At a glance
What is it—and why does it matter?
Orexin-A is classified as a peptide ligand and is listed under Ligand ID: 1697. The abstract states that orexin peptide pharmacokinetics are sparsely characterized and that reported plasma concentrations vary substantially because of methodological differences, limiting interpretation of circulating orexin levels and possible peripheral sources.
Sources for this introduction: [1] [2]
This published profile is a reference in progress. Findings retain their source context; missing topics are marked below.
What is it?
A molecule, not a product name.
Identity
Orexin-A (OXA) is classified as a neuropeptide (a peptide neurotransmitter/neuromodulator).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The neuropeptides orexin-A (OXA) and orexin-B (OXB)”
The orexinergic system in the retina: Expression and physiological impact-A review of the literature. · Abstract
pubmed:42150720:1073e3ee7bb5:1073e3ee7bb5
Identity
Orexin-A is described as a hypothalamic neuropeptide with roles in arousal regulation, stress responses, and emotional processing.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orexin-A, a hypothalamic neuropeptide involved in regulating arousal, stress response, and emotional processes”
Plasma orexin-A levels in women with postpartum depression: a prospective controlled study. · OBJECTIVE
pubmed:42307294:8511f7cf7b37:8511f7cf7b37
Identity
In this mammalian appetite-regulation review, Orexin A is included among the neuropeptides discussed as key regulators beyond the established hypothalamic arcuate nucleus (ARC) circuit.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Beyond the established hypothalamic Arcuate Nucleus (ARC) circuit, key regulators examined include neuropeptides like Orexin A, Oxyntomodulin, PACAP, and Galanin, alongside key receptor systems such as the Melanocortin-3 receptor (MC3R), the Endocannabinoid (ECS) and the Endorphin Systems.”
Regulators of Appetite in Mammals - Old and New players. · Abstract
pubmed:42274231:a21b0a7009ce:a21b0a7009ce
Identity
Orexin-A is classified as a peptide ligand and is listed under Ligand ID: 1697.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Name: orexin-A Ligand ID: 1697 Type: Peptide”
orexin-A · Identity and approval
iuphar-ligand:1697:0937e1823866:0937e1823866
How does it work?
Target, response, and disposition.
Mechanism
Full colocalization means orexin B labeling tracked the same orexin signal as orexin A under these conditions, so orexin B staining could be used to mark orexin fibers/neurons.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orexin A and B were fully colocalized, allowing orexin B to serve as a reliable marker.”
Formalin-induced pain preferentially activates orexin neurons in male mice. · Abstract
pubmed:42097393:c04332364eef:c04332364eef
Mechanism
The authors interpret their results as supporting a mediating role for orexinergic signaling in linking ambient light conditions to sleep and affective outcomes.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“These findings support the hypothesis that the orexinergic system mediates the effects of ambient light on sleep and affect,”
Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder. · CONCLUSIONS
pubmed:41508567:bde9d1d76494:bde9d1d76494
Mechanism
The reported results were interpreted as functional crosstalk between opioid and orexin signaling within the nucleus accumbens, consistent with mutual modulation during acute nociceptive processing.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“These findings indicate a bidirectional interaction between opioidergic and orexinergic systems within the NAc in regulating acute nociception.”
Orexinergic-Opioidergic Interactions Within the Nucleus Accumbens in the Modulation of Acute Pain: Evidence From the Tail-Flick Test in Rats. · CONCLUSIONS
pubmed:42530048:8f359dc82632:8f359dc82632
Mechanism
Prior reports (as summarized here) indicate lateral hypothalamic orexin neuron loss in post-mortem Parkinson’s disease and in several animal studies, with rats highlighted.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orexin neuron loss in the lateral hypothalamus has been reported in post-mortem Parkinson's disease patients and multiple animal studies, particularly in rats;”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Mechanism
The stated objective was measurement of plasma orexin-A in postpartum depression and exploration of its potential biological involvement in the condition.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The aim of this study was to assess plasma orexin-A levels in women with postpartum depression and to explore its potential biological involvement in postpartum depression.”
Plasma orexin-A levels in women with postpartum depression: a prospective controlled study. · OBJECTIVE
pubmed:42307294:8511f7cf7b37:8511f7cf7b37
Mechanism
Orexin peptides including orexin A signal via OX1R and OX2R to influence both sensory-discriminative and affective-motivational aspects of pain; the direction of effect can vary by peptide subtype, receptor distribution, circuit architecture, and pain modality.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orexin peptides (orexin A and orexin B) modulate both the sensory-discriminative and affective-motivational components of pain via their receptors (OX1R and OX2R) in a context-dependent manner, producing antinociceptive or pro-nociceptive effects depending on peptide subtype, receptor distribution, circuit architecture, and pain modality.”
Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia. · Abstract
pubmed:42460012:a9846ad06137:a9846ad06137
Mechanism
The stated objective was to evaluate whether orexin neuron loss progresses over time in the unilateral intrastriatal 6-OHDA mouse model.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The aim of this pilot study was to assess a time-dependent loss of orexin neurons in the unilateral intrastriatal 6-OHDA mouse model”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Pharmacokinetics
The abstract states that orexin peptide pharmacokinetics are sparsely characterized and that reported plasma concentrations vary substantially because of methodological differences, limiting interpretation of circulating orexin levels and possible peripheral sources.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“We also review the limited pharmacokinetic data available for orexin peptides and evaluate reported plasma concentrations, highlighting substantial methodological variability that complicates interpretation of circulating levels and their potential peripheral sources.”
The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications. · Abstract
pubmed:42609337:1f357b1ef544:1f357b1ef544
What has been studied?
What the evidence says.
Comparative evidence
The total number of orexin-immunoreactive neurons did not differ by sex or estrous stage in these mice.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The total number of orexin-immunoreactive neurons did not differ between the sexes or across estrous stages”
Formalin-induced pain preferentially activates orexin neurons in male mice. · Abstract
pubmed:42097393:c04332364eef:c04332364eef
Study findings
In a rat CA1 EED model induced by HFES, cortical (frontal cortex) orexin-A at 10 μg/10 μl decreased the incidence of large (7-10 mV) population spikes during EEDs while leaving overall EED duration unchanged, indicating site-specific effects.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“In contrast, cortical administration of orexin‑A selectively reduced the incidence of high‑amplitude (7-10 mV) population spikes during EEDs without affecting the duration of epileptiform activity.”
Modulation of electrically evoked hippocampal epileptiform activity by exogenous orexins in the rat CA1 field. · Abstract
pubmed:42370618:bdda096bc718:bdda096bc718
Study findings
c-Fos is used as an indicator of neuronal activation; after formalin-induced nociception, a larger fraction of orexin neurons showed c-Fos in males, suggesting greater functional recruitment in males in this paradigm.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“In contrast, formalin induced a significantly higher proportion of c-Fos-positive orexin neurons in males, indicating male-biased recruitment of orexin neurons during nociception, despite equivalent anatomical substrates.”
Formalin-induced pain preferentially activates orexin neurons in male mice. · Abstract
pubmed:42097393:c04332364eef:c04332364eef
Study findings
As a proof-of-concept finding, the study asserts that the unilateral intrastriatal 6-OHDA mouse model reproduces progressive loss of orexin A–immunopositive neurons.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This pilot study serves as a proof of concept that the unilateral intrastriatal 6-OHDA mouse model can successfully recapitulate the progressive loss of orexin A positive neurons”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Study findings
In a neurotoxic unilateral intrastriatal 6-OHDA mouse model, orexin A immunopositive neuron counts in the lateral hypothalamus progressively decreased on the lesioned side relative to the non-lesioned side.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“A progressive loss of orexin A positive neurons in the lateral hypothalamus was observed in the lesioned side relative to the non-lesioned side.”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Study findings
In this observational analysis, CSF orexin concentrations did not show statistical association with global sleep continuity metrics.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orexin was not associated with global sleep continuity metrics.”
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. · RESULTS
pubmed:42447420:0efa038e8709:0efa038e8709
Study findings
At 4 weeks after 6-OHDA induction in a unilateral intrastriatal mouse model, orexin A–immunoreactive neurons in the lateral hypothalamus were significantly reduced.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“A significant reduction of orexin A positive neurons in the lateral hypothalamus was observed at 4 weeks with further loss at 6-8 weeks post 6-OHDA induction.”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Study findings
Following unilateral intrastriatal 6-OHDA induction in mice, orexin A immunopositive neuron loss in the lateral hypothalamus continued, with further loss noted at 6-8 weeks.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“A significant reduction of orexin A positive neurons in the lateral hypothalamus was observed at 4 weeks with further loss at 6-8 weeks post 6-OHDA induction.”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Study findings
In this grass rat model, central orexin A administration increased daytime wakefulness in females.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“OXA treatment promoted daytime wakefulness in females,”
Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder. · RESULTS
pubmed:41508567:bde9d1d76494:bde9d1d76494
Study findings
As summarized in the abstract, the existing literature provides limited evidence for orexin neuron loss specifically in neurotoxic mouse models.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“however, evidence in neurotoxic mouse models remains limited.”
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. · Abstract
pubmed:42323123:743443206799:743443206799
Study findings
In an observational AD cohort, NREM oscillatory features (slow oscillation duration and sleep spindle density/power) showed inverse statistical associations with CSF orexin concentrations.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Longer SO duration and higher SP density and power were associated with lower CSF orexin concentrations (SP density: β = -187.37 pg/mL, 95% CI -344.93 to -29.80).”
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. · RESULTS
pubmed:42447420:0efa038e8709:0efa038e8709
Study findings
In this observational AD cohort, CSF orexin concentration was inversely associated with MMSE score.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Higher CSF orexin concentrations were associated with worse global cognition (ADAS-Cog: β = 0.014, 95% CI 0.003-0.024; MMSE: β = -0.01, 95% CI -0.011 to -0.004)”
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. · RESULTS
pubmed:42447420:0efa038e8709:0efa038e8709
Study findings
Across Parkinson’s disease models, orexin A and B are reported to preserve tyrosine hydroxylase expression, a marker commonly used for dopaminergic neuron phenotype/function.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“whereas orexin A and B preserve tyrosine hydroxylase expression”
Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation. · Abstract
pubmed:42063365:01e993ea1a4d:01e993ea1a4d
Study findings
Within rodent stress models, suvorexant treatment is reported to attenuate stress-associated elevations of the peptide orexin-A in the amygdala.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“In stress-exposed rodents, suvorexant reversed hyperarousal, avoidance, and anxiety-like behaviors, attenuated elevated orexin-A and CRF-R1 levels in the amygdala, and restored HPA axis function.”
A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits. · RESULTS
pubmed:42391109:2c0d24e110a7:2c0d24e110a7
Study findings
In this observational AD cohort, CSF orexin concentration was positively associated with YKL-40 (a biomarker measured in CSF in this study).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Higher orexin was also associated with higher pTau181 (β = 0.11, 95% CI 0.04-0.19), total tau, and YKL-40 (β = 0.37, 95% CI 0.17-0.57).”
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. · RESULTS
pubmed:42447420:0efa038e8709:0efa038e8709
Study findings
Within the reviewed preclinical/clinical literature, orexin-A levels are listed among molecular markers examined in relation to PTSD-like phenotypes.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Some studies investigated molecular markers, such as orexin-A levels, corticosterone, CRF-R1, serotonin, mitochondrial fission/fusion proteins, and mTOR signaling.”
A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits. · MATERIALS AND METHODS
pubmed:42391109:2c0d24e110a7:2c0d24e110a7
Study findings
In this observational AD cohort, CSF orexin concentration was positively associated with a tau pathology biomarker (pTau181).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Higher orexin was also associated with higher pTau181 (β = 0.11, 95% CI 0.04-0.19), total tau, and YKL-40 (β = 0.37, 95% CI 0.17-0.57).”
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. · RESULTS
pubmed:42447420:0efa038e8709:0efa038e8709
Study findings
In an in vivo rat electrophysiology model where HFES induced CA1 electrically evoked epileptiform discharges, intracerebroventricular orexin-A at 10 μg/10 μl shortened discharge duration within 20 minutes and eliminated the HFES-related progressive lengthening observed in controls.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Intracerebroventricular administration of orexin‑A significantly reduced the duration of EEDs within 20 minutes and abolished the progressive, HFES‑related prolongation of epileptiform discharges observed in control animals.”
Modulation of electrically evoked hippocampal epileptiform activity by exogenous orexins in the rat CA1 field. · Abstract
pubmed:42370618:bdda096bc718:bdda096bc718
Study findings
In dimLD-exposed animals, central orexin A administration increased anti-inflammatory cytokine expression (IL-4 and IL-10).
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“treating dimLD animals with OXA increased expression of anti-inflammatory cytokines IL-4 and IL-10,”
Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder. · RESULTS
pubmed:41508567:bde9d1d76494:bde9d1d76494
Study findings
In this case-control comparison, serum orexin-A concentration was decreased in the BD-M group versus controls, with statistical significance (p < 0.001).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Serum OXA, OXB, sOX1R, and sOX2R levels were significantly lower in the BD-M group (all p < 0.001).”
Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance. · RESULTS
pubmed:42096890:fb3547d1e9ad:fb3547d1e9ad
Study findings
In generalized linear models in an AD cohort, CSF orexin concentration was positively associated with ADAS-Cog (higher indicates worse cognition in this context).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Higher CSF orexin concentrations were associated with worse global cognition (ADAS-Cog: β = 0.014, 95% CI 0.003-0.024; MMSE: β = -0.01, 95% CI -0.011 to -0.004)”
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. · RESULTS
pubmed:42447420:0efa038e8709:0efa038e8709
Study findings
Measured 1 month postpartum, plasma orexin-A concentration was lower in the postpartum depression group than in matched healthy controls, with a reported p-value of 0.021.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Mean plasma orexin-A levels were significantly lower in women with postpartum depression compared to controls (65.2±10.8 vs. 79.9±6.4 pg/mL, p=0.021).”
Plasma orexin-A levels in women with postpartum depression: a prospective controlled study. · RESULTS
pubmed:42307294:8511f7cf7b37:8511f7cf7b37
Study findings
Across the sampled postpartum women, higher maternal age was associated with higher plasma orexin-A, with correlation r=0.328 (p=0.011).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orexin-A levels were positively correlated with maternal age (r=0.328, p=0.011)”
Plasma orexin-A levels in women with postpartum depression: a prospective controlled study. · RESULTS
pubmed:42307294:8511f7cf7b37:8511f7cf7b37
Study findings
Delivering orexin-A into the nucleus accumbens was reported to increase antinociception in a dose-dependent manner, indicating orexinergic signaling in this region can modulate acute nociceptive processing.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Intra-NAc injections of morphine and orexin-A produced significant and dose-dependent antinociceptive effects.”
Orexinergic-Opioidergic Interactions Within the Nucleus Accumbens in the Modulation of Acute Pain: Evidence From the Tail-Flick Test in Rats. · RESULTS
pubmed:42530048:8f359dc82632:8f359dc82632
Study findings
In Parkinson’s disease models, orexin A and B are described as increasing neuronal excitability, consistent with a functional neuromodulatory effect.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“promote neuronal excitability”
Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation. · Abstract
pubmed:42063365:01e993ea1a4d:01e993ea1a4d
Risks and interactions
Risks, organized for scanning.
This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.
Products and regulatory status
Same ingredient. Different records.
This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.
Administration context
The practical clinical context.
This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.
Additional research & classification gaps
28 archived statements are kept separate from drug-effect findings. Media studies, economic models, methods, and records with unresolved scope are not used as medical-effect evidence.
Inspect contextual research (28)
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
When comparing targeted LC-MS quantification of orexin-A fragments against a clinically relevant RIA assay, the fragment concentrations showed strong rank-order agreement (Spearman correlation).
Research context only—not evidence of a treatment effect.
- Identification and quantification of Hypocretin-1/Orexin-A 1-14 and 1-16 fragments in immunopurified cerebrospinal fluid using LC-MS: Comparison with radioimmunoassay (RIA) determinations.
Comparison with RIA yielded Spearman's correlation coefficients (ρ) of 0.91 and 0.94 for the 1-14 and 1-16 fragments, respectively.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Beyond orexinergic neurons, LH glutamatergic, GABAergic, and neurotensinergic populations are stated to participate in pain regulation with circuit-specific roles and partial anatomical/functional overlap with orexinergic circuitry.
Research context only—not evidence of a treatment effect.
- Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.
In addition, other neuronal populations within the LH, such as glutamatergic, GABAergic, and neurotensinergic neurons, also contribute to pain regulation in a circuit-specific manner and partially overlap anatomically and functionally with orexinergic neurons.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The workflow included fragment identification followed by targeted LC-MS quantification, which was then analytically compared against a clinically relevant RIA method.
Research context only—not evidence of a treatment effect.
- Identification and quantification of Hypocretin-1/Orexin-A 1-14 and 1-16 fragments in immunopurified cerebrospinal fluid using LC-MS: Comparison with radioimmunoassay (RIA) determinations.
Following the identification of fragments, quantitative targeted LC-MS measurements were compared to a clinically relevant RIA assay.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The abstract reports an inverse association between orexin-A and cholecystokinin, quantified by r=- 0.297 with p<0.05.
Research context only—not evidence of a treatment effect.
- Is Hashimoto's Thyroiditis Associated with Insulin Resistance Markers?
A negative correlation was observed between orexin-A levels and cocaine and amphetamine-regulated transcript and cholecystokinin levels (r=-0.365,p<0.05;r=- 0.297,p<0.05, respectively).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The conclusion characterizes peripheral orexin-system changes in acute mania as both decreased biomarker concentrations and disrupted inter-component network connectivity.
Research context only—not evidence of a treatment effect.
- Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance.
Peripheral orexin system alterations in acute mania are characterized not only by reduced biomarker levels but also by disrupted inter-component connectivity.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The conclusion notes that longitudinal research is required to distinguish whether the observed orexin-system alterations reflect state effects of acute mania versus trait markers.
Research context only—not evidence of a treatment effect.
- Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance.
Longitudinal studies are needed to clarify the state versus trait nature of these alterations.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The review’s synthesis frames LH orexinergic neurons as an integrative hub connecting circuit activity to behavioral and physiological changes that modulate pain.
Research context only—not evidence of a treatment effect.
- Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.
Collectively, these findings position LH orexinergic neurons as a central node linking neural circuit dynamics with the behavioral and physiological modulation of pain.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The review states that OXA increases the excitability of M2 ipRGCs, and this increased excitability is linked to enhancement of the pupillary light reflex (PLR).
Research context only—not evidence of a treatment effect.
- The orexinergic system in the retina: Expression and physiological impact-A review of the literature.
OXA enhances the pupillary light reflex (PLR) by increasing the excitability of specific intrinsically photosensitive retinal ganglion cells (M2 ipRGCs)
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Using LC-MS/MS on CSF, investigators could not detect intact orexin-A, but they detected two N-terminal peptide fragments corresponding to residues 1-14 and 1-16.
Research context only—not evidence of a treatment effect.
- Identification and quantification of Hypocretin-1/Orexin-A 1-14 and 1-16 fragments in immunopurified cerebrospinal fluid using LC-MS: Comparison with radioimmunoassay (RIA) determinations.
Full-length orexin-A was not detected in CSF, but two relatively abundant N-terminal orexin-A fragments, comprising amino acids 1-14 and 1-16, were identified by LC-MS/MS.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orexin A is part of a neuropeptide system most recognized for controlling sleep-wake regulation and energy homeostasis.
Research context only—not evidence of a treatment effect.
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.
is primarily known for its role in sleep-wake regulation and energy homeostasis.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The objective included assessing peripheral (serum) orexin-A levels in BD-M and evaluating associations with clinical characteristics and multivariate/system-level analyses.
Research context only—not evidence of a treatment effect.
- Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance.
This study aimed to examine peripheral levels of orexin-A (OXA), orexin-B (OXB), soluble orexin-1 receptor (sOX1R), and orexin-2 receptor (sOX2R) in BD-M and to explore their associations with clinical features, discriminative patterns, and system-level interactions.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The authors interpret the observed peripheral orexin-system differences as suggesting a potential role for orexinergic dysregulation in BD-M.
Research context only—not evidence of a treatment effect.
- Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance.
These findings suggest a potential role for orexinergic dysregulation in BD-M
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Across multiple models summarized, reduced orexin pathway signaling is described as being associated with resilience phenotypes.
Research context only—not evidence of a treatment effect.
- A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits.
Notably, reduced orexin signaling was associated with resilience in multiple models.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
In the lateral hypothalamus (LH), neurons synthesize the neuropeptide orexin-A.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
Neurons in the lateral hypothalamus (LH) synthesize orexin-A and orexin-B, neuropeptides that orchestrate feeding behavior and energy expenditure, thereby directly regulating energy homeostasis and associated behaviors.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orexin A is one of two orexin neuropeptides in the orexin (hypocretin) system; this system also includes orexin B and the receptors OX1R and OX2R.
Research context only—not evidence of a treatment effect.
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.
The orexin (hypocretin) system, composed of the neuropeptides orexin A and orexin B and their receptors OX1R and OX2R
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
The biomarker panel included orexin-A quantified in cerebrospinal fluid.
Research context only—not evidence of a treatment effect.
- Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience.
CSF was assayed for orexin-A, amyloid-β42 (Aβ42), phosphorylated tau181 (pTau181), total tau, and YKL-40.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orexin signaling (including orexin-A) is described as directly regulating energy homeostasis and behaviors associated with energy balance.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
Neurons in the lateral hypothalamus (LH) synthesize orexin-A and orexin-B, neuropeptides that orchestrate feeding behavior and energy expenditure, thereby directly regulating energy homeostasis and associated behaviors.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The abstract states that dysregulated orexin signaling is strongly implicated in metabolic disorders, with obesity highlighted in particular.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
Dysregulation of orexin signaling is strongly implicated in metabolic disorders, particularly obesity, as well as in psychiatric conditions including anxiety and depression, highlighting its central role in their comorbidity.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orexins (including orexin-A) are characterized as integrative neuromodulators coordinating autonomic, neuroendocrine, arousal, reward, and stress circuitry.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
Functioning as integrative modulators, orexins coordinate autonomic, neuroendocrine, arousal, reward, and stress circuits.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The orexin system is described as a regulator of arousal, sleep–wake cycling, and reward-related processing.
Research context only—not evidence of a treatment effect.
- Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance.
The orexin system regulates arousal, sleep-wake cycles, and reward processing
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orexin/hypocretin signaling is described as a regulator of arousal state, stress responsiveness, and REM sleep physiology.
Research context only—not evidence of a treatment effect.
- A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits.
The orexin (hypocretin) system, which regulates arousal, stress reactivity, and REM sleep, has emerged as a promising therapeutic target in PTSD.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The abstract characterizes orexin-A as a key neuroendocrine/autonomic regulator, with roles that include control of food intake.
Research context only—not evidence of a treatment effect.
- Is Hashimoto's Thyroiditis Associated with Insulin Resistance Markers?
Cholecystokinin, orexin-A, and cocaine and amphetamine-regulated transcript are essential regulators of various endocrine and autonomic processes, including food intake.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The orexin neuropeptides (including orexin-A) are described as orchestrating feeding behavior and energy expenditure.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
Neurons in the lateral hypothalamus (LH) synthesize orexin-A and orexin-B, neuropeptides that orchestrate feeding behavior and energy expenditure, thereby directly regulating energy homeostasis and associated behaviors.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence summarized in this review indicates LH orexinergic neurons participate in multiple non-pharmacological analgesic paradigms (stress-induced analgesia, olfactory modulation, electroacupuncture, exercise-induced hypoalgesia), implying involvement in circuit-level pain modulation.
Research context only—not evidence of a treatment effect.
- Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.
In parallel, emerging evidence indicates that orexinergic neurons are critically engaged in diverse non-pharmacological analgesic paradigms, including stress-induced analgesia, olfactory modulation, electroacupuncture, and exercise-induced hypoalgesia.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The conclusions attribute a mechanistic role to increased orexinergic activity, proposing it contributes to PTSD pathophysiology.
Research context only—not evidence of a treatment effect.
- A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits.
These findings suggest that orexinergic overactivation contributes to PTSD pathophysiology and that DORAs may offer an advantage over traditional sedatives by enhancing REM sleep and modulating stress signaling.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The abstract links dysregulated orexin signaling to psychiatric conditions, explicitly naming anxiety and depression.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
Dysregulation of orexin signaling is strongly implicated in metabolic disorders, particularly obesity, as well as in psychiatric conditions including anxiety and depression, highlighting its central role in their comorbidity.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The abstract states that the review summarizes recent advances in orexin-A neural circuitry relevant to feeding regulation.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
This review provides a comprehensive overview of recent advances in understanding orexin-A neural circuits in feeding regulation, emphasizing mechanistic insights into the interplay between orexin signaling, energy balance, and anxiety-obesity comorbidity.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The abstract states the review emphasizes mechanistic interplay among orexin signaling, energy balance, and anxiety–obesity comorbidity.
Research context only—not evidence of a treatment effect.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
This review provides a comprehensive overview of recent advances in understanding orexin-A neural circuits in feeding regulation, emphasizing mechanistic insights into the interplay between orexin signaling, energy balance, and anxiety-obesity comorbidity.
Research status + gaps
What still needs better answers?
- No publishable claim yet for: administration, contraindication, interaction, regulatory, safety
- 189 compiled claim(s) withheld by automated assurance: assurance_score_below_0.58 (118), assurance_score_below_0.72 (54), current_regulatory_source_required (49), extraction_ambiguity (144), high_risk_requires_regulatory_or_two_independent_sources (69), no_direct_support (169), proposal_not_staged (2)
These are the limits of this profile, not an exhaustive list of scientific uncertainties.
References + discovery
Open the records yourself.
- orexin-A ↗
iuphar-ligand · published 2026-08-28 · retrieved 2026-08-28T12:35:21Z
- Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder. ↗
pubmed · published 2026-12-01 · retrieved 2026-08-28T12:35:21Z
- Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation. ↗
pubmed · published 2026-07-22 · retrieved 2026-09-04T08:38:04Z
- Peripheral orexin system alterations in acute bipolar mania: Associations with clinical features and diagnostic performance. ↗
pubmed · published 2026-09-15 · retrieved 2026-08-28T12:35:21Z
- Formalin-induced pain preferentially activates orexin neurons in male mice. ↗
pubmed · published 2026-06-30 · retrieved 2026-09-05T09:00:33Z
- Identification and quantification of Hypocretin-1/Orexin-A 1-14 and 1-16 fragments in immunopurified cerebrospinal fluid using LC-MS: Comparison with radioimmunoassay (RIA) determinations. ↗
pubmed · published 2026-09-01 · retrieved 2026-08-28T12:35:21Z
- The orexinergic system in the retina: Expression and physiological impact-A review of the literature. ↗
pubmed · published 2026-07-01 · retrieved 2026-09-05T09:00:33Z
- Regulators of Appetite in Mammals - Old and New players. ↗
pubmed · published 2026-06-11 · retrieved 2026-09-04T08:38:04Z
- Plasma orexin-A levels in women with postpartum depression: a prospective controlled study. ↗
pubmed · published 2026-01-01 · retrieved 2026-09-05T09:00:33Z
- Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue. ↗
pubmed · published 2026-10-01 · retrieved 2026-08-28T12:35:21Z
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity. ↗
pubmed · published 2026-06-09 · retrieved 2026-09-05T09:00:33Z
- Modulation of electrically evoked hippocampal epileptiform activity by exogenous orexins in the rat CA1 field. ↗
pubmed · published 2026-06-15 · retrieved 2026-09-05T09:00:33Z
- A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits. ↗
pubmed · published 2026-07-02 · retrieved 2026-09-05T09:00:33Z
- Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. ↗
pubmed · published 2026-08-11 · retrieved 2026-09-05T09:00:33Z
- Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia. ↗
pubmed · published 2026-01-01 · retrieved 2026-09-05T09:00:33Z
- Orexinergic-Opioidergic Interactions Within the Nucleus Accumbens in the Modulation of Acute Pain: Evidence From the Tail-Flick Test in Rats. ↗
pubmed · published 2026-07-23 · retrieved 2026-09-05T09:00:33Z
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications. ↗
pubmed · published 2026-01-01 · retrieved 2026-09-05T09:00:33Z
- Is Hashimoto's Thyroiditis Associated with Insulin Resistance Markers? ↗
pubmed · published 2026-08-18 · retrieved 2026-08-28T12:35:21Z
Publication history and provenance
Version 2 · Automated assessment · 2026-09-05T09:00:33Z
04b1ff8d44c656b8affbad5adb72ae60d706d2aa0a0b9aef206a2c326c3e8b1c