Being no one, being One: The role of ego-dissolution and connectedness in the therapeutic effects of psychedelic experience

Kałużna and colleagues situate this review within the recent revival of scientific interest in classic, serotonergic psychedelics (5-HT2A agonists) and the growing evidence that psychedelic-assisted experiences can reduce symptoms across conditions such as depression, anxiety, addiction and end-of-life distress. Prior literature emphasises the importance of ‘‘set and setting’’ and of experiential content in determining therapeutic outcomes, yet specific subjective states that might mediate benefit remain incompletely characterised. Two candidate experiential constructs receive particular attention: ego-dissolution, a reduction in self-referential awareness, and connectedness, a sense of unity or relatedness with others, nature or the universe. The authors note that connectedness can be parsed into connection with others, with the world, and with the self; this review concentrates on the first two types that overlap conceptually with constructs like oceanic boundlessness and oneness, while excluding ‘‘connectedness with self’’ because it does not map cleanly onto those terms. The review sets out to determine the extent to which ego-dissolution and connectedness predict therapeutic outcomes after classic psychedelic experiences, whether the two phenomena are associated with each other, and whether their associations vary across psychological outcome domains. The paper was pre-registered and restricted to human studies of classic psychedelics, excluding non-classic agents such as MDMA or ketamine. The working hypotheses were that both ego-dissolution and connectedness would correlate positively with improvements in mental health and wellbeing, and that the two experiences would be positively correlated with each other.

This work is a mixed-methods systematic review and narrative synthesis, pre-registered on PROSPERO and conducted according to PRISMA principles. Searches were run to July 2021 in four electronic databases: MEDLINE, PsycINFO, AMED, and Web of Science; grey literature and manual journal searches were not performed. Studies of human participants were eligible if they reported classic-psychedelic-induced experiences of ego-dissolution and/or connectedness (measured quantitatively or described qualitatively) and reported post-experience mental health or wellbeing outcomes. Non-classic psychedelics, non-pharmacological induction methods, and studies treating social connectedness as a social-network outcome were excluded. Both quantitative and qualitative primary studies were eligible; reviews and meta-analyses were excluded. Screening used Covidence with four reviewers independently screening titles and abstracts; full-text screening was carried out by one reviewer with documented reasons for exclusion. Data extracted included study and participant characteristics, psychedelic substance and dose where available, context of administration, measures of ego-dissolution/connectedness, and mental health/wellbeing outcomes. Study quality, trustworthiness and appropriateness were appraised using the Mixed Methods Appraisal Tool (MMAT), following the MMAT structure of initial screening questions then design-specific items. Because included studies were methodologically heterogeneous, the team transformed quantitative data into qualitative descriptors and synthesised findings using narrative methods guided by ESRC guidance. Vote-counting of directional findings and inductive thematic analysis (including reciprocal translation across qualitative studies) were used to identify recurring themes and relationships. The authors also inspected heterogeneity by substance, study context (lab vs naturalistic), population, and methodological features, and carried out planned subgroup syntheses comparing ego-dissolution versus connectedness and examining outcome-domain differences. Effect sizes were considered when reported but were not pooled or compared quantitatively across studies.

The search yielded 15 eligible primary studies (published 2017–2021) comprising 2,182 participants; sample sizes ranged from 9 to 654. Study designs included eight quantitative, five qualitative, and two mixed-methods investigations. Psilocybin was the most commonly studied substance (seven studies), with other work on ayahuasca, DMT, mescaline and broader psychedelic use; 11 studies examined connectedness, 10 examined ego-dissolution, and six assessed both. Participant samples were predominantly from Western, anglophone countries: of studies reporting nationality (n = 2,048) about 52% were North American, 25% European, with the remainder from other regions. Ethnicity data (n = 525) showed 81% White where reported. Across studies reporting gender, approximately 28% were female, 70% male and 2% other or transgender/gender-fluid. Quality appraisal highlighted recurring concerns: moderately high attrition in surveys and observational studies, some highly specific clinical inclusion criteria that limit generalisability, limited attention to SSRI or other psychotropic confounders, and generally low cultural diversity. Despite heterogeneity, findings converged across methods. Quantitative and qualitative results indicated that both ego-dissolution and connectedness were positively associated with improvements in mental health and wellbeing measures in most studies. Ten studies reported immediate therapeutic effects of connectedness and eight reported longer-term effects (ranging from five weeks to 30 months or in retrospective surveys). Ego-dissolution showed more variable persistence: seven studies reported immediate therapeutic associations, but only three reported sustained associations beyond the short term (examples include reductions in alcohol use up to four weeks, and longer-term self-transformations in small samples). When outcome domains were disaggregated, the review found consistent positive associations with wellbeing measures: six of nine studies examining general wellbeing reported positive correlations for ego-dissolution and six for connectedness. For depression, ego-dissolution negatively correlated with depressive symptoms in four of six studies, and connectedness (often operationalised as oceanic boundlessness) predicted reduction in depressive symptoms in several studies, sometimes for weeks post-session. Anxiety outcomes were similarly mixed but generally favourable. Addiction outcomes were reported in four studies; qualitative and quantitative data linked experiences of interconnectedness or ego-dissolution to reductions in tobacco and alcohol use for some participants, including cases of sustained abstinence. PTSD findings were mixed: some qualitative work reported profound benefits in small, specific samples, while one survey found no significant correlation between ego-dissolution and PTSD symptom change. For maladaptive narcissism, one retrospective survey found a negative correlation with certain forms of connectedness but no association with ego-dissolution. A key pattern emerged in subgroup comparisons: connectedness tended to be more durable and was associated with positive social-emotional states such as love, compassion and belonging, whereas ego-dissolution often appeared to function as a precipitant for psychological change—facilitating insight and a new perspective on self—without itself typically persisting long after the drug effects subsided. Anxious or dread-like ego-dissolution correlated with worse outcomes in two studies. Contextual factors mattered in some reports: one study suggested outdoor settings augmented nature-relatedness effects, and a meditation-retreat context was associated with particularly persistent ego-dissolution effects. Overall, the authors judged the convergence of findings across diverse methodologies to lend credibility to the association of both constructs with therapeutic benefit, while noting that heterogeneity precludes precise effect-size estimates.

Kałużna and colleagues interpret the synthesis as consistent evidence that both ego-dissolution and connectedness are important correlates of therapeutic improvements following classic psychedelic experiences. They highlight a distinction between the two phenomena: ego-dissolution often operates as a transient state that enables psychological change—by interrupting self-focused cognition and permitting new perspectives—whereas connectedness can itself be a sustained, directly therapeutic experience, often accompanied by feelings of love, belonging and compassion that support interpersonal healing. The review's findings accord with prior theoretical and empirical work linking loneliness and self-focused rumination to poor mental health; connectedness therefore offers a plausible pathway to ameliorate disorders where isolation or maladaptive self-concern is prominent. Conversely, ego-dissolution aligns with literature suggesting reduced self-focus and rumination links to symptom reduction. The authors note that ego-dissolution, connectedness, mystical experience and psychological insight frequently co-occur during peak psychedelic effects, and one included study suggested that psychological insight may be the more proximate predictor of improvement when controlling for other experiential components. Limitations acknowledged by the reviewers include substantial methodological heterogeneity across included studies, variable follow-up durations, limited cultural and demographic diversity, moderate to high attrition in some designs, and challenges in cleanly separating overlapping subjective constructs (for example, mystical experience, awe, insight, ego-dissolution and connectedness). Measurement inconsistency and potential confounders (notably concomitant antidepressant use) were also noted. In terms of implications, the authors suggest tailoring psychedelic-therapy models: emphasising preparation aimed at facilitating safe entry into ego-dissolution (for example by reducing worry and fostering openness), and prioritising integration work that consolidates connectedness and its prosocial consequences. They further recommend future mediation analyses to test whether ego-dissolution operates via psychological insight or connectedness, and call for more research into context effects (setting, retreat-style formats, prior meditation experience), culturally diverse samples, clearer measurement of overlapping experiential constructs (new tools such as the PIS-6 were noted), and systematic reporting of integration procedures. Finally, the authors broaden the implications beyond psychedelic therapy, suggesting that non-pharmacological means that foster connectedness (nature exposure, social prescribing) or reduce self-focused cognition (mindfulness-based therapies) might harness similar therapeutic mechanisms for individuals where psychedelic therapy is unsuitable or unavailable.

The review concludes that both ego-dissolution and connectedness are associated with improvements in psychological wellbeing across several mental health domains—particularly depression, anxiety and substance use disorders—but that they differ in phenomenology and temporal profile. Connectedness appears more likely to be sustained and directly therapeutic, while ego-dissolution often precipitates insight that can lead to change. Given the heterogeneity of existing research, questions remain about mediators such as psychological insight, the role of context and integration, and generalisability across cultures. The authors propose that these distinctions can inform theory-building and the development of psychedelic-therapy models, and note broader relevance for mental health practice in emphasising connectedness and reduced self-focused cognition through other therapeutic avenues.