Journal of Psychopharmacology最新文献

{"title":"Catalyst for change: Psilocybin's antidepressant mechanisms-A systematic review.","authors":"Joshua Liebnau, Felix Betzler, André Kerber","doi":"10.1177/02698811241312866","DOIUrl":"https://doi.org/10.1177/02698811241312866","url":null,"abstract":"<p><strong>Background: </strong>Recent clinical trials suggest promising antidepressant effects of psilocybin, despite methodological challenges. While various studies have investigated distinct mechanisms and proposed theoretical opinions, a comprehensive understanding of psilocybin's neurobiological and psychological antidepressant mechanisms is lacking.</p><p><strong>Aims: </strong>Systematically review potential antidepressant neurobiological and psychological mechanisms of psilocybin.</p><p><strong>Methods: </strong>Search terms were generated based on existing evidence of psilocybin's effects related to antidepressant mechanisms. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, 15 studies were systematically reviewed, exploring various therapeutic change principles such as brain dynamics, emotion regulation, cognition, self-referential processing, connectedness, and interpersonal functioning.</p><p><strong>Results: </strong>Within a supportive setting, psilocybin promoted openness, cognitive and neural flexibility, and greater ability and acceptance of emotional experiences. A renewed sense of connectedness to the self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, characterized by reduced global and within default mode network connectivity, alongside increased between-network connectivity.</p><p><strong>Conclusions: </strong>Together, these changes may create a fertile yet vulnerable window for change, emphasizing the importance of a supportive set, setting, and therapeutic guidance. The results suggest that psilocybin, within a supportive context, may induce antidepressant effects by leveraging the interplay between neurobiological mechanisms and common psychotherapeutic factors. This complements the view of purely pharmacological effects, supporting a multileveled approach that reflects various relevant dimensions of therapeutic change, including neurobiological, psychological, and environmental factors.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811241312866"},"PeriodicalIF":4.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007079","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":"Ketamine: Therapeutic potential versus recreational misuse.","authors":"Mario F Juruena, Allan H Young","doi":"10.1177/02698811241308935","DOIUrl":"https://doi.org/10.1177/02698811241308935","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":"39 1","pages":"3-4"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023771","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":"Ketamine for refractory depression: Save the best for last?","authors":"Kabir Nigam, Franklin King, Fernando Espi Forcen","doi":"10.1177/02698811241282646","DOIUrl":"10.1177/02698811241282646","url":null,"abstract":"<p><p>Ketamine has recently been shown to be non-inferior to electroconvulsive therapy (ECT), one of psychiatry's most effective treatments for depression. Given the novelty of ketamine as well as its interventional nature, ketamine is currently viewed as an alternative to ECT and as such, considered a third-line agent for treatment-refractory depression. However, available data suggest that ketamine carries a low side-effect burden and is better tolerated than many second-line augmentation strategies for depression. With this combination of higher efficacy and lower side-effect burden in conjunction with what is known about treatment outcomes in relation to the duration of untreated illness, it is in the best interest of patients for the field of psychiatry to evaluate ketamine as a second-line augmentation strategy for refractory depression.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"5-7"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289782","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":"Combining bioinformatics, network pharmacology and artificial intelligence to predict the target genes of S-ketamine for treating major depressive disorder.","authors":"Zhou Xianjin, Shen Fuyi, Yang Ti, Li Shan, Zhao Kang, Wang Ying, Deng Shengqiong","doi":"10.1177/02698811241268884","DOIUrl":"10.1177/02698811241268884","url":null,"abstract":"<p><strong>Background: </strong>Ketamine has received attention owing to its rapid and long-lasting antidepressant effects; however, its clinical application is restricted by its addictiveness and adverse effects. S-ketamine, which is the S-enantiomer of ketamine, is considered safer and better tolerated by patients than ketamine.</p><p><strong>Aims: </strong>This study aimed to identify the key gene targets and potential signalling pathways associated with the mechanism of S-ketamine in major depressive disorder (MDD) treatment.</p><p><strong>Methods: </strong>The GSE98793 dataset was extracted from the Gene Expression Omnibus database, and differentially expressed genes were identified in blood samples from patients with MDD and healthy individuals. The hub genes among the differentially expressed genes were identified and enrichment analysis was performed. The therapeutic targets and related signalling pathways of S-ketamine in MDD treatment were analysed. The 3D structures of the target proteins were predicted using AlphaFold2, and molecular docking was performed to verify whether S-ketamine could be successfully docked to the predicted targets. A quantitative polymerase chain reaction was performed to determine the effect of ketamine on the screened targets. Among 228 target genes annotated using pharmacophore target gene analysis, 3 genes were identified and 2 therapeutic signalling pathways were discovered.</p><p><strong>Results: </strong>S-ketamine exerts downregulatory effects on TGM2 and HSP90AB1 expression but exerts an up-regulatory effect on ADORA3 expression. The protein structures of the therapeutic targets were successfully predicted using AlphaFold2.</p><p><strong>Conclusions: </strong>S-ketamine may alleviate depression by targeting specific genes, including <i>TGM2</i>, <i>HSP90AB1</i> and <i>ADORA3</i>, as well as signalling pathways, including the gonadotropin-releasing hormone and relaxin signalling pathways.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"66-75"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906884","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":"Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.","authors":"Henry A MacConnel, Mitch Earleywine, Steven Radowitz","doi":"10.1177/02698811241286726","DOIUrl":"10.1177/02698811241286726","url":null,"abstract":"<p><strong>Background: </strong>Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an <i>N</i>-methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments-including preparatory, integration, sensory immersion, and psychotherapy sessions-could decrease PTSD symptoms meaningfully.</p><p><strong>Methods: </strong>A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials.</p><p><strong>Results: </strong>Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), <i>d</i> = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, <i>d</i> = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms.</p><p><strong>Conclusion: </strong>Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"29-37"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468385","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":"Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature.","authors":"Gianmarco Ingrosso, Anthony J Cleare, Mario F Juruena","doi":"10.1177/02698811241303597","DOIUrl":"10.1177/02698811241303597","url":null,"abstract":"<p><strong>Background: </strong>Ketamine has demonstrated both rapid and sustained efficacy in treating depression, especially in treatment-resistant cases. However, concerns regarding the addictive potential of ketamine during long-term depression treatment persist among clinicians.</p><p><strong>Aim: </strong>This review aimed to summarise the evidence on addiction phenomena associated with ketamine treatment of depression.</p><p><strong>Methods: </strong>A comprehensive search was conducted in MEDLINE, Embase, PsycInfo and Global Health databases, with additional relevant studies identified through reference lists. Sixteen studies were included, comprising six randomised controlled trials, three single-arm open-label studies, one retrospective study, three case series and three case reports, for a total of 2174 patients.</p><p><strong>Results: </strong>The studies employed various routes of administration, including intravenous, intramuscular, intranasal, oral and sublingual. Ketamine was administered in the racemic form, except for the studies that utilised intranasal esketamine. Among the included population, four patients were reported to exhibit clear signs of tolerance to the antidepressant effect of ketamine or dependence on the drug, while the majority did not. Cases of addiction phenomena reported in studies that did not meet the inclusion criteria are also discussed.</p><p><strong>Conclusions: </strong>Despite the heterogeneity in study designs and outcome assessment methods, the review underscores the relative safety of ketamine treatment for adult patients with depression, emphasising the importance of medically supervised administration, vigilant monitoring and judicious dosing. Future long-term studies employing quantitative scales to assess dependence phenomena could contribute to strengthening the evidence for the safe and effective use of ketamine in the treatment of depression.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"49-65"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836472","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":"Ketamine use in a large global sample: Characteristics, patterns of use and emergency medical treatment.","authors":"Karen P Barrios, Dean J Connolly, Jason A Ferris, Larissa J Maier, Monica J Barratt, Adam R Winstock, Cheneal Puljević, Gail Gilchrist","doi":"10.1177/02698811241273850","DOIUrl":"10.1177/02698811241273850","url":null,"abstract":"<p><strong>Background: </strong>Ketamine's popularity has surged globally in the past decade, especially among young men. Emergency department visits due to its toxicity remain relatively rare, often linked to co-occurring use of other substances.</p><p><strong>Aims: </strong>Using data from the Global Drug Survey (GDS) 2018, this study explored the correlates associated with lifetime and past-year ketamine use, and estimated the socio-demographic characteristics, usage patterns and experiences of respondents seeking emergency medical treatment (EMT) after ketamine use.</p><p><strong>Methods: </strong>Secondary analysis of GDS 2018, an online cross-sectional survey on drug use patterns conducted between November 2017 and January 2018.</p><p><strong>Results: </strong>The survey received 130,761 valid responses, with 5.93% reporting lifetime ketamine use, of which 57.70% used ketamine within the past year. Predominantly, respondents were from Germany, England and Denmark. Within the past year, 8.55% met the criteria for ketamine dependence. Respondents who used ketamine in their lifetime tended to be young (mean (x̄) = 27.37 years), men, heterosexual and of white ethnicity. Younger age (x̄ = 24.84 years), gay sexual orientation, student status, past-year use of other drugs and no lifetime mental health diagnosis were associated with past-year ketamine use. Among 4477 respondents reporting past-year ketamine use, 120 adverse events were reported, with less than 0.10% prompting EMT seeking.</p><p><strong>Conclusion: </strong>The study reveals frequent ketamine use but low harm occurrence, underscoring the complex interplay between ketamine use, substance use and dependence, and related factors. This underscores the need to reassess EMT priorities, implement tailored harm reduction strategies and incorporate comprehensive screening for addressing ketamine and substance dependence challenges.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"8-22"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468384","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":"Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.","authors":"Luis Gutiérrez-Rojas, Julia Vendrell-Serres, J Antoni Ramos-Quiroga, Jon Iñaki Etxeandia-Pradera, Eduardo Aguilar, Ana Isabel De Santiago-Díaz, Daniel Hernández-Huerta, Vicente Tordera, Carlos Vázquez-Ventoso, Moisés Bolívar, Asunción Abril, Rubén Catalán-Barragán, Jesús García-Jiménez","doi":"10.1177/02698811241267837","DOIUrl":"10.1177/02698811241267837","url":null,"abstract":"<p><strong>Background: </strong>Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants.</p><p><strong>Aims: </strong>To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program.</p><p><strong>Methods: </strong>A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment.</p><p><strong>Results: </strong>The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy.</p><p><strong>Conclusion: </strong>ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"38-48"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902042","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":"Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study.","authors":"Ben Beaglehole, Paul Glue, Shona Neehoff, Shabah Shadli, Neil McNaughton, Bridget Kimber, Chrissie Muirhead, Aroha de Bie, Rachel Day-Brown, Natalie J Hughes-Medlicott","doi":"10.1177/02698811241301215","DOIUrl":"10.1177/02698811241301215","url":null,"abstract":"<p><strong>Background: </strong>Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment.</p><p><strong>Aim: </strong>To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl.</p><p><strong>Methods: </strong>This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5 mg/kg, 1.0 mg/kg or fentanyl 50 µg (psychoactive control). Pre-dosing with 4 mg oral ondansetron provided nausea prophylaxis. Eligible participants were aged between 18 and 50 years with severe treatment-resistant OCD. The primary efficacy measure was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Tolerability was measured with the Clinician-Administered Dissociative States Scale (CADSS). Repeated measures analysis of variance with orthogonal polynomial trends was used to assess the effect of drug treatment on Y-BOCS and CADSS scores.</p><p><strong>Results: </strong>Twelve participants were randomised and 10 completed the study (7 females, 3 males, mean age 33 years). Two participants dropped out due to not tolerating dissociative effects associated with the study medication. The reductions in Y-BOCS scores were greater and statistically dose-related for both ketamine doses than fentanyl (dose [linear], <i>F</i>(1, 9) = 6.5, <i>p</i> = 0.031). Score changes for all treatments were maximal at 1-2 h with a steady separation of scores out to 168 h. Ketamine was associated with short-term dissociative and cardiovascular effects.</p><p><strong>Conclusions: </strong>We provide further preliminary evidence for the efficacy and tolerability of IM ketamine in an outpatient cohort of OCD. Additional work is required to establish the optimal dosing regimen and longer-term role of ketamine for OCD. These findings are encouraging given the well-known limitations that exist for treatments in this area.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"23-28"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750816","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":"Hemispheric annealing and lateralization under psychedelics (HEALS): A novel hypothesis of psychedelic action in the brain.","authors":"Adam W Levin","doi":"10.1177/02698811241303599","DOIUrl":"https://doi.org/10.1177/02698811241303599","url":null,"abstract":"<p><p>Current models of psychedelic action in the brain propose changes along the dorsal-ventral and anterior-posterior axes but neglect to address the lateral axis. This article proposes a novel model of psychedelic action called HEALS (Hemispheric Annealing and Lateralization Under Psychedelics) which involves the reversal of the typical hierarchical relationship between the two hemispheres of the brain. In typical modes of consciousness, the hemispheres act in parallel process with the left predominating. Under psychedelics, as well as in other altered states of consciousness (ASCs), this hierarchy is reversed, with the right hemisphere released from inhibition by the left. In support of this model, the available neuroimaging evidence for lateralization under psychedelics is reviewed. Then, various cognitive and emotional changes observed under psychedelics are contrasted with those same functions in each hemisphere. These include attention; social and emotional intelligence; creativity and insight; and language. The article concludes with a review of laterality in other ASCs, such as meditative and trance states, and suggests that many phenomena associated with psychedelics, and other ASCs, might be explained by an atypical annealing between the hemispheres toward right hemisphere predominance.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811241303599"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864044","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}