Genetic and molecular studies suggest imbalances in major neurotransmitter systems as an important pathogenetic mechanism in substance use disorders (SUDs), however direct evidence for such dysregulation of the main excitatory (glutamate, GLU) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters – i.e. changes in the excitatory/inhibitory (E/I) balance – in patient populations is lacking. A method for noninvasive detection of signals from these neurotransmitters in the human brain is magnetic resonance spectroscopy (MRS). Recent development in scanner hardware and acquisition methods have made MRS more accessible and comparable across scanner sites, which allows to measure these neurotransmitters from large cohorts, and thus to identify changes in the I/E balance in distinct brain. In order to test the main hypothesis of this proposal - i.e. the existence of I/E imbalances in SUDs – we here aim to compare patients with a SUD diagnosis for either nicotine, alcohol, opiate, cocaine, or cannabis as well as drug-free healthy controls in a cross-sectional design by MRS.