Psilocybin in end of life care: Implications for further research

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.