Journal of Psychopharmacology最新文献

{"title":"Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model.","authors":"Monika Maciag, Olga Doszyn, Artur Wnorowski, Justyna Zmorzynska, Barbara Budzynska","doi":"10.1177/02698811251324596","DOIUrl":"10.1177/02698811251324596","url":null,"abstract":"<p><strong>Background: </strong>Mental disorders, including anxiety and depression, impact nearly 1 billion people worldwide. Recent research has highlighted the potential of certain amphetamine compounds in the therapy of psychiatric disorders, with 3,4-methylenedioxymethamphetamine (MDMA) emerging as a promising candidate.</p><p><strong>Aim: </strong>This study investigates the effects of MDMA on anxiety and social behaviours using 3-week-old zebrafish. Additionally, the role of oxytocin in regulating these behaviours was examined through the use of an oxytocin receptor agonist (WAY-267,464) and antagonist (L-368,899).</p><p><strong>Methods: </strong>Behavioural effects were assessed using the novel exploration test, light-dark preference test and social preference test. To explore the underlying mechanisms, changes in gene expression in serotonin, oxytocin and vasopressin systems and changes in AKT and EKR1/2 signalling pathways were analysed.</p><p><strong>Results: </strong>Acute MDMA exposure reduced thigmotactic behaviour and increased the social preference index, indicating anxiolytic and prosocial effects. However, these effects were biphasic - the lowest tested dose of 0.5 μM showed anxiogenic and prosocial effects. As the concentration increased, these effects reversed, with a peak at 2.5 μM. MDMA suppressed the expression of serotonin receptors (<i>htr1b</i> and <i>htr2b</i>) and transporter (<i>scl6a4</i>) genes while increasing oxytocin receptors (<i>oxtra</i> and <i>oxtrb</i>) genes, decreasing vasopressin receptor (<i>avpr1aa</i>) gene expression, and reducing AKT phosphorylation. The oxytocin receptor agonist mimicked MDMA's effects, while the antagonist had no significant effect on anxiety or social behaviour.</p><p><strong>Conclusions: </strong>MDMA demonstrates therapeutic potential for treating anxiety disorders and social impairments. Moreover, 3-week-old zebrafish proved to be a valuable model for neurobehavioural research and high-throughput screening of psychiatric treatments.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"373-393"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of ashwagandha (<i>Withania somnifera</i>) extract with Sominone (Somin-On™) to improve memory in adults with mild cognitive impairment: A randomized, double-blind, placebo-controlled study.","authors":"Hari Prakash Rai, Deo Nidhi Mishra","doi":"10.1177/02698811251324377","DOIUrl":"10.1177/02698811251324377","url":null,"abstract":"<p><strong>Background: </strong>Mild cognitive impairment (MCI) is a condition in which people have memory or thinking problems than other people of their age. This study evaluated the effectiveness and safety of ashwagandha extract standardized with Sominone (Somin-On™) in enhancing memory and cognitive functioning in adults with MCI.</p><p><strong>Methods: </strong>In this randomized double-blind, placebo-controlled pilot study, 40 subjects with MCI were randomized in a 1:1 ratio to receive either Somin-On™ (250 mg daily) or a placebo for 60 days. The outcome measures, improvement in memory and other cognitive functions after 30 and 60 days were assessed using Montreal Cognitive Assessment (MoCA); Mini-mental state examination (MMSE); Wechsler Memory Scale-III (WMS-III)); and Shepard mental rotation task.</p><p><strong>Results: </strong>Subjects treated with Somin-On™ showed significant improvements in immediate memory, general memory, working memory and visuospatial processing and the response assessed using WMS-III after 30 and 60 days outperforming the placebo group. Scores on the Shepard Mental Rotation test in Somin-On™ group showed a significant rise by 12.22% at 30 days and 31.67% at 60 days, from baseline. Significant improvement was observed with Somin-On™ in memory assessment scales viz. MoCA (7.83% at 30 days and 14.77% at 60 days, from baseline) and MMSE (9.26% at 30 days and 19.21% at 60 days, from baseline) compared to placebo group.</p><p><strong>Conclusions: </strong>The supplementation of Somin-On™ is an effective therapy to improve the immediate, general and working memory, as well as cognitive functions like attention and information processing speed in adults with MCI.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"350-363"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ayahuasca enhances the formation of hippocampal-dependent episodic memory without impacting false memory susceptibility in experienced ayahuasca users: An observational study.","authors":"Manoj K Doss, Lilian Kloft, Natasha L Mason, Pablo Mallaroni, Johannes T Reckweg, Kim van Oorsouw, Nina Tupper, Henry Otgaar, Johannes G Ramaekers","doi":"10.1177/02698811241301216","DOIUrl":"10.1177/02698811241301216","url":null,"abstract":"<p><strong>Background: </strong>Ayahuasca is an Amazonian brew with 5-HT_2A-dependent psychedelic effects taken by religious groups globally. Recently, psychedelics have been shown to impair the formation of recollections (hippocampal-dependent episodic memory for specific details) and potentially distort memory while remembering. However, psychedelics spare or enhance the formation of familiarity-based memory (cortical-dependent feeling of knowing that a stimulus has been processed).</p><p><strong>Aims: </strong>Given the growing literature on the plasticity-promoting effects of psychedelics, we investigated the acute impact of ayahuasca on recollection, familiarity, and false memory in an observational study of 24 Santo Daime members with >500 lifetime ayahuasca uses on average.</p><p><strong>Methods: </strong>Participants completed a false memory task at baseline and after they consumed a self-selected dose of ayahuasca prepared by their church (average dose contained 3.36 and 170.64 mg of <i>N,N</i>-dimethyltryptamine and β-carbolines, respectively).</p><p><strong>Results: </strong>Surprisingly, pre-encoding administration of ayahuasca enhanced hit rates, memory accuracy, and recollection but had no impact on familiarity or false memory. Although practice effects cannot be discounted, these memory enhancements were large and selective, as multiple measures of false memory and metamemory did not improve across testing sessions. β-carboline activity potentially accounted for this recollection enhancement that diverges from past psychedelic research. Although ayahuasca did not impact familiarity, these estimates were generally elevated across conditions compared to past work, alluding to a consequence of frequently driving cortical plasticity.</p><p><strong>Conclusions: </strong>When encoding and retrieval took place under acute ayahuasca effects in experienced ayahuasca users, susceptibility to memory distortions did not increase, potentially owing to enhancements in memory accuracy.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"339-349"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755266","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":"A three-stage strategy for conducting an experimental investigation: A recommendation to improve the reproducibility of reported conclusions.","authors":"Simon T Bate, S Clare Stanford, Lee Page","doi":"10.1177/02698811251319453","DOIUrl":"10.1177/02698811251319453","url":null,"abstract":"<p><p>The reproducibility of the results from preclinical research rests on many factors, including the selection of appropriate experimental designs for the individual experiments that constitute the investigation. The design of each of these experiments depends on their purpose within the entire investigation and the information to be gained from conducting them. Here, we explain and justify a three-stage strategy comprising a series of different types of experiment, each with a different purpose and design: a pilot study, a hypothesis-generating experiment and a final hypothesis-confirming experiment. Compliance with this three-stage strategy, over the course of an entire investigation, will not only strengthen its reproducibility but, importantly, can save time and other resources, including the total number of animals used.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"301-312"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between Parkinson's disease and sexual hyperactivity secondary to drug treatment: A systematic review.","authors":"Verónica Aparicio-López, María Rueda-Extremera, María Cantero-García","doi":"10.1177/02698811241277200","DOIUrl":"10.1177/02698811241277200","url":null,"abstract":"<p><strong>Introduction: </strong>This review addresses the prevalence of hypersexual behavior in Parkinson's patients and the underlying neurobiological mechanisms, identifying risk and protective factors, comparing incidence among different treatments, and proposing recommendations for management and prevention.</p><p><strong>Objective: </strong>To conduct a review on the relationship between Parkinson's disease and hypersexual behavior as a result of pharmacological treatment.</p><p><strong>Methodology: </strong>The search strategy, guided by PRISMA and PICOS criteria, focuses on the correlation between Parkinson's disease and hypersexual behavior due to pharmacological treatment. Utilizing databases like PubMed and Proquest, studies from the last 10 years in English or Spanish were selected, emphasizing clinical trials with Parkinson's patients under treatment. Inaccessible, irrelevant, or mixed-sample studies were excluded. The Cochrane Scale assessed the risk of bias.</p><p><strong>Results: </strong>Out of 122 records, 103 remained after eliminating duplicates; 48 were reviewed, and ultimately, 6 studies met the inclusion criteria for analysis.</p><p><strong>Conclusions: </strong>Synthesizing the risk and protective factors linked to hypersexual behavior in Parkinson's patients receiving pharmacological treatment underscores the critical need for early detection and incorporation of these factors into clinical care. The suggested guidelines for managing and preventing hypersexual behavior in these patients carry substantial practical implications.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"316-327"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A reflection on paradigmatic tensions within the FDA advisory committee for MDMA-assisted therapy.","authors":"Leor Roseman","doi":"10.1177/02698811241309611","DOIUrl":"10.1177/02698811241309611","url":null,"abstract":"<p><p>The recent rejection of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy by the U.S. Food and Drug Administration (FDA) is a dramatic moment in the re-emergence of psychedelic research. In this perspective, I argue that it represents a case study for paradigmatic tensions within psychopharmacology. The regulatory system is still influenced by a paradigm that sees the therapeutic effects of drugs as primarily biological, and context is noise to control for. An emergent paradigm considers the therapeutic effects of drugs as interactive with context. Psychedelics are the anomaly that questions the dominant paradigm, mainly due to the determination of psychedelic researchers that the medicines are drugs with psychotherapy. While some of the critique offered by the FDA towards MAPS/Lykos's studies is crucial, much of it is related to the experiential and psychotherapeutic elements - which the FDA claims not to regulate. This leads to some paradoxes within the regulatory procedure, which hint at a need for a shift in how psychedelic-assisted therapy is regulated and researched. Both regulators and researchers will need to find ways to accommodate each other in service of a successful integration of a new paradigm in which drugs and psychotherapy interact.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"313-315"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895534","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":"The anti-inflammation pharmacodynamics of lithium: Therapy of bipolar disorder.","authors":"Yuyang Zhou, Weizhi Zheng, Feichang Guo, Shijin Wu, Congjie Zhong","doi":"10.1177/02698811251326942","DOIUrl":"https://doi.org/10.1177/02698811251326942","url":null,"abstract":"<p><p>Bipolar disorder is a severe mental disorder that necessitates effective long-term treatment strategies. Clinically, lithium has demonstrated favorable outcomes in managing this condition. The inflammatory theory posits that bipolar disorder is influenced by an inflammatory response, and lithium is thought to mitigate this disorder by inhibiting such responses. In terms of the pharmacodynamics of blocking inflammatory mediators, lithium mainly acts on GSK-3β. Upon interaction with GSK-3β, lithium can suppress the gene expression of inflammatory mediators, subsequently reducing their secretion. This mechanism influences multiple downstream pathways, ultimately contributing to the therapeutic effects observed in bipolar disorder. Specifically, these pathways include the arachidonic acid pathway, nitric oxide synthase pathway, neurotransmitter pathway, and so on. This article reviews the pharmacodynamic targets and mechanisms of lithium, offering insights into the appropriate clinical application of lithium and the advancement of lithium pharmacotherapies.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251326942"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoamine neurotransmitter-related gene-based genome-wide association study of low-dose ketamine in patients with treatment-resistant depression.","authors":"Chung-Feng Kao, Shih-Jen Tsai, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Chen-Jee Hong, Ya-Mei Bai, Pei-Chi Tu, Mu-Hong Chen","doi":"10.1177/02698811251326939","DOIUrl":"https://doi.org/10.1177/02698811251326939","url":null,"abstract":"<p><strong>Background: </strong>Low-dose ketamine is an N-methyl-D-aspartate receptor antagonist that exerts an antidepressant effect on patients with treatment-resistant depression (TRD). This antidepressant effect may extend beyond the glutamatergic hypothesis. Nevertheless, the roles of genes encoding other monoamine neurotransmitters (i.e., serotonin and dopamine) in the neuromechanism of low-dose ketamine remain unknown.</p><p><strong>Methods: </strong>In this clinical trial, which involved 65 patients with TRD, 21 patients received 0.5 mg/kg ketamine, 20 received 0.2 mg/kg ketamine, and 24 received normal saline. All patients were genotyped for 684,616 single-nucleotide polymorphisms (SNPs). A total of 50 monoamine neurotransmitter-related candidate genes, including HTR2A and HTR2C from the serotoninergic system, CHRM4 and CHRNB1 from the cholinergic system, and DRD2 from the dopaminergic system, were selected to conduct a gene-based genome-wide association study of the antidepressant effects of ketamine.</p><p><strong>Results: </strong>Gene-set enrichment analysis revealed that the pathway underlying neuroactive ligand-receptor interaction (KEGG) played a pivotal role in the biomechanisms underlying ketamine's antidepressant effect. Specifically, the genes and SNPs related to the cholinergic system (e.g., rs2644247 in CHRM5), μ1 opioid receptor (e.g., rs2473546 in OPRM1), dopaminergic system (e.g., rs2617577 in SLC6A3), serotonergic system (HTR2A), cannabinoid receptor (CNR2), and σ1 receptor (SIGMAR1) were associated with the antidepressant effect of low-dose ketamine.</p><p><strong>Discussion: </strong>Low-dose ketamine has an antidepressant effect, which may be associated with multiple monoamine neurotransmitter systems and the σ1 receptor.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251326939"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the efficacy of metformin in reducing hyperprolactinemia among patients with schizophrenia: A meta-analysis of randomized controlled trials.","authors":"Kah Kheng Goh, Chun-Hsin Chen, Mong-Liang Lu","doi":"10.1177/02698811251326945","DOIUrl":"https://doi.org/10.1177/02698811251326945","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic treatment is commonly associated with hyperprolactinemia, leading to menstrual disturbances, sexual dysfunction, and decreased bone mineral density. Nearly all antipsychotic drugs can elevate prolactin levels, affecting up to 70% of patients with schizophrenia. We aim to evaluate the potential therapeutic role of metformin in reducing hyperprolactinemia among these patients.</p><p><strong>Methods: </strong>We systematically searched PubMed, CNKI, Embase, Cochrane, and Web of Science through January 31, 2024, for randomized controlled trials (RCTs) evaluating metformin's effect on prolactin levels in patients with schizophrenia. Data were extracted and synthesized using random-effects meta-analysis.</p><p><strong>Results: </strong>This meta-analysis included 10 RCTs with 1046 participants (584 received metformin and 462 received placebo or no treatment). Metformin significantly reduced prolactin levels compared to control groups (SMD = -0.98, 95% CI: -1.62, -0.35, <i>p</i> = 0.002; transformed MD = -34.88 ng/mL, 95% CI: -57.65, -12.46). Subgroup analyses indicated that higher doses (1500 mg), shorter treatment durations (<24 weeks), higher BMI (>25 kg/m²), and longer illness duration (>1 year) were associated with more significant prolactin reductions. Metformin was well tolerated with no significant increase in adverse events or all-cause discontinuation rates compared to the control group.</p><p><strong>Conclusion: </strong>This meta-analysis suggests that metformin shows potential as a treatment for antipsychotic-induced hyperprolactinemia, with a favorable tolerability profile in patients with schizophrenia, particularly at higher doses, shorter treatment durations, higher BMI, and longer illness duration. Despite the robustness of the findings, high heterogeneity necessitates cautious interpretation. Future research should explore demographic and clinical factors influencing the response to metformin for optimizing treatment.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251326945"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifetime classic psychedelic use and headaches: A cross-sectional study.","authors":"Zusanna Bjurenfalk, Alva Cosmo, Otto Simonsson, Caroline Ran","doi":"10.1177/02698811251324372","DOIUrl":"https://doi.org/10.1177/02698811251324372","url":null,"abstract":"<p><strong>Background: </strong>Migraine and cluster headache are two primary headache disorders for which conventional treatments are limited. Classic psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin are potentially promising new treatment candidates for these conditions.</p><p><strong>Aims: </strong>The aim of the present study was to investigate the possible relationship between the lifetime use of classic psychedelics and frequent bad headaches in a large British cohort sample.</p><p><strong>Methods: </strong>Using data (<i>N</i> = 11,419) collected in 1999-2000 as part of the 1958 British National Child Development Study, this cross-sectional study used multiple logistic regression, controlling for a range of potential confounders, to test the hypothesis that lifetime use of classic psychedelics would be associated with lower odds of having frequent bad headaches.</p><p><strong>Results: </strong>Lifetime use of classic psychedelics was associated with 25% lower odds of having frequent bad headaches (adjusted odds ratio = 0.75, 95% CI: 0.59-0.95, <i>p</i> = 0.016).</p><p><strong>Conclusions: </strong>The results of the present study add to the literature suggesting classic psychedelics as a possible future prophylactic treatment option for primary headache disorders.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251324372"},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}