Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Roland R Griffiths, Matthew W Johnson, Michael A Carducci, Annie Umbricht, William A Richards, Brian D Richards, Mary P Cosimano, Margaret A Klinedinst, Roland R Griffiths, Matthew W Johnson, Michael A Carducci, Annie Umbricht, William A Richards, Brian D Richards, Mary P Cosimano, Margaret A Klinedinst

Abstract

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Trial registration: ClinicalTrials.gov identifier: NCT00465595.

Keywords: Psilocybin; anxiety; cancer; depression; hallucinogen; mystical experience; symptom remission.

Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Roland Griffiths is on the Board of Directors of the Heffter Research Institute.

© The Author(s) 2016.

Figures

Figure 1.
Figure 1.
Flow diagram showing participation across the study.
Figure 2.
Figure 2.
Within-session time-course of psilocybin effects on cardiovascular and observer-rated measures. Cardiovascular (systolic and diastolic blood pressure, and heart rate) and observer (i.e. monitor)-rated overall drug effect, visual effects with eyes closed (as described by the participant), and joy/intense happiness. Data points show means; brackets indicate 1 SEM; circles show data after the low dose (n = 50); squares show data after the high dose (n = 50). Filled squares indicate the dose conditions were significantly different at the indicated time-point (p<0.05, planned comparisons). Y-axes for observer ratings show maximum possible scores.
Figure 3.
Figure 3.
Effects of psilocybin on selected outcome measures that were assessed at Baseline, Post-session 1 (5 weeks after Session 1), Post-session 2 (5 weeks after Session 2), and 6-month follow-up. Data points show means; brackets indicate 1 SEM; circles represent the group that received a low dose on the 1st session and a high dose on the 2nd session (n = 25, 25, 24, and 22 at Baseline, Post-session 1, Post-session 2, and 6 months, respectively); squares represent the group that received a high dose on 1st session and a low dose on the 2nd session (n = 26, 26, 25, and 24 at Baseline, Post-session 1, Post-session 2, and 6 months, respectively). Star symbol indicates a significant difference between the two groups at the Post-session 1 time-point (p<0.05, planned comparison). Cross symbol indicates a significant difference between the Post-session 1 and Post-session 2 time-points in the Low-Dose-1st (High-Dose-2nd) Group (p<0.05, planned comparison).
Figure 4.
Figure 4.
Effects of psilocybin on clinically significant response rate and symptom remission rate as assessed with clinician-rated measures of depression and anxiety. Data are percentage of participants fulfilling criteria at Post-session 1 (5 weeks after Session 1) and at 6 months. Asterisks indicates that the low and high-dose groups were significantly different at 5 weeks (p>0.001); data at 6 months show these effects were sustained at follow-up. See Table 6 for other details.
Figure 5.
Figure 5.
Relationship between the Mystical Experience Questionnaire (MEQ30) total score assessed at end of Session 1 and several illustrative outcome measures assessed 5 weeks after Session 1. Each panel shows scores on an outcome measure assessed 5 weeks after Session 1 as a function of the total MEQ30 score obtained 7 h after psilocybin administration on Session 1. MEQ30 scores are expressed as a percentage of maximum possible score. Data points represent individual participants (n = 50 or 51); blue circles represent the group that received the low dose on the 1st session; red squares represent the group that received the high dose on the 1st session. Correlation coefficients and p-values are shown.

References

    1. Arrieta O, Angulo LP, Nunez-Valencia C, et al. (2013) Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol 20: 1941–1948.
    1. Barrett FS, Johnson MW, Griffiths RR. (2015) Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J Psychopharmacol 29: 1182–1190.
    1. Beck AT, Steer RA. (1987) BDI Beck Depression Inventory Manual. San Antonio, San Diego, Orlando, New York, Chicago, Toronto: The Psychological Corporation Harcourt Brace Jovanovich, Inc.
    1. Benson PL, Donahue MJ, Erickson JA. (1993) The Faith Maturity Scale: Conceptualization, measurement, and empirical validation. Res Soc Sci Stud Religion 5: 1–26.
    1. Breitbart W, Rosenfeld B, Pessin H, et al. (2015) Meaning-centered group psychotherapy: An effective intervention for improving psychological well-being in patients with advanced cancer. J Clin Oncol 33: 749–754.
    1. Carhart-Harris RL, Bolstridge M, Rucker J, et al. (2016) Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. Lancet Psychiatry 3: 619–627.
    1. Carhart-Harris RL, Leech R, Hellyer PJ, et al. (2014) The entropic brain: A theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Human Neurosci 8(20): 1–22.
    1. Carhart-Harris RL, Erritzoe D, Williams T, et al. (2012) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A 109: 2138-2143.
    1. Cohen SR, Mount BM, Strobel MG, et al. (1995) The McGill Quality of Life Questionnaire: A measure of quality of life appropriate for people with advanced disease. A preliminary study of validity and acceptability. Palliat Med 9: 207–219.
    1. Colleoni M, Mandala M, Peruzzotti G, et al. (2000) Depression and degree of acceptance of adjuvant cytotoxic drugs. Lancet 356: 1326–1327.
    1. Derogatis LR. (1992) BSI Brief Symptom Inventory: Administration, Scoring, and Procedures Manual. Minneapolis, MN: National Computer Systems, Inc.
    1. Dittrich A. (1998) The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry 31(Suppl 2): 80–84.
    1. Faller H, Schuler M, Richard M, et al. (2013) Effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: Systematic review and meta-analysis. J Clin Oncol 31: 782–793.
    1. Gao K, Wu R, Kemp DE, et al. (2014) Efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar depression with generalized anxiety disorder and other comorbidities: A randomized, placebo-controlled trial. J Clin Psychiatry 75: 1062–1068.
    1. Garcia-Romeu A, Griffiths RR, Johnson MW. (2014) Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev 7: 157–164.
    1. Gasser P, Holstein D, Michel Y, et al. (2014) Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. Journal Nerv Ment Dis 202: 513–520.
    1. Grassi L, Caruso R, Hammelef K, et al. (2014) Efficacy and safety of pharmacotherapy in cancer-related psychiatric disorders across the trajectory of cancer care: A review. Int Rev Psychiatry 26: 44–62.
    1. Griffiths R, Richards W, Johnson M, et al. (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol 22: 621–632.
    1. Griffiths RR, Richards WA, McCann U, et al. (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 187: 268–283.
    1. Griffiths RR, Johnson MW, Richards WA, et al. (2011) Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects. Psychopharmacology 218: 649–665.
    1. Grob CS, Danforth AL, Chopra GS, et al. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 68: 71–78.
    1. Grof S, Goodman LE, Richards WA, et al. (1973) LSD-assisted psychotherapy in patients with terminal cancer. Int Pharmacopsychiatry 8: 129–144.
    1. Halberstadt AL. (2015) Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behav Brain Res 277: 99–120.
    1. Hayes AF. (2013) Introduction to Mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach. Guildford Press, New York.
    1. Hendricks PS, Johnson MW, Griffiths RR. (2015) Psilocybin, psychological distress, and suicidality. J Psychopharmacol 29: 1041–1043.
    1. Holland JC, Andersen B, Breitbart WS, et al. (2013) Distress management. J Natl Comp Cancer Network: JNCCN 11: 190–209.
    1. Hood RW, Jr, Hill PC, Spilka B. (2009) The Psychology of Religion: An Empirical Approach. New York: The Guilford Press.
    1. Hood RW, Jr, Ghorbani N, Watson PJ, et al. (2001) Dimensions of the mysticism scale: Confirming the three-factor structure in the United States and Iran. J Sci Study Relig 40: 691–705.
    1. ISCDD (2003) GRID-HAMD-17 Structured Interview Guide. San Diego, CA: International Society for CNS Drug Development.
    1. Johnson M, Richards W, Griffiths R. (2008) Human hallucinogen research: Guidelines for safety. J Psychopharmacol 22: 603–620.
    1. Johnson MW, Sewell RA, Griffiths RR. (2012) Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug Alcohol Depend 123: 132–140.
    1. Kast E. (1967) Attenuation of anticipation: A therapeutic use of lysergic acid diethylamide. Psychiatr Q 41: 646–657.
    1. MacLean KA, Leoutsakos JM, Johnson MW, et al. (2012) Factor analysis of the Mystical Experience Questionnaire: A study of experiences occasioned by the hallucinogen psilocybin. J Sci Stud Relig 51: 721–737.
    1. Matza LS, Morlock R, Sexton C, et al. (2010) Identifying HAM-A cutoffs for mild, moderate, and severe generalized anxiety disorder. Int J Methods Psychiatr Res 19: 223–232.
    1. McIntosh DN. (1999) Purpose in Life Test (Crumbaugh & Maholick, 1964). In: Hill PC, Hood RW. (eds) Measures of Religiosity. Birmingham, AL: Religious Education Press, pp.503–508.
    1. McNair DM, Lorr M, Droppleman LF. (1992) Profile of Mood States. San Diego, CA: edITS/Educational and Industrial Testing Service.
    1. Metzner R, Litwin G, Weil G. (1965) The relation of expectation and mood to psilocybin reactions: A questionnaire study. Psychedelic Rev 5: 3–39.
    1. Mitchell AJ, Chan M, Bhatti H, et al. (2011) Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: A meta-analysis of 94 interview-based studies. Lancet Oncol 12: 160–174.
    1. Nichols DE. (2016) Psychedelics. Pharmacol Rev 68: 264–355.
    1. Ostuzzi G, Matcham F, Dauchy S, et al. (2015) Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev 6: CD011006.
    1. Pargament KI, Koenig HG, Tarakeshwar N, et al. (2004) Religious coping methods as predictors of psychological, physical and spiritual outcomes among medically ill elderly patients: A two-year longitudinal study. J Health Psychol 9: 713–730.
    1. Peterman AH, Fitchett G, Brady MJ, et al. (2002) Measuring spiritual well-being in people with cancer: The functional assessment of chronic illness therapy – Spiritual Well-being Scale (FACIT-Sp). Ann Behav Med 24: 49–58.
    1. Pinquart M, Duberstein PR. (2010) Depression and cancer mortality: A meta-analysis. Psychol Med 40: 1797–1810.
    1. Prieto JM, Blanch J, Atala J, et al. (2002) Psychiatric morbidity and impact on hospital length of stay among hematologic cancer patients receiving stem-cell transplantation. J Clin Oncol 20: 1907–1917.
    1. Reker GT. (1992) The Life Attitude Profile-Revised (LAP-R). Peterborough, ON: Student Psychologists Press.
    1. Richards WA, Rhead JC, DiLeo FB, et al. , (1977) The peak experience variable in DPT-assisted psychotherapy with cancer patients. J Psychedelic Drugs 9: 1–10.
    1. Scheier MF, Carver CS. (1985) Optimism, coping, and health: assessment and implications of generalized outcome expectancies. Health Psychol 4: 219–247.
    1. Shear MK, Vander Bilt J, Rucci P, et al. (2001) Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A). Depress Anxiety 13: 166–178.
    1. Shim EJ, Park JH. (2012) Suicidality and its associated factors in cancer patients: Results of a multi-center study in Korea. Int J Psychiatry Med 43: 381–403.
    1. Skarstein J, Aass N, Fossa SD, et al. (2000) Anxiety and depression in cancer patients: Relation between the Hospital Anxiety and Depression Scale and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire. J Psychosom Res 49: 27–34.
    1. Spiegel D. (2015) Existential psychotherapy for patients with advanced cancer: Facing the future and the past. J Clin Oncol 33: 2713–2714.
    1. Spielberger CD. (1983) Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press, Inc.
    1. Strassman RJ, Qualls CR, Uhlenhuth EH, et al. (1994) Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry 51: 98–108.
    1. Studerus E, Kometer M, Hasler F, et al. (2011) Acute, subacute and long-term subjective effects of psilocybin in healthy humans: A pooled analysis of experimental studies. J Psychopharmacol 25: 1434–1452.
    1. VandeCreek L. (1999) The Death Transcendence Scale (Hood & Morris, 1983). In: Hill PC, Hood RW. (eds) Measures of Religiosity. Birmingham, AL: Religious Education Press, pp.442–445.
    1. Vollenweider FX, Kometer M. (2010) The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders. Nat Rev Neurosci 11: 642–651.
    1. Walker J, Sawhney A, Hansen CH, et al. (2014) Treatment of depression in adults with cancer: A systematic review of randomized controlled trials. Psychol Med 44: 897–907.
    1. Zigmond AS, Snaith RP. (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67: 361–370.

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