OSCR

Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms.

Overview

Authors: Francesco Bavato1,2, Andrea Steuer3, Anna M. Jacobsen1, Amelie Zacher1, Josua Zimmermann1,4, David M. Cole1,5, Antje Opitz6, Markus R. Baumgartner3, Ann-Kathrin Stock6, Christian Beste6, Boris B. Quednow1,4
ORCID iDs: Francesco Bavato, Andrea Steuer, Anna M. Jacobsen, Markus R. Baumgartner, Boris B. Quednow
  1. Experimental Pharmacopsychology and Psychological Addiction Research, Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich,Zurich, Switzerland
  2. Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University,Aarhus, Denmark
  3. Institute of Forensic Medicine, University of Zurich,Zurich, Switzerland
  4. Neuroscience Center Zurich, Joint Center of University of Zurich and Swiss Federal Institute of Technology Zurich,Zurich, Switzerland
  5. Translational Psychiatry Lab, University Psychiatric Clinics Basel, University of Basel,Basel, Switzerland
  6. Department of Child and Adolescent Psychiatry, TU Dresden,Dresden, Germany
Institutions: University of Zurich (Switzerland); Aarhus University (Denmark); University of Basel (Switzerland); Technische Universität Dresden (Germany)
Journal: Translational psychiatry, volume 16, issue 1, article 358
Dates: received 24 September 2025; accepted 30 April 2026; published online 21 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41398-026-04069-4 · PMID 42168162 · PMCID PMC13365191 · OpenAlex W4413761657
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.08.25.672112
Status: code on request
Categories: human (organism), other condition (population), clinical / translational (subfield)
Methods: Statistics, Preprocessing, Connectivity
Keywords: Diagnostic markers, Physiology
MeSH: Amphetamine-Related Disorders*, Methamphetamine*, N-Methyl-3,4-methylenedioxyamphetamine*, Tryptophan*, Adult, Cross-Sectional Studies, Female, Humans, Kynurenine, Male, Serotonin, Young Adult (* major topic)
Topic: Tryptophan and brain disorders (Biological Psychiatry, Neuroscience), according to OpenAlex
Funding: Swiss National Science Foundation (217637)
Citations: not cited yet (Europe PMC); 72 references in the paper

Abstract

Methamphetamine (METH, “Crystal Meth”) and 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) are two types of substituted amphetamines that share structural-chemical similarities but exhibit contrasting acute and chronic effects including addictive liability. Tryptophan (TRY) pathways are involved in pleiotropic physiological functions at the interface of brain-body connections. Preclinical evidence suggests that amphetamines may modulate these pathways and, thus, indirectly influence brain functions via persistent alterations of peripheral metabolites. However, little is known about alterations of TRY-related metabolites in the blood and their clinical implications in chronic users of MDMA and METH. Hence, we characterized serum levels of TRY-related metabolites in a comparative cross-sectional study including n = 36 chronic MDMA users, n = 33 chronic METH users, and n = 71 sex-matched, healthy controls. An ultra–high performance liquid chromatography–mass spectrometry method was used to determine TRY metabolites. Combining metabolite levels, metabolic ratios, and network analysis we found robust evidence of divergent pathway alterations between METH and MDMA users. Chronic METH use was particularly associated with a depletion of serum TRY and serotonin levels, and a general activation of kynurenine pathways, while chronic MDMA use was linked to a selective activation of the OH-kynurenine metabolic branch. Metabolite changes were associated with the severity of psychopathology in the depression and psychosis domains across groups. Altogether, our findings demonstrate differential changes of serum TRY pathways in chronic MDMA and METH users. Persistent alterations of these pathways might contribute to the contrasting clinical profile of the substances and constitute a peripheral dimension of neurochemical plasticity with relevant implications for therapeutic targets.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

Code availability

Analyses were conducted in Python using standard statistical libraries. No custom algorithms were developed; scripts used for data processing and analysis are available from the corresponding author.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request, subject to appropriate ethical and institutional approvals.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 2 keywords, 12 MeSH terms, 1 funder, 69 references.

Cite

This paper

Bavato, F., Steuer, A., Jacobsen, A. M., Zacher, A., Zimmermann, J., Cole, D. M., Opitz, A., Baumgartner, M. R., Stock, A.-K., Beste, C., & Quednow, B. B. (2026). Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms. Translational psychiatry, 16(1), 358. https://doi.org/10.1038/s41398-026-04069-4

BibTeX

@article{bavato2026differential,
author = {Bavato, Francesco and Steuer, Andrea and Jacobsen, Anna M. and Zacher, Amelie and Zimmermann, Josua and Cole, David M. and Opitz, Antje and Baumgartner, Markus R. and Stock, Ann-Kathrin and Beste, Christian and Quednow, Boris B.},
title = {{Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms}},
journal = {Translational psychiatry},
year = {2026},
month = may,
volume = {16},
number = {1},
pages = {358},
publisher = {Nature Publishing Group},
issn = {2158-3188},
doi = {10.1038/s41398-026-04069-4},
url = {https://doi.org/10.1038/s41398-026-04069-4},
pmid = {42168162},
pmcid = {PMC13365191}
}

RIS

TY - JOUR
AU - Bavato, Francesco
AU - Steuer, Andrea
AU - Jacobsen, Anna M.
AU - Zacher, Amelie
AU - Zimmermann, Josua
AU - Cole, David M.
AU - Opitz, Antje
AU - Baumgartner, Markus R.
AU - Stock, Ann-Kathrin
AU - Beste, Christian
AU - Quednow, Boris B.
TI - Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms
T2 - Translational psychiatry
J2 - Transl Psychiatry
PY - 2026
DA - 2026/05/21
VL - 16
IS - 1
SP - 358
SN - 2158-3188
PB - Nature Publishing Group
DO - 10.1038/s41398-026-04069-4
UR - https://doi.org/10.1038/s41398-026-04069-4
LA - en
ER -

CSL-JSON

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