# PubMed extracts: LSD / psychedelics / Alzheimer's / dementia

## PMID 31853557: Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers.
- Journal/date: Psychopharmacology, 2020
- Authors: Neiloufar Family, Emeline L Maillet, Luke T J Williams, Erwin Krediet, Robin L Carhart-Harris, Tim M Williams
- URL: https://pubmed.ncbi.nlm.nih.gov/31853557/

Abstract/extract:
UNLABELLED: Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease. OBJECTIVE: This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response. METHODS: This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days). RESULTS: Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 μg (n = 12), 10 μg (n = 12), or 20 μg (n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment. CONCLUSIONS: Our results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer's disease (AD).

## PMID 32973482: Psychedelics as a Treatment for Alzheimer's Disease Dementia.
- Journal/date: Frontiers in synaptic neuroscience, 2020
- Authors: Simon Andrew Vann Jones, Allison O'Kelly
- URL: https://pubmed.ncbi.nlm.nih.gov/32973482/

Abstract/extract:
Currently, there are no disease-modifying treatments for Alzheimer's disease (AD) or any other dementia subtype. The renaissance in psychedelic research in recent years, in particular studies involving psilocybin and lysergic acid diethylamide (LSD), coupled with anecdotal reports of cognitive benefits from micro-dosing, suggests that they may have a therapeutic role in a range of psychiatric and neurological conditions due to their potential to stimulate neurogenesis, provoke neuroplastic changes and reduce neuroinflammation. This inevitably makes them interesting candidates for therapeutics in dementia. This mini-review will look at the basic science and current clinical evidence for the role of psychedelics in treating dementia, especially early AD, with a particular focus on micro-dosing of the classical psychedelics LSD and psilocybin.

## PMID 38307424: Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.
- Journal/date: Ageing research reviews, 2024
- Authors: Jitendra Kumar Sinha, Anchal Trisal, Shampa Ghosh, Saurabh Gupta, Krishna Kumar Singh, Sung Soo Han
- URL: https://pubmed.ncbi.nlm.nih.gov/38307424/

Abstract/extract:
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.

## PMID 37569888: A Brief Review on the Potential of Psychedelics for Treating Alzheimer's Disease and Related Depression.
- Journal/date: International journal of molecular sciences, 2023
- Authors: Alexander Pilozzi, Simmie Foster, David Mischoulon, Maurizio Fava, Xudong Huang
- URL: https://pubmed.ncbi.nlm.nih.gov/37569888/

Abstract/extract:
Alzheimer's disease (AD), the most common form of senile dementia, is poised to place an even greater societal and healthcare burden as the population ages. With few treatment options for the symptomatic relief of the disease and its unknown etiopathology, more research into AD is urgently needed. Psychedelic drugs target AD-related psychological pathology and symptoms such as depression. Using microdosing, psychedelic drugs may prove to help combat this devastating disease by eliciting psychiatric benefits via acting through various mechanisms of action such as serotonin and dopamine pathways. Herein, we review the studied benefits of a few psychedelic compounds that may show promise in treating AD and attenuating its related depressive symptoms. We used the listed keywords to search through PubMed for relevant preclinical, clinical research, and review articles. The putative mechanism of action (MOA) for psychedelics is that they act mainly as serotonin receptor agonists and induce potential beneficial effects for treating AD and related depression.

## PMID 41707907: Hallucinogenic Therapy in Alzheimer's Disease targeting Mitochondria-Associated Membranes.
- Journal/date: Neuroscience, 2026
- Authors: Fernando Minauro-Sanmiguel, Hector Vargas-Perez
- URL: https://pubmed.ncbi.nlm.nih.gov/41707907/

Abstract/extract:
Mitochondrial dysfunction is increasingly recognized as a central driver of Alzheimer's disease (AD), contributing to neuroinflammation, synaptic failure, and energy collapse.Emerging preclinical evidence suggests that classic hallucinogens, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, may restore mitochondrial integrity by activating Serotonin 2A (5-HT2A) and sigma-1(Sig-1R) receptors. In experimental models, these pathways are associated with enhanced mitochondrial biogenesis, reduced oxidative stress, and preservation of ER-mitochondrial coupling. DMT and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) specifically engage Sig-1R at mitochondria-associated membranes, improving calcium homeostasis and cellular resilience. While these mechanisms are mechanistically compelling, evidence for clinical efficacy in AD remains limited and largely preclinical. Accordingly, this framework is presented as a hypothesis-generating model suggesting that mitochondrial-centered psychedelic mechanisms warrant further investigation,provided that neuropsychiatric safety, patient selection, and translational feasibility are carefully addressed.

## PMID 39892847: Psychedelics in neuroinflammation: Mechanisms and therapeutic potential.
- Journal/date: Progress in neuro-psychopharmacology & biological psychiatry, 2025
- Authors: Junia Lara de Deus, Juliana Marino Maia, Renato Nery Soriano, Mateus R Amorim, Luiz G S Branco
- URL: https://pubmed.ncbi.nlm.nih.gov/39892847/

Abstract/extract:
Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Additionally, psychedelics affect critical signaling pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and mechanistic target of rapamycin (mTOR) pathways, promoting neuroplasticity and exerting anti-inflammatory effects. Beyond the serotonergic system, other neurotransmitter systems-including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems-also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.

## PMID 35158230: LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility.
- Journal/date: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2022
- Authors: Isabel Wießner, Rodolfo Olivieri, Marcelo Falchi, Fernanda Palhano-Fontes, Lucas Oliveira Maia, Amanda Feilding
- URL: https://pubmed.ncbi.nlm.nih.gov/35158230/

Abstract/extract:
Psychedelics acutely impair cognitive functions, but these impairments decline with growing experiences with psychedelics and microdoses may even exert opposing effects. Given the recent evidence that psychedelics induce neuroplasticity, this explorative study aimed at investigating the potential of psychedelics to sub-acutely change cognition. For this, we applied a randomized, double-blind, placebo-controlled, crossover study with 24 healthy volunteers receiving 50 μg lysergic acid diethylamide (LSD) or an inactive placebo. Sub-acute changes in cognition were measured 24 h after dosing, including memory (Rey-Osterrieth Complex Figure, ROCF; 2D Object-Location Memory Task, OLMT; Rey Auditory-Verbal Learning Test, RAVLT), verbal fluency (phonological; semantic; switch), design fluency (basic; filter; switch), cognitive flexibility (Wisconsin Card Sorting Test, WCST), sustained and switching attention (Trail Making Test, TMT), inhibitory control (Stroop Task) and perceptual reasoning (Block Design Test, BDT). The results show that when compared to placebo and corrected for Body Mass Index (BMI) and abstinence period from psychedelics, LSD sub-acutely improved visuospatial memory (ROCF immediate recall points and percentage, OLMT consolidation percentage) and phonological verbal fluency and impaired cognitive flexibility (WCST: fewer categories achieved; more perseveration, errors and conceptual level responses). In conclusion, the low dose of LSD moderately induced both "afterglow" and "hangover". The improvements in visuospatial memory and phonological fluency suggest that LSD-assisted therapy should be explored as a novel treatment perspective in conditions involving memory and language declines such as brain injury, stroke or dementia.