Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

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Beyond dopamine: Exploring anti-inflammatory mechanisms of antipsychotics 超越多巴胺:探索抗精神病药物的抗炎机制。
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-20 DOI: 10.1016/j.pnpbp.2025.111459
Nicole Šafářová , Marián Kolenič , Filip Španiel
{"title":"Beyond dopamine: Exploring anti-inflammatory mechanisms of antipsychotics","authors":"Nicole Šafářová ,&nbsp;Marián Kolenič ,&nbsp;Filip Španiel","doi":"10.1016/j.pnpbp.2025.111459","DOIUrl":"10.1016/j.pnpbp.2025.111459","url":null,"abstract":"<div><div>Schizophrenia is increasingly recognized as a disorder with a prominent neuroimmune component. Researchers have observed elevated markers of inflammation (e.g., cytokines, CRP, and NLR) not only during first-episode psychosis but also in chronic stages, suggesting that immune dysregulation may play a key role in the illness's pathophysiology. Yet, current pharmacological treatment mainly targets dopaminergic dysregulation, which is effective in reducing positive symptoms but is ineffective in managing negative symptoms and cognitive decline associated with schizophrenia.</div><div>Antipsychotics (APs) may exert anti-inflammatory effects, possibly through attenuating glial activation and modulation of the immune pathways, though these effects remain still underexplored. That is why, in this narrative review, we synthesize evidence from in vitro, animal, and human studies to examine whether APs influence inflammatory processes and assess their potential in mitigating the refractory symptoms of schizophrenia through the immune modulation.</div><div>Despite promising findings, several key uncertainties persist: inflammatory markers exhibit inconsistent patterns across studies, methodological approaches differ considerably, and antipsychotic-induced metabolic alterations further complicate interpretation. To fully understand the anti-inflammatory potential of APs, future research should identify the most effective compounds, determine optimal treatment timing, and rigorously control for confounding factors. Crucially, a paradigm shift is needed: clinical trials must adopt biomarker-guided stratification, and drug development should focus on agents that modulate the innate immunity. These steps are essential for developing more effective treatments for the refractory symptoms of schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111459"},"PeriodicalIF":5.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692482","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}
引用次数: 0
Updates on first- and second-generation antidepressants used in the treatment of traumatic brain injury-induced depression 第一代和第二代抗抑郁药用于治疗创伤性脑损伤引起的抑郁症的最新进展
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-20 DOI: 10.1016/j.pnpbp.2025.111458
Nicla Tranchida , Francesca Inferrera , Salvatore Cuzzocrea , Marika Cordaro , Rosanna Di Paola
{"title":"Updates on first- and second-generation antidepressants used in the treatment of traumatic brain injury-induced depression","authors":"Nicla Tranchida ,&nbsp;Francesca Inferrera ,&nbsp;Salvatore Cuzzocrea ,&nbsp;Marika Cordaro ,&nbsp;Rosanna Di Paola","doi":"10.1016/j.pnpbp.2025.111458","DOIUrl":"10.1016/j.pnpbp.2025.111458","url":null,"abstract":"<div><div>One of the leading causes of disability leading to depression and other neuropsychiatric complications is traumatic brain injury, especially among young people. Post-TBI depression is a common condition with a significant impact on quality of life, recovery, and rehabilitation. In the last years, the second-generation antidepressants SNRIs and SSRIs have been applied as treatments for depression in patients with TBI. Due to the more favorable side effect profiles, these agents are considered over first-generation antidepressants. While further studies are needed to identify specific mechanisms and interactions with drug-induced brain trauma effects, preliminary studies do suggest that second-generation antidepressants may be useful in treating post-TBI depression. This review focus on the benefits, challenges, and emerging scientific evidence regarding the use second-generation antidepressants in TBI patients.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111458"},"PeriodicalIF":5.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687125","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}
引用次数: 0
Role of gut microbiota and its functional products in prenatal alcohol-induced anxiety-like behavior 肠道菌群及其功能产物在产前酒精诱导的焦虑样行为中的作用
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-18 DOI: 10.1016/j.pnpbp.2025.111454
Kingston E. Wong , Carolina Luft , Victoria R. Vella , Garrett R.J. Ainsworth-Cruickshank , Kanishka K. Wijesundara , Parker J. Holman , Tamara S. Bodnar , Charlis Raineki
{"title":"Role of gut microbiota and its functional products in prenatal alcohol-induced anxiety-like behavior","authors":"Kingston E. Wong ,&nbsp;Carolina Luft ,&nbsp;Victoria R. Vella ,&nbsp;Garrett R.J. Ainsworth-Cruickshank ,&nbsp;Kanishka K. Wijesundara ,&nbsp;Parker J. Holman ,&nbsp;Tamara S. Bodnar ,&nbsp;Charlis Raineki","doi":"10.1016/j.pnpbp.2025.111454","DOIUrl":"10.1016/j.pnpbp.2025.111454","url":null,"abstract":"<div><div>Prenatal alcohol exposure (PAE) has been shown to increase vulnerability to anxiety. Alterations in the gut microbiota and its functional products (<em>i.e.</em>, short-chain fatty acids, SCFAs) are a potential mechanism underlying anxiety behaviors induced by PAE. Here, we used a rat model of PAE to examine the impact of alcohol consumption during gestation on anxiety-like behaviors, gut microbiota, and SCFA levels in adult male and female offspring. PAE male and female rats exhibited increased anxiety-like behavior on the open field test; moreover, control animals displayed striking sex differences in the light-dark test, but sex differences were attenuated among PAE males and females. Furthermore, using an anxiety index composed of open field and light-dark behaviors, we showed that PAE animals had higher anxiety scores compared to controls. PAE did not affect bacterial diversity and community structure; however, in males, PAE reduced the abundance of the Firmicutes phylum, increased the abundance of the Bacteroidota phylum, and decreased the abundance of the <em>Lachnospiraceae NK4A136</em> group genus compared to controls. In females, PAE increased abundance of <em>Turicibacter</em> genus compared to controls. PAE did not affect fecal SCFA levels; however, lower levels of butyric and valeric acid were associated with higher anxiety among PAE females. This study identified several bacterial taxa and SCFAs potentially involved in the mechanisms through which PAE induces anxiety-like behaviors. These findings also underscore the importance of considering sex differences when assessing anxiety-like behavior and gut microbiota to identify potential biomarkers for interventions targeting mental health issues in individuals with PAE.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111454"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676609","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}
引用次数: 0
The role of GABA, glutamate, and Glx levels in treatment of major depressive disorder: A systematic review and meta-analysis GABA、谷氨酸和Glx水平在治疗重度抑郁症中的作用:一项系统综述和荟萃分析
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-18 DOI: 10.1016/j.pnpbp.2025.111455
Kate Godfrey , Hannah Douglass , David Erritzoe , Suresh Muthukumaraswamy , David Nutt , Rachael Sumner
{"title":"The role of GABA, glutamate, and Glx levels in treatment of major depressive disorder: A systematic review and meta-analysis","authors":"Kate Godfrey ,&nbsp;Hannah Douglass ,&nbsp;David Erritzoe ,&nbsp;Suresh Muthukumaraswamy ,&nbsp;David Nutt ,&nbsp;Rachael Sumner","doi":"10.1016/j.pnpbp.2025.111455","DOIUrl":"10.1016/j.pnpbp.2025.111455","url":null,"abstract":"<div><div>This systematic review and meta-analysis aims to explore a possible role of gamma-aminobutyric acid (GABA) and glutamate, as measured by Magnetic Resonance Spectroscopy (MRS), in the treatment outcomes of people with Major Depressive Disorder (MDD). Despite the prevalence of MDD and various treatment modalities, the neurobiological mechanisms of each remain poorly understood. We synthesised data from 41 longitudinal studies comprising 918 individuals with MDD, spanning four primary treatment modalities: selective serotonin reuptake inhibitors (SSRIs), ketamine, repetitive transcranial magnetic stimulation (rTMS), and electroconvulsive therapy (ECT).</div><div>Pooled analyses revealed a significant increase in Glx levels post-treatment across modalities, with this effect persisting in responder-only subgroups and analyses restricted to prefrontal regions. In contrast, no consistent changes were observed in GABA or glutamate levels following treatment. These results suggest that modulation of Glx, but not bulk GABA or glutamate, may be a common neurobiological mechanism underlying therapeutic response in MDD. However, a role for GABAergic systems cannot be excluded, as functionally relevant changes may occur without detectable shifts in overall concentration. We recommend future studies prioritise reporting by responder status and employ higher-field MRS techniques to more precisely characterise treatment-related bulk metabolite changes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111455"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676566","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}
引用次数: 0
Cannabidiol improves L-DOPA-induced dyskinesia and modulates neuroinflammation and the endocannabinoid, endovanilloid and nitrergic systems 大麻二酚改善左旋多巴诱导的运动障碍,调节神经炎症和内源性大麻素、内源性香草素和氮能系统。
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-18 DOI: 10.1016/j.pnpbp.2025.111456
Glauce Crivelaro Nascimento , Gabriela Gonçalves Bálico , Bianca Andretto de Mattos , Mauricio Dos-Santos-Pereira , Igor Gustavo Carvalho Oliveira , Maria Eugênia Costa Queiroz , Lilian do Carmo Heck , Luiz Carlos Navegantes , Francisco Silveira Guimarães , Elaine Del-Bel
{"title":"Cannabidiol improves L-DOPA-induced dyskinesia and modulates neuroinflammation and the endocannabinoid, endovanilloid and nitrergic systems","authors":"Glauce Crivelaro Nascimento ,&nbsp;Gabriela Gonçalves Bálico ,&nbsp;Bianca Andretto de Mattos ,&nbsp;Mauricio Dos-Santos-Pereira ,&nbsp;Igor Gustavo Carvalho Oliveira ,&nbsp;Maria Eugênia Costa Queiroz ,&nbsp;Lilian do Carmo Heck ,&nbsp;Luiz Carlos Navegantes ,&nbsp;Francisco Silveira Guimarães ,&nbsp;Elaine Del-Bel","doi":"10.1016/j.pnpbp.2025.111456","DOIUrl":"10.1016/j.pnpbp.2025.111456","url":null,"abstract":"<div><div>Despite the widespread use of L-3,4-dihydroxyphenylalanine (L-DOPA) as the gold standard for dopamine (DA) replacement in Parkinson's Disease (PD), its prolonged administration frequently leads to L-DOPA-induced dyskinesia (LID), a significant therapeutic challenge. Modulating the endocannabinoid system has emerged as a promising approach for managing LID. This study explored whether cannabidiol (CBD), a non-psychoactive compound of <em>Cannabis sativa</em>, and PECS-101, a fluorinated derivative of CBD, could mitigate the onset and progression of LID. We used unilateral 6-hydroxydopamine-lesioned rats, treated with L-DOPA (10 mg kg − 1) for three weeks to induce severe abnormal involuntary movements (AIMs). Treatments were administered during the final two weeks. CBD (30 mg kg − 1) and PECS-101 (3 and 30 mg kg − 1) significantly reduced AIMs without impairing the motor benefits of L-DOPA. The antidyskinetic effects of CBD were associated with decreased striatal Fos-B and phospho-ERK expression and were independent of lesion severity. CBD effects were prevented by antagonists of CB1 (1 mg kg − 1) and PPARγ (4 mg kg − 1) receptors. Co-administration of TRPV-1 antagonist capsazepine (5 mg kg − 1) enhanced the antidyskinetic effects of CBD. Combining the capsazepine with the neuronal nitric oxide synthase inhibitor, 7-nitroimidazole (10 mg kg − 1) enhanced these effects. CBD did not alter striatal DA levels but significantly increased the concentrations of anandamide and 2-arachidonoylglycerol in dyskinetic animals. The antidyskinetic effects of CBD were associated with a reduction of the enhanced striatal glia and peripheral inflammation markers. These findings suggest that CBD alleviates LID by interacting with the nitrergic neurotransmission and TRPV-1, CB1, and PPARγ receptors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111456"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676608","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}
引用次数: 0
Diagnosis-informed neuro-subtyping reveals subgroups of autism spectrum disorder with reliable and distinct functional connectivity profiles 诊断信息的神经亚型显示自闭症谱系障碍的亚组具有可靠和独特的功能连接概况。
IF 3.9 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-16 DOI: 10.1016/j.pnpbp.2025.111452
Yaping Wang , Zehua Chen , Peilun Song , Gary Yu-Hin Lam , Xin Kang , Patrick C.M. Wong , Xiujuan Geng
{"title":"Diagnosis-informed neuro-subtyping reveals subgroups of autism spectrum disorder with reliable and distinct functional connectivity profiles","authors":"Yaping Wang ,&nbsp;Zehua Chen ,&nbsp;Peilun Song ,&nbsp;Gary Yu-Hin Lam ,&nbsp;Xin Kang ,&nbsp;Patrick C.M. Wong ,&nbsp;Xiujuan Geng","doi":"10.1016/j.pnpbp.2025.111452","DOIUrl":"10.1016/j.pnpbp.2025.111452","url":null,"abstract":"<div><h3>Background</h3><div>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by heterogeneous symptoms and neurobiological features, which hinders the identification of reliable biomarkers. Until recently, ASD neuro-subtyping has emerged to detect neural features in each subgroup.</div></div><div><h3>Methods</h3><div>We implemented neuro-subtyping of ASD using a semi-supervised clustering method, HeterogeneitY through DiscRiminative Analysis (HYDRA), guided by the labeling information of ASD/controls, together with a multi-scale dimension reduction method of high-dimensional input features. Functional connectivity was estimated as neural features for subtyping subjects from a large dataset with ∼2000 subjects. Systematic evaluation of clustering performance was conducted and the semi-supervised approach was compared with unsupervised K-means, commonly used for neuro-subtyping, combined with different types of feature reduction methods.</div></div><div><h3>Results</h3><div>We successfully detected two clusters, the hyper-connectivity subtype and hypo-connectivity subtype, each exhibiting distinct connectivity patterns between and within large networks, with high reliability. The semi-supervised clustering approach demonstrated superior performance compared to the unsupervised approach. We observed cluster effect on functional connectivities, for instance, the hyper-connectivity cluster shows hyper-connectivity within major large networks and hyper/hypo-connectivities between networks, such as hyper-connectivity between default mode and attention networks, and hypo-connectivity between default mode and visual/auditory networks. In contrast, the hypo-connectivity cluster displayed the opposite connectivity patterns. Furthermore, we found varying correlations between connectivities and main symptoms of ASD across subtypes.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that the semi-supervised approach has the potential to subtype ASD into distinct and reliable clusters. The clusters effectively differentiate heterogeneous neural markers based on functional connectivity patterns, meanwhile establish distinct neurobehavioral relationships across each subtype, which is a critical step towards developing individualized diagnosis and treatment strategies in the future.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111452"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669012","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}
引用次数: 0
Corrigendum to “Differential effects of gestational Cannabis smoke and phytocannabinoid injections on male and female rat offspring behavior” [Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111241] “妊娠期大麻烟雾和植物大麻素注射对雄性和雌性大鼠后代行为的差异影响”的更正[Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111241]。
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-13 DOI: 10.1016/j.pnpbp.2025.111431
T. Black, I.L. Barnard, S.L. Baccetto, Q. Greba, S.N. Orvold, F.V.L. Austin-Scott, G.B. Sanfuego, T.J. Onofrychuk, A.E. Glass, R.M. Andres, L.M. Macfarlane, J.C. Adrian, A.L. Heidt, D.L. McElroy, R.B. Laprairie, J.G. Howland
{"title":"Corrigendum to “Differential effects of gestational Cannabis smoke and phytocannabinoid injections on male and female rat offspring behavior” [Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111241]","authors":"T. Black,&nbsp;I.L. Barnard,&nbsp;S.L. Baccetto,&nbsp;Q. Greba,&nbsp;S.N. Orvold,&nbsp;F.V.L. Austin-Scott,&nbsp;G.B. Sanfuego,&nbsp;T.J. Onofrychuk,&nbsp;A.E. Glass,&nbsp;R.M. Andres,&nbsp;L.M. Macfarlane,&nbsp;J.C. Adrian,&nbsp;A.L. Heidt,&nbsp;D.L. McElroy,&nbsp;R.B. Laprairie,&nbsp;J.G. Howland","doi":"10.1016/j.pnpbp.2025.111431","DOIUrl":"10.1016/j.pnpbp.2025.111431","url":null,"abstract":"","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111431"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568077","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}
引用次数: 0
Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials nn -二甲基色胺(DMT)在健康志愿者和重度抑郁症(MDD)患者中的安全性和耐受性:早期临床试验的系统回顾
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-13 DOI: 10.1016/j.pnpbp.2025.111419
Damian Swieczkowski , Aleksander Kwaśny , Wiesław Jerzy Cubała
{"title":"Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials","authors":"Damian Swieczkowski ,&nbsp;Aleksander Kwaśny ,&nbsp;Wiesław Jerzy Cubała","doi":"10.1016/j.pnpbp.2025.111419","DOIUrl":"10.1016/j.pnpbp.2025.111419","url":null,"abstract":"<div><div>Treatment-resistant depression (TRD) remains a challenge, with many patients unresponsive to standard antidepressants. NN-dimethyltryptamine (DMT), a fast-acting psychedelic, offers potential benefits due to its rapid onset and short duration. This review, registered with the Open Science Framework (DOI: <span><span>10.17605/OSF.IO/6D9WC</span><svg><path></path></svg></span>), summarizes the safety and tolerability of DMT in early-phase trials. A systematic review was conducted following PRISMA guidelines. Databases including PubMed, SCOPUS, Web of Science, and EMBASE were searched until October 2024. Eligibility criteria included clinical trials assessing safety and tolerability outcomes of DMT in healthy volunteers or patients with major depressive disorder (MDD). Risk of bias was assessed using RoB2 and ROBINS-I tools. Results were synthesized narratively. Out of 505 records, 5 trials were included in the review. Intravenous trials (NCT04711915, NCT04673383) showed increased systolic blood pressure (up to 25.7 %) and heart rate at higher doses, but these resolved quickly. The inhalation trial (NCT05573568) reported mild throat discomfort and respiratory irritation, while oral and intranasal trials (NCT04716335) noted mild nausea and dizziness, all of which were short-lived. No serious adverse events were reported, and DMT was generally well-tolerated. Psychotomimetic effects, including ego dissolution and mystical experiences, were dose-dependent but manageable. Randomized trials exhibited low to moderate risk of bias, whereas non-randomized trials showed serious risk. Limitations include the small number of trials and the predominance of healthy volunteer samples. Funded by the Medical University of Gdańsk; the funder had no role. Although promising, further large-scale, well-controlled studies are needed to establish DMT's safety and efficacy in TRD populations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111419"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250835","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}
引用次数: 0
Behavioural and pharmacological evaluation of the psilocybin analogue baeocystin in Wistar rats 裸盖菇素类似物baeocytin对Wistar大鼠的行为学和药理学评价。
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-13 DOI: 10.1016/j.pnpbp.2025.111439
Hynek Danda , Kristýna Mazochová , Klára Šíchová , Vladimír Mazoch , Lucie Olejníková-Ladislavová , Kateřina Syrová , Bronislav Jurásek , Petra Cihlářová , Radek Jurok , Tomáš Páleníček , Martin Kuchař
{"title":"Behavioural and pharmacological evaluation of the psilocybin analogue baeocystin in Wistar rats","authors":"Hynek Danda ,&nbsp;Kristýna Mazochová ,&nbsp;Klára Šíchová ,&nbsp;Vladimír Mazoch ,&nbsp;Lucie Olejníková-Ladislavová ,&nbsp;Kateřina Syrová ,&nbsp;Bronislav Jurásek ,&nbsp;Petra Cihlářová ,&nbsp;Radek Jurok ,&nbsp;Tomáš Páleníček ,&nbsp;Martin Kuchař","doi":"10.1016/j.pnpbp.2025.111439","DOIUrl":"10.1016/j.pnpbp.2025.111439","url":null,"abstract":"<div><div>Baeocystin is a naturally occurring tryptamine-based compound found in various psychoactive mushrooms, including in several species of <em>Psilocybe genus</em>. Due to its structural similarity to psilocybin, which has shown a therapeutic potential in treatment of psychiatric disorders, there is a growing interest in investigating whether baeocystin exhibits comparable effects. This study investigated the pharmacokinetic profile and acute behavioural effects of baeocystin in Wistar rats.</div><div>Behavioural assessments including locomotor activity and its spatial characteristics (in the open field test) and sensorimotor gating measured by prepulse inhibition were evaluated after subcutaneous administration of 1.25 or 5 mg/kg baeocystin. Pharmacokinetics and brain-serum ratios were analysed after the 5 mg/kg sc. dose.</div><div>Pharmacokinetics demonstrated that both baeocystin and its metabolite, norpsilocin, have a very limited ability to cross the blood-brain barrier. Consistent with the pharmacokinetic profile, baeocystin had no significant effects on locomotor activity, exploratory behaviour, anxiety-like responses, or sensorimotor gating at doses of either 1.25 or 5 mg/kg.</div><div>In conclusion, our results suggest that baeocystin has minimal to no behavioural effects in rats, probably due to its poor permeability across the blood-brain barrier. This limited penetration may account for its negligible neurobiological and psychedelic activity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111439"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576924","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}
引用次数: 0
Impact of brain redox biomarkers on the emotional and cognitive-related states in male and female adolescent rats: A descriptive analysis 脑氧化还原生物标志物对雄性和雌性青春期大鼠情绪和认知相关状态的影响:描述性分析
IF 5.3 2区 医学
Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-07-13 DOI: 10.1016/j.pnpbp.2025.111447
Giulia Federica Mancini , Benedetta Di Cesare , Maria Bove , Vladyslav Sikora , Anna Virgilio , Maria Morena , Filippo Caraci , Luigia Trabace , Marco Andrea Riva , Patrizia Campolongo , Stefania Schiavone
{"title":"Impact of brain redox biomarkers on the emotional and cognitive-related states in male and female adolescent rats: A descriptive analysis","authors":"Giulia Federica Mancini ,&nbsp;Benedetta Di Cesare ,&nbsp;Maria Bove ,&nbsp;Vladyslav Sikora ,&nbsp;Anna Virgilio ,&nbsp;Maria Morena ,&nbsp;Filippo Caraci ,&nbsp;Luigia Trabace ,&nbsp;Marco Andrea Riva ,&nbsp;Patrizia Campolongo ,&nbsp;Stefania Schiavone","doi":"10.1016/j.pnpbp.2025.111447","DOIUrl":"10.1016/j.pnpbp.2025.111447","url":null,"abstract":"<div><div>Redox imbalance can affect several processes within the brain (e.g., synaptic plasticity, neurotransmitters release and their related pathways), leading to altered emotional and cognitive states. These effects can be particularly detrimental during adolescence, a critical period for brain development when some of the brain areas regulating emotional and cognitive functions, such as prefrontal cortex (PFC) and hippocampus (HIPP), are not fully matured yet. Nonetheless, the role of redox markers in the modulation of emotional and cognitive states in adolescent rodents remains under-investigated. Here, we performed correlation analyses between behavior and biomolecular data of redox markers measured in PFC and HIPP of male and female adolescent naïve rats, together with the evaluation of possible sex differences. Our results reveal sex differences in anxiety-like behavior as well as exploratory activity in the open field test, and in fear memory in the auditory fear conditioning task. Moreover, female rats showed decreased NADPH oxidase 2 (NOX-2) and catalase protein levels in PFC, alongside reduced nuclear factor erythroid 2-related factor 2 (NRF-2) and increased lipid peroxidation content in HIPP, thus highlighting sex differences in these redox markers. When considering both sexes together, NRF-2 and NOX-2 expression in PFC and HIPP correlated with several emotional- and cognitive-related behavioral parameters, suggesting that redox status might affect brain maturation, and thus behavior, during adolescence. Collectively, these findings point towards a possible role of redox-related markers in the occurrence of emotional and cognitive behaviors, providing new insights into their potential as pharmacological targets for the treatment of psychiatric disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111447"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644158","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}
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