Systematic Review of the Effect of Psychedelic-Assisted Therapy on Attitudes Toward Death, Life, and Spirituality on Symptoms of Distress, Depression, and/or Anxiety in Patients with Life-Threatening Illness.

Background: The underlying mechanism(s) of action of psychedelic-assisted therapy (PAT) to reduce distress, depression, and/or anxiety symptoms in life-threatening illness are poorly understood. It has been postulated that addressing death anxiety, and components of spiritual and existential distress, may be mediating factors. Method: This systematic review describes the current evidence base regarding the impact of PAT on attitudes toward life, death, and spirituality. MEDLINE, Embase, PsychINFO, and PubMed databases were systematically searched for original clinical research articles on PAT for distress, depression, and/or anxiety symptoms in life-threatening illness, with outcome measures related to attitudes toward life, death, and spirituality. The risk of bias was assessed using Joanna Briggs Institute critical appraisal checklists. A descriptive analysis was conducted. Results: A total of 14 articles met the inclusion criteria. Improvements in distress, depression, and/or anxiety symptoms were associated with reduced demoralization, reduced hopelessness, improvements in spirituality, greater death acceptance, a greater sense of optimism toward life, and a greater sense of meaningful existence. Mixed results were found in other attitudes toward life and death. Conclusions: This review identifies several mechanisms by which PAT may improve distress, depression, and/or anxiety symptoms in patients with life-threatening illness, via effects on a range of attitudes toward life, death, and spirituality. Results need to be considered with caution, given the paucity and quality of available data. This review also identifies gaps in the current evidence base for consideration in future research.