TY - JOUR
T1 - Psilocybin for dementia prevention?
T2 - The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases
AU - Haniff, Zarah R
AU - Bocharova, Mariia
AU - Mantingh, Tim
AU - Rucker, James J
AU - Velayudhan, Latha
AU - Taylor, David M
AU - Young, Allan H
AU - Aarsland, Dag
AU - Vernon, Anthony C
AU - Thuret, Sandrine
N1 - Funding Information:
For the purposes of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Accepted Author Manuscript version arising from this submission. This work was supported by the Wellcome Trust (RE20960); the Medical Research Council (MRC) Centre grant (MR/N026063/1) and the National Institute for Health Research (NIHR) (CS-2017-17-007). Prof. A.H. Young's independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health and Social Care.
Funding Information:
This work was supported by the Wellcome Trust ( RE20960 ); the Medical Research Council (MRC) Centre grant ( MR/N026063/1 ) and the National Institute for Health Research (NIHR) ( CS-2017-17-007 ). Prof. A.H. Young's independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London . The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2024 The Authors
PY - 2024/6
Y1 - 2024/6
N2 - Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases. Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.
AB - Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases. Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.
UR - http://www.scopus.com/inward/record.url?scp=85190293530&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2024.108641
DO - 10.1016/j.pharmthera.2024.108641
M3 - Review article
C2 - 38583670
SN - 0163-7258
VL - 258
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
M1 - 108641
ER -