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Although existential suffering is amongst the most devastating forms of distress experienced by many patients nearing the end-of-life, it is often unsatisfactorily addressed due to a paucity of effective interventions. However, both historic and recent studies of psychedelic-assisted psychotherapy have reported marked alleviation of this suffering. As such, this article seeks to advance the rationale for the use of psychedelic substances in the provision of psychedelic-assisted psychotherapy for patients nearing the end-of-life. It begins with an overview of the classic psychedelics and their application in psychotherapy, highlighting recent studies. This is followed with a conceptual overview of existential suffering at the end-of-life and the process of selftranscendence. These sections are then integrated in a theoretical rationale for psychedelic-assisted mystical states as a means of facilitating the development of self-transcendence and, through it, the remediation of existential suffering. The paper concludes with a discussion of practical and philosophical considerations germane to the safe and ethical application of psychedelics in healthcare. In particular, developmental considerations for assessing both therapist and patient applicability in utilizing this modality are proposed.