Use of the Classic Hallucinogen Psilocybin for Treatment of Existential Distress Associated with Cancer

  • Charles S. GrobEmail author
  • Anthony P. Bossis
  • Roland R. Griffiths


This chapter reviews the potential of a treatment approach that uses psilocybin, a novel psychoactive drug, to ameliorate the psychospiritual distress and demoralization that often accompany a life-threatening cancer diagnosis. The focus of cutting-edge research beginning in the 1950s, the investigation of classic hallucinogens had a major impact on the evolving field of psychiatry, contributing to early discoveries of basic neurotransmitter systems and to significant developments in clinical psychopharmacology. While published reports of therapeutic breakthroughs with difficult-to-treat and refractory patient populations were initially met with mainstream professional enthusiasm, by the late 1960s and early 1970s the growing association of hallucinogens with widespread indiscriminate use led to the temporary abandonment of this promising psychiatric treatment model. After a hiatus lasting several decades, however, regulatory and scientific support has grown for the resumption of clinical research investigations exploring the safety and efficacy of a treatment model utilizing the classic hallucinogen, psilocybin, in a subject population that had previously demonstrated positive therapeutic response, patients with existential anxiety due to a life-threatening cancer diagnosis.


Palliative Care Advanced Cancer Patient Mystical Experience Terminal Cancer Patient Existential Anxiety 
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  1. 1.
    Berringer K. Der mescalinrausch. Berlin: Springer; 1927.Google Scholar
  2. 2.
    Bleuler M. Comparison of drug-induced and endogenous psychoses in man. In: Breatly PB, Deniker R, Raduco-Thomas D, editors. Proceedings of the first international congress of neuropsychopharmacology. Amsterdam: Elsevier; 1958.Google Scholar
  3. 3.
    Brady MJ, Peterman AH, Fitchett G, Mo M, Cella D. A case for including spirituality in quality of life measurement in oncology. Psychooncology. 1999;8:417–28.PubMedCrossRefGoogle Scholar
  4. 4.
    Breitbart W, Gibson C, Chochinov HM. Palliative care. In: Levenson JL, editor. The American psychiatric publishing textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publisher; 2005.Google Scholar
  5. 5.
    Breitbart W, Rosenfeld B, Pessin H, Kaim M, Funesti-Esch J, Galietta M, Nelson CJ, Brescia R. Depression, hopelessness, and desire for hastened death in terminally ill patients with cancer. J Am Med Assoc. 2000;284:2907–11.CrossRefGoogle Scholar
  6. 6.
    Breitbart W, Rosenfeld B, Gibson C, Pessin H, Poppito S, Nelson C, Tomarken A, Kosinski A, Berg A, Jacobson C, Sorger B, Abbey J, Olden M. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial. Psychooncology. 2010;19:21–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Blinderman C, Cherny N. Existential issues do not necessarily result in existential suffering: lessons from cancer patients in Israel. Palliat Med. 2005;19:371–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Bucke RM. Cosmic consciousness. Philadelphia, PA: Innes & Sons; 1901.Google Scholar
  9. 9.
    Cassel EJ. The nature of suffering and the goals of medicine. N Engl J Med. 1982;306:639–45.PubMedCrossRefGoogle Scholar
  10. 10.
    Chandler AL, Hartman MA. Lysergic acid die­thylamide (LSD-25) as a facilitating agent in psychotherapy. Arch Gen Psychiatry. 1960;2:286–9.CrossRefGoogle Scholar
  11. 11.
    Chochinov HM, Wilson KG, Lander S. Depression, hopelessness, and suicidal ideation in the terminally ill. Psychosomatics. 1998;39:336–70.CrossRefGoogle Scholar
  12. 12.
    Chochinov HM, Hack T, Hassard T, Krisjanson L, McClemont S, Harlos M. Understanding the will to live in patients nearing death. Psychosomatics. 2005;46:7–10.PubMedCrossRefGoogle Scholar
  13. 13.
    Chochinov HM, Cann BJ. Interventions to enhance the spiritual aspects of dying. J Palliat Med. 2005;8(Supplement 1):S103–15.PubMedCrossRefGoogle Scholar
  14. 14.
    Chochinov HM, Hack T, Hassard T, Kristjanson LJ, McClemont S, Harlos M. Dignity therapy: a novel psychotherapeutic intervention for patients near the end of life. J Clin Oncol. 2005;23:5520–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Cohen S. LSD and the anguish of dying. Harper’s. 1965 Sept: 69–78Google Scholar
  16. 16.
    Cohen SR, Mount BM, Tomas JN, Mount LF. Existential well-being is an important determinant of quality of life. Cancer. 1996;77:576–86.PubMedCrossRefGoogle Scholar
  17. 17.
    Derogatis LR, Morrow GR, Fetting J, Penman D, Piasetsky C, Schmale AM, Henrichs M, Carnicke CL. J Am Med Assoc. 1983;249:751–7.CrossRefGoogle Scholar
  18. 18.
    Doblin R. Pahnke’s Good Friday experiment: a ­long-term follow-up and methodological critique. J Transpersonal Psychol. 1991;23:1–28.Google Scholar
  19. 19.
    Durkin I, Kearney M, O’Siorain L. Psychiatric disorder in a palliative care unit. Palliat Med. 2003;17: 212–8.CrossRefGoogle Scholar
  20. 20.
    Edwards A, Pang N, Shiu V, Chan C. The understanding of spirituality and the potential role of spiritual care in end-of-life and palliative care: a meta-study of qualitative research. Palliat Med. 2010;24(8):753–70.PubMedCrossRefGoogle Scholar
  21. 21.
    Fernsler J, Klemm P, Miller M. Spiritual well-being and demands of illness in people with colorectal cancer. Cancer Nurs. 1999;22:134–40.PubMedCrossRefGoogle Scholar
  22. 22.
    Field M, Cassel C, editors. Approaching death: improving care at the end-of-life. Washington, DC: National Academy Press; 1997.Google Scholar
  23. 23.
    Fisher G. Psychotherapy for the dying: principles and illustrative cases with special reference to the use of LSD. Omega. 1970;1:3–15.Google Scholar
  24. 24.
    Frankl VE. Man’s search for meaning. Boston, MA: Beacon; 1984.Google Scholar
  25. 25.
    Frankl VF. The will to meaning: foundations and applications of logotherapy. New York: Penguin; 1988.Google Scholar
  26. 26.
    Galfin JM, Walkins ER, Harlow T. Psychological distress and rumination in palliative care patients and their caregivers. J Palliat Med. 2010;13: 1345–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Greenberg L, Lantz MS, Likourezos A, Burack OR, Chichin E, Carter J. Screening for depression in nursing home palliative care patients. J Geriatr Psychiatry Neurol. 2004;17:212–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Griffiths RR, Grob CS. Hallucinogens as medicine. Sci Am. 2010;303(December):77–9.Google Scholar
  29. 29.
    Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology (Berl). 2011;218:649–65.CrossRefGoogle Scholar
  30. 30.
    Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl). 2006;187:268–83.CrossRefGoogle Scholar
  31. 31.
    Griffiths RR, Richards WA, Johnson MW, McCann U, Jesse R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 2008;22(6):621–32.PubMedCrossRefGoogle Scholar
  32. 32.
    Grinspoon L, Bakalar JB. Psychedelic drugs reconsidered. New York: Basic Books; 1979.Google Scholar
  33. 33.
    Grinspoon L, Bakalar JB. Can drugs be used to enhance the psychotherapeutic process? Am J Psychother. 1986;40:393–404.PubMedGoogle Scholar
  34. 34.
    Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer G. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011;68:71–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Grof S, Goodman LE, Richards WA, Kurland AA. LSD-assisted psychotherapy in patients with terminal cancer. Int Pharmacopsychiatry. 1973;8:129–44.PubMedGoogle Scholar
  36. 36.
    Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose effects study. Psychopharmacology (Berl). 2004;172:145–56.CrossRefGoogle Scholar
  37. 37.
    Henoch I, Danielson E. Existential concerns among patients with cancer and interventions to meet them: an integrative literature review. Psychooncology. 2009;18:225–36.PubMedCrossRefGoogle Scholar
  38. 38.
    Henry M, Cohen R, Lee V, Sauthier P, Provencher D, Drouin P, Gauthier P, Gotlieb W, Lau S, Drummond N, Gilbert L, Stanimir G, Sturgeon J, Chasen M, Mitchell J, Nixon Huang L, Ferland M, Mayo N. The meaning making intervention (MMi) appears to increase meaning in life in advanced ovarian cancer: a randomized controlled pilot study. Psychooncology. 2010;19:1340–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Hills J, Paice JA, Cameron JR, Shott S. Spirituality and distress in palliative care consultation. J Palliat Med. 2005;8:782–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Hofmann A. LSD—my problem child: reflections on sacred drugs, mysticism and science. Los Angeles, CA: J.P. Tarcher; 1985.Google Scholar
  41. 41.
    Hotoph M, Chidgey J, Addington-Hall J, Ly KL. Depression in advanced disease: a systematic review. Part 1. Prevalence and case finding. Palliat Med. 2002;16:81–97.CrossRefGoogle Scholar
  42. 42.
    Hotopf M, Price A. Palliative care psychiatry. Psychiatry. 2009;8:212–5.CrossRefGoogle Scholar
  43. 43.
    Huxley A. The perennial philosophy. New York: Harper & Brothers; 1945.Google Scholar
  44. 44.
    Isbell H. Comparison of the reactions induced by psilocybin and LSD-25 in man. Psychopharmacologia. 1959;1:29–38.PubMedCrossRefGoogle Scholar
  45. 45.
    Jacob P, Shulgin AT. Structure-activity relationships of the classic hallucinogens and their analogs. NIDA Res Monogr. 1994;146:74–91.PubMedGoogle Scholar
  46. 46.
    James W. The varieties of religious experience. New York: Longman’s Green, and Co.; 1919.Google Scholar
  47. 47.
    Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22:603–20.PubMedCrossRefGoogle Scholar
  48. 48.
    Jones JM, Huggins MA, Rydall AC, Rodin GM. Symptomatic distress, hopelessness, and the desire for hastened death in hospitalized cancer patients. J Psychosom Res. 2003;55:411–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Jung C. Psychology and religion. New Heaven, CT: Yale University Press; 1938.Google Scholar
  50. 50.
    Kandasamy A, Chaturvedi S, Desai G. Spirituality, distress, depression, anxiety, and quality of life in patients with advanced cancer. Indian J Cancer. 2011;48:55–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Kast EC. The measurement of pain, a new approach to an old problem. J New Drugs. 1962;2:344–51.PubMedGoogle Scholar
  52. 52.
    Kast EC, Collins VJ. Lysergic acid diethylamide as an analgesic agent. Anesth Analg. 1964;43:285–91.PubMedCrossRefGoogle Scholar
  53. 53.
    Kelly B, Burnett P, Pelusi D, Badger S, Varghese F, Robertson M. Terminally ill cancer patients’ wish to hasten death. Palliat Med. 2002;16:339–45.PubMedCrossRefGoogle Scholar
  54. 54.
    Kissane D, Clarke DM, Street AF. Demoralization syndrome-A relevant psychiatric diagnosis for palliative care. J Palliat Care. 2001;17:12–21.PubMedGoogle Scholar
  55. 55.
    Kluver H. Mescal: the ‘Divine’ plant and its psychological effects. London: Keegan Paul; 1928.Google Scholar
  56. 56.
    Lajoie DH, Shapiro SI. Definitions of transpersonal psychology: the first twenty-three years. J Transpersonal Psychol. 1992;24:79–98.Google Scholar
  57. 57.
    Lee V. The existential plight of cancer: meaning making as a concrete approach to the intangible search for meaning. Support Care Cancer. 2008;16:779–85.PubMedCrossRefGoogle Scholar
  58. 58.
    LeMay K, Wilson KG. Treatment of existential distress in life threatening illness: a review of manualized interventions. Clin Psychol Rev. 2008;28: 472–93.PubMedCrossRefGoogle Scholar
  59. 59.
    Lethborg C, Aranda S, Cox S, Kissane D. To what extent does meaning mediate adaptation to cancer? The relationship between physical suffering, meaning in life, and connection to others in adjustment to cancer. Palliat Support Care. 2007;5:377–88.PubMedCrossRefGoogle Scholar
  60. 60.
    Lin HR, Bauer-Wu SM. Psycho-spiritual well-being in patients with advanced cancer: an integrative review of the literature. J Adv Nurs. 2003;44:69–80.PubMedCrossRefGoogle Scholar
  61. 61.
    Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;32:57–71.PubMedCrossRefGoogle Scholar
  62. 62.
    Maslow AH. Religions, values, and peak experience. Columbus, OH: Ohio State University Press; 1964.Google Scholar
  63. 63.
    McClain CS, Rosenfeld B, Breitbart W. Effect of spiritual well-being on end-of-life despair in terminally-ill cancer patients. Lancet. 2003;361:1603–7.PubMedCrossRefGoogle Scholar
  64. 64.
    McMillan SC, Weitzner M. How problematic are various aspects of quality of life in patients with cancer at the end of life? Oncol Nurs Forum. 2000;27:817–23.PubMedGoogle Scholar
  65. 65.
    Metzner R. Teonanacatl: sacred mushroom of visions. Verona, CA: Four Trees Press; 2004.Google Scholar
  66. 66.
    Moadel A, Morgan C, Fatone A, Grennan J, Carter J, Laruffa G, Skummy A, Dutcher J. Seeking meaning and hope: self-reported spiritual and existential needs among an ethnically-diverse cancer population. Psychooncology. 1999;8:378–85.PubMedCrossRefGoogle Scholar
  67. 67.
    Moreno FA, Wiegand CB, Taitano K, Delgado PL. Safety, tolerability and efficacy of psilocybin in patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006;67:1735–40.PubMedCrossRefGoogle Scholar
  68. 68.
    Morita T, Tsunoda J, Inoue S, Chihara S. An exploratory factor analysis of existential suffering in Japanese terminally ill cancer patients. Psychooncology. 2000;9:164–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Murata H. Spiritual pain and its care in patients with terminal cancer: construction of a conceptual framework by philosophical approach. Palliat Support Care. 2003;1:15–21.PubMedCrossRefGoogle Scholar
  70. 70.
    National Institute for Clinical Excellence. Improving supportive and palliative care for adults with cancer. London: National Institute for Clinical Excellence; 2004.Google Scholar
  71. 71.
    The National Comprehensive Cancer Network: Distress Management Clinical Practice Guidelines in Oncology.; 2010)
  72. 72.
    Nelson CJ, Rosenfeld B, Breitbart W, Galietta M. Spirituality, religion, and depression in the terminally ill. Psychosomatics. 2002;43:213–20.PubMedCrossRefGoogle Scholar
  73. 73.
    Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101:131–81.PubMedCrossRefGoogle Scholar
  74. 74.
    Osmond H. A review of the clinical effects of psychotomimetic agents. Ann N Y Acad Sci. 1957;66:418–34.PubMedCrossRefGoogle Scholar
  75. 75.
    Otto R. The idea of the holy. London: Oxford University Press; 1923.Google Scholar
  76. 76.
    Pahnke W. Drugs and mysticism: an analysis of the relationship between psychedelic drugs and the mystical consciousness. Thesis presented to the President and Fellows of Harvard University for the Ph.D. in Religion and Society; 1963Google Scholar
  77. 77.
    Pahnke WN. The psychedelic mystical experience in the human encounter with death. Harvard Theol Rev. 1969;62:1–21.Google Scholar
  78. 78.
    Passie T. A history of the use of psilocybin in psychotherapy. In: Metzner R, editor. Teonanacatl: sacred mushroom of vision. El Verano, CA: Four Trees Press; 2004.Google Scholar
  79. 79.
    Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol. 2002;7:357–64.PubMedCrossRefGoogle Scholar
  80. 80.
    Presti DE, Nichols DE. Biochemistry and neuropharmacology of psilocybin mushrooms. In: Metzner R, editor. Teonanacatl: sacred mushroom of vision. El Verano, CA: Four Trees Press; 2004.Google Scholar
  81. 81.
    Puchalski C, Ferrell B, Virani R, Otis-Green S, Baird P, Bull J, Chochinov M, Handzo G, Nelson-Becker H, Prince-Paul M, Pugliese K, Sulmasy D. Improving the quality of spiritual care as a dimension of palliative care: the report of the consensus conference. J Palliat Med. 2009;12:885–904.PubMedCrossRefGoogle Scholar
  82. 82.
    Puchalski CM, Romer AL. Taking a spiritual history allows clinicians to understand patients more fully. J Palliat Med. 2000;3:129–37.PubMedCrossRefGoogle Scholar
  83. 83.
    Puchalski CM, Kilpatrick SD, McCullough ME, Larson DB. A systematic review of spiritual and religious variables in Palliative Medicine, American Journal of Hospice and Palliative Care, Hospice Journal, Journal of Palliative Care, and Journal of Pain and Symptom Management. Palliat Support Care. 2003;1:7–13.PubMedCrossRefGoogle Scholar
  84. 84.
    Richards WA, Rhead JC, DiLeo FB, Yensen R, Kurland AA. The peak experience variable in DPT-assisted psychotherapy with cancer patients. J Psychedelic Drugs. 1977;9:1–10.CrossRefGoogle Scholar
  85. 85.
    Riedlinger TJ. The sacred mushroom seeker: essays for R. Gordon Wasson. Portland, OR: Dioscorides Press; 1990.Google Scholar
  86. 86.
    Rodin G, Lo C, Mikulincer M, Donner A, Gagliese L, Zimmermann C. Pathways to distress: the multiple determinants of depression, hopelessness, and the desire for hastened death in metastatic cancer patients. Soc Sci Med. 2009;68:562–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Rodin G, Zimmermann C, Rydall A, Jones J, Shepherd FA, Moore M, Fruh M, Donner A, Gagliese L. The desire for hastened death in patients with metastatic cancer. J Pain Symptom Manage. 2007;6: 661–75.CrossRefGoogle Scholar
  88. 88.
    Rousseau P. Spirituality and the dying patient. J Clin Oncol. 2000;18:2000–2.PubMedGoogle Scholar
  89. 89.
    Saunders CM. The management of terminal malignant disease. London: Edward Arnold; 1978.Google Scholar
  90. 90.
    Saunders C. Spiritual pain. J Palliat Care. 1988;4: 29–32.PubMedGoogle Scholar
  91. 91.
    Schultes RE, Hofmann A. Plants of the gods: their sacred, healing and hallucinogenic powers. Rochester, VT: Healing Arts Press; 1992.Google Scholar
  92. 92.
    Sinclair S, Pereira J, Raffin S. A thematic review of the spirituality literature within palliative care. J Palliat Med. 2006;9:464–79.PubMedCrossRefGoogle Scholar
  93. 93.
    Storey P, Knight CF. UNIPAC Two: alleviating psychological and spiritual pain in the terminally ill. Gainesville, FL: American Academy of Hospice and Palliative Medicine; 1997.Google Scholar
  94. 94.
    Studerus E, Gamma A, Vollenweider FX. Psychometric evaluation of the altered states of consciousness rating scale (OAV). PLoS One. 2010;5: 1–19.CrossRefGoogle Scholar
  95. 95.
    Tanyi RA. Towards clarification of the meaning of spirituality. J Adv Nurs. 2002;39:500–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Vachon M, Fillion L, Achille M. A conceptual analysis of spirituality at the end of life. J Palliat Med. 2009;12:53–7.CrossRefGoogle Scholar
  97. 97.
    Vollenweider FX, Leenders KL, Scharfetter C, Maguire P, Stadelmann O, Angst J. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology. 1997;16:357–72.PubMedCrossRefGoogle Scholar
  98. 98.
    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.PubMedCrossRefGoogle Scholar
  99. 99.
    Weisman AD. Early diagnosis of vulnerability in cancer patients. Am J Med Sci. 1976;271:187–96.PubMedCrossRefGoogle Scholar
  100. 100.
    Weisman AD, Worden JW. The existential plight in cancer: significance of the first 100 days. Int J Psychiatry Med. 1976;7:1–15.PubMedCrossRefGoogle Scholar
  101. 101.
    Wilson KG, Chochinov HM, de Faye BJ, Breitbart W. Diagnosis and management of depression in palliative care. In: Chochinov HM, Breitbart W, editors. Handbook of psychiatry in palliative medicine. New York: Oxford University Press; 2000. p. 25–49.Google Scholar
  102. 102.
    Wilson KG, Chochinov HM, Skirko MG, Allard P, Chary S, Gagnon PR, Macmillan K, De Luca M, O’Shea F, Kuhl D, Fainsinger RL, Clinch JJ. Depression and anxiety disorders in palliative cancer care. J Pain Symptom Manage. 2007;33:118–29.PubMedCrossRefGoogle Scholar
  103. 103.
    World Health Organization: WHO definition of ­palliative care. Accessed Feb 2011

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Authors and Affiliations

  • Charles S. Grob
    • 1
    Email author
  • Anthony P. Bossis
    • 2
  • Roland R. Griffiths
    • 3
  1. 1.Department of PsychiatryHarbor-UCLA Medical CenterTorranceUSA
  2. 2.Department of PsychiatryNew York University School of MedicineNew YorkUSA
  3. 3.Departments of Psychiatry and NeuroscienceJohns Hopkins University School of MedicineBaltimoreUSA

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