Psychedelic-Inspired Approaches for Treating Neurodegenerative Disorders
The authors propose that psychedelic‑inspired treatments, acting primarily via the 5‑HT2A receptor to enhance neurotrophic signalling, neuronal growth and immune modulation, could rescue cortical atrophy common to neurodegenerative diseases. They further suggest these compounds may help treat behavioural and psychological symptoms of dementia and warrant targeted preclinical and clinical investigation.
Authors
- David Olson
Published
Abstract
Psychedelics are increasingly being recognized for their potential to treat a wide range of brain disorders including depression, post‐traumatic stress disorder (PTSD), and substance use disorder. Their broad therapeutic potential might result from an ability to rescue cortical atrophy common to many neuropsychiatric and neurodegenerative diseases by impacting neurotrophic factor gene expression, activating neuronal growth and survival mechanisms, and modulating the immune system. While the therapeutic potential of psychedelics has not yet been extended to neurodegenerative disorders, we provide evidence suggesting that approaches based on psychedelic science might prove useful for treating these diseases. The primary target of psychedelics, the 5‐HT2A receptor, plays key roles in cortical neuron health and is dysregulated in Alzheimer's disease. Moreover, evidence suggests that psychedelics and related compounds could prove useful for treating the behavioral and psychological symptoms of dementia (BPSD). While more research is needed to probe the effects of psychedelics in models of neurodegenerative diseases, the robust effects of these compounds on structural and functional neuroplasticity and inflammation clearly warrant further investigation. image
Research Summary of 'Psychedelic-Inspired Approaches for Treating Neurodegenerative Disorders'
Introduction
Progressive loss of dendritic arbors, dendritic spines and synapses in cortical regions that support cognition, memory and mood is a central pathological feature of Alzheimer's disease (AD), frontotemporal dementia (FTD) and related neurodegenerative disorders. Neuroinflammation is increasingly recognised as a key component of AD pathophysiology. The introduction frames these changes as mechanistic links between neurodegeneration and the neuropsychiatric symptoms often seen in dementia, and suggests that interventions able to both promote cortical neuron growth and modulate inflammation could have substantial therapeutic value. This review examines evidence from molecular, cellular, preclinical and limited human studies that compounds inspired by psychedelic science — principally 5-HT2A receptor ligands and related "psychoplastogens" — might address neuronal atrophy, impaired neurotrophic signalling and aberrant immune activation that characterise neurodegenerative diseases. The authors set out to synthesise findings on mechanisms (for example, 5-HT2A-mediated plasticity, BDNF/TrkB and mTOR signalling, mitochondrial effects and immunomodulation), behavioural implications for the behavioural and psychological symptoms of dementia (BPSD), and distinctive properties of multi-component preparations such as ayahuasca. The review highlights gaps in knowledge and outlines key unanswered questions that should guide future work.
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Study Details
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- APA Citation
Saeger, H. N., & Olson, D. E. (2022). Psychedelic-Inspired Approaches for Treating Neurodegenerative Disorders. Journal of Neurochemistry, 162(1), 109-127. https://doi.org/10.1111/jnc.15544
References (56)
Papers cited by this study that are also in Blossom
Bement, W., Banks, M. I., Zahid, Z. et al. · Molecular Biology of the Cell (2021)
Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Bouso, J. C., Doblin, R., Farré, M. et al. · Journal of Psychoactive Drugs (2008)
Rodríguez-Fornells, A., Ribeiro, S., Sanches, R. F. et al. · European Neuropsychopharmacology (2015)
Buchborn, T., Schröder, H., Höllt, V. et al. · Journal of Psychopharmacology (2014)
Cameron, L. P. · ACS Chemical Neuroscience (2018)
Cameron, L. P., Benson, C. J., Defelice, B. C. et al. · ACS Chemical Neuroscience (2019)
Cameron, L. P., Tombari, R. J., Lu, J. et al. · Nature (2020)
Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)
Show all 56 referencesShow fewer
Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
Dakic, V., De Moraes Maciel, R., Drummond, H. et al. · PeerJ (2016)
Galvão-Coelho, N. L., de Almeida, R. N., de Menezes Galvão, A. C. et al. · Frontiers in Psychology (2019)
Dong, C., Ly, C., Dunlap, L. E. et al. · Cell (2021)
Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · Therapeutic Advances in Psychopharmacology (2016)
Family, N., Maillet, E. L., Williams, L. T. J. et al. · Psychopharmacology (2019)
Feder, A., Parides, M. K., Murrough, J. W. · JAMA Psychiatry (2014)
Flanagan, T. W., Nichols, C. D. · International Review of Psychiatry (2018)
Flanagan, T. W., Billac, G. B., Landry, A. N. et al. · ACS Pharmacology and Translational Science (2020)
Frost, D., Meechoovet, B., Wang, T. et al. · PLOS ONE (2011)
Gonza ´lez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. · Neuron (2007)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Halberstadt, A. L., Chatha, M., Klein, A. K. et al. · Neuropharmacology (2020)
Hanks, J. B., González-Maeso, J. · ACS Chemical Neuroscience (2012)
Hesselgrave, N., Troppoli, T. A., Wulff, A. B. et al. · PNAS (2021)
Holze, F., Vizeli, P., Ley, L. et al. · Neuropsychopharmacology (2020)
Hutten, N. R. P. W., Mason, N. L., Dolder, P. C. et al. · ACS Pharmacology and Translational Science (2020)
Kočárová, C., Horacek, J., Carhart-Harris, R. L. · Frontiers in Psychiatry (2021)
Kozłowska, U., Klimczak, A., Wiatr, K. et al. · Biorxiv (2021)
Nichols, C. D., Wiatr, K., Figiel, M. et al. · Journal of Neurochemistry (2021)
Krupitsky, E. M., Burakov, A. M., Romanova, T. N. et al. · Journal of Substance Abuse Treatment (2002)
Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R. et al. · Trends in Pharmacological Sciences (2017)
Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L. et al. · Frontiers in Molecular Neuroscience (2018)
Lu, J., Tjia, M., Mullen, B. et al. · Molecular Psychiatry (2021)
Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)
Greb, A. C., Vargas, M. V., Duim, W. C. et al. · ACS Pharmacology and Translational Science (2020)
Martin, D. A., Nichols, C. D., Nichols, Á. C. D. · Current Topics in Behavioral Neurosciences (2017)
Lason, W., Carnicella, S., Mash, D. C. et al. · Frontiers in Pharmacology (2019)
Mcgowan, J. C., Lagamma, C. T., Lim, S. C. et al. · Neuropsychopharmacology (2017)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Grob, C. S., Mithoefer, M. C., Brewerton, T. D. · Lancet Psychiatry (2016)
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T. et al. · Journal of Psychopharmacology (2010)
Nau, F., Miller, J., Saravia, J. et al. · American Journal of Physiology (2015)
Nichols, C. D., Nichols, D. E., Johnson, M. W. · Clinical Pharmacology and Therapeutics (2016)
Olson, J. A. · Neuroscience Insights (2018)
Olson, D. E. · ACS Pharmacology and Translational Science (2020)
Preller, K. H., Burt, J. B., Adkinson, B. et al. · eLife (2018)
Savalia, N., Shao, L-X,, Kwan, A. C. · Trends in Neuroscience (2021)
Shao, L-X,, Liao, C., Gregg, I. et al. · Neuron (2021)
Szabo, A. · Frontiers in Immunology (2015)
Ahmad, M., Szabo, A., Kovacs, A. et al. · Frontiers in Neuroscience (2016)
Uthaug, M. V., Lancelotta, R., Szabo, A. et al. · Psychopharmacology (2019)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)
Yaden, D. B., Griffiths, R. R. · ACS Pharmacology and Translational Science (2020)
Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)
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Peterson, A., Largent, E. A., Sisti, D. et al. · AJOB Neuroscience (2022)
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