ReviewDepression and anxiety2016
Kappa-Opioid Antagonists for Psychiatric Disorders: From Bench to Clinical Trials.
Review in Depression and anxiety, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 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
- 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
- A randomized proof-of-mechanism trial applying the 'fast-fail' approach to evaluating κ-opioid antagonism as a treatment for anhedonia.Nature medicine · 2020Trial
- Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.Molecular psychiatry · 2019Trial
- Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans.Hormones and behavior · 2018Trial
- 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
- Stress-induced adaptations in nucleus accumbens dopamine D1 receptor-expressing cells correspond to social avoidance behavior in male mice.IBRO neuroscience reports · 2026Article
- Kappa Opioid Receptor Availability in Borderline Personality Disorder: An In Vivo Investigation With [Biological psychiatry · 2026Article
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Probing biomarkers and clinical utility of reward learning across species using the Probabilistic Reward Task: 20 years of findings.Nature. Mental health · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Kappa-Opioid Receptor Antagonism Prolongs the Antidepressant Effects of Ketamine in Adult Mice with Depression-like Behavior Induced by Adolescent Chronic Unpredictable Stress.International journal of molecular sciences · 2026Article
- Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A.Biomedicines · 2026Review
- The opioid system in endometriosis: implications for endometrial receptivity and reproductive outcomes.Frontiers in endocrinology · 2026Review
- Multisystem regulation of reward and addiction: beyond the dopaminergic system.Frontiers in pharmacology · 2026Review
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- A Comparison of Methods for Testing and Implementing Community Health Interventions in Childhood: A Realist Review.Children (Basel, Switzerland) · 2025Review
- Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed With Positron Emission Tomography Imaging and Neuronally Derived Exosomes.Biological psychiatry · 2025Article
- A switch in kappa opioid receptor signaling from inhibitory to excitatory induced by stress in a subset of cortically-projecting dopamine neurons.bioRxiv : the preprint server for biology · 2025Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Kappa-opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry. This research established that exposure to drugs of abuse or stress increases the activity of the transcription factor CREB (cAMP response element binding protein) in the NAc, which leads to elevated expression of the opioid peptide dynorphin that in turn causes core signs of depressive- and anxiety-related disorders. Disruption of KORs-the endogenous receptors for dynorphin-produces antidepressant- and anxiolytic-like actions in screening procedures that identify standard drugs of these classes, and reduces stress effects in tests used to study addiction and stress-related disorders. Although interest in this target is high, prototypical KOR antagonists have extraordinarily persistent pharmacodynamic effects that complicate clinical trials. The development of shorter acting KOR antagonists together with more rapid designs for clinical trials may soon provide insight on whether these drugs are efficacious as would be predicted by preclinical work. If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans.
Indexed as
Identifiers
What OpenQuestion holds
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.