Orexin B
Also known as: Hypocretin-2, Hcrt-2, OXB, Orexin-B
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Orexin B
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Key Facts: Orexin B
- Category
- Cognitive
- FDA Status
- Not FDA Approved
- Clinical Status
- Not FDA approved for any use and not on FDA's 503A compounding lists. No registered human trials found. Approved drugs in this system act on the receptors, not with the peptide: orexin receptor blockers (suvorexant, lemborexant, daridorexant) for insomnia, and the oral OX2R agonist oveporexton (Orzeyful), FDA-approved August 5, 2026 for narcolepsy type 1. WADA: not named on the 2026 Prohibited List, but as a pharmacological substance with no regulatory approval for human use it falls under S0 (Non-approved substances), prohibited at all times.
- Banned in Sport (WADA)
- Not named on the WADA list, but WADA's S0 catch-all bans any substance without human therapeutic approval, which covers it. Prohibited at all times.
- Administration
- Intracerebroventricular or local injection in animal studies
- Typical Dose
- No established human dose
- Frequency
- Not established
- Duration
- Acute single-dose animal experiments
How does Orexin B work?
Orexin B binds OX2R about as strongly as orexin A does, but binds OX1R roughly 20 times more weakly, so it behaves as a relatively OX2R-preferring signal. OX2R is the receptor that matters most for staying awake and keeping REM sleep in its place: a broken OX2R gene causes inherited narcolepsy in dogs, and the newest approved narcolepsy drug is an OX2R agonist. Structurally, orexin B is a linear chain without the two disulfide bridges that make orexin A more stable. A 1999 mouse study found that injected orexin B was rapidly degraded in blood and none reached the brain intact, while orexin A crossed easily. That is the main reason human research has focused on orexin A.
What does the research show?
Orexin B has been studied for almost 30 years, but almost entirely as a research tool in animals and tissue. The 1998 discovery paper in Cell (Sakurai and colleagues) showed both orexins increased food intake when injected into rat brains. Work since then has mapped its role in arousal, feeding, and more recently pain: 2026 mouse research found orexin B acting at OX2R could trigger migraine-like headache pain in male but not female mice. We could not find any published study giving orexin B to humans, by nose or by injection, and no registered clinical trials. If you want the orexin story with actual human data, see orexin A. Orexin B on its own is a preclinical compound with a real biological role and no tested human use.
What doses have been studied?
Note: Animal study doses may not translate directly to humans.
Typical Dosingⓘ
Community experience
No established human dose
No published human dosing data
Not established
Orexin B has never been given to humans in a published study, so there is no human dosing data at all. Animal studies delivered it directly into the brain, which tells you nothing about a human dose by any practical route. Animal data also suggests it is broken down in the blood before reaching the brain.
Research Dosingⓘ
Scientific studies
No human research doses exist. Published work uses direct brain or tissue delivery in animals.
Doses from Studies
Central (into the brain) injection in rodents only
Duration
Acute single-dose animal experiments
Administration
Intracerebroventricular or local injection in animal studies
When and how is Orexin B taken?
Best Time to Take
Not established
No studied human frequency
Food Recommendation
With or without food
Why This Timing?
There is no human research on orexin B. Because the orexin system promotes wakefulness, anything that activated it would logically belong earlier in the day, but that is theory only.
What are the side effects of Orexin B?
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●No human safety data exists
- ●Rapidly degraded in blood in animal work, so injected product is unlikely to reach the brain
- ●Increased appetite in animal studies
- ●Linked to migraine-like pain signaling in male mice
- ●Possible sleep disruption (wake-promoting system)
References
- https://pubmed.ncbi.nlm.nih.gov/9491897/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3058259/
- https://pubmed.ncbi.nlm.nih.gov/10087007/
- https://pubmed.ncbi.nlm.nih.gov/10458611/
- https://pubmed.ncbi.nlm.nih.gov/10481909/
- https://pubmed.ncbi.nlm.nih.gov/42302125/
Research This Peptide Further
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Orexin B
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Frequently Asked Questions
What does Orexin B do?
Orexin B (hypocretin-2) is the sister peptide of orexin A. Both are cut from the same precursor protein in the hypothalamus and both help regulate wakefulness and appetite. Orexin B is a 28-amino-acid linear peptide that mostly acts through the OX2R receptor, the receptor most tied to narcolepsy. The catch for anyone hoping to use it: it falls apart fast in the blood, barely reaches the brain from the bloodstream, and has never been given to humans in a published study.
How does Orexin B work?
Orexin B binds OX2R about as strongly as orexin A does, but binds OX1R roughly 20 times more weakly, so it behaves as a relatively OX2R-preferring signal. OX2R is the receptor that matters most for staying awake and keeping REM sleep in its place: a broken OX2R gene causes inherited narcolepsy in dogs, and the newest approved narcolepsy drug is an OX2R agonist. Structurally, orexin B is a linear chain without the two disulfide bridges that make orexin A more stable. A 1999 mouse study found that injected orexin B was rapidly degraded in blood and none reached the brain intact, while orexin A crossed easily. That is the main reason human research has focused on orexin A.
Is Orexin B FDA approved?
No, Orexin B is not currently FDA approved. Current status: Not FDA approved for any use and not on FDA's 503A compounding lists. No registered human trials found. Approved drugs in this system act on the receptors, not with the peptide: orexin receptor blockers (suvorexant, lemborexant, daridorexant) for insomnia, and the oral OX2R agonist oveporexton (Orzeyful), FDA-approved August 5, 2026 for narcolepsy type 1. WADA: not named on the 2026 Prohibited List, but as a pharmacological substance with no regulatory approval for human use it falls under S0 (Non-approved substances), prohibited at all times.
Is Orexin B banned in sport?
Not named on the WADA list, but WADA's S0 catch-all bans any substance without human therapeutic approval, which covers it. Prohibited at all times.
What are the side effects of Orexin B?
Reported side effects include: No human safety data exists, Rapidly degraded in blood in animal work, so injected product is unlikely to reach the brain, Increased appetite in animal studies, Linked to migraine-like pain signaling in male mice, Possible sleep disruption (wake-promoting system). Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Orexin B?
Community-reported common dose: No established human dose (Not established). Range: No published human dosing data. Administration: Intracerebroventricular or local injection in animal studies. Community-reported doses. Not medical advice. Consult healthcare provider.
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