Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms
bioRxiv Preprint Server August 25, 2025 Francesco Bavato, Andrea Steuer, Anna M. Jacobsen et al. preprint
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct changes in blood metabolites derived from tryptophan, a building block for serotonin and other signaling molecules. METH use was linked to lower serotonin levels and broad activation of the kynurenine pathway, while MDMA use was associated with a specific increase in a different branch of that pathway. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that lasting alterations in tryptophan metabolism may help explain the different clinical effects of the two drugs and could point to new therapeutic targets.