, Volume 14, Issue 3, pp 734–740 | Cite as

Potential Therapeutic Effects of Psilocybin



Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

Key Words

Psilocybin psychedelic cancer addiction depression anxiety 



Support for effort by the authors has been provided by the Heffter Research Institute and National Institute on Drug Abuse grant R01DA003889. Roland R. Griffiths is on the Board of Directors of the Heffter Research Institute, Santa Fe, NM, USA.


  1. 1.
    Schultes RE. Hallucinogens of plant origin. Science 1969;163:245-254.CrossRefPubMedGoogle Scholar
  2. 2.
    Lowy B. New records of mushroom stones from Guatemala. Mycologia 1971;63:983-993.CrossRefPubMedGoogle Scholar
  3. 3.
    Schultes RE, Hofmann A. Plants of the gods: their sacred, healing, and hallucinogenic powers. Rochester, VT: Healing Arts Press; 1992.Google Scholar
  4. 4.
    Heffter A. Ueber Pellote. Beitrag zur chemischen und pharmakologischen Kenntnis der Cacteen. Naunyn-Schmiedebergs Arch Exp Pathol Pharmacol 1898;40:385-429.CrossRefGoogle Scholar
  5. 5.
    Perrine DM. Visions of the Night: Western medicine meets peyote 1887-1899. Heffter Rev Psychedel Res 2001;2:6-52.Google Scholar
  6. 6.
    Hofmann A, Ott J. LSD, my problem child. New York: McGraw-Hill; 1980.Google Scholar
  7. 7.
    Grinspoon L, Bakalar JB. Psychedelic drugs reconsidered. New York: Basic Books; 1979.Google Scholar
  8. 8.
    Grinspoon L. LSD Reconsidered. Sciences 1981;21:20-23.CrossRefGoogle Scholar
  9. 9.
    Kast EC, Collins VJ. Study of lysergic acid diethylamide as an analgesic agent. Anesth Analg 1964;43:285-291.CrossRefPubMedGoogle Scholar
  10. 10.
    Cohen S. LSD and the Anguish of Dying. Harpers Magazine 1965;231:69-72.Google Scholar
  11. 11.
    Kast E. Attenuation of anticipation: a therapeutic use of lysergic acid diethylamide. Psychiatr Q 1967;41:646-657.CrossRefPubMedGoogle Scholar
  12. 12.
    Kurland AA, Pahnke WN, Unger S, Savage C, Goodman LE. Psychedelic psychotherapy (LSD) in the treatment of the patient with a malignancy. In: Cerletti A, Bové F, editors. The Present Status of Psychotropic Drugs: Pharmacological and Clinical Aspects. Amsterdam: Excerpta Medica 1969:432-434.Google Scholar
  13. 13.
    Pahnke WN, Kurland AA, Goodman LE, Richards WA. LSD-assisted psychotherapy with terminal cancer patients. Curr Psychiatr Ther 1969;9:144-152.PubMedGoogle Scholar
  14. 14.
    Richards W, Grof S, Goodman L, Kurland A. LSD-assisted psychotherapy and the human encounter with death. J Transpers Psychol 1972;4:121-150.Google Scholar
  15. 15.
    Kurland AA, Grof S, Pahnke WN, Goodman LE. Psychedelic drug assisted psychotherapy. In: Goldberk IK, Malitz S, Kutscher AH, editors. Patients With Terminal Cancer Psychotheramacological Agents for the Terminally Ill and Bereaved. New York: Columbia University Press; 1973. p. 86-133.Google Scholar
  16. 16.
    Halifax J, Grof S. The Human Encounter with Death. 1st ed. New York: E. P. Dutton; 1977.Google Scholar
  17. 17.
    Richards WA, Rhead JC, DiLeo FB, Yensen R, Kurland AA. The peak experience variable in DPT-assisted psychotherapy with cancer patients. J Psychedel Drugs 1977;9:1-10.CrossRefGoogle Scholar
  18. 18.
    Richards WA, Rhead JC, Grof S, Goodman LE, Di Leo F, Rush L. DPT as an adjunct in brief psychotherapy with cancer patients. OMEGA J Death Dying 1980;10:9-26.CrossRefGoogle Scholar
  19. 19.
    Grof S. LSD Psychotherapy. 1st ed. Pomona, CA: Hunter House; 1980.Google Scholar
  20. 20.
    Richards WA. Psychedelic drug-assisted psychotherapy with persons suffering from terminal cancer. J Altered States Consciousness 1979;5:309-319.Google Scholar
  21. 21.
    Kurland AA. LSD in the supportive care of the terminally ill cancer patient. J Psychoactive Drugs 1985;17:279-290.CrossRefPubMedGoogle Scholar
  22. 22.
    Chwelos N, Blewett DB, Smith CM, Hoffer A. Use of d-lysergic acid diethylamide in the treatment of alcoholism. Q J Stud Alcohol 1959;20:577-590.PubMedGoogle Scholar
  23. 23.
    Smart RG, Storm T, Baker EF, Solursh L. A controlled study of lysergide in the treatment of alcoholism: I. The effects on drinking behavior. Q J Stud Alcohol 1966;27:469-482.PubMedGoogle Scholar
  24. 24.
    Hollister LE, Shelton J, Krieger G. A controlled comparison of lysergic acid diethylamide (LSD) and dextroamphetamine in alcoholics. Am J Psychiatry. 1969;125:1352-1357.CrossRefPubMedGoogle Scholar
  25. 25.
    Ludwig A, Levine J, Stark L, Lazar R. A clinical study of LSD treatment in alcoholism. Am J Psychiatry 1969;126:59-69.CrossRefPubMedGoogle Scholar
  26. 26.
    Kurland A, Savage C, Pahnke WN, Grof S, Olsson JE. LSD in the treatment of alcoholics. Pharmacopsychiatry 1971;4:83-94.CrossRefGoogle Scholar
  27. 27.
    Savage C, McCabe OL. Residential psychedelic (LSD) therapy for the narcotic addict: a controlled study. Arch Gen Psychiatry 1973;28:808-814.CrossRefPubMedGoogle Scholar
  28. 28.
    Tomsovic M, Edwards RV. Lysergide treatment of schizophrenic and nonschizophrenic alcoholics: a controlled evaluation. Q J Stud Alcohol 1970;31:932-949.PubMedGoogle Scholar
  29. 29.
    Bowen WT, Soskin RA, Chotlos JW. Lysergic acid diethylamide as a variable in the hospital treatment of alcoholism: a follow-up study. J Nerv Mental Dis 1970;150:111-118.CrossRefGoogle Scholar
  30. 30.
    Stamets P. Psilocybin mushrooms of the world. Berkeley, CA: Ten Speed Press; 1996.Google Scholar
  31. 31.
    Nichols, DE. Psychedelics. Pharmacol Rev 2016;68:264-355CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Winter JC, Rice KC, Amorosi DJ, Rabin RA. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 2007;87:472-480.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol 2002;7:357-364.CrossRefPubMedGoogle Scholar
  34. 34.
    Fantegrossi WE, Woods JH, Winger G. Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys. Behav Pharmacol 2004;15:149-157.CrossRefPubMedGoogle Scholar
  35. 35.
    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;218:649-665.CrossRefGoogle Scholar
  36. 36.
    Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol 2008;22:603-620.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Johnson MW, Sewell RA, Griffiths RR. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug Alcohol Depend 2012;123:132-140.CrossRefPubMedGoogle Scholar
  38. 38.
    Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 2011;68:71-78.CrossRefPubMedGoogle Scholar
  39. 39.
    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;30:1181-1197.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    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;30:1165-1180.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Gasser P, Holstein D, Michel Y, et al. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis 2014;202:513-520.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 2016;3:619-627CrossRefPubMedGoogle Scholar
  43. 43.
    Dyck E. ‘Hitting highs at rock bottom’: LSD treatment for alcoholism, 1950–1970. Soc Hist Med 2006;19:313-329.CrossRefGoogle Scholar
  44. 44.
    Krebs TS, Johansen P. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol 2012;26:994-1002.CrossRefPubMedGoogle Scholar
  45. 45.
    Fabregas JM, Gonzlez D, Fondevila S, et al. Assessment of addiction severity among ritual users of ayahuasca. Drug Alcohol Depend 2010;111:257-261.CrossRefPubMedGoogle Scholar
  46. 46.
    Albaugh BJ, Anderson PO. Peyote in the treatment of alcoholism among American Indians. Am J Psychiatry 1974;131:1247-1250.PubMedGoogle Scholar
  47. 47.
    Bergman RL. Navajo peyote use: its apparent safety. Am J Psychiatry 1971;128:695-699.CrossRefPubMedGoogle Scholar
  48. 48.
    Blum K, Futterman SFL, Pascarosa P. Peyote, a potential ethnopharmacologic agent for alcoholism and other drug dependencies: possible biochemical rationale. Clin Toxicol 1977;11:459-472.CrossRefPubMedGoogle Scholar
  49. 49.
    Calabrese JD. Spiritual healing and human development in the Native American church: toward a cultural psychiatry of peyote. Psychoanal Rev 1997;84:237-255.PubMedGoogle Scholar
  50. 50.
    de Rios MD, Grob CS, Baker JR. Hallucinogens and redemption. J Psychoactive Drugs 2002;34:239-248.CrossRefPubMedGoogle Scholar
  51. 51.
    Garrity JF. Jesus, peyote, and the holy people: alcohol abuse and the ethos of power in Navajo healing. Med Anthropol Q 2000;14:521-542.CrossRefPubMedGoogle Scholar
  52. 52.
    Halpern JH. The use of hallucinogens in the treatment of addiction. Addict Res 1996;4:177-189.CrossRefGoogle Scholar
  53. 53.
    Pascarosa P, Futterman S. Ethnopsychedelic therapy for alcoholics: observations in the peyote ritual of the Native American Church. J Psychedelic Drugs 1976;8:215-221.CrossRefGoogle Scholar
  54. 54.
    Prue B. Indigenous supports for recovery from alcoholism and drug abuse: the Native American Church. J Ethn Cult Divers Soc Work 2013;22:271-287.CrossRefGoogle Scholar
  55. 55.
    Roy C. Indian peyotists and alcohol. Am J Psychiatry 1973;130:329-330.CrossRefPubMedGoogle Scholar
  56. 56.
    Thomas G, Lucas P, Capler NR, Tupper KW, Martin G. Ayahuasca-assisted therapy for addiction: Results from a preliminary observational study in Canada. Curr Drug Abuse Rev 2013;6:30-42.CrossRefPubMedGoogle Scholar
  57. 57.
    Lattin D. Distilled Spirits: Getting High, then Sober, with a Famous Writer, a Forgotten Philosopher, and a Hopeless Drunk. Berkeley, CA: University of California Press; 2012.Google Scholar
  58. 58.
    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;28:983-992.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    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.CrossRefPubMedGoogle Scholar
  60. 60.
    Garcia-Romeu A, Griffiths R R, Johnson M. W. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev 2014;7:157-164.CrossRefPubMedGoogle Scholar
  61. 61.
    Johnson MW, Garcia-Romeu A, Johnson PS, Griffiths RR. An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. J Psychopharmacol 2017 Jan 1.Google Scholar
  62. 62.
    Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa P, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol 2015;29:289-299.CrossRefPubMedGoogle Scholar
  63. 63.
    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;67:1735-1740.CrossRefPubMedGoogle Scholar
  64. 64.
    Sewell RA, Halpern JH, Pope HG. Response of cluster headache to psilocybin and LSD. Neurology 2006;66:1920-1922.CrossRefPubMedGoogle Scholar
  65. 65.
    Schindler EA, Gottschalk CH, Weil MJ, Shapiro RE, Wright DA, Sewell RA. Indoleamine hallucinogens in cluster headache: results of the Clusterbusters medication use survey. J Psychoact Drugs 2015;47:372-381.CrossRefGoogle Scholar
  66. 66.
    Karst M, Halpern JH, Bernateck M, Passie T. The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: an open, non-randomized case series. Cephalalgia 2010;30:1140-1144.CrossRefPubMedGoogle Scholar
  67. 67.
    Carhart-Harris RL, Erritzoe D, Williams T, et al. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci 2012;109:2138-2143.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Nichols DE, Johnson MW, Nichols CD. Psychedelics as medicines: an emerging new paradigm. Clin Pharmacol Ther 2017;101:209-219.CrossRefPubMedGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2017

Authors and Affiliations

  1. 1.Department of Psychiatry and Behavioral SciencesJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of NeuroscienceJohns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations