Orexin-A
Master wakefulness peptide — deficiency causes narcolepsy. Intranasal orexin-A restores alertness and cognitive performance.
Research facts
| Half-life | ~1–2 minutes (IV) / extended CNS effect intranasally |
|---|---|
| Route | Intranasal / IV (research) |
| Typical dose | 25–250 mcg intranasal (research) |
| Frequency | As needed (wakefulness) |
| Solvent | Sterile saline |
| pH | 5.5–7.5 |
| Stability | 30 days at +4°C |
Mechanism of action
Orexin-A (hypocretin-1) is a 33-amino acid neuropeptide produced exclusively by approximately 10,000–20,000 neurons in the lateral hypothalamus. It activates OX1R and OX2R receptors to promote wakefulness, maintain alertness, and coordinate energy balance. Loss of orexin neurons causes narcolepsy with cataplexy. Intranasal orexin-A bypasses the blood-brain barrier via olfactory nerve pathways and has shown striking effects in non-human primates: administration during sleep deprivation completely restored cognitive performance (reaction time, accuracy) while the animals appeared as rested as controls despite having had no sleep.
Documented effects (research-model)
- Narcolepsy causation — fundamental role in wakefulness
- Intranasal NHP study: restored full cognitive performance during sleep deprivation
- OX2R antagonists (suvorexant) are FDA-approved — validates pathway
- Potential application in shift work, jet lag, narcolepsy treatment
- No stimulant side effects in preliminary research
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Experimental Research | 25–250 mcg intranasal | As needed for wakefulness | Acute use only | Sterile nasal preparation |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- DSIP HIGH
Orexin-A promotes wakefulness and alertness; DSIP promotes restorative sleep. Complementary circadian biology interventions.
Myths & misconceptions
Evidence gaps
- Human clinical trials for sleep deprivation have not been completed.
- Long-term effects of exogenous orexin-A on endogenous orexin neuron function.
- Optimal dose and formulation for intranasal CNS delivery in humans.
Safety notes
No completed human clinical data. Based on NHP study, appeared well-tolerated. Concerns about long-term receptor sensitivity and endogenous orexin system modulation. Research context only.
Biomarkers to monitor
Primary-source citations
- PMID 23169946 — Orexin-A counteracts sleep deprivation-induced cognitive impairment in non-human primates (Transl Psychiatry. 2012)
Frequently asked
What is Orexin-A?
Orexin-A (Hypocretin-1 — Wakefulness-Promoting Neuropeptide) is a research compound classified in our library as Tier D — Animal or in-vitro data only.. Master wakefulness peptide — deficiency causes narcolepsy. Intranasal orexin-A restores alertness and cognitive performance.
What is the evidence tier for Orexin-A?
We classify Orexin-A as Tier D: Animal or in-vitro data only. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of Orexin-A?
For Orexin-A, typical research dose is 25–250 mcg intranasal (research), route is Intranasal / IV (research), half-life is ~1–2 minutes (IV) / extended CNS effect intranasally. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
What does Orexin-A stack well with?
Orexin-A stacks well with DSIP. Orexin-A promotes wakefulness and alertness; DSIP promotes restorative sleep. Complementary circadian biology interventions.
Is Orexin-A safe?
No completed human clinical data. Based on NHP study, appeared well-tolerated. Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.