On the need for a natural philosophy of psychedelics

Abstract

‘On the need for a natural philosophy of psychedelics’ provides a brief overview of the history of psychedelics in science and psychiatry, and a detailed review of recent evidence for their therapeutic and transformative efficacy. The chapter reviews clinical trials showing that one or two controlled psychedelic experiences can durably reduce symptoms of anxiety, depression, and addiction, and can cause lasting psychological benefits in healthy subjects. The chapter also reviews evidence that these beneficial effects are mediated by the occurrence of ‘mystical-type’ experiences. This evidence gives rise to the Comforting Delusion Objection that is the central focus of the book. Existing responses involve (i) rejecting philosophical naturalism, or (ii) downplaying the importance of epistemic factors in the evaluation of psychiatric treatments. The chapter raises problems for both approaches, and outlines a new one: to show that the Objection fails even if naturalism is true and the epistemic status of psychedelic therapy is important.

A dual-receptor model of serotonergic psychedelics

“…While appealing for its simplicity, this model cannot account for the mediating role that the acute phenomenological experience and its correlated neural activity play in driving positive clinical outcomes (Yaden & Griffiths, 2020). In contrast, frameworks privileging changes to subjective experience have focused on the role of belief alteration (Safron, 2020; Letheby, 2021), typically in the form of belief relaxation as a result of psychedelic use both acutely and post-acutely (R. L. Carhart-Harris & Friston, 2019).…”

“…Given that all classic psychedelics have significant affinity for the 5-HT2a receptor system, they have been characterized as a prototypical example of a substance that induces an “active coping” response in an organism by R. L. Carhart-Harris and Nutt. This manifests in the acute psychedelic state which enables a state of “metaplasticity”—the dynamic regulation of the extent to which synaptic plasticity can be induced (Abraham & Bear, 1996; Nardou et al, 2023), enabling a re-evaluation of previously held beliefs and the spontaneous assumption of novel representations of self or environment (for a review of this effect across various forms of belief, see (Letheby, 2021)). In contrast, R. L. Carhart-Harris and Nutt propose MDMA as an exemplar “passive coping” substance due to its role in releasing endogenous serotonin, which preferentially activates the 5-HT1a receptor system.…”

Importance of Integrating Spiritual, Existential, Religious, and Theological Components in Psychedelic-Assisted Therapies

“…A recent systematic review focusing explicitly on mystical-type experiences as mediators of therapeutic change found associations between PAT-induced SERT experiences and outcomes in cancer-related distress, treatment-resistant depression, and substance use disorders . There is also evidence that psychedelics elicit changes in metaphysical beliefs and that the effectiveness of PATs can to some extent be attributed to these metaphysical insights . On the other hand, some have argued that subjective experiences represent a third variable related to, but unnecessary for, an actual, entirely biological mechanism of action in PAT (eg, neuroplasticity).…”

Psychedelic-induced mystical experiences: An interdisciplinary discussion and critique

“…One phenomenon that has garnered a particularly large amount of attention in contemporary psychedelic research is the so-called 'mystical experience' (18)(19)(20)(21). Psychometric assessments of mystical experiences have provided quantitative evidence for mystical-type phenomenology in the psychedelic experience, and findings have further indicated that such phenomenology may be central to the therapeutic action of these compounds-potentially mediating or moderating lasting symptom reductions in patients and improvements in well-being in healthy individuals (20,(22)(23)(24)(25).…”