Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct alterations in blood levels of tryptophan-related metabolites, which may help explain their different clinical effects. In a study of 36 chronic MDMA users, 33 chronic METH users, and 71 healthy controls, METH use was linked to depleted serum tryptophan and serotonin and broad activation of kynurenine pathways, whereas MDMA use was associated with selective activation of the OH-kynurenine branch. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that persistent changes in peripheral tryptophan metabolism may contribute to the substances' contrasting addiction and psychiatric profiles.
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.