … 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
- Jefsen, O., Højgaard, K., Christiansen, S. L., Elfving, B., Nutt, D. J., Wegener, G., & Müller, H. K. (2019). Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. Acta neuropsychiatrica, 31(4), 213–219. https://doi.org/10.1017/neu.2019.15
- Kate, Levenberg., Zachary, A., Cordner. (2022). Bipolar depression: a review of treatment options. General psychiatry, doi: 10.1136/gpsych-2022-100760
- López-Arnau, R., Camarasa, J., Carbó, M. L., Nadal-Gratacós, N., Puigseslloses, P., Espinosa-Velasco, M., Urquizu, E., Escubedo, E., & Pubill, D. (2022). 3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs. Frontiers in psychiatry, 13, 990405. https://doi.org/10.3389/fpsyt.2022.990405
- 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
- Muttoni, S., Ardissino, M., & John, C. (2019). Classical psychedelics for the treatment of depression and anxiety: A systematic review. Journal of affective disorders, 258, 11–24. https://doi.org/10.1016/j.jad.2019.07.076
- Nathaniel, Berenbaum. (2021). Depression: A Psychological Mood Disorder. doi: 10.36648/2471-9854.21.7.98
- Perez, N., Langlest, F., Mallet, L., De Pieri, M., Sentissi, O., Thorens, G., Seragnoli, F., Zullino, D., Kirschner, M., Kaiser, S., Solmi, M., & Sabé, M. (2023). Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 76, 61–76. https://doi.org/10.1016/j.euroneuro.2023.07.011
- Raithatha, S. A., Hagel, J. M., Matinkhoo, K., Yu, L., Press, D., Cook, S. G., Sharma, G., Dhananjaya, D., Jensen, G., Lee, J. B., Cai, C., Gallant, J., Bains, J., Tucker, J. E., & Facchini, P. J. (2024). Novel Psilocin Prodrugs with Altered Pharmacological Properties as Candidate Therapies for Treatment-Resistant Anxiety Disorders. Journal of medicinal chemistry, 67(2), 1024–1043. https://doi.org/10.1021/acs.jmedchem.3c01225
- Roseman, L., Nutt, D. J., & Carhart-Harris, R. L. (2018). Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression. Frontiers in pharmacology, 8, 974. https://doi.org/10.3389/fphar.2017.00974
- Rosenblat, J. D., Meshkat, S., Doyle, Z., Kaczmarek, E., Brudner, R. M., Kratiuk, K., Mansur, R. B., Schulz-Quach, C., Sethi, R., Abate, A., Ali, S., Bawks, J., Blainey, M. G., Brietzke, E., Cronin, V., Danilewitz, J., Dhawan, S., Di Fonzo, A., Di Fonzo, M., Drzadzewski, P., … McIntyre, R. S. (2024). Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin. Med (New York, N.Y.), 5(3), 190–200.e5. https://doi.org/10.1016/j.medj.2024.01.005
- Sarris, J., Pinzon Rubiano, D., Day, K., Galvão-Coelho, N. L., & Perkins, D. (2022). Psychedelic medicines for mood disorders: current evidence and clinical considerations. Current opinion in psychiatry, 35(1), 22–29. https://doi.org/10.1097/YCO.0000000000000759
- Siva, ManiMala, Y., Sanjana, Gautam., Goutham, Reddy, B. (2016). An Overview on Depression. Research and Reviews: Journal of Pharmacology and Toxicological Studies
- Śladowska, K., Kawalec, P., Brzostek, T., & Pilc, A. (2023). Potential use of psilocybin drugs in the treatment of depression. Expert opinion on emerging drugs, 28(4), 241–256. https://doi.org/10.1080/14728214.2023.2264180
- Sophie, R., Vaccarino., Sidney, H., Kennedy. (2021). Treatment resistant depression. doi: 10.1016/B978-0-12-821033-8.00003-4