ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS).
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Pro-dopaminergic pharmacological interventions for anhedonia in depression: a living systematic review and network meta-analysis of human and animal studies.EBioMedicine · 2025Pooled it
- The hierarchical taxonomy of psychopathology and the search for neurobiological substrates of mental illness: A systematic review and roadmap for future research.Journal of psychopathology and clinical science · 2024Pooled it
- Endogenous mu-opioid modulation of social connection in humans: a systematic review and meta-analysis.Translational psychiatry · 2024Pooled it
- Computationally Informed Insights Into Anhedonia and Treatment by Kappa Opioid Receptor Antagonism.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Trial
- Selective KOR antagonist alters functional patch sizes in individualized brain system: results from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS).Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Opioidergic modulation of monetary incentive delay fMRI responses.Psychopharmacology · 2025Trial
- A parallel-arm, randomized trial of Behavioral Activation Therapy for anhedonia versus mindfulness-based cognitive therapy for adults with anhedonia.Behaviour research and therapy · 2024Trial
- Efficacy and safety of aticaprant, a kappa receptor antagonist, adjunctive to oral SSRI/SNRI antidepressant in major depressive disorder: results of a phase 2 randomized, double-blind, placebo-controlled study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- Longitudinal associations between perceived stress and anhedonia during psychotherapy.Journal of affective disorders · 2023Trial
- Positive affect treatment targets reward sensitivity: A randomized controlled trial.Journal of consulting and clinical psychology · 2023Trial
- Navacaprant, a Novel and Highly Selective Kappa Opioid Receptor Antagonist, in Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial.Journal of clinical psychopharmacologyTrial
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- Probing biomarkers and clinical utility of reward learning across species using the Probabilistic Reward Task: 20 years of findings.Nature. Mental health · 2026Article
- Ketamine Improves Anhedonic Phenotypes Across Species: Translational Evidence From the Probabilistic Reward Task.Biological psychiatry global open science · 2026Article
- Reverse Translation.Perspectives on behavior science · 2026Article
- Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A.Biomedicines · 2026Review
- From Neural Circuits to Behavior: Examining the Central Role of Anhedonia in Major Depression.Advances in experimental medicine and biology · 2026Review
- Application of the research domain criteria in early-phase clinical development of transdiagnostic neurotherapeutics: A multidisciplinary perspective.Neuroscience applied · 2026Review
- The association of different dimensions of anhedonia in the relationship between depressive symptoms and self-harm in adolescents with mood disorders.Frontiers in psychiatry · 2026Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 12 institutions in 2 countries.
Funding
Abstract
Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.