Unravelling gender differences in cannabis cue-reactivity in individuals who use cannabis

The development of cannabis use disorder (CUD) shows notable gender differences. While men have a higher overall prevalence of CUD, women transition more rapidly from initial use to CUD and often present with more severe psychiatric symptoms when seeking treatment. Despite these clinical observations, research into the neural mechanisms underlying these gender differences remains limited. This study aimed to investigate gender-dependent differences in neural cue-reactivity and session-induced craving (change in craving from the beginning to end of the experimental session) among regular cannabis users and non-using controls, as well as gender-specific associations between neural cue-reactivity, craving, and cannabis use characteristics. A total of 66 regular cannabis users (27 women), who used cannabis 2 to 7 days per week, and 71 controls (31 women) completed a functional MRI cannabis cue-reactivity task involving exposure to cannabis-related and neutral images. Craving was measured twice using the Marijuana Craving Questionnaire, which measures craving related to the loss of control, relief from negative affect, anticipated positive outcomes, and intention to use. To assess session-induced craving, craving at the end of the experimental session was subtracted from craving at the beginning of the experimental session. Results revealed that women who use cannabis displayed blunted neural cue-reactivity in the right insula and putamen compared to men, a pattern opposite to that seen in controls. Among women, but not men, session-induced relief and reward craving correlated positively with cue-reactivity in the right superior frontal gyrus, cerebellum, and precentral gyrus. Additionally, cannabis use severity was linked to cue-reactivity in the precentral gyrus in women only: These findings underscore complex, gender-related interactions between neural responses, craving, and cannabis use severity, emphasizing the need for gender-tailored research to address critical gaps in understanding the development and treatment of CUD.