본문 바로가기
KERD
논문KCI 등재

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a “breakthrough therapy” for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin’s potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials, DB-RCTs) trials exploring psilocybin’s impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over 6 months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

Abstract

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a “breakthrough therapy” for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin’s potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials, DB-RCTs) trials exploring psilocybin’s impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over 6 months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

참고문헌 (39)

  1. Serretti A, "Anhedonia and depressive disorders", Clin Psychopharmacol Neurosci, 21, pp.401~409 (2023)
  2. Shin C, "Efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression : a randomized rater-blinded 6-week clinical trial", Clin Psychopharmacol Neurosci, 21, pp.135~146 (2023)
  3. Fava M, "The challenges of defining and managing treatment-resistant depression in research and practice", World Psychiatry, 22, pp.350~351 (2023)
  4. Perez N, "Psilocybin-assisted therapy for depression : a systematic review and dose-response meta-analysis of human studies", Eur Neuropsychopharmacol, 76, pp.61~76 (2023)
  5. Lowe H, "The therapeutic potential of psilocybin", Molecules, 26, pp.2948~ (2021)
  6. Van Court RC, "Diversity, biology, and history of psilocybin-containing fungi : suggestions for research and technological development", Fungal Biol, 126, pp.308~319 (2022)
  7. Doblin R, "Pahnke’s"good friday experiment" : a long-term follow-up and methodological critique", J Transpers Psychol, 23, pp.1~28 (1991)
  8. Doblin R, "Dr. Leary’s concord prison experiment : a 34-year follow-up study", J Psychoactive Drugs, 30, pp.419~426 (1998)
  9. Redden WM, "Hallucinogen use and misuse in older adults", Clin Geriatr Med, 38, pp.55~66 (2022)
  10. Sharma P, "Psilocybin history, action and reaction : a narrative clinical review", J Psychopharmacol, 37, pp.849~865 (2023)
  11. Drug Enforcement Administration (DEA), Department of Justice, "Definition of"positional isomer"as it pertains to the control of schedule I controlled substances. Final rule", Fed Regist, 72, pp.67850~67852 (2007)
  12. "In close vote, denver becomes 1st us city to decriminalize psychedelic mushrooms" (2019)[URL]
  13. "Oregon psilocybin services act" (2019)[URL]
  14. "Oregon health authority public health division:division 333—psilocybin"[URL]
  15. "Oregon measure 109, psilocybin mushroom services program initiative (2020)"[URL]
  16. Siegel JS, "Psychedelic drug legislative reform and legalization in the US", JAMA Psychiatry, 80, pp.77~83 (2023)
  17. Vargas MV, "Psychedelics and other psychoplastogens for treating mental illness", Front Psychiatry, 12, pp.727117~ (2021)
  18. Raval NR, "A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain", Int J Mol Sci, 22, pp.835~ (2021)
  19. Muttoni S, "Classical psychedelics for the treatment of depression and anxiety : a systematic review", J Affect Disord, 258, pp.11~24 (2019)
  20. Mason NL, "Me, myself, bye : regional alterations in glutamate and the experience of ego dissolution with psilocybin", Neuropsychopharmacology, 45, pp.2003~2011 (2020)
  21. Nau F Jr, "Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo", PLoS One, 8, pp.e75426~ (2013)
  22. Nkadimeng SM, "Anti-inflammatory effects of four psilocybin-containing magic mushroom water extracts in vitro on 15-lipoxygenase activity and on lipopolysaccharide-induced cyclooxygenase-2 and inflammatory cytokines in human U937 macrophage cells", J Inflamm Res, 14, pp.3729~3738 (2021)
  23. Mertens LJ, "Therapeutic mechanisms of psilocybin : Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatmentresistant depression", J Psychopharmacol, 34, pp.167~180 (2020)
  24. Carhart-Harris RL, "Psilocybin for treatment-resistant depression : fMRI-measured brain mechanisms", Sci Rep, 7, pp.13187~ (2017)
  25. Ling S, "Molecular mechanisms of psilocybin and implications for the treatment of depression", CNS Drugs, 36, pp.17~30 (2022)
  26. Mahapatra A, "Role of psilocybin in the treatment of depression", Ther Adv Psychopharmacol, 7, pp.54~56 (2017)
  27. raclopride, "Neuropsychopharmacology", 1999, 424~433
  28. Daniel J, "Clinical potential of psilocybin as a treatment for mental health conditions", Ment Health Clin, 7, pp.24~28 (2018)
  29. Carhart-Harris RL, "Psilocybin with psychological support for treatment-resistant depression : an open-label feasibility study", Lancet Psychiatry, 3, pp.619~627 (2016)
  30. Carhart-Harris RL, "Psilocybin with psychological support for treatment-resistant depression : six-month follow-up", Psychopharmacology(Berl), 235, pp.399~408 (2018)
  31. Lyons T, "More realistic forecasting of future life events after psilocybin for treatment-resistant depression", Front Psychol, 9, pp.1721~ (2018)
  32. Roseman L, "Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression", Front Pharmacol, 8, pp.974~ (2018)
  33. Davis AK, "Effects of psilocybin-assisted therapy on major depressive disorder : a randomized clinical trial", JAMA Psychiatry, 78, pp.481~489 (2021)
  34. Gukasyan N, "Efficacy and safety of psilocybin-assisted treatment for major depressive disorder : prospective 12-month follow-up", J Psychopharmacol, 36, pp.151~158 (2022)
  35. Griffiths RR, "Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer : a randomized double-blind trial", J Psychopharmacol, 30, pp.1181~1197 (2016)
  36. Ross S, "Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer : a randomized controlled trial", J Psychopharmacol, 30, pp.1165~1180 (2016)
  37. Carhart-Harris R, "Trial of psilocybin versus escitalopram for depression", N Engl J Med, 384, pp.1402~1411 (2021)
  38. von Rotz R, "Single-dose psilocybin-assisted therapy in major depressive disorder : a placebo-controlled, double-blind, randomised clinical trial", EClinicalMedicine, 56, pp.101809~ (2022)
  39. Goodwin GM, "Single-dose psilocybin for a treatment-resistant episode of major depression", N Engl J Med, 387, pp.1637~1648 (2022)

관련 논문AI추천

이 간행물의 다른 논문 (19건)