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

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.

Figure 1.

Flow diagram showing participation across the study.

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.

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.

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.

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.