Cue-elicited prefrontal gamma-aminobutyric acid (GABA) dynamics in cannabis use disorder.
Alexandra Gaillard, Daniel J Fehring, Philip J Sumner, Alisha Randhawa, Susan L. Rossell
Neuropsychopharmacology September 15, 2026 DOI: 10.1038/s41386-026-02563-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Peer reviewed |
|---|---|
| Sample size | 41 |
| Population | Adults with cannabis use disorder (n=22; 11 females) and matched non-cannabis-using controls (n=19; 9 females) |
| Measures | Magnetic resonance spectroscopy (HERMES), GANNET |
| Topics | Cannabis |
| Key findings | Individuals with cannabis use disorder and controls had similar overall GABA+ levels in the dorsolateral prefrontal cortex, but the cannabis use disorder group showed increases in GABA+ during cannabis cue reactivity compared with neutral cue reactivity, irrespective of presentation order. The authors indicate that cue reactivity may reveal neurometabolic alterations not observable under rest conditions and propose cue-elicited GABA dynamics as a clinically relevant biomarker. |
Abstract
Chronic cannabis use drives neuroadaptations in reward and stress-related circuits that condition the brain to the drug and its associated cues. 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 = 22; 11 females) compared to matched non-cannabis using controls (n = 19; 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 (F1,16 = 7.31, p = 0.016, n2p = .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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Overall prefrontal GABA+ levels were similar between groups, but the cannabis use disorder group showed increased GABA+ during cannabis cue reactivity compared with neutral cues.
Synthesized
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |