For laboratory and research use only. Not for human consumption.
Cognitive

Orexin A

Also known as: Hypocretin-1, Hcrt-1, OXA, Orexin-A

Clinical Trials
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Key Facts: Orexin A

Category
Cognitive
FDA Status
Not FDA Approved
Clinical Status
Orexin A itself is not FDA approved for any use and is not on FDA's 503A compounding lists. Related approved drugs work on the same system but are not the peptide: the orexin receptor blockers suvorexant (Belsomra), lemborexant (Dayvigo) and daridorexant (Quviviq) for insomnia, and the OX2R agonist pill oveporexton (Orzeyful), FDA-approved August 5, 2026 for adults with narcolepsy type 1 (U.S. launch was pending DEA scheduling). WADA: orexin A is 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), which is 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
Intranasal spray
Typical Dose
435 nmol (about 1.5 mg) intranasal
Frequency
Single dose in studies
Duration
Single doses only in published human studies
Also Known As
Hypocretin-1, Hcrt-1, OXA, Orexin-A

How does Orexin A work?

Orexin A activates both orexin receptors (OX1R and OX2R) with high affinity. Those receptors sit on brainstem and hypothalamic arousal centers (the histamine, noradrenaline, dopamine and acetylcholine systems), so orexin acts like a stabilizer that keeps the brain locked in the wake state and stops it slipping into REM sleep at the wrong time. Losing it causes narcolepsy: orexin knockout mice and dogs with a broken OX2R gene both develop narcolepsy, and giving orexin A into the brain of narcoleptic mice suppressed cataplexy. Orexin also drives appetite and raises sympathetic nerve activity. A mouse study found orexin A crosses the blood-brain barrier fairly well, and the nasal route is used in humans to deliver more of it to the brain.

What does the research show?

The human data comes from a handful of small, placebo-controlled crossover studies, mostly from one group in Kiel, Germany. In 2008, intranasal orexin A improved smell detection thresholds in 7 narcolepsy patients. In 2011, a single 435 nmol nasal dose before bed in 8 patients did not change nighttime wakefulness but reduced REM sleep and wake-to-REM transitions. In 2014, the same dose given in the morning to 14 patients reduced wake-REM transitions and improved divided attention (fewer errors). In 2022, 500 nmol in 10 healthy men acutely raised sympathetic nerve activity to blood vessels, without changing blood pressure or heart rate. In sleep-deprived monkeys, nasal orexin A reversed some of the drop in memory performance (Deadwyler, 2007). That is the whole human record: single doses, tiny groups, short-term outcomes. The real clinical action has moved to small-molecule drugs that mimic orexin at OX2R. Takeda's oveporexton (brand name Orzeyful) was FDA-approved on August 5, 2026 for narcolepsy type 1, which validates the target but is not the same thing as using the peptide.

Trial Progress:Preclinical
Pre
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II
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IV
FDA

What doses have been studied?

Human Trials·A few small single-dose placebo-controlled pilot studies (7 to 14 people each); no efficacy trials

Typical Dosingⓘ

Community experience

Common Dose

435 nmol (about 1.5 mg) intranasal

Range

435-500 nmol (about 1.5-1.8 mg) intranasal

Frequency

Single dose in studies

These are the amounts used in small research studies, not a treatment protocol. Every published human study gave one dose and measured effects over hours or one night. Repeated daily use has never been studied. Doses in studies are reported in nmol; the mg figures are approximate conversions.

Research Dosingⓘ

Scientific studies

Doses used in small human research studies (single intranasal doses)

Duration

Single doses only in published human studies

Administration

Intranasal spray

When and how is Orexin A taken?

Best Time to Take

Morning

Single dose in all published human studies

Food Recommendation

With or without food

Why This Timing?

Orexin A promotes wakefulness, and the 2014 narcolepsy study that measured daytime alertness and attention gave it in the morning. An earlier study dosed before bed to study REM sleep, which is a research design, not a use case.

What are the side effects of Orexin A?

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

  • ●Long-term human safety is unknown: published studies used single doses
  • ●Increased sympathetic (fight-or-flight) nerve activity seen in healthy men
  • ●Possible sleep disruption if taken late, since it promotes wakefulness
  • ●Increased appetite in animal studies
  • ●Theoretical blood pressure concerns with repeated use
  • ●Nasal irritation possible with any intranasal peptide

References

Research This Peptide Further

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Frequently Asked Questions

What does Orexin A do?

Orexin A (also called hypocretin-1) is a 33-amino-acid brain peptide made by a small cluster of neurons in the hypothalamus, and it is one of the main signals that keeps you awake. People with narcolepsy type 1 have lost most of these neurons, and orexin is undetectable in their spinal fluid. Orexin A itself is not an approved drug, but a few small German studies have sprayed it into the nose of narcolepsy patients and healthy men with measurable effects. Interesting science, very early stage.

How does Orexin A work?

Orexin A activates both orexin receptors (OX1R and OX2R) with high affinity. Those receptors sit on brainstem and hypothalamic arousal centers (the histamine, noradrenaline, dopamine and acetylcholine systems), so orexin acts like a stabilizer that keeps the brain locked in the wake state and stops it slipping into REM sleep at the wrong time. Losing it causes narcolepsy: orexin knockout mice and dogs with a broken OX2R gene both develop narcolepsy, and giving orexin A into the brain of narcoleptic mice suppressed cataplexy. Orexin also drives appetite and raises sympathetic nerve activity. A mouse study found orexin A crosses the blood-brain barrier fairly well, and the nasal route is used in humans to deliver more of it to the brain.

Is Orexin A FDA approved?

No, Orexin A is not currently FDA approved. Current status: Orexin A itself is not FDA approved for any use and is not on FDA's 503A compounding lists. Related approved drugs work on the same system but are not the peptide: the orexin receptor blockers suvorexant (Belsomra), lemborexant (Dayvigo) and daridorexant (Quviviq) for insomnia, and the OX2R agonist pill oveporexton (Orzeyful), FDA-approved August 5, 2026 for adults with narcolepsy type 1 (U.S. launch was pending DEA scheduling). WADA: orexin A is 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), which is prohibited at all times.

Is Orexin A 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 A?

Reported side effects include: Long-term human safety is unknown: published studies used single doses, Increased sympathetic (fight-or-flight) nerve activity seen in healthy men, Possible sleep disruption if taken late, since it promotes wakefulness, Increased appetite in animal studies, Theoretical blood pressure concerns with repeated use. Individual responses vary based on dosage, duration, and personal health factors.

What is the typical dose of Orexin A?

Community-reported common dose: 435 nmol (about 1.5 mg) intranasal (Single dose in studies). Range: 435-500 nmol (about 1.5-1.8 mg) intranasal. Administration: Intranasal spray. Community-reported doses. Not medical advice. Consult healthcare provider.

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