Exploring Psilocybin’s Antidepressant Mechanisms Through Feelings of Connectedness: A Systematic Review

Abstract

After thorough investigations on the therapeutic use of classic psychedelics such as psilocybin or LSD came to an abrupt end in the 1960s, modern research was revived in the last 5-10 years, initiating the so-called ‘psychedelic renaissance’. A series of clinical phase I and II trials produced promising early findings on the antidepressant effect of psilocybin, a serotonin 5-HT2A receptor agonist. While results on the quantitative antidepressant effect of psilocybin become more and more profound, a deeper understanding of the therapeutic mechanisms behind the antidepressant effect is needed. In contrast to SSRIs, psilocybin hypothetically acts not primarily as a symptom alleviator and more as a catalyst for common therapeutic change principles. One key element that draws researchers attention is patients' universal experience of connectedness (to self, others and the world) within the psychedelic experience. This study aims to shed light on the therapeutic relevance of feeling connected under psilocybin and draw parallels to existing and well researched common factors of psychotherapy. By integrating existing conceptual models on the physiological and psychological effects, this review seeks to contribute to a holistic understanding of how psilocybin may facilitate antidepressant therapeutic change processes.

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