The role of psychedelics in palliative care reconsidered: A case for psilocybin
Venue: Journal of psychopharmacology

Psychiatric research with classic hallucinogens has enjoyed a resurgence of late. While studies performed in the late 1960s and early 1970s with lysergic acid diethylamide (LSD) and psilocybin demonstrated therapeutic promise by producing a rapid and sustained reduction in anxiety, improvement in mood, and enhanced quality of life in patients with terminal cancer (Grof, 1973) a fuller exploration of their use in palliative medicine was curtailed by the establishment of a strict federal regulatory environment. Now, after decades of research inactivity, the potential of psychedelics to alleviate the distress associated with a terminal illness has been significantly advanced by the results of two recent studies investigating the efficacy of psilocybin in the treatment of anxiety and depression in patients with life threatening cancer. Using double blind, placebo controlled, crossover designs, the studies conducted at Johns Hopkins University (JHU) and New York University (NYU) were methodologically rigorous and broad in the scope of their outcome variables. Both studies demonstrated that a single dose of psilocybin can produce both an acute and enduring reduction in depression symptoms, anxiety, and existential distress in patients with lifethreatening cancer. That the studies replicated one another is a source of confidence in their findings. However, there were also informative differences between the studies. The group at JHU led by Griffiths et al. investigated the effects of a very low dose (1 3 mg/70 kg, placebo like) versus high dose (22 mg/70 kg) of psilocybin administered five weeks apart in 51 patients diagnosed with lifethreatening cancer and suffering with symptoms of depression and/or anxiety (Griffiths et al. 2016) The group at NYU led by Ross et al. compared the effect of high dose psilocybin (0.3 mg/ kg, ~21 mg/ 70 kg) with niacin (used as an "active" control) in 29 patients, and both groups received targeted psychotherapy (Ross et al. 2016) All patients were screened and prepared for the study intervention through several meetings with staff who established rapport and provided an understanding of the range of altered states of consciousness that might be encountered during their treatment sessions. The psilocybin experience was well tolerated by all patients, and there were no serious medical or psychological adverse events. Both studies evaluated a broad range of outcome measures, including the common measures of anxiety and depression, as well as quality of life, spirituality, and mystical experiences. In the Griffiths et al. trial, high dose psilocybin produced large and sustained decreases in clinicianand patient rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning and optimism, and decreases in anxiety related to death. In the NYU trial, psilocybin produced rapid, substantial, and enduring reductions in cancer related anxiety and depression, improved quality of life, increased spiritual well being, and improved measures of existential distress, and was associated with improved attitudes toward death. At follow up at six and ahalf months, the initial robust clinical effects observed after the administration of a single dose of psilocybin endured in 60 80% of the patients, and when patients were asked (six and a half months post drug administration) to reflect on what they thought of their psilocybin session, 52% and 70% rated the psilocybin experience as the singular or top 5 most spiritually significant, or the singular or top 5 most personally meaningful experience of their entire lives, respectively, while 87% reported increased lifesatisfaction or well being attributed to the experience (Ross et al. 2016) The findings that single dose psilocybin can produce acute and sustained improvements in cancer related anxiety and depression is perhaps the most important and novel finding of the two studies, and add to and extend the findings of a similarly designed trial in patients with terminal cancer where a single low dose (0.2 mg/kg) of psilocybin showed non significant trends for benefit compared with placebo (Grob et al. 2011) In both studies, mediation analysis indicates that the mystical experience was a significant mediator of the effects of psilocybin dose on therapeutic outcomes. Mystical experience is defined as encountering a profound sense of unity, transcendence of time and space, deeply felt positive mood, noetic quality (sense of understanding) ineffability, transiency, and paradoxicality infused with a renewed sense of purpose and meaning (Griffiths, 2006, 2008, 2011; Grob et al. 2013) Further evidence for the The role of psychedelics in palliative care reconsidered: A case for psilocybin