Hallucinogenic Therapy in Alzheimer's Disease targeting Mitochondria-Associated Membranes.
Fernando Minauro-Sanmiguel, Hector Vargas-Perez
Neuroscience April 6, 2026 DOI: 10.1016/j.neuroscience.2026.02.028 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Population | Preclinical models of Alzheimer's disease |
| Interventions | Psilocybin LSD DMT Mescaline 5-MeO-DMT |
| Topics | Neuroplasticity Serotonin |
| Keywords | Alzheimer’s disease Mitochondria Neuroinflammation Psychedelics Sigma-1 receptor |
| Key points | Proposes that classic hallucinogens may restore mitochondrial integrity in Alzheimer's disease via 5-HT2A and sigma-1 receptor pathways, but evidence remains preclinical and hypothesis-generating. |
Abstract
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.
Comparable studies
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| Study | Year | Design | Participants |
|---|---|---|---|
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential? | 2021 | Theoretical or philosophical paper | |
| A complex systems perspective on psychedelic brain action. | 2023 | Theoretical or philosophical paper | |
| Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy | 2021 | Theoretical or philosophical paper | |
| Therapeutic mechanisms of psychedelics and entactogens. | 2023 | Theoretical or philosophical paper |
Citations in the library
Cites 32
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
and 27 more in the library