Psychedelic Rejuvenation Hypothesis: A Framework for Cellular and Psychological Restoration
Tony R. Montgomery, Demond M. Grant
November 17, 2025 DOI: 10.31124/advance.175630073.36585408/v2 via OpenAlex
Summary
Classical psychedelics like psilocybin, LSD, and DMT may serve not only as treatments for mental health disorders but also as preventive agents for overall health. They appear to rejuvenate both cellular and psychological functions by influencing aging pathways related to neuroplasticity and inflammation. Psychological benefits include increased emotional flexibility and stress reduction, which could lead to lasting lifestyle improvements. Future research is needed to explore their potential in promoting healthspan and systemic rejuvenation.
Study at a glance
| Key finding | Psychedelics may act as catalysts for sustained psychological and cellular rejuvenation, impacting aging pathways and improving mental health beyond traditional treatment applications. |
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Abstract
Recent research into classical psychedelics, such as psilocybin, LSD, and DMT, has highlighted their therapeutic potential for mental health disorders. However, emerging evidence suggests their utility may extend beyond treatment into the realm of preventive medicine. This manuscript proposes a novel framework positioning psychedelics as agents of cellular and psychological rejuvenation. Drawing from preclinical and early human studies, we explore how psychedelics modulate core aging pathways including neuroplasticity, inflammation, mitochondrial function, and telomere dynamics. These compounds appear to not only repair dysregulated brain states but also engage biological mechanisms implicated in resilience, longevity, and cognitive preservation. The psychological benefits, such as increased openness, emotional flexibility, and stress reduction, are supported by durable shifts in brain network dynamics, particularly through 5-HT₂A receptor activation and increased neural entropy. We argue that these effects mirror well-known adaptations to exercise and other hormetic stressors. Integration, often overlooked in research, may be the behavioral bridge that converts these neurobiological changes into lasting lifestyle improvements, making psychedelics not just a reset, but a catalyst for sustained change. While limitations exist, including the need for long-term data and diverse sampling, this framework encourages a shift in how we study and apply psychedelics, not solely as treatments, but as tools for proactive health optimization. Future research should investigate how psychedelics, when combined with intentional integration and lifestyle interventions, might extend healthspan and promote whole-system rejuvenation.