OnePin Peptide Library · Cognitive & Mood
Orexin A
Hypocretin-1 · OX-A
Orexin A (also called Hypocretin-1) is a 33-amino-acid neuropeptide produced by lateral hypothalamic neurons. It is one of two endogenous orexin peptides (along with Orexin B / Hypocretin-2) that promote wakefulness, arousal, appetite, and energy expenditure via OX1R and OX2R receptors. Loss of orexin neurons causes narcolepsy with cataplexy in humans - the major clinical context for orexin pharmacology.
Intranasal preferred for CNS access. Reconstitute with bac water; refrigerate. Disulfide-containing - keep cold and protect from oxidation.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
Orexin A binds both orexin receptors (OX1R and OX2R) in approximately equal affinity, distinguishing it from Orexin B which is OX2R-selective:
OX1R Activation
Selectively expressed on dopaminergic VTA neurons and locus coeruleus norepinephrine neurons - drives reward-related behavior and arousal.
OX2R Activation
Expressed on tuberomammillary nucleus histaminergic neurons - drives wake-promotion. OX2R signaling is the primary wake-promoting orexin pathway (basis of OX2R-selective insomnia therapy with the antagonist class).
Wakefulness Maintenance
Endogenous orexin neurons fire during wake state and silence during sleep. Loss of these neurons (autoimmune destruction in narcolepsy with cataplexy) produces the disease. Exogenous Orexin A can theoretically substitute - main delivery challenge is CNS penetration.
Appetite / Feeding
Lateral hypothalamic orexin signaling stimulates feeding behavior - high-dose orexin administration produces hyperphagia.
Sympathetic Activation
Orexin signaling increases sympathetic tone - heart rate, blood pressure, energy expenditure all rise. Relevant to cardiovascular caution at high doses.
Disulfide-Containing
Two intramolecular disulfide bonds - chemistry-incompatible with copper-conjugated peptides like GHK-Cu.
What to expect
Acute wakefulness within 15-30 min of intranasal dose.
Effects fade with plasma clearance.
No long-term cumulative effects characterized.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Keep separate
Side effects & safety
Commonly reported
- Nasal irritation (intranasal)
- Mild tachycardia
- Possible insomnia at high doses or evening dosing
Less common & notes
- Hypertension at high doses (sympathetic activation).
- Anxiety or agitation.
- Cardiovascular events theoretically possible at supraphysiologic doses.
- Long-term safety not characterized in humans.
- The intact orexin peptide has poor systemic distribution and the therapeutic window for non-narcolepsy use is unclear.
Pharmacokinetics
Storage. Refrigerate. Light-sensitive. Reconstituted: 14-21 days. Disulfide-containing - keep cold.
Regulatory status
Not FDA-approved. Investigational status only. WADA: not specifically prohibited but may fall under stimulant regulations in sport contexts.
Put it to work
Calculate, log & track
Open Orexin A straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
Open Orexin A in the app →Go deeper
The guide & community
The complete Orexin A walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
Join the community ↗