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Orexin-A

A neuropeptide that regulates wakefulness, arousal, and appetite. Its deficiency causes narcolepsy.

EmergingLimited Data

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This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician

What is Orexin-A?

Orexin-A (also called Hypocretin-1) is a 33-amino acid neuropeptide produced by neurons in the lateral hypothalamus. It is a master regulator of the sleep-wake cycle, arousal, and energy homeostasis. Loss of orexin-producing neurons causes narcolepsy type 1. Research into orexin replacement therapy and orexin receptor agonists is active.

Why People Talk About It

Narcolepsy treatment (orexin replacement)

Emerging

Wakefulness and alertness promotion

Emerging

Appetite and metabolism regulation

Emerging

How It Works

Orexin-A is the brain's 'wake-up signal.' It activates arousal centers throughout the brain, keeping you alert and awake. When orexin neurons are destroyed (as in narcolepsy), people experience uncontrollable sleepiness.

Common Questions

Safety Information

Important Safety Notes

Common Side Effects

Limited human dataPotential for appetite changesPossible cardiovascular effects

Cautions

  • Not FDA-approved
  • Very limited human safety data
  • May affect blood pressure and heart rate

What We Don't Know

Human safety profile is not well-established. Most data comes from animal studies and the inverse pharmacology of orexin receptor antagonists (sleep drugs like suvorexant).

Published Research

33 studies

Exploring the role of Orexin-A neuropeptide in Parkinson's disease: A systematic review and meta-analysis

Meta-AnalysisPMID: 38781804

Changes in biochemical markers following a spinal manipulation - a systematic review update

Meta-AnalysisPMID: 37671460

Cerebrospinal fluid orexin in Alzheimer's disease: a systematic review and meta-analysis

Meta-AnalysisPMID: 34364094

Orexin-A in Patients With Lewy Body Disease: A Systematic Review and Meta-Analysis

Meta-AnalysisPMID: 34867809

Associations of plasma hypocretin-1 with metabolic and reproductive health: Two systematic reviews of clinical studies

Systematic ReviewPMID: 32259696

Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity

Randomized Controlled TrialPMID: 41599851

Effects of different doses of dexmedetomidine combined with stellate ganglion block in patients undergoing laparoscopic radical resection of colorectal cancer

Randomized Controlled TrialPMID: 41489352

Propofol versus sevoflurane anesthesia on postoperative sleep quality in older patients after major abdominal surgery: A randomized clinical trial

Randomized Controlled TrialPMID: 40460592

The Effect of Digital Addiction Training on University Students' Digital Addiction, Sleep Quality, and Orexin-A Levels: Randomized Controlled Trial

Randomized Controlled TrialPMID: 40797228

Influence of Intermittent Fasting on Body Composition, Physical Performance, and the Orexinergic System in Postmenopausal Women: A Pilot Study

Randomized Controlled TrialPMID: 40218879

Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia

Randomized Controlled TrialPMID: 36883238

Intranasal orexin A modulates sympathetic vascular tone: a pilot study in healthy male humans

Randomized Controlled TrialPMID: 35044844

The effect of β-caryophyllene on food addiction and its related behaviors: A randomized, double-blind, placebo-controlled trial

Randomized Controlled TrialPMID: 35809704

Acute assessment of subjective appetite and implicated hormones after a hypnosis-induced hallucinated meal: a randomized cross-over pilot trial

Randomized Controlled TrialPMID: 32418064

The immediate effects of cervical spine manipulation on pain and biochemical markers in females with acute non-specific mechanical neck pain: a randomized clinical trial

Randomized Controlled TrialPMID: 30935335

[Impacts of the repetitive transcranial acupuncture stimulation on the content of serum orexin A in patients with post-stroke insomnia]

Randomized Controlled TrialPMID: 30672231

Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy

Randomized Controlled TrialPMID: 28364870

Inverse Association of Peripheral Orexin-A with Insulin Resistance in Type 2 Diabetes Mellitus: A Randomized Clinical Trial

Randomized Controlled TrialPMID: 29145540

Glucagon regulates orexin A secretion in humans and rodents

Randomized Controlled TrialPMID: 25063274

The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy

Randomized Controlled TrialPMID: 24406723

Changes in biochemical markers of pain perception and stress response after spinal manipulation

Randomized Controlled TrialPMID: 24450367

Influence of season and nutritional status on the direct effects of leptin, orexin-A and ghrelin on luteinizing hormone and growth hormone secretion in the ovine pituitary explant model

Randomized Controlled TrialPMID: 24906931

Acute effects of different glycemic index diets on serum motilin, orexin and neuropeptide Y concentrations in healthy individuals

Randomized Controlled TrialPMID: 22414624

Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy

Randomized Controlled TrialPMID: 22036605

Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1)

Randomized Controlled TrialPMID: 18718966

Circulating Concentrations of Orexin A Predict Left Ventricular Myocardial Remodeling

Clinical TrialPMID: 27855816

Evaluating Crossbred Red Rice Variants for Postprandial Glucometabolic Responses: A Comparison with Commercial Varieties

Clinical TrialPMID: 27213446

Migraine preventive drug-induced weight gain may be mediated by effects on hypothalamic peptides: the results of a pilot study

Clinical TrialPMID: 21216871

Plasma orexin A increases at emergence from sevoflurane-fentanyl anesthesia in patients undergoing ophthalmologic surgery

Clinical TrialPMID: 20655366

Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia

Clinical TrialPMID: 12486284

Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1

Clinical TrialPMID: 37494485

Narcolepsy and the hypocretin system--where motion meets emotion

ReviewPMID: 16990828

Orexin Deficiency in Narcolepsy: Molecular Mechanisms, Clinical Phenotypes, and Emerging Therapeutic Frontiers

ReviewPMID: 41076550

Always consult a qualified clinician

This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician

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Quick Facts

Class
Neuropeptide
Evidence
Emerging
Safety
Limited Data
Updated
Mar 2026
Citations
33PubMed

Also known as

Hypocretin-1OX-A

Tags

SleepCognitiveWakefulnessAppetite

Evidence Score

Overall Confidence45%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.

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