Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacology & Therapeutics Pub Date : 2024-04-06 DOI:10.1016/j.pharmthera.2024.108641
Zarah R. Haniff , Mariia Bocharova , Tim Mantingh , James J. Rucker , Latha Velayudhan , David M. Taylor , Allan H. Young , Dag Aarsland , Anthony C. Vernon , Sandrine Thuret
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Abstract

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.

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用迷幻药预防痴呆症?迷幻药在改变重度抑郁症和神经退行性疾病相关机制方面的潜在作用
重度抑郁是继发痴呆症的既定风险因素,晚年抑郁也可能是痴呆症的前兆状态。考虑到目前临床开发痴呆症疾病调节疗法所面临的挑战,研究重点正转向预防和改变风险因素,以改变神经退行性疾病的发展轨迹。了解情感症状和认知能力下降的机理共性可能会发现一些生物标志物,有助于在疾病的临床前阶段及早识别那些有可能发展成痴呆症的人,从而进行及时干预。成人海马神经发生(AHN)是一种描述齿状回终生诞生新神经元的现象,它与空间学习、记忆和情绪调节有关。小胶质细胞是中枢神经系统中的先天性免疫系统巨噬细胞,它通过多种机制仔细调节 AHN。AHN 的破坏与痴呆症和重度抑郁症有关,而小胶质细胞病变则是多种神经退行性疾病的标志。在这种情况下,迷幻药作为一种具有速效抗抑郁特性的血清素能激动剂,有可能改善与重度抑郁症和神经退行性疾病相关的交叉病理生理过程。在这篇叙述性综述中,我们将重点关注迷幻药对成人海马神经发生和小胶质细胞形态与功能影响的证据基础;这可能表明迷幻药具有调节多种作用机制的潜力,并可能对改变高危人群从重度抑郁症发展为痴呆症的过程产生影响。
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来源期刊
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
期刊介绍: Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.
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Lipoprotection in cardiovascular diseases. Nutraceuticals target androgen receptor-splice variants (AR-SV) to manage castration resistant prostate cancer (CRPC). Editorial Board The voltage sensitivity of G-protein coupled receptors: Unraveling molecular mechanisms and physiological implications. Oxytocin in neurodevelopmental disorders: Autism spectrum disorder and Prader-Willi syndrome.
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