This literature review (2023) examines the potential of natural and synthetic psychedelics in treating Alzheimer’s Disease (AD) and related dementias. It highlights the plastogenic effects of serotonergic psychedelics and their ability to promote neuronal survival, glutamate-driven neuroplasticity, and reduce Aβ-induced neurotoxicity, illustrating the potential for these substances to address multiple facets of AD pathology.
Abstract of The potential of psychedelics for treating Alzheimer’s disease
“Alzheimer’s Disease (AD) is a currently incurable but increasingly prevalent fatal and progressive neurodegenerative disease, demanding consideration of therapeutically relevant natural products and their synthetic analogues. This paper reviews evidence for effectiveness of natural and synthetic psychedelics in the treatment of AD causes and symptoms. The plastogenic effects of serotonergic psychedelics illustrate that they have efficacy for addressing multiple facets of AD pathology. We review findings illustrating neuroplasticity mechanisms of classic (serotonergic) and non-classic psychedelics that indicate their potential as treatments for AD and related dementias. Classic psychedelics modulate glutamatergic neurotransmission and stimulate synaptic and network remodeling that facilitates synaptic, structural and behavioral plasticity. Up-regulation of neurotrophic factors enable psychedelics to promote neuronal survival and glutamate-driven neuroplasticity. Muscimol modulation of GABAAR reduces Aβ-induced neurotoxicity and psychedelic Sig-1R agonists provide protective roles in Aβ toxicity. Classic psychedelics also activate mTOR intracellular effector pathways in brain regions that show atrophy in AD. The potential of psychedelics to treat AD involves their ability to induce structural and functional neural plasticity in brain circuits and slow or reverse brain atrophy. Psychedelics stimulate neurotrophic pathways, increase neurogenesis and produce long-lasting neural changes through rewiring pathological neurocircuitry. Psychedelic effects on 5-HT receptor target genes and induction of synaptic, structural, and functional changes in neurons and networks enable them to promote and enhance brain functional connectivity and address diverse mechanisms underlying degenerative neurological disorders. These findings provide a rationale for immediate investigation of psychedelics as treatments for AD patients.”
Authors: Michael J. Winkelman, Attila Szabo & Ede Frecska
Summary of The potential of psychedelics for treating Alzheimer’s disease
Alzheimer’s disease (AD) is the most common cause of dementia and a leading cause of death globally. Psychedelics have been shown to have neuromodulatory effects on AD, mainly via the serotonergic system.
Winkelman et al. review evidence that classic psychedelic compounds, including 5HT2A agonists, are potential therapeutic agents for addressing both causes and symptoms of Alzheimer’s disease and other dementias.
The potential therapeutic applications of psychedelics in AD are an emerging topic, and this paper provides an overview on the molecular neurobiology of interacting downstream pathways and effects of psychedelics on cell types other than neurons.
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The potential of psychedelics for the treatment of Alzheimer's disease and related dementias
https://doi.org/10.1016/j.euroneuro.2023.07.003
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Winkelman, M. J., Szabo, A., & Frecska, E. (2023). The potential of psychedelics for the treatment of Alzheimer's disease and related dementias. European Neuropsychopharmacology, 76, 3-16. https://doi.org/10.1016/j.euroneuro.2023.07.003