Background: There is similarity in schizophrenia and methamphetamine-induced psychosis neurobiology. Few studies have directly compared neurometabolites in thalamo-cortical circuitry across these disorders or assessed the relationship with peripheral cytokines. This study compared neurometabolites and neuronal integrity in thalamo-cortical circuitry, and investigated associations with peripheral cytokine levels in both disorders. Methods: Ninety-five participants were recruited – 36 with schizophrenia, 27 with methamphetamine-induced psychosis, and 32 healthy controls. All participants underwent a magnetic resonance imaging scan, which included magnetic resonance spectroscopy. Glutamatergic and neuroinflammatory neurometabolites were examined. Serum cytokine concentrations included Interleukin 1-beta, Interleukin-8, Interleukin-10, Tumor Necrosis Factor alpha and Interferon gamma. Parametric data were analyzed with one-way analysis of variance and non-parametric data were analyzed with Kruskal Wallis tests. Associations were determined using Spearman’s rank-order coefficient. Results: The methamphetamine-induced psychosis group had lower n-acetyl aspartate with n-acetyl-aspartyl glutamate in left dorsolateral prefrontal cortex and left frontal white matter, compared to controls. In schizophrenia, positive associations were found between glutamate and n-acetyl aspartate and n-acetyl aspartate with n-acetyl-aspartyl glutamate in the anterior cingulate cortex. In the methamphetamine-induced psychosis group, positive relationships were found between myo-inositol in the left thalamus and bilateral anterior cingulate cortex. Conclusion: In schizophrenia, there is suggestion of dysfunction in neuronal tissues in the glutamate-glutamine cycle within the thalamo-cortical circuit. In methamphetamine-induced psychosis, there is evidence of compromised neuronal integrity associated with chronic disease progression, and suggestion of aberrant neuroinflammatory regulation in the thalamus-ACC circuit. This study highlights similarities and differences in the psychobiology of the two disorders