The potential of psychedelics for the treatment of Alzheimer's disease and related dementias

Michael James Winkelman; Attila Szabo; Ede Frecska

doi:10.1016/j.euroneuro.2023.07.003

The potential of psychedelics for the treatment of Alzheimer's disease and related dementias

Eur Neuropsychopharmacol. 2023 Nov:76:3-16. doi: 10.1016/j.euroneuro.2023.07.003. Epub 2023 Jul 12.

Authors

Michael James Winkelman¹, Attila Szabo², Ede Frecska³

Affiliations

¹ School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, United States.
² Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway. Electronic address: attila.szabo@medisin.uio.no.
³ Department of Psychiatry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

PMID: 37451163
DOI: 10.1016/j.euroneuro.2023.07.003

Abstract

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 GABA_AR 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.

Keywords: Dementia; Neuroinflammation; Neuroplasticity; Psychedelics.

Publication types

Review

MeSH terms

Alzheimer Disease* / drug therapy
Alzheimer Disease* / pathology
Atrophy / pathology
Brain
Hallucinogens* / pharmacology
Hallucinogens* / therapeutic use
Humans
Neurodegenerative Diseases* / drug therapy
Neurodegenerative Diseases* / pathology

Substances

Hallucinogens