A Brief Review on the Potential of Psychedelics for Treating Alzheimer’s Disease and Related Depression

Title & Introduction

• Paper Title: A Brief Review on the Potential of Psychedelics for Treating Alzheimer’s Disease and Related Depression
• Published In: International Journal of Molecular Sciences, 2023
• Authors: Alexander Pilozzi, Simmie Foster, David Mischoulon, Maurizio Fava, Xudong Huang
• Objective: This review investigates the potential role of psychedelics in addressing Alzheimer’s disease (AD) and associated depression, focusing on their neurochemical effects and therapeutic mechanisms.
• Importance: With limited treatments for Alzheimer’s and the growing societal burden of the disease, innovative approaches such as psychedelic-assisted therapies could offer novel avenues for symptom relief and potentially slow disease progression.

Summary & Takeaways

Key Takeaway: Psychedelics might provide a novel therapeutic strategy for Alzheimer’s disease and its depressive symptoms by leveraging their unique neurochemical effects.

Practical Application: Future research should focus on refining dosing strategies, particularly microdosing, to maximize benefits while minimizing risks.

Key Background Information

• Context: Alzheimer’s disease affects 60–80% of dementia patients and is characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation. Current therapies are limited to symptomatic relief with moderate efficacy.
• Hypothesis: Psychedelics, through mechanisms such as serotonin receptor modulation and neuroplasticity, may alleviate AD-related cognitive decline and depressive symptoms.

Methodology

• Study Design: Literature review of preclinical and clinical studies on psychedelic compounds.
• Participants: Data were derived from various studies on human and animal models; no new clinical trial was conducted in this review.
• Intervention/Exposure: Investigated compounds included psilocybin, LSD, mescaline, DMT, and ketamine, focusing on their neurochemical impacts.
• Controls: Comparative efficacy and side effects of psychedelics versus traditional therapies were evaluated.
• Duration: Varied across reviewed studies; findings often highlighted acute and long-term effects.

Key Findings

Primary Outcomes:

Psychedelics primarily target serotonin receptors (e.g., 5-HT2A, 5-HT2C) and exhibit potential to reduce AD symptoms via:

• Enhanced neuroplasticity (e.g., increased dendritic spine density).
• Reduction of neuroinflammation.
• Modulation of amyloid-beta burden and cognitive decline.

Secondary Outcomes:

• Ketamine, unlike classical psychedelics, showed NMDA receptor-mediated effects but had mixed results in memory and mood improvement.
• Microdosing LSD and psilocybin improved mood and cognitive focus without hallucinogenic effects in anecdotal and preliminary studies.

Interpretation & Implications

• Conclusion: Psychedelics show promise in treating Alzheimer’s and related depression by enhancing neuroplasticity, reducing inflammation, and modulating neurotransmitter systems.
• Implications: While results are preliminary, psychedelics could complement current AD therapies and address treatment-resistant depression. Microdosing might offer a safer administration route.
• Limitations: Many studies are preclinical or lack rigorous controls. Long-term effects and safety profiles require further exploration.

Researchers & Publication

• Researchers: Alexander Pilozzi, Simmie Foster, David Mischoulon, Maurizio Fava, Xudong Huang
• Publication Name: International Journal of Molecular Sciences
• Study URL: https://doi.org/10.3390/ijms241512513