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.

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

“…The initial double-blind, randomized, placebo-controlled clinical studies in the modernera of psychedelic therapy (psilocybin) showed an immediate and sustained antidepressant and anxiolytic effect in people with depressive symptoms associated with life-threatening cancer (80-82) (Table 1). In subgroups, these antidepressant and anxiolytic effects were sustained for several years (97), as were reductions in suicidal ideation and loss of meaning (98). Similarly, recent data suggest efficacy for another group with high levels of loss, those who survived Acquired immunodeficiency syndrome (AIDS) (101).…”

Models of Psychedelic-Assisted Psychotherapy: A Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic, Trans-Drug Model

“…Psychedelic medicines are well known to catalyze profound encounters with mystical or spiritual content ( Griffiths et al, 2006 ; Breeksema et al, 2020 ; Podrebarac et al, 2021 ) and existential concerns, such as mortality ( Swift et al, 2017 ), alienation ( Watts et al, 2017 ), or questions of life meaning ( Ross et al, 2016 , 2021 ; Belser et al, 2017 ). This is perhaps not surprising, given the historical and current use of psychedelic plants and fungi in the religious practices of many cultures worldwide ( Schultes et al, 2001 ).…”

Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors

“…In addition, multiple administrations are required, and these drugs most often must be taken in combination with a classic antidepressant after their intake. Psilocybin could be an interesting alternative because it (i) acts on mechanisms that are implicated in SB and SI physiopathology [5]; (ii) could produce results with just one administration [4]; (iii) acts rapidly [19]; (iv) may not require co-therapy with a classic antidepressant after intake [20]; (v) has demonstrated sustained long-term efficacy (up to 6 months) [2]; and (vi) does not present any risk of addiction or discontinuation syndrome [2]. For patients taking an antidepressant therapy, a wash-out period of at least 7 days will be needed for psilocybin intake.…”