Psychedelics as Novel Therapeutics in Alzheimer’s Disease: Rationale and Potential Mechanisms
This theory-building paper (2021) makes a case for using psychedelics to treat Alzheimer's Disease (AD). The effects psychedelics have on neuroplasticity, inflammation and brain functional connectivity are discussed in relation to the pathophysiology of AD. Additionally, results from animal studies have shown psychedelics positively impact learning and memory which could have implications for the treatment of AD.
Authors
- Albert Garcia-Romeu
Published
Abstract
Serotonin 2A receptor (5-HT2AR) agonist “classic psychedelics” are drawing increasing interest as potential mental health treatments. Recent work suggests psychedelics can exert persisting anxiolytic and antidepressant effects lasting up to several months after a single administration. Data indicate acute subjective drug effects as important psychological factors involved in observed therapeutic benefits. Additionally, animal models have shown an important role for 5-HT2AR agonists in modulating learning and memory function with relevance for Alzheimer’s Disease (AD) and related dementias. A number of biological mechanisms of action are under investigation to elucidate 5-HT2AR agonists’ therapeutic potential, including enhanced neuroplasticity, anti-inflammatory effects, and alterations in brain functional connectivity. These diverse lines of research are reviewed here along with a discussion of AD pathophysiology and neuropsychiatric symptoms to highlight classic psychedelics as potential novel pharmacotherapies for patients with AD. Human clinical research suggests a possible role for high-dose psychedelic administration in symptomatic treatment of depressed mood and anxiety in early-stage AD. Preclinical data indicate a potential for low- or high-dose psychedelic treatment regimens to slow or reverse brain atrophy, enhance cognitive function, and slow progression of AD. In conclusion, rationale and potential approaches for preliminary research with psychedelics in patients with AD are presented, and ramifications of this line of investigation for development of novel AD treatments are discussed.
Research Summary of 'Psychedelics as Novel Therapeutics in Alzheimer’s Disease: Rationale and Potential Mechanisms'
Introduction
Garcia-Romeu and colleagues frame Alzheimer’s disease (AD) as an urgent unmet medical need given its growing prevalence and the lack of reliably disease‑modifying therapies. They note that symptomatic treatments such as acetylcholinesterase inhibitors and memantine provide modest benefits, and recent antibody approaches remain controversial with regard to safety, accessibility, and clinical impact. Against this background, the paper situates renewed interest in classic serotonergic psychedelics (5-HT2A receptor agonists such as psilocybin, LSD, and DMT/ayahuasca) as potential novel therapeutics across psychiatric and neurobiological targets relevant to AD. This review sets out to synthesise preclinical and clinical evidence linking psychedelic pharmacology to mechanisms implicated in AD pathology, including promotion of neuroplasticity, modulation of BDNF- and mTOR-related signalling, anti‑inflammatory effects, and changes in large‑scale brain network connectivity. The authors aim to evaluate how these converging lines of evidence could justify targeted early‑stage clinical investigation of both high‑dose, psychologically assisted and lower‑dose psychoplastogenic regimens in people with early AD or mild cognitive impairment (MCI).
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Study Details
- Study Typeindividual
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- APA Citation
Garcia-Romeu, A., Darcy, S., Jackson, H., White, T., & Rosenberg, P. (2021). Psychedelics as Novel Therapeutics in Alzheimer’s Disease: Rationale and Potential Mechanisms. Current Topics in Behavioral Neurosciences, 287-317. https://doi.org/10.1007/7854_2021_267
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