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These changes underlie craving and heighten its sensitivity to cue- and stress-induced triggers, sustaining drug intake and promoting relapse. Task-based functional magnetic resonance imaging of drug cue reactivity paradigms has shown the dorsolateral prefrontal cortex (dlPFC) as one region commonly activated during cue-elicited craving. However, the state-induced dynamics of critical neurometabolites in cannabis use disorder remain to be investigated. The present study addresses this gap by investigating gamma-aminobutyric acid (GABA) and Glx (glutamate and glutamine) in the dlPFC during cannabis cue reactivity in individuals with cannabis use disorder (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200922; 11 females) compared to matched non-cannabis using controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919; 9 females). Magnetic resonance spectroscopy (HERMES) data were acquired from the dlPFC during a cue reactivity paradigm and analyzed using GANNET. We found that, while individuals with cannabis use disorder and controls had similar overall GABA+ levels, they responded differently to cue reactivity, where individuals with cannabis use disorder showed increases in GABA+ during cannabis cue reactivity compared to neutral cue reactivity, irrespective of presentation order (\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>1,16<\/jats:sub>\n                    \u2009=\u20097.31,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.016,\n                    <jats:italic>n<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:sub>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u2009.31). These findings indicate that cannabis cue reactivity may reveal neurometabolic alterations that are not observable under rest conditions. These findings also establish MRS cue-reactivity paradigms as a valuable tool for probing the neurobiology of cannabis use disorder and identify cue-elicited GABA dynamics as a clinically relevant biomarker amenable to therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02563-3","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:50:41Z","timestamp":1789494641000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cue-elicited prefrontal gamma-aminobutyric acid (GABA) dynamics in cannabis use disorder"],"prefix":"10.1038","author":[{"given":"Alexandra","family":"Gaillard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Fehring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Sumner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Randhawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-8252","authenticated-orcid":false,"given":"Susan L.","family":"Rossell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2563_CR1","unstructured":"United Nations Office on Drugs and Crime. 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