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Clinical Trial
. 2016 Dec;30(12):1165-1180.
doi: 10.1177/0269881116675512.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

Stephen Ross  1   2   3   4   5   6 , Anthony Bossis  7   2   4 , Jeffrey Guss  7   2   4 , Gabrielle Agin-Liebes  8 , Tara Malone  7 , Barry Cohen  9 , Sarah E Mennenga  7 , Alexander Belser  10 , Krystallia Kalliontzi  2 , James Babb  11 , Zhe Su  3 , Patricia Corby  2 , Brian L Schmidt  2
Affiliations
Clinical Trial

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

Stephen Ross et al. J Psychopharmacol. 2016 Dec.

Abstract

Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression.

Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks.

Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.

Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress.

Trial registration: ClinicalTrials.gov Identifier: NCT00957359.

Keywords: Psilocybin; anxiety; cancer; depression; mystical experience; psychedelic.

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Conflict of interest statement

Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
CONSORT diagram.
Figure 2.
Figure 2.
Interventions and assessments schedule. Temporal relationships between drug administration, psychosocial interventions, and assessments. Prep PT: preparatory psychotherapy; 1-day pre-D1: 1 day prior to dose 1; Dose 1: dosing session 1; 1-day post-D1: 1 day after dose 1; Post-integrative PT: post-integrative psychotherapy; 2-wks post-D1: 2 weeks after dose 1; 6-wks post-D1: 6 weeks after dose 1; Safety prep for D2: safety preparation for dosing dose 2; 1-day pre-D2: 1 day prior to dose 2; Dose 2: dosing session 2; 1-day post-D2: 1 day after dose 2; 6-wks post-D2: 6 weeks after dose 2; 26-wks post-D2: 2 weeks after dose 2.
Figure 3.
Figure 3.
Primary outcome variables: cancer-related anxiety and depression (pre-crossover). Means (±SE) for primary outcome measures are shown in the two treatment groups at the following time points: baseline (psilocybin first n=14, niacin first n=15), 1 day pre-dose 1 (psilocybin first n=14, niacin first n=15), 1 day post-dose 1 (psilocybin first n=14, niacin first n=15), 2 weeks post-dose 1 (psilocybin first n=14, niacin first n=14), 6 weeks post-dose 1 (psilocybin first n=14, niacin first n=14), 7 weeks post-dose 1 (psilocybin first n=12, niacin first n=14). Asterisks indicate significance level of between-group t-tests. Effect sizes, represented as Cohen’s d, are shown above time points at which the treatment groups differ. Closed points represent significant within-group differences relative to scores at baseline.
Figure 4.
Figure 4.
Primary outcome variables: cancer-related anxiety and depression (post-crossover). Means (±SE) for primary outcome measures are shown in the two treatment groups at the following time points: baseline (psilocybin first n=14, niacin first n=15), 1-day pre dose-1 (psilocybin first n=14, niacin first n=15), 1 day post-dose 1 (psilocybin first n=14, niacin first n=15), 6 weeks post-dose 1 (psilocybin first n=14, niacin first n=14), 7 weeks post-dose 1 (1 day pre-dose 2) (psilocybin first n=12, niacin first n=14), 1 day post-dose 2, 6 weeks post-dose 2 (psilocybin first n=12, niacin first n=11), 26 weeks post-dose 2 (psilocybin first n=11, niacin first n=12). Asterisks indicate significance level of between-group t-tests. Closed points represent significant within-group differences relative to scores at baseline.
Figure 5.
Figure 5.
Percentage of participants with anti-depressant or anxiolytic response rates and anti-depressant symptom remission. Percentages of participants in each treatment group who met criteria for anti-depressant or anxiolytic response or anti-depressant symptom remission (BDI, HAD D) at 1 day post-dose 1 (psilocybin first n=14, niacin first n=15), 7 weeks post-dose 1 (psilocybin first n=12, niacin first n=14) and at 26 weeks post-dose 2 (psilocybin first n=11, niacin first n=12). Asterisks indicate significance level of between-group comparisons at each time point.
Figure 6.
Figure 6.
Secondary outcome measures: existential distress, quality of life, spirituality, persisting effects attributed to psilocybin administration. (Top) Percentage of participants that reported ‘among the top 5’ or ‘the single most’ personally meaningful and spiritually significant experiences, ‘moderate’, ‘strong’ or ‘extreme’ positive behavioral change, and ‘increased moderately’ or ‘increased very much’ wellbeing or life satisfaction on the Persisting Effects Questionnaire (PEQ). Asterisks indicate significance level of comparison to the niacin first group at 2 weeks post-dose 1. There were no significant differences between the psilocybin first group at 2 weeks post-dose 1 versus the psilocybin first group at 26 weeks post-dose 2. (Bottom) Secondary measures of cancer-related existential distress (DEM, HAI, DAS, DTS), quality of life (WHO-Bref) and spirituality (FACIT). Measures are shown at 2 weeks post-dose 1 (psilocybin first n=14, niacin first n=14) and at 26 weeks post-dose 2 (psilocybin first n=11, niacin first n=12); asterisks indicate significance level of comparison to the niacin first group at 2 weeks post-dose 1. There were no significant differences between the psilocybin first group at 2 weeks post-dose 1 versus the psilocybin first group at 26 weeks post-dose 2.
Figure 7.
Figure 7.
Subjective effects of psilocybin and relationship of mystical experience to clinical outcomes. (Top) Subjective effects as measured by the Mystical Experience Questionnaire (MEQ 30) in each treatment group at 7 hours post-session 1 (psilocybin first n=14, niacin first n=15), 7 hours post-session 2 (psilocybin first n=12, niacin first n=14), and 26 weeks post-dose 2 (psilocybin first n=11, niacin first n=12). Asterisks indicate significance level of between-group differences. (Bottom) Mediation model in which total scores on the MEQ transmit a portion of the effects of psilocybin versus niacin treatment on change in anxiety and depression is shown.
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