Systemic barriers to the quality of online healthcare consultation: A qualitative study of provider-side factors and incentive misalignment.

Alcohol use disorder (AUD) is a chronic, relapsing condition contributing to substantial morbidity and mortality worldwide (). Craving, a cornerstone symptom of AUD, serves as a key prognostic indicator associated with risk of relapse and treatment failure (, , , , ). Higher pretreatment craving prospectively predicted more heavy drinking days (≥4 drinks for women/≥5 drinks for men) and average drinks per drinking day while in outpatient behavioral treatment (), underscoring the role of craving as a critical biobehavioral process influencing AUD treatment outcomes. Therefore, targeting craving in treatment development studies is essential for assessing a potential mechanism of change that supports AUD recovery. Craving is a multidimensional construct central to several addiction theories and can be broadly defined as wanting to drink alcohol or use drugs (,). The interplay between alcohol craving, arousal, and stress is intricately linked with disruptions in both central and peripheral stress physiology (,). Behaviorally, alcohol cues and stressors trigger dynamic increases in craving that predict higher alcohol consumption among individuals in treatment for AUD (). Like cues, stress can provoke craving both through distress-relief motives and enhanced reward anticipation (,), creating a feed-forward cycle of increased drinking and sensitized wanting (,). Biologically, chronic drinking disrupts prefrontal-striatal reward and stress circuits and alters autonomic and hypothalamic-pituitary-adrenal axis function (,). These effects partially reflect alterations in noradrenergic and adrenergic pathways, key modulators of sympathetic arousal () and cue and stress reactivity (). Animal studies have shown that alcohol both stimulates noradrenergic activity and increases drinking through changes in this system (), leading to interest in adrenergic-targeted therapeutics. Several AUD medications appear to influence craving. Naltrexone, an opioid antagonist, reduces craving by mitigating endogenous opioid effects (), which may forestall relapse by blunting the rewarding effects of drinking (). Naltrexone also appears to be particularly effective for individuals with heavier drinking patterns () or those with elevated baseline alcohol craving levels (,). Gabapentin, although not U.S. Food and Drug Administration approved for AUD, reduces relapse shortly after detoxification through withdrawal-related mechanisms (,), although the effects are modest ().