Neuropsychopharmacology

As the global burden of addiction intensifies, the neurobiological commonalities and distinctions between substance use disorders (SUDs) and behavioral addictions (BAs) remain poorly characterized. This coordinate-based meta-analysis of 59 fMRI articles (n = 2,951) mapped the neural signatures of visual cue-reactivity across the addictive disorders. Our results revealed a universal core network shared by SUDs and BAs centered in the bilateral opercular inferior frontal gyrus, suggesting a shared...

ImportanceTraumatic brain injury (TBI) increases the risk of developing psychiatric symptoms such as post-traumatic stress disorder (PTSD), depression and anxiety, however biological risk and resiliency factors that explain the significant heterogeneity in outcomes are limited. Although 5-10% of the population carries natural autoantibodies to the NMDA receptor (anti-NMDAR1) it is unknown if carrying anti-NMDAR1 autoantibodies modifies risk for psychiatric outcomes after TBI. ObjectiveSince TBI...

Despite decades of clinical implementation of medications for opioid use disorder (OUD), overdose mortality rates remain high, underscoring a critical gap in treatments that target brain mechanisms driving addiction. Mindfulness-Oriented Recovery Enhancement (MORE) has demonstrated efficacy in reducing opioid use and craving, hypothetically by restructuring the salience of drug and natural rewards. Yet, to date, MOREs neurobiological mechanisms remain unclear. In this first functional magnetic r...

BackgroundTheta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD)...

Alcohol use disorder (AUD) is a chronic, relapsing condition and a major public health problem. However, few medications are approved to treat AUD, and those available show limited efficacy. Drug repurposing is a cost-effective strategy to identify novel therapeutic uses for existing medications. Here, we describe a pipeline that integrates genetic and electronic health record (EHR) data to identify and evaluate drugs to be repurposed for treating AUD. Our approach comprises 1) alcohol-associate...

Substance use disorder (SUD) recovery typically requires transformative change and prioritizing long-term healthy goals. Unfortunately, successful recovery is threatened by relapse rates that often exceed 50% in the first year. We previously reported on an experiential virtual reality (VR) SUD recovery intervention using personalized future self-avatars that produced emotional engagement and positive behavioral change, ie, stronger connection with the future self and future rewards and reduced c...

Alcohol use disorder (AUD) remains a major public health problem, with few effective medications and suboptimal adherence. L-type calcium channel blockers (LTCCBs) have genetic and preclinical support as potential treatments for AUD. We evaluated whether brain penetrant (BP)-LTCCBs are associated with reduced alcohol consumption by conducting two preregistered (https://osf.io/huawv) observational cohort studies using electronic health records (EHRs) from the US Department of Veterans Affairs (VA...

BackgroundEarly low-level alcohol use predicts subsequent alcohol use and problems. Impulsivity and poor inhibitory control also predict later problematic alcohol use. However, few studies prospectively examine early sipping in combination with modeling impulsivity and inhibitory control change over time as predictors of adolescent alcohol use. MethodsData Release 6.0 from the Adolescent Brain Cognitive Development (ABCD) Study was used (n=11,866; 48% Female). A series of linear mixed-effect mo...

Background and AimsAlcohol is the top substance used by US emerging adults under legal drinking age (underage emerging adults; U-EA; ages 18-19). U-EA are unlikely to seek or receive indicated alcohol interventions. It is imperative to find brief, effective interventions to reduce U-EA drinking. Developmental neuroscience reflects that peers hold higher neural salience during adolescence, as evidenced by differential neural response with real and/or simulated peers, even when those peers were no...

Background and AimsSubstance use disorders (SUDs) are heritable and share genetic variance with externalizing and internalizing psychopathology. Although recent gene identification efforts have demonstrated the value of modeling the shared genetic architecture among SUDs and externalizing, most research has thus far failed to account for overlap with internalizing. In this study, we aim to characterize the genetic relationships of both externalizing and internalizing with SUDs. Design and setti...

Changes in basic associative learning processes have been identified in several psychiatric conditions. However, it remains unknown whether these findings result from ongoing psychopathology or represent an underlying transdiagnostic risk factor for multiple clinical states. In this study, 72 participants with subclinical psychopathology, 23 of whom met criteria for the clinical high-risk for psychosis transdiagnostic risk syndrome (CHR+), completed a fear conditioning and generalization paradig...

PTSD is defined by a core of inter-connected symptom clusters. It is currently unclear whether this pattern of interconnections remains stable across the lifespan or differs across key developmental periods. Synthesising seven international trauma-exposed samples (N=5,470), we compared network interrelationships among core self-reported and/or caregiver-reported PTSD symptom clusters (re-experiencing, avoidance and arousal) in preschoolers, school-aged children, adolescents, and adults. For self...

Background and AimsCocaine use disorder (CUD) is an increasingly widespread concern worldwide. Various pharmacological treatments have been investigated for CUD, but their efficacy remains unclear, and none have been licensed for treatment. Therefore, we assessed the comparative effectiveness, safety, and acceptability of pharmacological interventions for the treatment of CUD and prevention of relapse. DesignSystematic review and network meta-analyses of double-blind randomized controlled trial...

AimsTo characterize decreases in overdose mortality in the United States between 2023 and 2024 by substance involvement, geography, race/ethnicity, demographic, and other key dimensions. DesignPopulation-based study of national death records. SettingUnited States. Participants/casesAll individuals who died from drug overdose between January 1999 and December 2024. MeasurementsAnnual or monthly (annualized) overdose deaths per 100,000 population. Year and month of occurrence of overdose death...

Tobacco use disorder (TUD) remains a leading cause of preventable mortality, and existing pharmacotherapies yield 12-month abstinence rates below 30%. As cannabis legalization expands, approximately 18-22% of people who use tobacco report concurrent cannabis use, yet the impact of co-use on cessation outcomes and the therapeutic potential of endocannabinoid system (ECS) modulation remain unclear. We conducted a translational systematic review and meta-analysis following PRISMA 2020 guidelines, s...

BackgroundGabapentin and pregabalin have potential utility for treating alcohol use disorder (AUD), but their comparative effectiveness in reducing alcohol consumption in real-world settings is unknown. We compared changes in alcohol consumption associated with gabapentin or pregabalin treatment with those of matched unexposed comparators. MethodsWe identified patients who were prescribed gabapentin or pregabalin for [≥]60 days for any indication between 1 January 2009 and 30 June 2022 using...

Background and AimsAlcohol use disorder (AUD) remains a major public health concern, with persistent disparities in access to evidence-based treatment. This study aimed to examine associations between perceived discrimination in healthcare settings (PDHS), patient-clinician communication (PCC), and receipt of treatment for AUD, and compared these with sociodemographic and insurance-related factors. DesignCross-sectional analysis using structural equation modeling (SEM), logistic and multinomial...

BackgroundSubstance use disorders (SUD) are associated with a high global burden of disease, with 5.4% of all disability-adjusted life years lost due to alcohol and illicit drugs. Highly prevalent multimorbidity includes polysubstance use, mental health conditions, and other non-communicable and infectious diseases. Where traditional treatments are insufficient alone, music therapy (MT) is highly engaging and improves motivation and reduces craving; however, its long-term effects are unknown. Th...

BackgroundBipolar disorder (BIP) frequently co-occurs with heightened substance use (SU) and substance use disorders (SUDs). Although the strong co-occurrence of these heritable traits points to shared genetic susceptibility, the extent to which there are differences in how SU and SUD overlap with BIP genetic architecture remains unclear. MethodsWe quantified the polygenic overlap between BIP and SUDs (alcohol, cannabis, opioid, and tobacco), and BIP and SU traits (drinks per week, lifetime can...

Ozempic, along with exercise and diet, is effective in helping individuals lose weight. Prior studies have reported misuse of Ozempic. This descriptive study used a nationally representative sample of persons in the U.S. from the National Survey on Drug Use and Health to identify self-reported use of an Ozempic injection for which the person was not prescribed. In 2024, 28,691 individuals ages 12 and older self-reported ever injecting Ozempic that was not prescribed to them. The entire sample wh...