Addiction Biology最新文献

{"title":"Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention","authors":"Isis Rita Anzel Koutrouli,&nbsp;Vojtěch Brejtr,&nbsp;Marek Schwendt,&nbsp;Kacper Witek,&nbsp;Chrysostomos Charalambous,&nbsp;Kristýna Aleksič,&nbsp;Nina Miniariková,&nbsp;Eva Lhotková,&nbsp;Martin Toman,&nbsp;Marek Nikolič,&nbsp;Radek Jurok,&nbsp;Petra Cihlářová,&nbsp;Vladimír Mazoch,&nbsp;Pavel Ryšánek,&nbsp;Martin Kuchař,&nbsp;Klára Šíchová,&nbsp;Tomáš Páleníček","doi":"10.1111/adb.70111","DOIUrl":"10.1111/adb.70111","url":null,"abstract":"<p>Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-administration (IVSA). Rats were trained on a fixed ratio 1 (FR1) schedule with cocaine dose-escalation during the acquisition phase (0.25 mg/kg/infusion, followed by 0.5 mg/kg/infusion). Following acquisition, animals were randomised into treatment groups and then subjected to 10 days of extinction. Psilocybin (1.25 mg/kg and 5 mg/kg) or ibogaine (10 mg/kg and 40 mg/kg) was administered subcutaneously and intraperitoneally, respectively, on extinction days 1 and 5. A cue-induced reinstatement test was conducted 6 days after the last treatment. Both treatments significantly modulated behaviour during extinction; psilocybin reduced active lever pressing 1 day after the second dose, with a nonsignificant reduction already apparent after the first dose, while the effect of ibogaine was significant even after the first administration. However, neither compound significantly altered reinstatement behaviour, although psilocybin showed a trend toward attenuation. The applied treatment had no side effects on general locomotor activity or anxiety-like behaviour, as measured in the open field test 24 h after each administration. These findings support a role for psilocybin and ibogaine in facilitating extinction learning and suggest possible protective effects against relapse, warranting further research into their antiaddictive efficacy.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol Use Disorder With Metabolic Dysfunction Is Associated With Adverse Health Impacts in a United States Clinical Setting","authors":"Alexandra C. Wagner,&nbsp;Jeesun Jung,&nbsp;Joshua Reitz,&nbsp;Tyler Perlstein,&nbsp;LaToya Sewell,&nbsp;Melanie L. Schwandt,&nbsp;Nancy Diazgranados,&nbsp;Josephin Wagner,&nbsp;Daniel B. Rosoff,&nbsp;Falk W. Lohoff","doi":"10.1111/adb.70128","DOIUrl":"10.1111/adb.70128","url":null,"abstract":"<p>The combined disease burden of excessive alcohol consumption and metabolic dysfunction (MD) is an escalating global concern. Although it is well established that both factors adversely impact health, the biological characteristics and comorbidities of their overlap remain understudied in the United States. The present study investigated whether concurrent MD and alcohol use disorder (AUD) is associated with worse liver-related and psychiatric health. A total of 1220 participants were recruited through the Natural History Protocol at the National Institutes of Health (NIH) and categorized into the following four groups: healthy controls (HC), individuals with MD (metHC), individuals with current AUD without MD (AUD) and those with both current AUD and MD (metAUD). Sociodemographic and clinical biomarkers, liver injury indices (Fibrosis-4 [FIB-4], LiverRisk, NAFLD fibrosis score [NFS]), liver enzymes and inflammatory markers (GGT, AST, ALT, CRP), liver function tests (albumin, bilirubin, PT-INR), psychiatric and substance use comorbidities as well as current smoking were assessed in the four groups using analysis of covariance (ANCOVA). In addition, the clinical biomarkers were compared across three groups: mild (&lt; 3 MD criteria) and severe (≥ 3) metAUD, as well as AUD only. Liver enzymes, noninvasive liver fibrosis scores and liver function tests showed additive effects across metHC, AUD and metAUD compared to HC, with the largest effects in metAUD for GGT, AST, ALT, CRP, albumin, direct bilirubin, FIB-4, LiverRisk and NFS (<i>p</i> &lt; 0.001). Psychiatric disorders also exhibited the most significant association with metAUD (<i>p</i> &lt; 0.001). Within AUD, greater MD severity was associated with higher GGT, ALT, CRP, NFS and any DSM anxiety disorders (<i>p</i> &lt; 0.05). These findings suggest that MD in the context of AUD is associated with greater liver dysfunction and psychiatric burden, supporting MD-targeted treatment strategies in clinical care for AUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent Binge Ethanol Exposure Confers Lasting Adult Alcohol Tolerance due to Neuroimmune Activation: Reversal by Inhibition of HMGB1","authors":"Fulton T. Crews,&nbsp;Ryan P. Vetreno","doi":"10.1111/adb.70119","DOIUrl":"10.1111/adb.70119","url":null,"abstract":"<p>Epidemiological studies suggest heavy adolescent binge drinking is strongly associated with later development of an alcohol use disorder (AUD). Alcohol tolerance (i.e., an acquired reduction in acute alcohol responsivity) is a universally recognized symptom of AUD, but the direct contribution of adolescent binge drinking to adult alcohol tolerance is poorly understood. To investigate the contributions of adolescent binge ethanol exposure to lasting acquisition of acute tolerance, we used our ethanol response battery (ERB) to assess intoxication rating, hypothermia, motor coordination and balance across cumulative ethanol doses (i.e., 0.0, 0.5, 1.0, 2.0 and 3.0 g/kg) in adult female Wistar rats following adolescent intermittent ethanol (AIE), lipopolysaccharide (LPS) and glycyrrhizic acid treatment following AIE. We report AIE confers lasting alcohol tolerance across cumulative ethanol doses and blunts acute ethanol-induced increases in proinflammatory HMGB1 plasma levels. Adolescent LPS (1.0 mg/kg, i.p.) treatment, which mimics AIE-induced HMGB1-mediated neuroinflammation, induces adult alcohol tolerance and blunts HMGB1 release across cumulative ethanol doses on the ERB. Assessment of proinflammatory HMGB1 involvement in AIE-induced acquisition of lasting alcohol tolerance showed that post-AIE administration of the HMGB1 inhibitor glycyrrhizic acid reversed the AIE-induced acquisition of alcohol tolerance in adulthood. These data reveal that (1) adolescent binge drinking confers long-lasting low ethanol responsivity (i.e., tolerance), (2) proinflammatory neuroimmune activation contributes to the development of alcohol tolerance and (3) blockade of proinflammatory HMGB1 signalling reverses AIE-induced acquisition of alcohol tolerance in adulthood. These findings suggest a potential mechanistic target for the development of novel therapeutics for the treatment of AUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative Urgency Mediates the Effect of Family Conflict on Cannabis Positive Expectancy: The Moderating Role of Anterior Cingulate Cortex","authors":"Rabeeh Azarmehr,&nbsp;Cullin J. Howard,&nbsp;Steven M. Kogan,&nbsp;Charles Geier,&nbsp;Assaf Oshri","doi":"10.1111/adb.70131","DOIUrl":"10.1111/adb.70131","url":null,"abstract":"<p>Cannabis positive expectancies, favourable beliefs about cannabis effects, are a key risk factor for cannabis initiation and problematic use during adolescence. Prior research demonstrated a robust association between cannabis positive expectancies and increased use among adolescents, yet less is known about the developmental aetiology, biobehavioural mechanisms and cognitive context that contribute to these expectancies. The present study examines the intermediary role of negative urgency, a facet of impulsivity characterized by rash action under distress. Additionally, the study investigates whether anterior cingulate cortex (ACC) activation during emotional reward processing moderates this indirect effect. We conducted a longitudinal moderated mediation model with three waves of data from the Adolescent Brain and Cognitive Development (ABCD) study, analysing 6638 youths (baseline M_age = 10.1 years; 47.8% female). Family conflict at baseline predicted increased cannabis positive expectancies ΔT5T7 through increases in negative urgency at T5 (<i>β</i> = 0.017, <i>p</i> &lt; 0.001, 95% CI [0.045, 0.069]). Heightened ACC activity at T5 (anticipatory large loss), including bilateral caudal and rostral regions, intensified negative urgency's impact on cannabis positive expectancy ΔT5T7: Left caudal (<i>β</i> = 0.081, <i>p</i> &lt; 0.001, 95% CI [0.041, 0.122]), right caudal (<i>β</i> = 0.062, <i>p</i> = 0.004, 95% CI [0.020, 0.105]), right rostral (<i>β</i> = 0.041, <i>p</i> = 0.026, 95% CI [0.001, 0.081]) and left rostral (<i>β</i> = 0.052, <i>p</i> = 0.01, 95% CI [0.012, 0.092]). This study highlights how neural activity amplifies stress-related effects on adolescent substance use expectations, suggesting emotional decision-making as a target for prevention.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Topological Properties of White-Matter Functional Networks in Young Smokers","authors":"Zhenzhen Mai,&nbsp;Dahua Yu,&nbsp;Gengdi Huang,&nbsp;Xiaojiao Li,&nbsp;Xuwen Wang,&nbsp;Fang Dong,&nbsp;Yongxin Cheng,&nbsp;Juan Wang,&nbsp;Yuxin Ma,&nbsp;Lin Luo,&nbsp;Kai Yuan,&nbsp;Ting Xue","doi":"10.1111/adb.70125","DOIUrl":"10.1111/adb.70125","url":null,"abstract":"<p>Smoking addiction is a common mental disorder, and numerous imaging studies have shown that adolescents with smoking addiction exhibit abnormalities in brain function and structure. This study aims to investigate changes in the topological characteristics of the white matter (WM) functional network in young smokers. Forty-two young smokers and 42 age-, gender-, and education-matched nonsmokers were included in the study. The functional connectome of white matter and graph theory were used to study these participants. Two-sample <i>t</i>-test were used for the detection of the abnormal graph properties in young smokers. Pearson correlation was applied for the correlation analyses between properties and clinical indicators of smoking. The global level WM functional network analyses showed that the <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>C</mi>\u0000 <mi>p</mi>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {C}_p $$</annotation>\u0000 </semantics></math> and <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>E</mi>\u0000 <mtext>local</mtext>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {E}_{local} $$</annotation>\u0000 </semantics></math> values were higher in young smokers than in the control group, and the <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>E</mi>\u0000 <mtext>local</mtext>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {E}_{local} $$</annotation>\u0000 </semantics></math> was positively correlated with the age of first smoking. At the node level, five nodes of the WM functional network exhibited abnormal node properties in the WM regions of the bilateral hippocampal parahippocampal gyrus (CGH), bilateral superior longitudinal fasciculus (SLF), bilateral inferior frontal gyrus (IFO), middle cerebellar peduncle (MCP), and the bilateral anterior commissure (ACR) in young smokers. The node degree centrality value of MCP was positively correlated with age of first smoking. Our neuroimaging findings provide evidence of WM functional alterations associated with nicotine addiction, which may enhance our understanding of the neural mechanisms underlying smoking addiction in young smokers.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Vape Products Elicits Neural Activity Patterns Indicative of Approach Motivation Among Young People","authors":"Stefan Bode,&nbsp;Daniel Feuerriegel,&nbsp;Jane Yook,&nbsp;Michelle I. Jongenelis","doi":"10.1111/adb.70130","DOIUrl":"10.1111/adb.70130","url":null,"abstract":"<p>Previous research exploring the impact of exposure to e-cigarette (vape) products has been limited by a reliance on self-report measures, responses to which require self-reflection and insight. The present study sought to address these limitations by using novel ‘neural decoding’ techniques to establish whether exposure to e-cigarette products triggers automatic and unconscious product approach tendencies. An electroencephalography (EEG) study was conducted in Australia. Participants (<i>n</i> = 38; 68% women; 17–23 years old) were presented with images of e-cigarette products for several seconds while their brain activity was recorded. The primary outcome variables were brain activity and ratings of product appeal, curiosity and wanting. Results suggest that young people's vape approach tendencies can be predicted from brain activity as early as 100–300 ms after exposure, and then again over a sustained time period 350–800 ms after exposure. These findings were not restricted to those who currently vape, with similar patterns observed in young people who had never vaped or had tried vaping products in the past. Findings provide neuroscientific evidence for the presence of fast and automatic processing of vape products, which results in immediate approach tendencies. This suggests that approach attitudes and behavioural intentions that occur in response to exposure to vape products precede deliberate processing, and that exposure to e-cigarette products has an immediate effect on young people's neural processing. This novel neural approach to understanding marketing for e-cigarettes offers valuable insights into how fast and automatic product-based marketing of e-cigarettes unfolds in young people's brains, with implications for product regulation.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress of Exosome-Derived microRNA in Alcohol Use Disorders: A Critical Review","authors":"Bo Zhang,&nbsp;Ting ting Xie,&nbsp;Qiang Ma,&nbsp;Ya ping Jiang,&nbsp;Yu mei Wang","doi":"10.1111/adb.70124","DOIUrl":"10.1111/adb.70124","url":null,"abstract":"<p>Alcohol use disorder (AUD) is a chronic, relapsing condition that causes extensive systemic damage, yet clinically actionable biomarkers remain lacking. Exosome-derived microRNAs (exo-miRNAs) have emerged as highly stable extracellular indicators of disease state and active regulators of alcohol-induced pathological processes. Unlike proteins or lipids, miRNAs are selectively packaged, cell-type specific and mechanistically linked to inflammation, hepatocellular injury, synaptic dysfunction and neuroimmune signalling. Here, we provide an integrated and updated review of how chronic alcohol exposure reshapes exo-miRNA cargo across organs—particularly the liver, immune system and central nervous system. We summarize the biogenesis and selective sorting of exo-miRNAs, highlight key candidate miRNAs such as miR-122, miR-155, miR-192, miR-29a, miR-30a and miR-124 and analyse their representative gene targets and downstream effects. Furthermore, we distinguish exo-miRNAs with diagnostic potential from those representing promising therapeutic targets and discuss major limitations, including specificity relative to other drugs of abuse. By integrating mechanistic and translational evidence, this review aims to clarify the biological and clinical value of exo-miRNAs and to provide guidance for future precision-medicine strategies in AUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146068009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydrotestosterone and Finasteride Effects on Alcohol Cue-Elicited Brain Activity in Males With Heavy Episodic Drinking","authors":"Rafat Boroumand-Jazi,&nbsp;Sabine Hoffmann,&nbsp;Iris Reinhard,&nbsp;Patrick Bach,&nbsp;Wolfgang H. Sommer,&nbsp;Marlene Kundlacz,&nbsp;Christian P. Müller,&nbsp;Matthias Reichl,&nbsp;Haoye Tan,&nbsp;Leonard P. Wenger,&nbsp;Anne Beck,&nbsp;Sabine Vollstädt-Klein,&nbsp;Falk Kiefer,&nbsp;Christiane Mühle,&nbsp;Sarah Gerhardt,&nbsp;Bernd Lenz","doi":"10.1111/adb.70123","DOIUrl":"10.1111/adb.70123","url":null,"abstract":"<p>Preliminary animal and human studies have shown that blood dihydrotestosterone concentrations are increased in males with alcohol use disorder, and 5α-reductase inhibitors, which decrease dihydrotestosterone concentrations, reduce alcohol consumption. To gain mechanistic insight, we studied the effects of reduced dihydrotestosterone concentrations following pharmacological 5α-reductase inhibition on alcohol cue-elicited brain activity and alcohol craving in males with problematic alcohol use. To this end, this randomized, placebo-controlled, crossover challenge experiment investigated associations between dihydrotestosterone concentrations and brain functional magnetic resonance imaging (fMRI) activity during exposure to visual alcohol cues and alcohol craving following a single dose of 5 mg finasteride versus placebo in 50 males with heavy episodic drinking. We used finasteride because it specifically inhibits 5α-reductase II activity, which is the main enzyme converting testosterone to dihydrotestosterone. Dihydrotestosterone concentrations were lower in the finasteride condition in comparison to the placebo condition, but not significantly associated with brain activation patterns or craving. In the exploratory analyses, we found higher brain activity during exposure to visual stimuli in the right and left caudate nuclei, the right superior frontal gyrus and the left insula in the finasteride condition versus the placebo condition. Moreover, finasteride versus placebo was associated with a higher wish to not drink alcohol. The results of this experimental study do not support the à priori hypothesis that dihydrotestosterone concentrations play a role in brain activation during exposure to visual alcohol cues, but indicate that finasteride effects may be mediated by other pathways. Future studies are requested to investigate the effects of reduced dihydrotestosterone concentrations over a longer time and to shed light on the molecular mechanisms underlying the here observed effects of finasteride.</p><p><b>Trial Registration:</b> DRKS00020569</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CO2 Reactivity but Not CO2-Induced Orexin/c-Fos Colocalization Differentially Predicts Alcohol-Seeking Behaviour After Extinction and Retrieval-Extinction in Rats","authors":"Marissa Raskin,&nbsp;Marcelle Olvera,&nbsp;Kylee A. Smith,&nbsp;Roberto Cofresí,&nbsp;Jason Shumake,&nbsp;Michael J. Telch,&nbsp;Michael W. Otto,&nbsp;Jasper A. J. Smits,&nbsp;Rueben Gonzales,&nbsp;Hongjoo J. Lee,&nbsp;Marie-H. Monfils","doi":"10.1111/adb.70116","DOIUrl":"10.1111/adb.70116","url":null,"abstract":"<p>Cues associated with alcohol consumption can trigger cravings, seeking behaviour and relapse after abstinence in individuals with alcohol use disorder (AUD). These conditioned responses can be attenuated through extinction learning, a core component of cue exposure therapy (CET). CET is effective in some individuals with AUD but not all, so it is necessary to develop strategies to identify and intervene with individuals unlikely to benefit from CET. Another method for attenuating conditioned responding is retrieval-extinction, which renders the original associative memory labile via distinct neural mechanisms. We recently demonstrated that CO₂ reactivity predicts extinction memory for both fear and food cues, and fear memory after retrieval-extinction, and CO₂-induced orexin/c-Fos colocalization predicts fear extinction memory. The purpose of the current study was to examine whether the predictive power of CO₂ reactivity might extend to alcohol-seeking behaviour after extinction or retrieval-extinction in male and female rats. We also examined the relationship between CO₂ reactivity, return of alcohol-seeking behaviour and CO₂-induced orexin/c-Fos colocalization. Male and female rats first underwent alcohol drinking induction in the homecage followed by dependence via exposure to chronic intermittent ethanol vapour or control air and homecage drinking. All rats then underwent Pavlovian alcohol conditioning followed by either standard extinction or retrieval-extinction. They then received a long-term memory (LTM) test and CO₂ challenge followed by euthanasia for brain harvesting. CO₂ reactivity differentially predicted LTM after extinction and retrieval-extinction. There were no relationships between orexin/c-Fos colocalization and CO₂ reactivity or LTM. The predictive power of CO₂ reactivity extends to alcohol-seeking behaviour after extinction and retrieval-extinction in alcohol dependent and nondependent male and female rats, while its relationship with orexin/c-Fos colocalization does not. CO₂ reactivity could be used as a screening tool to determine whether an individual may be a good candidate for CET or a retrieval-extinction–based approach.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Heroin Use and Depression: NHANES 2005–2018","authors":"Bei Li,&nbsp;Zhuojun Yang,&nbsp;Xiaoxiao Zhang,&nbsp;Mei Yang,&nbsp;Hong Qiu,&nbsp;Yulan Ren","doi":"10.1111/adb.70127","DOIUrl":"10.1111/adb.70127","url":null,"abstract":"<p>Heroin use and major depression are each leading contributors to global disability and premature mortality, yet evidence for a specific association between the two remains fragmented and is often derived from small, treatment-seeking samples. We conducted a cross-sectional analysis of nationally representative data from the 2005–2018 National Health and Nutrition Examination Survey, including 19 022 US adults aged ≥ 20 years with complete information on heroin use, depression status, and relevant covariates. Clinically significant depression was defined as a PHQ-9 score ≥ 10. After multivariable adjustment for sociodemographic, behavioural, and clinical factors, including polysubstance use and chronic medical conditions, lifetime heroin use was independently associated with depression (adjusted OR = 1.85, 95% CI 1.43–2.40; <i>p</i> &lt; 0.001). Subgroup analyses demonstrated that this association was robust and modified by age and smoking status, with significant interaction effects observed (<i>p</i> for interaction &lt; 0.05). Restricted cubic spline analysis among participants with a history of heroin use (<i>n</i> = 439) revealed a non-linear relationship between age at first heroin use and depression risk (<i>p</i> for non-linearity = 0.032), with the highest predicted probability of depression among individuals who initiated use at or before 20.4 years of age. These findings indicate that lifetime heroin use is associated with a substantially increased risk of clinically significant depression in the general US population, particularly among younger adults and current smokers, underscoring the need for integrated screening and concurrent treatment of substance-use and mood disorders.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}