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Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross‐over, randomized, double‐blind, placebo‐controlled trial with non‐treatment‐seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1‐week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue‐reactivity procedure and alcohol self‐administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue‐induced saliva output. During the alcohol self‐administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild‐moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress‐induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone‐induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non‐treatment seekers and suggests future treatment‐oriented trials should investigate mifepristone in people with AUD. [ABSTRACT FROM AUTHOR]

Objectives: Management of alcohol use disorder (AUD) is rarely used in patients with liver disease. We performed a systematic review to examine the impact of AUD management among patients with liver disease. Methods: Twenty studies fulfilling the inclusion and exclusion criteria on 38,329 patients (7072 receiving AUD intervention) with liver disease (15 with liver disease and 6 liver transplant [LT] recipients) were analyzed. One study was common to both groups. Variable follow-up period across studies was weighted for sample size and converting to person-years. Primary outcome was alcohol use, and secondary outcomes were liver decompensation and patient mortality. Results: Abstinence and alcohol relapse rates/person-year with AUD intervention among liver disease patients were 0.41 (0.27–0.55) and 0.42 (0.30–0.755), similar for integrated (colocated liver and addiction clinics) versus concomitant (separate hepatology and addiction clinics) intervention. Compared with standard of care, odds for decompensation with AUD intervention (n = 1), 30-day readmission (n = 1), and patient mortality (n = 2) were lower by 44%, 59%, and 58% respectively. Similar figures were 1.24 (0.86–1.80) for abstinence and 0.52 (0.24–0.14) for relapse. Among LT recipients, odds for alcohol relapse and mortality with follow-up integrated with addiction team versus hepatology alone were 0.48 (0.25–0.72) and 0.29 (0.08–0.99), respectively. Conclusions: Follow-up of LT recipients in an integrated clinic with addiction team is associated with improved outcomes. Simultaneous management of AUD in patients with liver disease improves liver-related outcomes. Large prospective studies are needed to examine benefits of AUD intervention in patients with liver disease. [ABSTRACT FROM AUTHOR]

While the illicit use and misuse of stimulants like cocaine and methylphenidate (MP) has increased, there remains no FDA‐approved treatments for psychostimulant use disorders (PSUD). Oxytocin (OT) has shown promise as a potential pharmacotherapy for PSUD. Dopamine (DA) neurotransmission plays a significant role in PSUD. We have recently shown that OT blunts the reinforcing effects of MP but, surprisingly, enhanced MP‐induced stimulation of DA levels. Such effects have been suggested as a result of activation of OT receptors or, alternatively, could be mediated by direct actions of OT on MP blockade of the DA transporter. Here, we employed fast scan cyclic voltammetry (FSCV) to investigate the effects of systemic OT on MP‐induced changes in the dynamics of DA, phasic release and uptake, in the nucleus accumbens shell (NAS) of Sprague–Dawley rats. We also tested the systemic effects of an antagonist of OT receptors, atosiban, to counteract the OT enhancement of dopaminergic effects of MP under microdialysis procedures in the NAS in rats. Administration of OT alone (2 mg/kg; i.p.) did not significantly modify evoked NAS DA dynamics measured by FSCV, and when administered 10 min before MP (0.1, 0.3, 1.0 mg/kg; i.v.), OT did not potentiate MP‐induced increases in phasic DA release and did not alter DA clearance rate, suggesting no direct interactions of OT with the MP‐induced blockade of DA uptake. Also, OT alone did not elicit significant changes in tonic, extracellular NAS DA levels measured by microdialysis. However, consistent with previous studies, we observed that OT pretreatments (2 mg/kg; i.p.) potentiated MP‐induced (0.1, 0.3, 1.0 mg/kg; i.v.) efflux of extracellular NAS DA levels. This effect was abolished when rats were pretreated with atosiban (2 mg/kg; i.p.), suggesting that OT receptors mediate this OT action. Overall, our results suggest that OT receptors mediated OT potentiation of MP‐induced stimulation of extracellular NAS DA levels, likely driven by modulation of DA receptor signaling pathways, without affecting MP blockade of DAT. [ABSTRACT FROM AUTHOR]