Psilocybin in end of life care: Implications for further research

This commentary (2016) examines the study design and the outcome measures of two randomized controlled studies that used psilocybin to treat mood and anxiety in patients undergoing palliative care. It can be concluded that the experiences of salience, meaningfulness, and healing that accompany the powerful spiritual experiences elicited by psilocybin, mediate the antidepressant and anxiolytic outcomes measures. Future investigations may investigate these phenomena in their own right, as well as replicate these findings in diverse clinical populations that aim to implement more robust blinding measures.

Abstract

“This issue of the Journal of Psychopharmacology contains two important randomized controlled studies on the use of psilocybin to treat mood and anxiety (including adjustment disorders) in carefully selected and supervised patients with later stage malignancies. Ross et al. (2016) studied 29 cancer patients using a two session, double-blind, crossover (seven weeks after administration of dose 1) design employing psilocybin first then niacin second, or niacin first and psilocybin second. Both groups had extensive orientation to the trial and psychotherapy with supportive, psychodynamic, and existential elements. They found that psilocybin produced an immediate and ongoing anxiolytic and antidepressant response, with 83% in the psilocybin-first group (vs. 14% in the niacin-first group) meeting criteria for antidepressant response seven weeks after dose 1. Pre-crossover results were significant post initial drug administration, although Beck Depression Inventory between groups was significant at the p<0.05 level one day prior to initial drug administration but not at baseline. At follow-up at six and a half months (after both groups received psilocybin), antidepressant or anxiolytic response rates were in the 60–80% range depending upon measure. Subjects’ mystical or spiritual experiences were highly correlated with clinical response and mediated four out of six primary outcome measures. Griffiths et al. (2016) studied 51 cancer patients using a two session, double-blind, crossover (five weeks after administration of dose 1) design employing high-dose psilocybin first then very low-dose (placebo-like) psilocybin second, or very low-dose (placebo-like) psilocybin first and high-dose psilocybin second. The use of low-dose psilocybin as its own control, instructional language to subjects and that which aimed to minimize the placebo response, and extensive supportive meetings with study personnel (but not formalized psychotherapy) were distinctive element of the study design. It was found that high-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety. Five weeks after session 1, 92% in the high-dose psilocybin-first group (vs. 32% in the low dose-first group) showed a clinically significant response and 60% versus 16% symptom remission. At follow-up at six months (after both groups received high-dose psilocybin), these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Subjects’ mystical or spiritual experiences were highly correlated with clinical response and mediated seven of the primary outcome measures.”

Author: Paul Summergrad

Summary

Ross et al. (2016) studied 29 cancer patients using a two-session, double-blind, crossover design. They found that psilocybin produced an immediate and ongoing anxiolytic and antidepressant response, with 83% of subjects in the psilocybin-first group meeting criteria for antidepressant response seven weeks after dose 1.

Griffiths et al. (2016) studied 51 cancer patients using a two-session, double-blind, crossover design. They found that high-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, and that these decreases were sustained at six months.

In both studies, subjects reported improvements in attitudes toward death and the experience of deeply meaningful spiritual experience. Adverse events were limited and included expected increases in blood pressure, pulse, nausea and vomiting, and transient anxiety or occasional psychotic symptoms, which remitted rapidly.

Placebo responsiveness and expectations are complex issues to isolate, but active drug responses are more substantial than placebo responses in moderately depressed patients.

The results of these studies have implications for ongoing research and clinical care with psychedelic agents, including the development of additional compounds with similar mechanisms of action.

The history of psychedelics and their legal status as highly restricted compounds make this a more complex issue. Despite extensive evidence of their safety in well-selected individuals under careful supervision, their prior history and the general history of expansion of indications for clinical agents is an important cautionary tale.

Neuroimaging studies with psilocybin and other psychedelic agents have suggested changes in the coupling of the posterior cingulate cortex and the medical prefrontal cortex, and the medial temporal lobe and the neocortex.

The experience of psilocybin by study participants was profound and meaningful, and the benefit of these experiences continued to affect them months later, despite their serious medical conditions.

These carefully designed studies show that powerful spiritual experiences are associated with a sense of salience, meaningfulness, and healing, which may be important for understanding mental health and other matters.

Two studies using psilocybin to treat psychologically distressed late-stage cancer patients with depressed mood and anxiety found acute, substantial, and enduring antidepressant and anxiolytic effects in 60 – 80% of study participants. The spiritual effect of psilocybin on the session day mediated the improvement in therapeutic outcomes.