Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer

Abstract

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained improvements in depression, demoralization, and hopelessness in people with cancer. Converging epidemiologic and clinical trial findings suggests a potential antisuicidal effect of this treatment. To probe our hypothesis that PAP relieves SI through its beneficial impacts on depression and demoralization (LoM in particular), we performed secondary analyses assessing within- and between-group differences with regard to LoM and an SI composite score. Among participants with elevated SI at baseline, PAP was associated with within-group reductions in SI that were apparent as early as 8 h and persisted for 6.5 months postdosing. PAP also produced large reductions in LoM from baseline that were apparent 2 weeks after treatment and remained significant and robust at the 6.5 month and 3.2 and 4.5 year follow-ups. Exploratory analyses support our hypothesis and suggest that PAP may be an effective antisuicidal intervention following a cancer diagnosis due to its positive impact on hopelessness and demoralization and its effects on meaning-making in particular. These preliminary results implicate psilocybin treatment as a potentially effective alternative to existing antidepressant medications in patients with cancer that are also suicidal, and warrant further investigation in participants with elevated levels of depression and suicidality.

Figure 1

Temporal relationships between drug administration, psychosocial interventions, and assessments in the main trial and ancillary long-term follow-up trial. Prep PT = preparatory psychotherapy; D1 = double-blind dosing 1; Post-Integrative PT = post-integrative psychotherapy.

Figure 2

CONSORT flow diagram depicting number of participants from parent trial and ancillary long-term follow-up trial that completed assessment time points included in the current analyses.

Figure 3

Effects of treatment on SI and LoM. (a) Mean (±SE) scores on SI and LoM at baseline and each precrossover assessment; (b) mean (±SE) scores on SI and LoM at Baseline and each postcrossover assessment. Dotted lines indicate medication sessions. Open shapes indicate a within-group difference from baseline score at p < 0.05, and * denotes a between-group difference at p < 0.05.

Figure 4

Relationships between SI, LoM, and other depressive symptoms: (a) Correlation between LoM and SI scores collapsed across assessment time point; (b) correlation between change from baseline to 2 weeks post dose 1 in SI.

Figure 5

Proposed theoretical causal model. Therapeutic effects of psilocybin therapy in the treatment of DHD and SI following a cancer diagnosis. 5HT2A: serotonin 2A receptor; CSTC: cortico-striato-thalamo-cortical; DMN: default mode network.