The potential of psychedelics for the treatment of Alzheimer's disease and related dementias.
Michael James Winkelman, Attila Szabo, Ede Frecska
European Neuropsychopharmacology November 1, 2023 DOI: 10.1016/j.euroneuro.2023.07.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Neuroplasticity |
| Keywords | Dementia Neuroinflammation Psychedelics |
| Citations | 26 |
| Key findings | Psychedelics induce neuroplasticity and may slow or reverse brain atrophy in Alzheimer's disease by modulating glutamatergic transmission, up-regulating neurotrophic factors, and rewiring pathological neurocircuitry. |
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 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.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 19
- Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways Ageing Research Reviews February 1, 2024
- Effects of Psychedelics in Older Adults: A Prospective Cohort Study. American Journal of Geriatric Psychiatry May 19, 2024
- Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases Pharmacology & Therapeutics April 6, 2024
- Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity. Neuropsychiatric Disease and Treatment 2025
- Therapeutic potential of psychedelics: History, advancements, and unexplored frontiers. Progress in Neuro-Psychopharmacology and Biological Psychiatry April 20, 2024
and 14 more in the library
Cites 64
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
and 59 more in the library