Psychedelic therapy as relational medicine: psychosocial mechanisms in clinical and naturalistic contexts

This thesis explores the psychosocial mechanisms underlying therapeutic responses to psychedelic interventions, advancing an enactive biopsychosocial perspective that foregrounds dynamic and reciprocal causal relationships between biological, psychological, and social processes. While clinical studies increasingly demonstrate the efficacy of serotonergic psychedelics for a range of mental health conditions, the contribution of relational factors - such as therapeutic alliance, group dynamics, and socially enriched settings - remains insufficiently understood. To better characterize the role of psychosocial dynamics, three empirical studies were conducted across clinical, naturalistic, and digitally mediated settings. Study 1 (Chapter 3) analysed data from a randomized controlled trial comparing psilocybin with escitalopram, demonstrating that therapeutic alliance predicted depression outcomes in the psilocybin arm, mediated by the quality of acute subjective psychedelic effects. Study 2 (Chapter 4) examined data from naturalistic psychedelic group experiences, identifying 'communitas', a transient state of intense togetherness and shared humanity, as a key predictor of enduring improvements in well-being and connectedness, and shifts in metaphysical beliefs. Study 3 (Chapter 5) evaluated a group-based virtual reality program leveraging psychedelic-like states, finding positive psychological effects in participants with life-threatening illnesses, underscoring the relevance of context even in non-pharmacological psychotropic interventions. Together, these findings suggest that rather than functioning solely as biomedical interventions, psychedelics may act as amplifiers of relational processes and be best understood as hybrid pharmaco-psychosocial interventions. This work supports the clinical integration of psychedelics as part of psychosocially enriched therapeutic paradigms and contributes to broader debates about the role of relational context and intersubjectivity in mental health care.