Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Disordered connectivity configuration of triple-network model and visual-network in tobacco use disorder","authors":"Yang Liu ,&nbsp;Mengzhe Zhang ,&nbsp;Ya Tian ,&nbsp;Sha Zhou ,&nbsp;Yufei Shen ,&nbsp;Longyao Ma ,&nbsp;Bohui Mei ,&nbsp;Weijian Wang ,&nbsp;Shaoqiang Han ,&nbsp;Yong Zhang","doi":"10.1016/j.pnpbp.2026.111703","DOIUrl":"10.1016/j.pnpbp.2026.111703","url":null,"abstract":"<div><h3>Background</h3><div>Tobacco use disorder (TUD) is recognized as a significant neurobehavioral disorder, associated with alterations in functional network connectivity (FNC) within and between the triple-network and visual-network.</div></div><div><h3>Methods</h3><div>We recruited 87 male TUD patients and 45 male healthy control (HC), collecting resting-state functional magnetic resonance imaging(rs-fMRI) and smoking-related clinical scales. Group independent component analysis (ICA) combined with a sliding window method and k-means clustering analysis was used to assess static and dynamic time-varying FNC within networks. Spectral dynamic causal modelling (Sp DCM) and Parametric empirical bayes (PEB) framework were used to explore the aberrant effective connectivity (EC) among these networks in TUD.</div></div><div><h3>Results</h3><div>Compared to HC, TUD patients exhibited within-network hyperconnectivity in the middle temporal gyrus (MTG) of the salience network (SAL), medial prefrontal cortex (MPFC) of the default mode network (DMN), and superior frontal gyrus (SFG) of the higher-order visual-network (HVN), alongside hypoconnectivity in the superior parietal lobule (SPL) of the HVN and posterior cingulate cortex (PCC) of the primary visual-network (PVN). Statically, increased connectivity was observed between SAL and executive control network (ECN). Dynamically, hyperconnectivity between SAL and PVN was identified in State I. EC analysis revealed enhanced self-inhibition within SAL, increased excitatory drive from ECN to SAL and HVN, and decreased excitatory influence from PVN to HVN in TUD. Correlation analyses indicated that static SAL-ECN connectivity positively correlated with Russell Reasons for Smoking Questionnaire (RRSQ)IV-VII scores, while EC from ECN to HVN negatively correlated with Fagerstr¨om Test for Nicotine Dependence (FTND) scores and cigarettes per day.</div></div><div><h3>Conclusions</h3><div>This study reveals a novel, hierarchical dysregulated connectivity configuration involving the triple-network and visual-network in TUD, characterized by static hyperconnectivity, dynamic state-specific abnormalities, and a causal model of enhanced top-down control coupled with disrupted bottom-up processing. This study also provides new insights into the neurobiology of TUD in males, highlighting the need for future studies to investigate sex-specific effects. These findings advance the neurobiological understanding of TUD and emphasize potential network-based targets for neuromodulation therapies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111703"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural brain effects of alcohol use patterns in alcohol use disorder: A systematic review and Meta-analysis","authors":"Thomas Bernabeu ,&nbsp;Sabine Vollstädt-Klein ,&nbsp;Falk Kiefer ,&nbsp;Benjamin Rolland","doi":"10.1016/j.pnpbp.2026.111684","DOIUrl":"10.1016/j.pnpbp.2026.111684","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) is associated with significant structural alterations in gray and white matter of the brain, which has potential implications for cognitive and emotional functions. These alterations appear to be related to alcohol use patterns. This study aims to systematically review voxel-based morphometry studies to identify consistent patterns of gray matter and white matter alterations in patients with AUD compared to healthy control subject and explore their associations with alcohol consumption patterns. A systematic review of neuroimaging studies was conducted, analyzing gray matter (GM) and white matter (WM) differences between healthy individuals and patients with AUD. Special attention was given to the relationship between alcohol consumption variables (e.g., duration, quantity, frequency) and GM and WM volumes. AUD patients showed significant GM alterations in the right cingulate (SDM-Z = −6.013), right insula (SDM-Z = −6.088) and left Heschl gyrus (SDMZ = −5.254) compared to healthy control subject. WM alterations were found in the corpus callosum (SDM-Z = −3.537). Meta-regressions revealed dose-dependent associations: AUDIT scores (SDM-Z = −3.143), drinks/day (SDM-Z = −3.504), lifetime drinking (SDM-Z = 3.460), and years of dependence (SDM-Z = 3.063) were each negatively correlated with regional GM volume. Earlier age at first drink was associated with WM volume in the corpus callosum (SDM-Z = 3.229). Longer abstinence was correlated with larger WM volumes. This meta-analysis underscores the associations between alcohol consumption patterns and brain structure and provides evidence of dose-dependent associations between alcohol consumption and neuroanatomical differences.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111684"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol (CBD) does not reduce cocaine reward or self-administration in a mouse model of schizophrenia genetic susceptibility","authors":"Rose Chesworth ,&nbsp;Georgia Watt ,&nbsp;Erin McLemon ,&nbsp;Tim Karl","doi":"10.1016/j.pnpbp.2026.111676","DOIUrl":"10.1016/j.pnpbp.2026.111676","url":null,"abstract":"<div><div>Cannabidiol (CBD) is a non-intoxicating <em>Cannabis sativa</em> plant compound with some preclinical studies reporting efficacy for the treatment of psychiatric disorders, including schizophrenia and substance abuse. Considering that there are high rates of substance use in individuals with schizophrenia, CBD may be effective in the simultaneous treatment of both disorders. However, this exciting possibility has not been investigated preclinically, and CBD has only been evaluated for substance use treatment in healthy animals. Thus, to address this question thereby focusing on cocaine as an example for substance use, we used a mouse model of genetic risk for schizophrenia, heterozygous <em>transmembrane domain neuregulin 1</em> mice (<em>Nrg1 TM</em> HET), which importantly show addiction-like responses to cocaine and altered schizophrenia-relevant behaviours to cannabinoids. We examined the efficacy of intraperitoneal administration of selected doses of CBD in reducing cocaine-induced conditioned place preference and locomotion (at a dose of 10 mg/kg) as well as in decreasing cocaine self-administration (at a dose of 20 mg/kg) in male <em>Nrg1 TM</em> HET and wildtype-like controls. The effects of prior CBD administration on the cessation and relapse-like behaviour for cocaine self-administration were also determined. The selected dose of CBD reduced cocaine place preference, cocaine locomotion and cocaine self-administration in wildtype-like littermates. However, CBD was ineffective in reducing these behaviours in <em>Nrg1 TM</em> HET mice. Furthermore, prior CBD treatment did not affect cessation of cocaine self-administration or relapse-like behaviour in either genotype, indicating that acute CBD administration may be needed to reduce these behaviours. Together, our findings show that CBD at the dose chosen can reduce cocaine reward, locomotion and self-administration in healthy animals. Importantly, the selected CBD treatment designs may not be effective in reducing cocaine-induced mouse behaviours in the presence of schizophrenia risk mutations including mutant <em>Nrg1 TM</em>. These findings advocate for research evaluating CBD's efficacy in models of substance use susceptibility or other psychiatric disorders, to determine the circumstances and treatment designs under which CBD is and is not effective for substance use treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111676"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of short-term declarative memory by selective activation of the locus coeruleus–retrosplenial cortex dopaminergic pathway and its pathological alterations in Parkinson's disease","authors":"Yalong Yan ,&nbsp;Linyun Gao ,&nbsp;Xiyu Qiang ,&nbsp;Yuxiang Qiu ,&nbsp;Yixin Shen ,&nbsp;Chunyan Mu ,&nbsp;Chuanxi Tang","doi":"10.1016/j.pnpbp.2026.111680","DOIUrl":"10.1016/j.pnpbp.2026.111680","url":null,"abstract":"<div><div>Short-term declarative memory impairment, encompassing deficits in spatial working memory and object recognition, represents a prevalent non-motor symptom of Parkinson's disease (PD). Despite its clinical significance, the neural circuit mechanisms underlying this cognitive dysfunction remain poorly understood. Here, we identify a previously underappreciated dopaminergic projection from the locus coeruleus (LC) to the retrosplenial cortex (RSC) as a critical regulator of short-term declarative memory. Using optogenetic activation of LC dopaminergic neurons, we evoked dopamine release in the RSC and combined this manipulation with fiber photometry to monitor calcium dynamics during short-term declarative memory tasks, including the Y-maze and novel object recognition (NOR). These experiments revealed task-dependent activation of the LC–RSC pathway. Notably, this pathway exhibited functional impairment in PD model mice, as LC-evoked dopaminergic signals in the RSC were markedly attenuated and accompanied by reduced tyrosine hydroxylase expression in the LC. To establish causality, we selectively inhibited the LC–RSC pathway using a chemogenetic approach, which recapitulated deficits in spatial working memory and object recognition and disrupted local field potential (LFP) activity in the RSC, demonstrating that this pathway is necessary for normal short-term declarative memory processing. Collectively, these findings demonstrate that the LC–RSC dopaminergic pathway plays a pivotal role in mediating PD-related short-term declarative memory impairment, providing a circuit-level framework and potential therapeutic target for early cognitive intervention in PD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111680"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The astrocytes in the prefrontal cortex contribute to the rapid antidepressant-like effects of psilocybin in the chronic restraint stress mouse model","authors":"Yong-xing Qiao ,&nbsp;Wei Dai ,&nbsp;Yi-shan Yao ,&nbsp;Qian-qian Wei,&nbsp;Chen-xing Yue,&nbsp;Yong-yu Yin,&nbsp;Yun-feng Li,&nbsp;Li-ming Zhang","doi":"10.1016/j.pnpbp.2026.111698","DOIUrl":"10.1016/j.pnpbp.2026.111698","url":null,"abstract":"<div><div>Psilocybin showed a rapid antidepressant response in several clinical trials, which offers new hope for treating depression. Astrocytes were associated with the etiology of depression and might contribute to the onset of psilocybin. In this study, we investigated the fast antidepressant effect of psilocybin and tested variations of GFAP (astrocytic markers) and C3 protein (markers of A1 astrocyte) expression after psilocybin treatment in the chronic restraint stress (CRS) mouse model. We next defined the modulating impact of psilocin (psilocybin's main active metabolite) on primary astrocytes as well as A1 astrocytes in vitro. The depletion of astrocytes was achieved by AAV injection to further verify the astrocytic role underlying the action of psilocybin. Psilocybin and ketamine (positive control) rapidly reversed the depressive-like behaviors in the CRS mice. Both psilocybin and ketamine inhibited the CRS-induced astrocytic loss and increased C3 protein in the prefrontal cortex (PFC). Psilocin up-regulated the activation and proliferation of primary astrocytes, and strengthened astrocytic ATP/lactate/glutamate release and mitochondrial function. Psilocin reversed A1 astrocyte-induced impairments in ATP/lactate/glutamate release and mitochondrial function. In vivo, depletion of astrocytes in the prelimbic (PrL) region of mPFC might affect the antidepressant action of psilocybin in unstressed mice. Our findings might be significant for a better understanding of astrocytic mechanisms in the action of psilocybin.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111698"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severity-dependent alterations of EEG microstate dynamics in obsessive-compulsive disorder","authors":"Xinyue Zhang ,&nbsp;Rongrong Zhu ,&nbsp;Qihui Guo ,&nbsp;Dongmei Wang ,&nbsp;Xiang-Yang Zhang","doi":"10.1016/j.pnpbp.2026.111691","DOIUrl":"10.1016/j.pnpbp.2026.111691","url":null,"abstract":"<div><h3>Background</h3><div>While elevated symptom severity in obsessive-compulsive disorder (OCD) is associated with a profound clinical burden and escalating psychiatric risks, the underlying large-scale network dynamics remain poorly understood. Electroencephalogram (EEG) microstate analysis offers a window into these rapid network fluctuations, though studies in this area remain limited.</div></div><div><h3>Methods</h3><div>Resting-state 64-channel EEG was recorded from a total sample of 120 participants. After quality control, we analyzed resting-state EEG data from 101 participants, comprising 65 OCD patients (35 males; mean age = 28.24 ± 8.74 years) and 36 healthy controls (19 males; mean age = 24.67 ± 13.56 years). Patients were stratified into severe (<em>n</em> = 30) and non-severe (<em>n</em> = 35) groups based on Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores. Then, we compared microstate parameters across groups and employed machine learning (ML) to identify severity-related features.</div></div><div><h3>Results</h3><div>Distinct microstate patterns emerged based on severity. Non-severe patients showed altered microstates B and C, whereas severe patients exhibited significant deficits in microstate D and elevated microstate A. In the combined OCD cohort and the severe group, YBOCS scores had no significant relationship with microstate parameters, while YBOCS-compulsion scores negatively correlated with coverage A and TP B → A in the non-severe group. Moreover, the ML model successfully distinguished severe from non-severe cases (Balanced Accuracy = 69.76%; AUC = 0.78).</div></div><div><h3>Conclusion</h3><div>Our findings indicate that OCD severity maps onto distinct, severity-dependent microstate profiles rather than a linear network disruption. The successful classification of severity subgroups via ML further underscores the neurophysiological heterogeneity of the disorder, suggesting that precision psychiatry strategies should be tailored to the specific network status associated with different disease stages.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111691"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics-based management of newborns affected by hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia","authors":"Immacolata Rulli ,&nbsp;Angelo Mattia Carcione ,&nbsp;Serafina Perrone ,&nbsp;Virginia Beretta ,&nbsp;Lucia Marseglia ,&nbsp;Eloisa Gitto","doi":"10.1016/j.pnpbp.2026.111692","DOIUrl":"10.1016/j.pnpbp.2026.111692","url":null,"abstract":"<div><div>Perinatal asphyxia (PA) is caused by reduced blood flow or oxygen levels around the time of birth. Neonatal hypoxic-ischemic encephalopathy (HIE) specifically refers to the neurological damage resulting from PA and ischemia and is the most frequent cause of mortality and morbility in newborns. Therapeutic hypothermia (TH) is nowadays the standard of care to treat newborns with hypoxic-ischemic encephalopathy (HIE). However, pharmacokinetic (PK) changes during TH can impact the efficacy and safety of administered drugs. In this narrative review, we critically examined the main PK changes that occur during TH, focusing on alterations in drug distribution, metabolism and elimination. Hypothermia slows hepatic metabolism, reducing the clearance of some drugs and prolonging their half-life, while reduced tissue perfusion can alter drug distribution. Additionally, TH can affect protein binding of drugs and their ability to cross the blood-brain barrier, with significant implications for the management of seizures, sedation and antibiotic therapy. This review analyzes the available evidence on PK changes for drugs commonly used during TH, such as sedatives, analgesics and antibiotics and discusses the clinical implications for dose personalization and the management of side effect risks. Finally, future research areas are proposed to optimize pharmacological treatment in patients undergoing TH.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111692"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurocognitive mechanisms underlying alcohol-related emotional association bias among alcohol use disorder: Evidence from a hierarchical drift-diffusion model and event-related potentials","authors":"Zijing Wang ,&nbsp;Dapeng Zhang ,&nbsp;Jiayi Zhu ,&nbsp;Fanfan Luo ,&nbsp;Dongli Fan ,&nbsp;Luxing Cai ,&nbsp;Fei Cheng ,&nbsp;Jing Tian ,&nbsp;Shiyan Qu ,&nbsp;Jiang Du ,&nbsp;Tianzhen Chen ,&nbsp;Min Zhao","doi":"10.1016/j.pnpbp.2026.111699","DOIUrl":"10.1016/j.pnpbp.2026.111699","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate behavioral pattern of emotional association bias toward alcohol-related cues in alcohol use disorder (AUD) and its neurophysiological mechanisms.</div></div><div><h3>Methods</h3><div>47 individuals with AUD and 32 healthy Control (HC) were recruited in this cross-sectional study. All participants completed an emotional association bias task with electroencephalography recording. A hierarchical drift-diffusion model (HDDM) was used to characterize the behavioral patterns. Event-related potentials (ERP) analysis were conducted to explore the specific ERP component associated with alcohol cue-related emotional processing.</div></div><div><h3>Results</h3><div>Compared to HCs, individuals with AUD exhibited heightened automaticity in processing alcohol-related positive cues, as indicated by a significantly lower decision threshold (<em>P</em> &lt; 0.001). They also showed a stronger implicit emotional bias toward alcohol-related cues, reflected by enhanced EPN amplitudes (<em>P</em> = 0.043). Furthermore, individuals with AUD demonstrated difficulties disengaging from alcohol-related positive cues, as evidenced by slower drift rates (<em>P</em> &lt; 0.001) and longer non-decision times (<em>P</em> &lt; 0.001) than HCs. Importantly, mediation analysis revealed that LPP amplitude significantly mediated the relationship between group and non-decision time, with an inconsistent mediation pattern, suggesting that enhanced late-stage neural processing partially compensates for behavioral deficits.</div></div><div><h3>Conclusion</h3><div>These findings suggest that individuals with AUD exhibit specific emotional association biases toward alcohol and distinct neurophysiological mechanisms, providing insights into the underlying cognitive and neural processes and offering potential support for interventions targeting emotion regulation and emotional association bias modification in AUD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111699"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fentanyl and alcohol co-exposure induce robust, sustained hyperlocomotion and neural circuit disruption in larval zebrafish","authors":"Courtney Hillman ,&nbsp;James Kearn ,&nbsp;Matthew J. Winter ,&nbsp;Matthew O. Parker","doi":"10.1016/j.pnpbp.2026.111685","DOIUrl":"10.1016/j.pnpbp.2026.111685","url":null,"abstract":"<div><div>The increasing prevalence of poly-substance misuse, particularly co-use of synthetic opioids and alcohol, poses significant health risks, yet their combined neurobehavioral effects remain poorly understood. Here we used larval zebrafish to investigate interactions between fentanyl and ethanol, employing behavioral assays and <em>in vivo</em> whole-brain calcium imaging. Co-exposure induced a distinctive biphasic locomotor response characterized by initial suppression followed by sustained hyperlocomotion, which was replicated with other opioids but not with GABAA modulators, indicating an opioid- and ethanol-specific effect. Imaging revealed widespread neuronal hyperactivity and dysregulation during co-exposure compared to individual treatments. These findings reveal complex neurobehavioral mechanisms underlying opioid and alcohol co-use, highlighting ethanol's potentiation of opioid effects and suggesting larval zebrafish as a valuable model for studying poly-substance abuse. This work provides foundational insights that may inform future therapeutic strategies for managing opioid-alcohol co-intoxication.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111685"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoid-based interventions for behavioral outcomes in children and adolescents with autism spectrum disorder: A systematic review of safety and effectiveness","authors":"Quezia Damaris Jones Severino Vasconcelos ,&nbsp;Renê Felipe de Freitas ,&nbsp;Madna Costa Freitas ,&nbsp;Isadora Porto de Andrade ,&nbsp;Carla Barbosa Brandão ,&nbsp;Cidianna Emanuelly Nascimento ,&nbsp;Kelly Rose Neves ,&nbsp;Paulo Sávio Magalhães ,&nbsp;Valter Barbosa Filho ,&nbsp;Giovanna Lima Oliveira ,&nbsp;Matheus Alisson Melo de Moura ,&nbsp;Gislei Frota Aragão","doi":"10.1016/j.pnpbp.2026.111697","DOIUrl":"10.1016/j.pnpbp.2026.111697","url":null,"abstract":"<div><h3>Background</h3><div>Autism spectrum disorder (ASD) lacks effective options for core symptoms. Cannabinoids, especially cannabidiol (CBD) and combined CBD:Δ9-tetrahydrocannabinol (THC) formulations, are of interest, but clinical evidence is heterogeneous.</div></div><div><h3>Purpose</h3><div>To evaluate the effectiveness and safety of cannabinoid-based interventions for behavioral outcomes in children and adolescents with ASD.</div></div><div><h3>Methods</h3><div>Six databases (Scopus, Web of Science, Embase, Cochrane Library, PubMed, PsycINFO) were searched from February 2024 to June 2025. Risk of bias was assessed using RoB 2 (randomized controlled trials [RCTs]) and the Newcastle–Ottawa Scale (non-RCTs); certainty was evaluated with GRADE.</div></div><div><h3>Results</h3><div>Twelve studies (4 RCTs, 8 non-RCTs) were included; six ongoing trials were identified. Most interventions used full-spectrum extracts with high CBD:THC ratios (often 20:1), with titration up to ∼10 mg/kg/day; doses varied across studies. Responder rates for global improvement vs placebo (49% vs 21%) and greater improvement in social communication. No between-group differences were observed for sleep or overall symptom severity, and repetitive behaviors showed a non-significant trend toward improvement. Non-RCTs studies suggested benefits but had high risk of bias and very low certainty. Adverse events were mostly mild and non-serious (e.g., somnolence, appetite changes, sleep problems, irritability); no treatment-related serious adverse events were reported.</div></div><div><h3>Conclusions</h3><div>Evidence remains limited. A whole-plant 20:1 extract improved global clinical impression and social communication in one RCT, whereas other standardized outcomes were null. Current data support only cautious, adjunctive use under medical supervision. Larger, well-designed RCTs using validated outcomes are needed to clarify efficacy, optimal formulations, and long-term safety. <em>PROSPERO registration:</em> CRD42024508518.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111697"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}