Women who use cannabis regularly showed blunted brain responses to cannabis cues in reward regions compared to men, with unique brain-craving associations found only in women.
Addiction neuroscientists, sex-differences researchers, and CUD treatment developers.
Women cannabis users showed blunted insula and putamen cue-reactivity compared to men, opposite to the pattern in non-using controls
What the researchers found
Women cannabis users showed blunted neural cue-reactivity in the right insula and putamen compared to male users, a pattern opposite to controls. Among women only, session-induced craving correlated with cue-reactivity in the right superior frontal gyrus, cerebellum, and precentral gyrus. Cannabis use severity was linked to precentral gyrus cue-reactivity exclusively in women.
Why it matters
Women transition more rapidly from initial cannabis use to cannabis use disorder. Understanding the distinct neural mechanisms in women could explain this accelerated progression and inform sex-specific treatments.
The numbers in context
66 cannabis users (27 women), 71 controls (31 women). Cannabis users used 2-7 days/week. Women showed blunted insula and putamen cue-reactivity vs men. Brain-craving correlations in frontal gyrus, cerebellum, and precentral gyrus found only in women.
How the study worked
fMRI cue-reactivity study with 66 regular cannabis users (27 women, using 2-7 days/week) and 71 controls (31 women). Cannabis-related and neutral images presented during scanning. Craving measured twice with the Marijuana Craving Questionnaire.
What this study cannot tell us
Moderate sample size limits statistical power for sex-stratified analyses. Cross-sectional design cannot determine if neural differences preceded or resulted from cannabis use. Craving measures are self-reported. Participants were non-treatment-seeking.
How to read the evidence
Well-designed fMRI study with sex-stratified analysis, but moderate sample and cross-sectional design limit causal conclusions.
When this study was published
2025 publication.
The bigger picture
The sex reversal pattern (blunted in women users but enhanced in women controls, opposite in men) suggests that regular cannabis use may fundamentally reorganize reward circuitry differently by sex, potentially contributing to the faster CUD progression seen in women.
Questions still open
- Does the blunted cue-reactivity in women reflect tolerance or a distinct neurobiological vulnerability?
- Would sex-specific treatment approaches improve CUD outcomes for women?
Read the original research
Unravelling gender differences in cannabis cue-reactivity in individuals who use cannabis.
Progress in neuro-psychopharmacology & biological psychiatry, 142, 111515
Citation
Kaag, A M; Cousijn, J; Kroon, E. (2025). Unravelling gender differences in cannabis cue-reactivity in individuals who use cannabis.. Progress in neuro-psychopharmacology & biological psychiatry, 142, 111515. https://doi.org/10.1016/j.pnpbp.2025.111515
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