Evidence map›Paper›PMID 41136352›Full record

ReviewTranslational psychiatry2025

Found in translation: orexin receptor antagonism for the treatment of opioid use disorder.

Joel S Raymond, Robin D Vareed, Jamie Peters, Morgan H James

Abstract readReview
In one paragraph

Review in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Joel S RaymondDepartment of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
Robin D VareedDepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Jamie PetersDepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Morgan H JamesDepartment of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. morgan.james@sydney.edu.au.ORCID http://orcid.org/0000-0001-9298-8607

Funding

Extinction Circuits Controlling Heroin SeekingR01DA045836 · NIDA · UNIVERSITY OF COLORADO DENVER · PI PETERS, JAMIE · 2018 to 2022
$1.7M
Orexin (hypocretin) signaling in ventral tegmental area as a common mediator of sleep disturbances and drug demand in cocaine abstinenceR01DA061303 · NIDA · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Gary S. Aston-Jones, Morgan H. James · 2024 to 2026
$1.1M
Prefrontal circuits controlling heroin seekingR01DA061766 · NIDA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI JAMIE PETERS · 2025 to 2026
$952k
Orexin/hypocretin as a common mediator of stress and reward behavior in cocaine addictionR00DA045765 · NIDA · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI JAMES, MORGAN H. · 2021 to 2023
$747k
Corticostriatal-hypothalamic circuits and opioid seekingF31DA059203 · NIDA · UNIVERSITY OF COLORADO DENVER · PI VAREED, ROBIN D · 2023 to 2023
$15k
NIDA NIH HHS F31 DA059203NIDA NIH HHS R00 DA045765NIDA NIH HHS R01 DA045836NIDA NIH HHS R01 DA061303NIDA NIH HHS R01 DA061766U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) F31DA059203U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R00 045765U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R01 061303
6 · The paper itself

Abstract

Existing pharmacological treatment options for opioid use disorder (OUD) face challenges that limit their efficacy. Accumulating preclinical evidence implicates the orexin/hypocretin system in numerous aspects of OUD development and symptomology: opioid use, opioid-associated cue-driven drug seeking, and opioid withdrawal states that lead to relapse. Further, these studies indicate that selective and dual orexin receptor antagonists (SORAs and DORAs) could constitute promising treatments for OUD and other substance use disorders. Several DORAs have already been approved by the FDA for the treatment of insomnia, making their prospective repurposing potentially straightforward. To this end, recent clinical trials have demonstrated multifaceted efficacy of DORAs for ameliorating opioid craving, withdrawal, and related sleep disturbances in individuals with OUD. Consequently, warranted calls are mounting for the broader use of these agents in the treatment of OUD. This review adopts a translational approach to achieve several aims: (1) to outline the fundamental theories of orexin system function and relate orexinergic dysfunction to the disordered motivation and withdrawal states that characterize OUD; (2) to provide an up-to-date evaluation of preclinical and clinical evidence bases supporting the efficacy of orexin receptor antagonism for the treatment of OUD; (3) to discuss key clinical considerations of repurposing DORAs for OUD treatment, including safety and side effects (i.e., respiratory depression, anhedonia, and risk for abuse); and (4) to highlight the ongoing clinical efforts to determine therapeutic efficacy and safety profiles of DORAs for use in OUD populations.

Indexed as

Opioid-Related DisordersOrexin Receptor AntagonistsAnimalsHumansOrexin ReceptorsSubstance Withdrawal SyndromeTranslational Research, BiomedicalOrexin Receptor AntagonistsOrexin Receptors

Identifiers

PMID41136352
PMCPMC12552597

What OpenQuestion holds

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Registered trials

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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.