No evidence for exosome treatment in reducing alcohol relapse – a failed confirmatory multi-center study

Meinhardt MW, Habelt B, Skorodumov I, Schwarz C, Bernhardt N, Winter C, Hardar R, Müller CP, Israel Y, Ezquer F, Spanagel R (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Addiction Neuroscience Elsevier

Book Volume: 17

Article Number: 100234

DOI: 10.1016/j.addicn.2025.100234

Abstract

Preclinical studies have suggested that intranasal administration of mesenchymal stem cell-derived exosomes can reduce alcohol intake and relapse-like behavior in rodents. To assess the translational potential of these findings, we conducted a preregistered, multi-center preclinical randomized controlled trial (preRCT) across several German research sites. Using the alcohol deprivation effect (ADE) model in both male and female Wistar rats, we evaluated whether exosome treatment attenuates relapse-like drinking behavior following repeated deprivation phases. Given the hurdles in standardizing exosome isolation, dosage, and intranasal delivery into the brain, we performed first a functional validation experiment of intranasally delivered exosomes. For providing such a functional proof, we conducted electrocorticography (ECoG) recording and showed that exosomes are capable of mitigating impaired electrophysiological activity in the prefrontal cortex in rats that underwent the ADE procedure. However, contrary to previously published positive findings, our confirmatory multi-site preRCT results did not demonstrate a significant reduction in ethanol consumption during an ADE in Wistar rats following exosome treatment. No sex or site-specific effects were observed. Given the absence of efficacy, the study was terminated early in alignment with the 3R principles of animal research ethics. These findings suggest that the previously reported benefits of exosome treatment may be model-specific and do not generalize to a broader genetic background or experimental model. Our results emphasize the necessity of replication across diverse preclinical models and rat lines prior to clinical translation and highlight the importance of publishing null results to improve transparency and reproducibility in addiction research.

Authors with CRIS profile

Peter Christian Müller Professur für Suchtmedizin

Involved external institutions

Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universidad de Chile CL Chile (CL) Universidad del Desarrollo CL Chile (CL)

How to cite

APA:

Meinhardt, M.W., Habelt, B., Skorodumov, I., Schwarz, C., Bernhardt, N., Winter, C.,... Spanagel, R. (2025). No evidence for exosome treatment in reducing alcohol relapse – a failed confirmatory multi-center study. Addiction Neuroscience, 17. https://doi.org/10.1016/j.addicn.2025.100234

MLA:

Meinhardt, Marcus W., et al. "No evidence for exosome treatment in reducing alcohol relapse – a failed confirmatory multi-center study." Addiction Neuroscience 17 (2025).

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