The prevalence of hazardous drinking among females has increased more in the past decades as compared to among males. While it is well-known that females suffer more from the negative effects of alcohol use than males, the mechanisms that explain sex differences in hazardous drinking remain poorly understood. The current study aimed to investigate sex differences in the relationship between cue-induced (relief and reward) craving and cue-induced heart rate variability in a sample of hazardous drinkers. One hundred fourteen hazardous drinkers (61 females) underwent an alcohol cue-exposure paradigm consisting of exposure to alcohol-related pictures, personalized script imagery, and alcohol paraphernalia. Relief- and reward cravings were measured before and after exposure using the Desire for Alcohol Questionnaire. Heart Rate Variability was measured continuously during the exposure using an electrocardiograph. While there was a significant increase in both reward and relief craving following the alcohol exposure paradigm, these effects were not moderated by sex. Importantly, however, exposure to alcohol cues was associated with a stronger reduction in Heart Rate Variability among males compared to female hazardous drinkers. Lastly, exposure-related reduction in Heart Rate Variability was significantly stronger in individuals that reported more exposure-induced relief craving, but these effects were not moderated by sex. In summary, our findings suggest that while there were no sex differences in exposure-induced Heart Rate Variability, there was in exposure-induced craving. These findings may pave the way for developing sex-specific interventions specifically targeting Heart Rate Variability, including Heart Rate Variability biofeedback.

Cocaine use disorder (CUD) is becoming more prevalent in females, but research into sex-dependent neural mechanisms underlying cocaine use is lacking. Accordingly, the main objective of the current study was to investigate sex-dependent differences in the neural correlates of cocaine and emotional cue reactivity within regular cocaine users (CUs) and non-cocaine-using controls (non-CUs). A cocaine and emotional cue-reactivity fMRI paradigm was completed by 31 male and 26 female CUs and 28 male and 26 female non-CUs. A region of interest analysis was performed to test for sex-specific differences in cocaine and emotional cue-induce activation of the dorsal striatum (DS), ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC). Although there were no significant sex-dependent differences between CUs and non-CUs in neural cocaine and emotional cue reactivity, exploratory analyses demonstrated that the association between cocaine cue-induced activation of the DS and amygdala and cocaine use severity was significantly moderated by sex: while this association was positive female CUs, it was negative in male CUs. Similarly, the relationship between emotional cue-induced activation of the dACC and VS and years of regular cocaine use was also moderated by sex: while this association was negative in female CUs, it was positive in male CUs. While exploratory, the current findings highlight the importance of taking into account sex differences when studying the underlying mechanism of CUD, as this may pave the way for the identification of sex-specific treatment targets.