Therapeutic properties of ayahuasca component N,N-Dimethyltryptamine in a pre-clinical model of Parkinson's disease.
Javier Calleja‐conde, Víctor Echeverry‐alzate, Marina Sanz-Sancristóbal, Sandra Alonso‐gil, Elena Giné, Kora Bühler, Jose A. López-moreno, Ana Pérez‐castillo, José Á. Morales-García
Experimental Neurology May 12, 2026 DOI: 10.1016/j.expneurol.2026.115822 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Preclinical model of Parkinson's disease |
| Interventions | N N-dimethyltryptamine (DMT) |
| Topics | DMT 5-MeO-DMT Ayahuasca |
| Keywords | Neurodegeneration Neuroinflammation Parkinson Sigma-1 receptor |
| Key points | DMT administration reduced neuroinflammation and preserved neurons in the nigrostriatal pathway, and improved behavioral symptoms, in a preclinical model of Parkinson's disease. |
Abstract
Parkinson's disease is a progressive neurodegenerative disorder with increasing global prevalence, primarily driven by population ageing. A hallmark of the disease is the degeneration of nigrostriatal dopaminergic neurons, accompanied by marked activation of glial cells and a sustained neuroinflammatory response. Current pharmacological treatments are limited to symptomatic relief and do not halt or reverse disease progression. Ayahuasca, a traditional Amazonian psychoactive brew, has attracted growing scientific interest for its potential therapeutic effects in neuropsychiatric and neurodegenerative conditions. Its principal psychoactive compound, N,N-dimethyltryptamine (DMT), acts as an agonist at the 5-HT2A serotonin receptor-responsible for its hallucinogenic properties-and at the sigma-1 receptor, a molecular target implicated in neuroprotection and modulation of inflammation. This study investigates the neuroprotective and anti-inflammatory potential of DMT in a preclinical model of Parkinson's disease. Our findings demonstrate that DMT administration results in molecular changes within the nigrostriatal pathway consistent with reduced neuroinflammation and neuronal preservation. Furthermore, behavioral assessments indicate symptomatic improvements following treatment. These results support the therapeutic potential of DMT as a disease-modifying agent in Parkinson's disease and warrant further investigation.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cites 21
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews Expert Review of Clinical Pharmacology August 13, 2018
- Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PLoS One 2014
- Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies Brazilian Journal of Psychiatry March 1, 2016
and 16 more in the library