Biological sex and hormonal contraceptive associations with drug cue reactivity in cannabis use disorder.

Biological sex differences in Cannabis Use Disorder (CUD) progression, cannabis withdrawal severity, and pharmacotherapy response have been reported, suggesting that CUD mechanisms may differ by sex. Drug cue reactivity is an established predictor of drug use behavior, but the literature on sex differences in drug cue reactivity is mixed, including in CUD. One possible moderator of sex differences in drug cue reactivity is hormonal contraceptive (HC) use. The aim of the present study was to test whether sex differences in neural cannabis cue reactivity and craving varied by female HC use in a CUD sample. As part of a larger study, 152 adults reporting frequent cannabis use completed a drug cue reactivity task during electrocenphalogram recording. Late positive potential (LPP) amplitude modulation by cannabis cues was used to measure neural cue reactivity. Craving after the cue reactivity task was also assessed. Males (n = 74) and naturally-cycling females (n = 26), who did not differ from each other, showed significantly greater LPP enhancement to cannabis vs. neutral cues compared to HC-using females (n = 52), an effect mostly driven by neutral cues. Craving was significantly higher in naturally-cycling but not HC-using females compared to males, but only in covariate-unadjusted analyses. Exploratory analyses of HC and menstrual phase characteristics indicate a progesterone-related mechanism may underlie HC effects on cannabis cue reactivity. The present study's results suggest that mixed findings on drug cue reactivity sex differences may be due to variability in HC use, which has implications for sex-specific models of CUD progression and treatment.

Neurophysiological error processing and addiction self-awareness correlates of reduced insight in cannabis use disorder.

BACKGROUND AND AIMS: Cannabis use disorder (CUD) prevalence has increased, while perceived risks of cannabis use and CUD treatment need have decreased. Chronic cannabis use may also impair the neural and behavioral mechanisms of insight, further hampering treatment-seeking. This study aimed to measure whether CUD is characterized by reduced self-monitoring in drug-related contexts (objectively-assessed insight), subserved by functional neural abnormalities in error-processing and manifested clinically as decreased awareness of the need to change. DESIGN: Case-control laboratory study was used. SETTING: University setting was in Alabama, USA. PARTICIPANTS: There were 42 CUD participants and 47 age-, sex-, and nicotine use-matched controls. MEASUREMENTS: Participants completed a probabilistic choice task, adapted for the first time for CUD, in which they selected pleasant, unpleasant, neutral, and cannabis-related images according to their preference. Reduced versus accurate insight was operationalized as the correspondence between self-reported and actual most chosen image type. Neurophysiological error-processing during an inhibitory control task was recorded using electroencephalography. Participants with CUD completed measures of cannabis problem recognition and motivation to change. FINDINGS: Compared with controls, the CUD group made significantly more cannabis selections on the choice task (mean difference [MD] = 8.11, 95% confidence interval [CI] [4.88 11.35], p < 0.001) and had significantly reduced insight into cannabis choice (odds ratio [OR] = 9.69, 95% CI [1.06 88.65], p = 0.04). CUD participants with reduced insight on the choice task had significantly decreased neurophysiological reactivity to errors on the inhibitory control task (error-related negativity) compared with CUD participants with accurate insight (MD = 2.64 µV, 95% CI [0.74 µV 4.54 µV], p = 0.008) and controls (MD = 4.05 µV, 95% CI [1.29 µV 6.80 µV], p = 0.005). Compared with CUD participants with accurate insight on the choice task, CUD participants with reduced insight reported significantly less agreement that they had a cannabis problem (MD = -5.06, 95% CI [-8.49-1.62], p = 0.003). CONCLUSIONS: People with CUD who show reduced insight on a drug-related choice task may also have decreased early neural error-processing and less cannabis problem recognition.

Physiological stress modulation of neural drug cue reactivity in cannabis use disorder.

OBJECTIVE: Rates of daily cannabis use and cannabis use disorder (CUD) are increasing in the United States. Prominent addiction theories suggest that stress potentiation of drug cue incentive salience is a central feature of disordered versus recreational drug use, which has been corroborated using a neurophysiological index of drug cue incentive salience (i.e., the late positive potential [LPP]) in adults who regularly use cannabis. However, the mechanism through which acute stress potentiates the cannabis LPP in CUD is unclear. METHOD: To address this gap, cannabis LPPs were measured before and after a stress induction in 95 adults who regularly use cannabis. Physiological (hypothalamic-pituitary-adrenal [HPA] axis, heart rate, skin conductance) and subjective stress reactivity were also measured. RESULTS: Based on prior work, we hypothesized that cortisol stress reactivity would predict poststress cannabis LPP enhancement in more severe CUD. The hypothesis was supported and specific to HPA-axis versus autonomic or subjective stress reactivity. CONCLUSIONS: Acute stress potentiation of the cannabis LPP, likely via HPA-axis activation, may be a biomarker of heavy/disordered cannabis use in adults who regularly use cannabis. (PsycInfo Database Record (c) 2023 APA, all rights reserved).