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Death and Near-Death Experiences in Ketamine and Psychedelic Therapy

Michael Alvear

preprint DOI: 10.2139/ssrn.7206360 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and synthesis Randomized Open-label Case report
Interventions ketamine psilocybin DMT
Topics Esketamine Ketamine Near-death experience Psychedelic-assisted therapy
Key findings Near-death-like phenomenology is a recurring feature of certain drug therapies, with ketamine and DMT most closely reproducing spontaneous near-death experiences, and experience intensity correlating with reduced death anxiety and depressive symptoms in psilocybin trials.

Abstract

Patients undergoing ketamine-or psychedelic-assisted therapy for cancer-related distress, treatment-resistant depression, or end-of-life existential fear frequently report experiences resembling death or near-death: a sense of leaving the body, encountering something transcendent, or having died and returned. This synthesis reviews peer-reviewed evidence on how often this occurs, why it may occur, which drugs most closely reproduce the phenomenology of spontaneous near-death experience, and whether experience intensity tracks with clinical improvement. Evidence is drawn from randomized controlled trials, a meta-analysis, a Cochrane systematic review, large-scale survey and computational comparisons, and open-label case series, each verified directly against PubMed and Crossref records. Findings indicate that near-death-like phenomenology is a recurring rather than incidental feature of certain drug therapies; that ketamine and DMT most closely reproduce the phenomenology of spontaneous near-death experience across independent methodologies; that experience intensity correlates with reductions in death anxiety and depressive symptoms in psilocybin trials; and that a plausible neurophysiological basis for near-death phenomenology exists independent of any drug, though contested. Evidence quality varies substantially by claim: psilocybin's effect on anxiety and depression in life-threatening illness rests on low-certainty randomized evidence; its effect on existential distress specifically rests on a single small trial; and ketamine's link to reduced existential distress has not yet been tested in any randomized trial.

Comparable studies

Other systematic reviews and meta-analyses on ketamine and psychedelic-assisted therapy, most cited first.

Study Year Design Participants
A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review. Adults with treatment-resistant depression 2024 Systematic review
Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome. Patients with depression or substance use disorder 2024 Systematic review and meta-analysis n = 654
Ketamine and Ketamine-Assisted Psychotherapy for Psychiatric and Existential Distress in Patients with Serious Medical Illness: A Narrative Review. Patients with serious medical illness in a palliative care setting 2025 Systematic review
Psychedelic-Assisted Therapies for Psychosocial Symptoms in Cancer: A Systematic Review and Meta-Analysis Adults with cancer 2025 Systematic review and meta-analysis n = 455
How Do People Who Undergo Ketamine Treatment for a Psychiatric Problem Subjectively Experience This Intervention? A Meta-Synthesis of Qualitative Studies. People who received ketamine treatment for a psychiatric problem 2025 Systematic review and thematic meta-synthesis n = 24

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