Review article
Psilocybin as a disease-modifying drug—a salutogenic approach in psychiatry
Dtsch Arztebl Int 2024; 121: 868-74. DOI: 10.3238/arztebl.m2024.0224
; ; ; ; ;
For technical reasons, the English full text will be published approximately two weeks after the German print edition has been published.
Abteilung für Molekulares Neuroimaging, Zentralinstitut für Seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim: Moritz Spangemacher, Lea J. Mertens, M.Sc.; Luca V. Färber, M.Sc.; Prof. Dr. med. Gerhard Gründer
Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim: Moritz Spangemacher
Deutsches Zentrum für Psychische Gesundheit (DZPG), Standort Mannheim – Heidelberg – Ulm: Moritz Spangemacher, Lea J. Mertens, M.Sc.; Luca V. Färber, M.Sc.; Prof. Dr. med. Gerhard Gründer
MIND Foundation, Berlin: Dr. med. Andrea Jungaberle, Dr. sc. hum. Henrik Jungaberle, Prof. Dr. med. Gerhard Gründer
OVID Clinic, Berlin: Dr. med. Andrea Jungaberle, Dr. sc. hum. Henrik Jungaberle, Prof. Dr. med. Gerhard Gründer
*Die Autorin und der Autor teilen sich die Erstautorenschaft
Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim: Moritz Spangemacher
Deutsches Zentrum für Psychische Gesundheit (DZPG), Standort Mannheim – Heidelberg – Ulm: Moritz Spangemacher, Lea J. Mertens, M.Sc.; Luca V. Färber, M.Sc.; Prof. Dr. med. Gerhard Gründer
MIND Foundation, Berlin: Dr. med. Andrea Jungaberle, Dr. sc. hum. Henrik Jungaberle, Prof. Dr. med. Gerhard Gründer
OVID Clinic, Berlin: Dr. med. Andrea Jungaberle, Dr. sc. hum. Henrik Jungaberle, Prof. Dr. med. Gerhard Gründer
*Die Autorin und der Autor teilen sich die Erstautorenschaft
| 1. | Statistisches Bundesamt: Krankenhäuser nach Fachabteilungen, 2024. www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Gesundheit/Krankenhaeuser/Tabellen/krankenhaeuser-fa.html (last accessed on 10 September 2024). |
| 2. | Ludwig WD, Mühlbauer B, Seifert R: Arzneiverordnungs-Report 2023. Berlin, Heidelberg: Springer 2024. |
| 3. | Ormel J, Hollon SD, Kessler RC, Cuijpers P, Monroe SM: More treatment but no less depression: the treatment-prevalence paradox. Clin Psychol Rev 2022; 91: 102111. CrossRef MEDLINE |
| 4. | McGrath JJ, Al-Hamzawi A, Alonso J, et al.: Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries. Lancet Psychiatry 2023; 10: 668–81. |
| 5. | Cipriani A, Furukawa TA, Salanti G, et al.: Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018; 391: 1357–66. CrossRef MEDLINE |
| 6. | Trivedi MH, Rush AJ, Wisniewski SR, et al.: Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006; 163: 28–40 CrossRef MEDLINE |
| 7. | IsHak WW, Greenberg JM, Balayan K, et al.: Quality of life: the ultimate outcome measure of interventions in major depressive disorder. Harv Rev Psychiatry 2011; 19: 229–39. CrossRef MEDLINE |
| 8. | Rush AJ, Trivedi MH, Wisniewski SR, et al.: Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163: 1905–17. CrossRef MEDLINE |
| 9. | Fava GA: May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance. Ther Adv Psychopharmacol 2020; 10: 2045125320970325. CrossRef MEDLINE PubMed Central |
| 10. | Berlim MT, Turecki G: Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry 2007; 52: 46–54. CrossRef MEDLINE |
| 11. | Baldessarini RJ, Tondo L, Ghiani C, Lepri B: Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatry 2010; 167: 934–41. CrossRef MEDLINE |
| 12. | Sahker E, Furukawa TA, Luo Y, Ferreira ML, Okazaki K, Chevance A, et al.: Estimating the smallest worthwhile difference of antidepressants: a cross-sectional survey. BMJ Ment Health 2024; 27: e300919. CrossRef MEDLINE PubMed Central |
| 13. | Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA: The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry 2023; 28: 3243–56. CrossRef MEDLINE PubMed Central |
| 14. | Ghaemi SN: Symptomatic versus disease-modifying effects of psychiatric drugs. Acta Psychiatrica Scandinavica 2022; 146: 251–7. CrossRef MEDLINE |
| 15. | Mittelmark MB, Bauer GF, Vaandrager L, Pelikan JM, Sagy S, Eriksson M, et al.: The handbook of salutogenesis. Springer 2022. |
| 16. | Antonovsky A: Health, stress and coping: new perspectives on mental and physical well-being. San Francisco: Jossey-Bass 1979. |
| 17. | Gründer G, Jungaberle H: The potential role of psychedelic drugs in mental health care of the future. Pharmacopsychiatry 2021; 54: 191–9. CrossRef MEDLINE |
| 18. | Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D: Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 1998; 9: 3897–902. CrossRef MEDLINE |
| 19. | Yaden DB, Griffiths RR: The subjective effects of psychedelics are necessary for their enduring therapeutic effects. ACS Pharmacol Transl Sci 2021; 4: 568–72. CrossRef MEDLINE PubMed Central |
| 20. | Gründer G, Brand M, Mertens LJ, et al.: Treatment with psychedelics is psychotherapy: beyond reductionism. Lancet Psychiatry 2024; 11: 231–6. CrossRef MEDLINE |
| 21. | Nardou R, Sawyer E, Song YJ, et al.: Psychedelics reopen the social reward learning critical period. Nature 2023; 618: 790–8. CrossRef MEDLINE PubMed Central |
| 22. | Daws RE, Timmermann C, Giribaldi B, et al.: Increased global integration in the brain after psilocybin therapy for depression. Nature medicine 2022; 28: 844–51. CrossRef MEDLINE |
| 23. | Deco G, Sanz Perl Y, Johnson S, Bourke N, Carhart-Harris RL, Kringelbach ML: Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression. Nature Mental Health 2024: 1–15 CrossRef |
| 24. | Reed MB, Vanicek T, Seiger R, et al.: Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval. Neuroimage 2021; 236: 118039. CrossRef MEDLINE PubMed Central |
| 25. | Moliner R, Girych M, Brunello CA, et al.: Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci 2023; 26: 1032–41 CrossRef MEDLINE PubMed Central |
| 26. | Sekssaoui M, Bockaert J, Marin P, Bécamel C: Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT(2A) receptor the unique player? Neuropsychopharmacology 2024; 49: 747–56. CrossRef MEDLINE PubMed Central |
| 27. | Carhart-Harris R, Giribaldi B, Watts R, et al.: Trial of psilocybin versus escitalopram for depression. N Engl J Med 2021; 384: 1402–11. CrossRef MEDLINE |
| 28. | Goodwin GM, Aaronson ST, Alvarez O, et al.: Single-dose psilocybin for a treatment-resistant episode of major depression: impact on patient-reported depression severity, anxiety, function, and quality of life. J Affect Disord 2023; 327: 120–7. CrossRef MEDLINE |
| 29. | Gründer G, Brand M, Kärtner L, et al.: [Are psychedelics fast acting antidepressant agents?]. Nervenarzt 2022; 93: 254–62. |
| 30. | Hurst KT, Vogeley A, Greenstein DK, et al.: Long-term follow-up of participants in ketamine clinical trials for mood disorders. J Affect Disord 2024; 357: 134–7. CrossRef MEDLINE |
| 31. | Reif A, Bitter I, Buyze J, et al.: Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med 2023; 389: 1298–309 CrossRef MEDLINE |
| 32. | Mertens LJ, Koslowski M, Betzler F, Evens R, Gilles M, Jungaberle A: Methodological challenges in psychedelic drug trials: efficacy and safety of psilocybin in treatment-resistant major depression (EPIsoDE)—rationale and study design. Neuroscience Applied 2022; 1: 100104. CrossRef |
| 33. | Wirtz MA: Dorsch. Lexikon der Psychologie. Psychotherapie. https://dorsch.hogrefe.com/stichwort/psychotherapie (last accessed on 28 October 2024). |
| 34. | Cuijpers P, Miguel C, Harrer M, et al.: Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients. World Psychiatry 2023; 22: 105–15. CrossRef MEDLINE PubMed Central |
| 35. | Branchi I: The double edged sword of neural plasticity: increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover. Psychoneuroendocrinology 2011; 36: 339–51. CrossRef MEDLINE |
| 36. | Doss MK, Považan M, Rosenberg MD et al.: Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Transl Psychiatry 2021; 11: 574. CrossRef MEDLINE PubMed Central |
| 37. | Gukasyan N, Nayak SM: Psychedelics, placebo effects, and set and setting: insights from common factors theory of psychotherapy. Transcult Psychiatry 2022; 59: 652–64. CrossRef MEDLINE |
| 38. | Schlag AK, Aday J, Salam I, Neill JC, Nutt DJ: Adverse effects of psychedelics: from anecdotes and misinformation to systematic science. J Psychopharmacol 2022; 36: 258–72. CrossRef MEDLINE PubMed Central |
| 39. | Simonsson O, Mosing MA, Osika W, et al.: Adolescent psychedelic use and psychotic or manic symptoms. JAMA Psychiatry 2024; 81: 579–85. CrossRef MEDLINE PubMed Central |
| 40. | Evans J, Robinson OC, Argyri EK, et al.: Extended difficulties following the use of psychedelic drugs: a mixed methods study. PLoS One 2023; 18: e0293349. CrossRef MEDLINE PubMed Central |
| e1. | Rosenblat JD, Meshkat S, Doyle Z, et al.: Psilocybin-assisted psychotherapy for treatment resistant depression: a randomized clinical trial evaluating repeated doses of psilocybin. Med 2024; 5: 190–200.e5. CrossRef MEDLINE |
| e2. | Raison CL, Sanacora G, Woolley J, et al.: Single-dose psilocybin treatment for major depressive disorder: a randomized clinical trial. Jama 2023; 330: 843–53 CrossRef MEDLINE PubMed Central |
| e3. | Goodwin GM, Aaronson ST, Alvarez O, et al.: Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med 2022; 387: 1637–48 CrossRef MEDLINE |
| e4. | von Rotz R, Schindowski EM, Jungwirth J, et al.: Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine 2023; 56: 101809. CrossRef MEDLINE PubMed Central |
| e5. | Bogenschutz MP, Ross S, Bhatt S, et al.: Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry 2022; 79: 953–62 CrossRef MEDLINE PubMed Central |
| e6. | Davis AK, Barrett FS, May DG, et al.: Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry 2021; 78: 481–9. CrossRef MEDLINE PubMed Central |
| e7. | Gukasyan N, Davis AK, Barrett FS, et al.: Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: prospective 12-month follow-up. J Psychopharmacol 2022; 36: 151–8. CrossRef MEDLINE PubMed Central |
| e8. | Carhart-Harris R, Giribaldi B, Watts R, et al.: Trial of psilocybin versus escitalopram for depression. N Engl J Med 2021; 384: 1402–11. CrossRef MEDLINE |
| e9. | Erritzoe D, Barba T, Greenway KT, et al.: Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. eClinicalMedicine, Volume 76, 102799. CrossRef |
| e10. | Griffiths RR, Johnson MW, Carducci MA, et al.: Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol 2016; 30: 1181–97. CrossRef MEDLINE PubMed Central |
| e11. | Ross S, Bossis A, Guss J, et al.: Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 2016; 30: 1165–80. CrossRef MEDLINE PubMed Central |
| e12. | Agin-Liebes GI, Malone T, Yalch MM, et al.: Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol 2020; 34: 155–66. CrossRef MEDLINE |
| e13. | Agrawal M, Richards W, Beaussant Y, et al.: Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder. Cancer 2024; 130: 1137–46. CrossRef MEDLINE |
| e14. | Peck SK, Shao S, Gruen T, et al.: Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study. Nat Med 2023; 29: 1947–53. CrossRef MEDLINE PubMed Central |
| e15. | Aaronson ST, van der Vaart A, Miller T, et al.: Single-dose synthetic psilocybin with psychotherapy for treatment-resistant bipolar type II major depressive episodes: a nonrandomized open-label trial. JAMA Psychiatry 2024; 81: 555–62. CrossRef MEDLINE PubMed Central |
| e16. | Lewis BR, Garland EL, Byrne K, et al.: HOPE: a pilot study of psilocybin enhanced group psychotherapy in patients with cancer. J Pain Symptom Manage 2023; 66: 258–69. CrossRef MEDLINE |
| e17. | Schneier FR, Feusner J, Wheaton MG, et al.: Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder. J Psychiatr Res 2023; 161: 364–70. CrossRef MEDLINE PubMed Central |
| e18. | Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR: Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 2014; 28: 983–92. CrossRef MEDLINE PubMed Central |
| e19. | Johnson MW, Garcia-Romeu A, Griffiths RR: Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse 2017; 43: 55–60. CrossRef MEDLINE PubMed Central |
| e20. | Moreno FA, Wiegand CB, Taitano EK, Delgado PL: Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry 2006; 67: 1735–40. CrossRef MEDLINE |