How the Brains of People Seeking Cannabis Use Disorder Treatment Respond to Cannabis Cues

What the researchers found

In 65 treatment-seeking participants with moderate or severe CUD, viewing cannabis images (vs neutral) activated bilateral prefrontal cortex, anterior cingulate, visual cortex, and striatum. Functional connectivity increased between the medial prefrontal cortex and both the amygdala and visual cortex. Unexpectedly, self-reported craving negatively correlated with left ventral striatum activation, suggesting that higher craving was associated with reduced reward area response to cues.

Why it matters

Understanding how the brain responds to cannabis cues in treatment-seeking individuals could help predict treatment success and develop targeted interventions. The negative correlation between craving and reward area activation challenges simple models of addiction.

The numbers in context

65 participants (37 from varenicline trial, 28 from rTMS trial). 32% female. Mean age: 30.4 years. Craving negatively correlated with left ventral striatum (R2=-0.32, p=.01). No significant differences between study cohorts.

How the study worked

Secondary analysis of 65 participants from two clinical trials (varenicline and rTMS for CUD). fMRI cue-reactivity task comparing cannabis vs neutral images after 24 hours of abstinence. Craving measured with Marijuana Craving Questionnaire. 32% female, mean age 30.4 years.

What this study cannot tell us

Secondary analysis of two separate trials. Cross-sectional design. 24-hour abstinence may not fully eliminate acute effects. Visual cue-reactivity may not capture all forms of craving. Cannot determine causation.

How to read the evidence

Moderate: largest treatment-seeking CUD cue-reactivity sample to date, replicated across two cohorts, but cross-sectional and secondary analysis.

When this study was published

Published in 2025.

The bigger picture

The finding that higher craving correlates with lower, not higher, reward area activation may reflect desensitization in heavy users or a disconnect between subjective craving and neural reward processing. This has implications for how brain-based biomarkers might be used in treatment.

Questions still open

• Why does higher craving correlate with lower reward activation?
• Could cue-reactivity patterns predict treatment outcomes?
• Would longer abstinence change the brain activation pattern?

Common questions

Read the original research

Exploring the Utility of a Functional Magnetic Resonance Imaging Cannabis Cue-Reactivity Paradigm in Treatment-Seeking Adults With Cannabis Use Disorder.

Biological psychiatry. Cognitive neuroscience and neuroimaging, 10(5), 522-530

Citation

Sahlem, Gregory L; Dowdle, Logan T; Baker, Nathaniel L; Sherman, Brian J; Gray, Kevin M; McRae-Clark, Aimee L; Froeliger, Brett; Squeglia, Lindsay M. (2025). Exploring the Utility of a Functional Magnetic Resonance Imaging Cannabis Cue-Reactivity Paradigm in Treatment-Seeking Adults With Cannabis Use Disorder.. Biological psychiatry. Cognitive neuroscience and neuroimaging, 10(5), 522-530. https://doi.org/10.1016/j.bpsc.2024.09.006

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