Annals of palliative medicineAug 21, 2024

Psilocybin-assisted therapy for deep emotional distress: practical advice for treatment

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

Psychedelic drugs, including psilocybin and LSD, may offer rapid and sustained relief from existential distress in patients with life-threatening illnesses.

Existential distress is linked to reduced quality of life and increased suicidal thoughts among patients with severe illnesses.
Traditional treatments for existential distress show limited effectiveness and short duration.
Psychedelic-assisted psychotherapy has been associated with significant reductions in existential and psychiatric distress.
The narrative review discusses the history of psychedelic medicine and highlights modern clinical trial findings from the past 20 years.
Specific considerations for using psilocybin in therapy include patient selection, dosing, and safeguards against adverse effects.

Simplified

Existential distress is commonly experienced by patients diagnosed with a life-threatening illness. This condition has been shown to adversely impact quality of life and is correlated with increased suicidal ideation and requests for hastened death. While palliative care teams are experienced in treating depression and anxiety, existential distress is a distinct clinical condition for which traditional medications and psychotherapy approaches demonstrate limited efficacy or duration of effect. Psychedelic drugs, including psilocybin and lysergic acid diethylamide (LSD), in conjunction with psychotherapy have been shown to produce rapid and sustained reductions in existential and psychiatric distress and may be a promising treatment for patients facing existential distress in palliative care settings. In this narrative review article, we describe the history of psychedelic medicine including early studies and the modern wave of research over the past 20 years, which includes high quality clinical trial data. This review outlines specific considerations for therapeutic application of psilocybin including pharmacokinetics, patient selection, dosing, protocol designs, and safeguards to reduce potential adverse effects to help guide future psychedelic practitioners. With growing public interest and evolving state level policy reforms allowing access to psychedelic treatments, it is critical for palliative care providers to gain familiarity with the current state of science and the potential of psilocybin assisted psychotherapy in the treatment of existential distress.

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Psilocybin-assisted therapy for deep emotional distress: practical advice for treatment

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