Depressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)PTSDSubstance Use Disorders (SUD)Neurological InjuryNeurocognitive DisordersImmunology & InflammationPublic Health, Prevention & Behaviour ChangePsilocybin

From Psychiatry to Neurology: Psychedelics as Prospective Therapeutics for Neurodegenerative Disorders

This review evaluates preclinical and early clinical evidence that psychedelic tryptamines, particularly psilocybin, could be repurposed from psychiatry to neurology as prospective therapeutics for brain injury and neurodegenerative disorders. It highlights findings that psychedelics promote neuroplasticity, synaptogenesis and neural progenitor proliferation and reduce pro‑inflammatory cytokines (e.g. IL‑1β, IL‑6, TNF‑α), while emphasising that the precise molecular mechanisms and neural–glial interactions remain to be determined.

Authors

  • David Nichols
  • Charles Nichols

Published

Journal of Neurochemistry
meta Study

Abstract

The studies of psychedelics, especially psychedelic tryptamines like psilocybin, are rapidly gaining interest in neuroscience research. Much of this interest stems from recent clinical studies demonstrating that they have a unique ability to improve the debilitating symptoms of major depressive disorder (MDD) long‐term after only a single treatment. Indeed, the Food and Drug Administration (FDA) has recently designated two Phase III clinical trials studying the ability of psilocybin to treat forms of MDD with "Breakthrough Therapy" status. If successful, the use of psychedelics to treat psychiatric diseases like depression would be revolutionary. As more evidence appears in the scientific literature to support their use in psychiatry to treat MDD on and substance use disorders (SUD), recent studies with rodents revealed that their therapeutic effects might extend beyond treating MDD and SUD. For example, psychedelics may have efficacy in the treatment and prevention of brain injury and neurodegenerative diseases such as Alzheimer's Disease. Preclinical work has highlighted psychedelics’ ability to induce neuroplasticity and synaptogenesis, and neural progenitor cell proliferation. Psychedelics may also act as immunomodulators by reducing levels of proinflammatory biomarkers, including IL‐1β, IL‐6, and tumor necrosis factor‐α (TNF‐α). Their exact molecular mechanisms, and induction of cellular interactions, especially between neural and glial cells, leading to therapeutic efficacy, remain to be determined. In this review, we discuss recent findings and information on how psychedelics may act therapeutically on cells within the central nervous system (CNS) during brain injuries and neurodegenerative diseases. image

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Research Summary of 'From Psychiatry to Neurology: Psychedelics as Prospective Therapeutics for Neurodegenerative Disorders'

Introduction

Research into classical and novel psychedelic compounds has re-emerged after decades of prohibition, driven by recent clinical studies showing long-lasting improvements in major depressive disorder (MDD) after very limited dosing. These compounds — typically acting through serotonin 5-HT2A receptor activation and including psilocybin, DMT, 5‑MeO‑DMT, mescaline and LSD — are being reconsidered not only for psychiatric indications such as treatment‑resistant depression (TRD) and PTSD but also for broader neuroscientific and therapeutic applications. The authors frame psychedelics as agents that influence core central nervous system (CNS) functions, with demonstrated effects on network connectivity, synaptic structure and certain inflammatory pathways. Kozlowska and colleagues set out to review and synthesise recent preclinical and clinical evidence on how psychedelics affect neural tissue homeostasis and immune responses in the CNS. The stated aim is to examine mechanisms — neuroplasticity, neurogenesis, gliogenesis and immunomodulation — by which psychedelics might be repurposed as therapeutics for neurodegenerative disorders and brain injury, and to identify research directions that would support such applications.

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Study Details

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