From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders

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.

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans

“…5-HT 2A agonists, such as psilocybin, have drawn interest for their anxiolytic and antidepressant effects. There is increasing evidence that 5-HT 2A receptor agonists modulate learning and memory function by improving neuroplasticity, functional neuronal connectivity, and activating anti-inflammatory pathways ( de Vos et al, 2021 ; Garcia-Romeu et al, 2021 ; Kozlowska et al, 2021 ). It was also demonstrated that the neocortical 5-HT 2A receptor binding is decreased in patients with AD ( Hasselbalch et al, 2008 ), which is correlated to cognitive impairment.…”

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

“…Dendritic change can alter the enhancement and suppression of membrane excitability, which may create opposing actions on dendritic excitability that promote plasticity (Savalia et al, 2021). Although the cellular mechanisms leading to therapeutic efficacy are not yet understood, serotonergic psychedelics stimulation of neural and glial cells may reduce inflammation and reduce oxidative stress and act as disease-modifying therapeutics in neurodegenerative disorders (Kozlowska et al, 2021). Biomarkers of plasticity are also demonstrated in clinical research, showing elevation of blood plasma brain-derived neurotrophic factor (BDNF) after administration of 200 mg of LSD compared with placebo (Holze et al, 2021).…”

“…LSD is a powerful partial agonist at cortical and subcortical 5-HT2A receptors of GABAergic interneurons (Marek and Aghajanian, 1996;Inserra et al, 2021a,b). Psychedelics also stimulate 5-HT1A receptors (Strassman, 1996;Carter et al, 2005;Pokorny et al, 2016) and 5-HT2B receptors (Kozlowska et al, 2021). Stimulation of the 5-HT1A receptor and GABA interneurons by LSD both inhibit and disinhibit prefrontal pyramidal cell activity (Llad o-Pelfort et al, 2012;Celada, et al, 2013a;Llad o-Pelfort et al, 2018) and show downstream effects on dopaminergic (Vollenweider et al 1999) and glutamatergic systems (Mason et al, 2020;Vollenweider and Preller, 2020).…”

Editorial: Exciting developments in neurochemistry research and publishing

“…From molecular mechanisms in cultured cells (Agbaegbu Iweka et al, 2021; Bendahmane et al, 2020), neurochemical mechanisms in intact organisms (Abreu et al, 2021; Becker et al, 2021), new imaging and quantitative methodologies providing insight into neurochemical changes (Abdalla et al, 2020; Arber et al, 2021; Blank & Hopf, 2021; Dienel, 2021) and critical biomarkers in disease (Altmayer et al, 2021; Chakraborty & Basu, 2021; Chatterjee et al, 2021; Eden et al, 2021; Geula et al, 2021; Ginsberg et al, 2021; Glezer et al, 2021), the scope of the Journal of Neurochemistry has broadened to respond to the demands of our scientific community. Neurochemical mechanisms of disease are a popular topic covering neuropsychiatric and developmental disorders (Haase et al, 2021; Kozlowska et al, 2021; Liu & McNally, 2021; Nie et al, 2021; Nomura et al, 2021) and neurodegenerative diseases (Brosseron et al, 2021; Butler et al, 2021; Chatterjee et al, 2021; Korecka & Shaw, 2021; Sathe et al, 2021; Trinh et al, 2021; Yuede et al, 2021). Similarly, studies into neuroinflammation and neuroimmunology are a growing area within the journal, such that in 2021 we published a special issue dedicated to this topic (https://onlinelibrary.wiley.com/toc/14714159/2021/158/1).…”