Journal of Psychopharmacology最新文献

{"title":"Defining the intervention before estimating efficacy in DMT-assisted therapy.","authors":"Kenjiro Shiraishi","doi":"10.1177/02698811261488484","DOIUrl":"https://doi.org/10.1177/02698811261488484","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261488484"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989458","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":"Adjunctive GLP-1 receptor agonists for cardiometabolic risk in antipsychotic-treated patients: A GRADE-assessed meta-analysis of randomized trials.","authors":"Elsayed S Moubarak, Mohamed S Elgendy, Omar Elkoumi, Ahmed A Ibrahim, AlMothana Manasrah, Jamal Ahmad, Malak A Hassan, Omar ElSayed Rageh, Abdelrahman Aly Mohamed, Amr Elzahaby, Mohamed Abuelazm","doi":"10.1177/02698811261478625","DOIUrl":"https://doi.org/10.1177/02698811261478625","url":null,"abstract":"<p><strong>Background: </strong>Patients with schizophrenia spectrum or bipolar disorders have reduced life expectancy due to cardiometabolic risk. We conducted this meta-analysis to evaluate glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for their effects on cardiometabolic outcomes.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane up to May 2026 for randomized controlled trials (RCTs). We pooled continuous outcomes as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs) using random-effects models with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>We included 8 RCTs with 664 patients. Compared with control, GLP-1 RA significantly reduced body weight (MD: -6.74, 95% CI: -10.05 to -3.43), body mass index (BMI; MD: -2.37 kg/m², 95% CI: -3.52 to -1.23), waist circumference (MD: -4.27 cm, 95% CI: -6.65 to -1.89), HbA1c (MD: -0.61%, 95% CI: -1.06 to -0.17), and fasting glucose (MD: -6.82, 95% CI: -11.89 to -1.76). Subgroup analyses by GLP-1 RA type showed that semaglutide produced the greatest reductions in body weight (MD: -11.06 kg) and BMI (MD: -3.60 kg/m²), with significant between-subgroup differences (<i>p</i> < 0.05). Adverse events (AEs; <i>p</i> = 0.77), serious AEs (<i>p</i> = 0.09), and discontinuation due to AEs (<i>p</i> = 0.20) were similar between groups. However, GLP-1 RA was associated with a significantly higher risk of gastrointestinal (GI) AEs, including nausea, vomiting, and constipation (all <i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>GLP-1RA, particularly semaglutide, was associated with clinically meaningful improvements in antipsychotic-related cardiometabolic outcomes without compromising psychiatric stability or treatment adherence. However, the significant increase in GI AEs necessitates careful clinical titration. Larger RCTs with longer follow-up are needed to confirm these findings.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261478625"},"PeriodicalIF":5.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976760","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 effect of ketamine on mitochondrial bioenergetics, viability, and function: A systematic review.","authors":"Sabrina Wong, Gia Han Le, Simryn Selby, Stavroula Bargiota, Diana K Orsini, Sara Di Luch, Shreya Vasudeva, Gabrielle Lovell, Joshua D Rosenblat, Roger S McIntyre","doi":"10.1177/02698811261481085","DOIUrl":"https://doi.org/10.1177/02698811261481085","url":null,"abstract":"<p><strong>Background: </strong>Extant literature indicates mitochondrial dysfunction may contribute to the pathophysiology of depressive disorders. Preclinical data indicate that anesthetic doses of ketamine are associated with deficits in mitochondrial viability and function. Ketamine and esketamine have demonstrated rapid antidepressant effects in persons with difficult-to-treat depressive disorders. Herein, we aim to synthesize literature reporting on the effect of antidepressant doses of ketamine and esketamine in vivo versus in vitro on mitochondrial viability and function.</p><p><strong>Methods: </strong>We performed a systematic review of previous studies on PubMed, Ovid, and Scopus databases from inception to November 30, 2025. Preclinical studies reporting on the effect of antidepressant doses of ketamine and/or esketamine in mitochondrial viability, structure/morphology, bioenergetics, and metabolic function were sought for inclusion.</p><p><strong>Results: </strong>Thirteen studies were included. Lower ketamine/esketamine concentrations generally did not adversely affect membrane potential, oxidative phosphorylation, respiration, or bioenergetics, whereas higher concentrations or prolonged exposure induced mitochondrial dysfunction in some models. Additional evaluation of the safety of ketamine/esketamine on mitochondria in humans is required.</p><p><strong>Conclusion: </strong>Preliminary research suggests that ketamine at lower concentrations may not adversely affect brain mitochondrial viability or bioenergetic function, but requires further validation. The reported effects on mitochondrial viability and function are preclinical, model- and dose-dependent and derived from limited heterogeneous literature. This study generates the hypothesis that ketamine's antidepressant mechanism of action may be partially mediated by insulin-sensitive metabolic pathways, energetically supporting synaptic remodeling and neurogenesis. Incorporation of mitochondrial and metabolic biomarkers into ketamine clinical trials is a current research imperative.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261481085"},"PeriodicalIF":5.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900812","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":"Psychedelic therapy without durable effects: A review and re-evaluation of controlled studies between 1965 and 1977.","authors":"Torsten Passie, Michiel van Elk","doi":"10.1177/02698811261478606","DOIUrl":"https://doi.org/10.1177/02698811261478606","url":null,"abstract":"<p><p>Common wisdom in the psychedelic literature suggests that early controlled trials of psychedelic therapy were methodologically flawed. In this review we challenge this view and discuss 11 controlled studies that were conducted in the United States and Canada between 1965 and 1977 to evaluate psychedelic (peak) therapy for individuals suffering from alcohol and opioid use disorder and psychoneuroses. We provide a narrative review of the designs, methods, settings, treatment issues and results and show that these studies already adhered quite well to the regulatory and evidentiary standards of their time. These early psychedelic trials tried to effectively address common methodological problems that still threaten the validity of contemporary psychedelic clinical trials (e.g., regarding blinding and active control conditions). Our review indicates that despite a significant heterogeneity in the methods and research designs, most early controlled studies converge on the same conclusion: there are no durable improvements in the condition of patients treated with psychedelic therapy beyond a few weeks. We discuss implications for contemporary psychedelic science in terms of (a) patient selection (i.e., better prospects for non-chronic conditions), (b) the problems with a single-sided focus on mystical experiences as the primary mechanism of action, (c) the positive afterglow as a therapeutic window of opportunity and (d) the need for a strong psychotherapeutic framework to induce sustained therapeutic effects.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261478606"},"PeriodicalIF":5.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906528","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":"Psilocybin-induced changes in electroencephalography link acute and long-term effects.","authors":"Marek Nikolič, Tom Froese, Pedro A M Mediano, Vlastimil Koudelka, Jiří Horáček, Filip Tylš, Tomáš Páleníček","doi":"10.1177/02698811261473445","DOIUrl":"https://doi.org/10.1177/02698811261473445","url":null,"abstract":"<p><strong>Background: </strong>Psilocybin's therapeutic potential is neurophysiologically characterized by acute alpha power reductions and increased entropy. However, the systematic time-course of these changes from administration through the 24-hour sub-acute phase remains poorly characterized.</p><p><strong>Methods: </strong>In a double-blind, placebo-controlled, crossover trial (<i>N</i> = 20, 10 females), healthy participants received a medium dose ∼0.26 mg/kg of psilocybin. High-density resting-state electroencephalography and psychological states were assessed at baseline, 1, 3, 6, and 24 hours, with a 28-day follow-up.</p><p><strong>Results: </strong>Psilocybin acutely decreased alpha/beta power and increased gamma-band signal diversity (1-3 hours; returning to baseline at 6 hours). Increased gamma diversity correlated with acute psychological effects (Brief Psychiatric Rating Scale, <i>r</i> = 0.71), with the largest increases observed in participants with lower baseline complexity. At 24 hours, reduced delta/theta power correlated with Positive Life Changes (Persisting Effects Questionnaire) at 4 weeks (<i>r</i> = -0.47 to -0.57) but was independent of acute psychological intensity.</p><p><strong>Conclusion: </strong>Our findings corroborate known acute effects while identifying a distinct sub-acute \"afterglow\" associated with long-term outcomes. The dissociation between acute psychology and 24-hour spectral shifts suggests that therapeutic benefits may be driven by sub-acute reductions in top-down cortical hierarchy. These results highlight the significance of the sub-acute window for psychological transformation and suggest normalized diversity as a viable baseline biomarker of individual responsiveness to psychedelic intervention.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261473445"},"PeriodicalIF":5.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891910","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":"Safety, pharmacokinetics, and pharmacodynamics of intravenously administered deuterated <i>N,N</i>-dimethyltryptamine (CYB004) in healthy volunteers.","authors":"Katelijne V van der Heijden, Gabriel E Jacobs, Ellen H James, Pradeep J Nathan, Marije E Otto, Roman Bohoslavsky, Marieke L de Kam, Joop M A van Gerven, Amir Inamdar","doi":"10.1177/02698811261478616","DOIUrl":"https://doi.org/10.1177/02698811261478616","url":null,"abstract":"<p><strong>Background: </strong>Serotonergic psychedelics, such as <i>N,N</i>-dimethyltryptamine (DMT), have shown therapeutic potential in various psychiatric disorders. However, DMT demonstrates pharmacokinetic (PK) variability and a short half-life.</p><p><strong>Aims: </strong>This exploratory study investigated the PK, pharmacodynamic (PD), and safety profile of CYB004, a deuterated DMT analogue, following intravenous administration in healthy volunteers.</p><p><strong>Methods: </strong>CYB004, a deuterated DMT analogue, was evaluated in a randomized, double-blind, placebo-controlled, two-part study in healthy participants. Part 1 was a single-dose cohort, in which participants received a 5-minute intravenous 12.7 mg CYB004 bolus, followed by a 30-minute 15.41 mg infusion. Part 2 was a three-way crossover, during which two separate 5-minute 12.7 mg CYB004 boluses were administered. Outcome measures included PK of CYB004 and subjective, autonomic, neurophysiological, and adverse effects.</p><p><strong>Results: </strong>Although high CYB004 doses led to intense psychedelic experiences and participant withdrawals, lower doses achieving plasma concentrations similar to those in previous DMT studies demonstrated an acceptable safety profile. CYB004 demonstrated a PD profile that was similar to DMT at comparable plasma concentrations. PD effects consisted of subjective psychedelic effects, electroencephalography power band reductions, and autonomic nervous system activation. CYB004's half-life was approximately two-fold longer than DMT, prolonging the duration of psychedelic effects to ~40-60 minutes following brief intravenous administration. However, deuteration did not improve PK variability, with IV-administered CYB004 demonstrating moderate to high variability, largely driven by interindividual differences.</p><p><strong>Conclusion: </strong>CYB004 demonstrated PD effects comparable to DMT. However, CYB004 demonstrated an extended duration of these effects due to reduced clearance, while maintaining an acceptable safety profile at clinically relevant exposures despite PK variability.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261478616"},"PeriodicalIF":5.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887520","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":"Safety, tolerability and pharmacokinetics of an NMDA receptor subunit 2B-selective negative allosteric modulator, BI 1569912: Results of three partially randomised, placebo-controlled phase I trials.","authors":"Andreas Hünnemeyer, Yoichiro Ogama, Franco De Crescenzo, Rainer-Georg Goeldner, Akiko Harada, Tetsuya Katakabe, Andreas Scholz, Yury Shatillo, Sigurd D Süssmuth, Christian Keicher","doi":"10.1177/02698811261481073","DOIUrl":"https://doi.org/10.1177/02698811261481073","url":null,"abstract":"<p><strong>Background: </strong>BI 1569912 is an orally administered, GluN2B-selective negative allosteric modulator at the N-methyl-D-aspartate receptor.</p><p><strong>Aims: </strong>To investigate the safety, tolerability and pharmacokinetics (PK) of BI 1569912 in healthy males across three partially randomised, placebo-controlled, parallel-group phase I trials.</p><p><strong>Methods: </strong>Trial 1 evaluated single rising doses (SRD) of BI 1569912 versus placebo in Germany and assessed formulation and food effects on bioavailability. Trial 2 evaluated multiple rising doses (MRD) of BI 1569912 versus placebo in young and elderly participants in Germany. Trial 3 investigated single rising and multiple doses (MD) of BI 1569912 in participants in Japan, including PK to assess morning versus evening dosing.</p><p><strong>Results: </strong>Trial completion/randomisation numbers were: Trial 1 (SRD part, 54/55; bioavailability/food effect part, 8/13); Trial 2 (MRD part, 71/71; Elderly part, 12/12); Trial 3 (SRD part, 32/32; MD part, 12/12; evening PK part, 12/12). No deaths, serious adverse events (AEs), AEs of special interest, or discontinuations because of AEs were reported. There was no clinical evidence clearly suggestive of dissociation. After oral administration, BI 1569912 was rapidly absorbed and eliminated, with dose-proportional increases in plasma exposure. Formulation (oral solution vs tablet) did not affect PK. Administration with food reduced <i>C</i>_max and delayed <i>T</i>_max without affecting AUC; likewise, evening dosing lowered <i>C</i>_max versus morning while AUC remained similar. Steady state was achieved by Day 3 of multiple dosing. Exposure was similar between young and elderly participants. Urinary excretion of unchanged drug was negligible.</p><p><strong>Conclusions: </strong>BI 1569912 demonstrated favourable safety and PK profiles in healthy participants.<b>Clinical trial registration:</b> Trial 1 (ClinicalTrials.gov: NCT04445090 (1447-0001)); Trial 2 (ClinicalTrials.gov: NCT04978506 (1447-0002)); Trial 3 (ClinicalTrials.gov: NCT04958252 (1447-0004)).</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261481073"},"PeriodicalIF":5.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874467","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":"Association of incretin therapy with self-harm behaviors in people with psychiatric conditions: A retrospective cohort study.","authors":"Hailey Kalamaras, Raechel T White, Scott A Coon, Matthew Perkel, Amre A Elmaoued","doi":"10.1177/02698811261416077","DOIUrl":"10.1177/02698811261416077","url":null,"abstract":"<p><strong>Background: </strong>Incretin therapies have shown promise in managing antipsychotic-associated weight gain and psychological benefits in individuals with mental health disorders. In populations at high risk for suicidal behaviors, it is crucial to understand how these therapies affect risk of suicidality or self-harm.</p><p><strong>Aims: </strong>This study investigates the effect of incretin therapy on suicidality or self-harm in individuals with severe mental disorders (SMDs).</p><p><strong>Methods: </strong>A retrospective cohort study was developed using the TriNetX Research Network, a federated database collating de-identified data from electronic health records. Adult individuals diagnosed with a psychotic disorder and treated with an antipsychotic were included. Cohorts were differentiated based on concomitant incretin therapy and balanced using 1:1 propensity score matching. Psychiatric outcomes were compared during the 5 years following the index date.</p><p><strong>Results: </strong>After matching, each cohort consisted of 21,984 individuals. Receipt of incretin therapy was associated with reduced relative risk (RR) for suicidal ideation (RR: 0.48; 95% CI: 0.45-0.51; <i>p</i> < 0.0001), suicide attempts (RR: 0.64; 95% CI: 0.52-0.78; <i>p</i> < 0.0001), and self-harm (RR: 0.61; 95% CI: 0.56-0.67; <i>p</i> < 0.0001) compared to the no treatment group. Additionally, individuals receiving incretin therapy had lower risk for all-cause mortality (RR: 0.50; 95% CI: 0.46-0.53; <i>p</i> < 0.0001), overdose (RR: 0.57; 95% CI: 0.49-0.65; <i>p</i> < 0.0001), and substance use disorders (RR: 0.76; 95% CI: 0.74-0.77; <i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>Our findings suggest incretin therapies may have protective effects against various psychiatric and behavioral risks in individuals with SMD.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1430-1436"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201930","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":"Methamphetamine conditioned place preference in adolescent mice: Interaction between sex and strain.","authors":"Lewis Nunez Severino, Andre B Toussaint, Rachael M Langa, Grace McKenna, Isabella A Bodziony, Nesha S Burghardt","doi":"10.1177/02698811261420102","DOIUrl":"10.1177/02698811261420102","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine (METH) use is higher in adolescent women than adolescent men. While rodent studies support a sex difference in the reinforcing effects of METH, few have investigated sex differences in the underlying neural circuits, none of which tested rodents during adolescence.</p><p><strong>Aims: </strong>Investigate whether there are sex differences in the rewarding effects of METH in two strains of adolescent mice that are commonly used to generate transgenic lines. Identify changes in associated neural circuits.</p><p><strong>Methods: </strong>We tested METH-induced conditioned place preference (CPP) in male and female 129Sv/Ev and C57Bl/6 mice during middle adolescence using 1 mg/kg of METH. Cells expressing c-Fos protein were quantified in the nucleus accumbens (NAc) and area CA1 of the hippocampus following the postconditioning test.</p><p><strong>Results: </strong>In C57Bl/6 mice, METHinduced CPP in females, but not males. Conversely, METHinduced CPP in 129Sv/Ev males, but not females. In both strains, groups that exhibited CPP had more c-Fos+ cells in the NAc and CA1 than saline-treated control groups. The number of c-Fos+ cells in these two brain regions only correlated in groups that exhibited CPP. Finally, we found evidence of behavioral sensitization in 129Sv/Ev males only.</p><p><strong>Conclusions: </strong>Our study reveals that the rewarding effects of METH in adolescent mice are both sex- and strain-dependent, indicating that behavioral and neural responses to METH may result from an interaction between sex-specific and genetic mechanisms. Our work will guide the selection of appropriate background strains in future studies using genetically modified mice.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1467-1479"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321836","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 behavioural effects of the serotonin 1A receptor agonist buspirone on reward processing in healthy volunteers: A randomised, placebo-controlled study.","authors":"Alexander L W Smith, Sorcha Hamilton, Susannah E Murphy, Philip J Cowen, Catherine J Harmer","doi":"10.1177/02698811261430527","DOIUrl":"10.1177/02698811261430527","url":null,"abstract":"<p><strong>Background: </strong>The 5-HT_1A receptor is widely expressed throughout the brain and is implicated in reward processing; however, the acute effects of 5-HT_1A receptor agonism on reward and aversive processing in humans remain unclear.</p><p><strong>Aims: </strong>We investigate whether acute 5-HT_1A receptor agonism influences various stages of reward and aversive processing, specifically consummation, motivation and learning.</p><p><strong>Methods: </strong>In a double-blind, placebo-controlled study using a single 20 mg dose of buspirone, a serotonin 5-HT_1A receptor partial agonist, 62 healthy volunteers underwent 3 tasks: a taste task, an effort-expenditure decision task and a probabilistic instrumental learning task (PILT).</p><p><strong>Results: </strong>In healthy volunteers, acute buspirone increases the aversiveness of bitter tastes, non-significantly reduces willingness to exert effort and increases optimal choice during loss trials in the PILT.</p><p><strong>Conclusions: </strong>Speculatively, this could indicate that acute 5-HT_1A agonism may worsen several stages of aversive processing, with minimal effect on reward processing. The study was pre-registered (clinicaltrials.gov, Serotonin-receptor Agonism in Reward Processing, NCT05357547).</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1381-1391"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574382","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}