Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy

Hendricks situates the paper in the context of a renewed scientific interest in classic psychedelics (notably psilocybin) after decades of limited research. Earlier clinical and observational work indicates that classic psychedelics, when administered in controlled therapeutic contexts, can produce enduring positive changes across psychological and behavioural domains and show initial signals of efficacy for conditions such as depression, end-of-life distress and addiction. Despite accumulating clinical data and convergent neurobiological hypotheses (for example, changes in default mode network connectivity), Hendricks notes a gap in psychological-level explanations for how psychedelic-occasioned mystical experiences produce lasting benefit. The primary aim of the manuscript is to propose a psychological model that identifies the emotion awe as the principal mechanism underlying the salutary effects of mystical experiences occasioned by classic psychedelic-assisted psychotherapy. To support this proposal, Hendricks compares the core features, predictors and outcomes of awe and psychedelic-occasioned mystical experience, considers potential overlapping neural and molecular mechanisms, and outlines clinical implications and recommendations for advancing research and practice in this area.

The extracted text does not describe an explicit empirical methods section; rather, the paper presents a theoretical and integrative argument built from contemporary empirical findings across emotion science and psychedelic research. Hendricks synthesises prior experimental, clinical and observational studies, psychometric instruments, and neurobiological findings to construct the proposed model. The approach comprises conceptual comparison (contrasting core features and acute effects of awe with items and constructs measured in established psychedelic instruments such as the Mystical Experience Questionnaire (MEQ30), the Ego-dissolution Inventory and the Challenging Experience Questionnaire), review of predictors and outcomes reported in the respective literatures, and a speculative mapping to emerging neuroimaging and molecular findings. The author explicitly notes where evidence is limited or speculative (for example, the paucity of direct neuroscientific work on awe) and does not claim to have conducted a systematic review with prespecified search methods or formal inclusion criteria.

Hendricks presents several lines of evidence suggesting substantial overlap between awe and classic psychedelic-occasioned mystical experience. First, core phenomenological features align: emotion scientists characterise awe as arising from appraisals of vastness and the need for accommodation, producing a ‘‘small self’’—attenuated self-focus, feelings of connectedness or oneness, and perceived smallness. The MEQ30 and related psychedelic measures capture items that directly map onto awe (for example, 'sense of awe or awesomeness' and 'experience of amazement'), and other MEQ30 subscales (unity, insight, sacredness, time/space transcendence, ineffability) correspond to facets theorised as acute outcomes of awe. The Ego-dissolution Inventory similarly emphasises the small self, and the Challenging Experience Questionnaire documents dysphoric phenomena (fear, paranoia, death-related experiences) that resemble the dread sometimes associated with awe. Second, predictors of awe and psychedelic mystical experience appear to converge. Trait absorption and openness are highlighted in both literatures: pooled data from 23 controlled psilocybin studies (409 administrations to 261 volunteers) identified trait absorption as the second strongest predictor of mystical experience (regression coefficient = 0.35), with drug dose the leading predictor (regression coefficient = 0.78). Experimental work in the awe field links dispositional openness, lower need for cognitive closure, and trait absorption to greater propensity to experience awe; novelty of the eliciting stimulus is also emphasised. Similarly, context, mood and neuroticism are associated with challenging psychedelic experiences, and prior psychedelic exposure may reduce later intensity, consistent with habituation. Third, downstream outcomes show parallels. Experimental inductions of awe increase positive affect (gratitude, joy), life satisfaction, humility and short-term prosocial behaviour, and induce a sense of increased perceived time availability. Some evidence links dispositional awe to lower circulating interleukin-6 (IL-6), a proinflammatory cytokine. Psychedelic studies report enduring increases in positive affect, gratitude, life satisfaction, humility, prosocial attitudes and behaviours; placebo-controlled trials in patients with life-threatening cancer associated psilocybin-occasioned mystical experience with lasting decreases in anxiety and depression and improved quality of life. Naturalistic studies report lower population-level psychological distress, suicidality and criminal behaviour associated with classic psychedelic use, and ayahuasca use has been linked with increased mindfulness. Fourth, Hendricks outlines tentative neurobiological convergences. Classic psychedelics acutely decrease within-network connectivity and increase global functional connectivity across the brain, changes correlated with self-reported ego dissolution; increased connectivity in bilateral temporoparietal junction and bilateral insula—regions implicated in self–other boundary and bodily orientation—are particularly associated with ego-dissolution. Although there is no direct neuroimaging literature on awe yet, Hendricks proposes that similar increases in global connectivity could underpin awe-related small-self phenomena. At the molecular level, classic psychedelics are serotonin 2A receptor agonists and down-regulate cortical 5-HT2A receptors; given serotonin's role in social dominance and related behaviours, Hendricks suggests a tentative link between serotonergic modulation, reduced dominance or increased subservience/humility and the social effects of awe. Finally, the manuscript provides illustrative quotations (from nature experiences, astronaut reports and psychedelic reports) to demonstrate phenomenological similarity across elicitors, and notes measurement issues: while items measuring awe exist and the disposition to experience awe can be assessed (for example, via the Dispositional Positive Emotion Scale), there is no single, psychometrically validated, standard measure of awe tailored to test the proposed model.

Hendricks interprets the convergent evidence as supporting a model in which awe is the primary psychological catalyst of therapeutic change following classic psychedelic-occasioned mystical experience. In this model, psychedelic administration produces an experience appraised as vast and requiring accommodation—awareness of the small self—that mediates acute outcomes (insight, sacredness, positive mood, time/space transcendence, ineffability) and longer-term benefits (increased gratitude, well-being, humility, prosocial motivation, mindfulness and openness). The paper situates this model relative to earlier conceptualisations that emphasised insight, spiritual conversion or ego dissolution, arguing that awe offers a parsimonious way to integrate these constructs and to explain phenomena sometimes described as ‘‘quantum change’’. Drawing on dynamical systems theory, Hendricks proposes that awe's demand for accommodation could precipitate sudden, non-linear change when prior mental models are no longer tenable. Key limitations and uncertainties are explicitly acknowledged. Most notably, direct neuroscientific evidence for awe is lacking, making the proposed neural parallels speculative. The manuscript is theoretical rather than empirical and does not report systematic search methods; consequently, empirical validation is required. Measurement limitations include the absence of a singular, validated awe instrument and incomplete knowledge about whether induced awe can produce lasting increases in trait openness (whereas psychedelic experiences have been shown to do so). The author also notes practical constraints: classic psychedelics remain unapproved by major regulators and are highly controlled, so clinical integration is contingent on future safety and efficacy determinations. On the basis of the model, Hendricks offers multiple research and clinical recommendations. These include developing a standard psychometric measure of awe, promoting absorption during preparation (for example via mindfulness) to potentiate awe and mystical experience, and exploring administration contexts that elicit awe (natural or religious settings, or virtual reality) while ensuring safety. The author suggests tailoring music to individual preference to enhance awe, incorporating systems- or family-based therapies to capitalise on revived social connectedness, and using aftercare interventions (nature exposure, art, music, spiritual practices, mindfulness or gratitude training) to sustain an 'afterglow'. Consideration is also given to habituation—novelty is critical to awe—implying limited numbers of administrations or dose escalation as practical approaches. Hendricks frames these recommendations as hypotheses to guide future empirical work rather than established clinical protocols.

Hendricks concludes by reiterating the central proposal that awe functions as a principal psychological mechanism driving the therapeutic effects of classic psychedelic-occasioned mystical experiences. The manuscript offers a testable theoretical framework intended to generate hypotheses, motivate focused research (including measurement development and neuroscientific work on awe), and inform clinical-scientific practice as the field progresses. The author emphasises that the model is provisional and invites refinement as more empirical data accumulate.