Cognitive & Mood Endogenous Hypothalamic NeuropeptideNot FDA-approved · research compound

Orexin B

Hypocretin-2 · OX-B

Evidence: Studied in humans. Example dose: finalize with a provider. Not a fact-check stamp.

Per protocol – 100-200 mcg Nasal Investigational

OX2R-Selective AgonistInvestigational Narcolepsy TherapyResearch Chemical (no FDA approval)

Orexin B (Hypocretin-2) is the second of two endogenous orexin peptides produced by lateral hypothalamic neurons. It is a 28-amino-acid peptide with OX2R-selective binding (vs Orexin A which binds OX1R and OX2R equally). The OX2R selectivity makes Orexin B more focused on the histaminergic wake-promotion pathway (tuberomammillary nucleus) and less involved in OX1R-mediated reward/arousal pathways.

Quick Start

Route

Intranasal

Start low

Per protocol Nasal

Frequency

Investigational

Timing

Independent

Starting dose. Per protocol

Intranasal route. Refrigerate. Disulfide-containing peptide.

❋

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.

Tiered Protocols · lowest first

Conservative start

Per protocol · Intranasal · Investigational

conservative starter

Per protocol

Investigational

Expert

Wakefulness Support

100-200 mcg · Nasal · As needed

animal study · Sakurai et al. 1998 (Cell, 92:573-585)

Orexin B has a faster onset but shorter half-life and less stability than Orexin A. The study cited here is animal research. It shows the mechanism, not a human dose, and this amount is community practice rather than a trial result.

100-200 mcg

As needed

Reconstitution CalculatorU-100

Vial strength

BAC water

Vials in this mix

Syringe size

Target dose

050100u

Draw to

— units

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I will split this dose across more than one syringe

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How it works

Orexin B binds primarily to OX2R with ~10x greater affinity than for OX1R, distinguishing it from Orexin A's dual-receptor binding profile:

OX2R-Selective Wake Promotion

OX2R is the dominant orexin receptor on histaminergic tuberomammillary nucleus (TMN) neurons that drive wakefulness. Selective OX2R agonism is the most-targeted pathway for narcolepsy therapy.

Reduced OX1R Effects

Lower OX1R activation means less effect on dopaminergic VTA reward pathways and locus coeruleus arousal compared to Orexin A. This may reduce cardiovascular and reward-related side effects.

Same Therapeutic Application

Like Orexin A, candidate narcolepsy replacement therapy. The OX2R selectivity may give Orexin B a cleaner clinical profile in principle.

Disulfide-Containing

Like Orexin A, contains intramolecular disulfide bonds - chemistry-incompatible with copper-conjugated peptides.

Same BBB Challenge

Intact peptide poorly crosses BBB. Intranasal route bypasses this for clinical research.

What to expect

Early

Days 1–7

Acute wakefulness within 15-30 min intranasal.

Mid

Weeks 2–4

Effects fade with plasma clearance.

Later

Weeks 4–12

No long-term effects characterized.

Evidence

HumanPresent

AnimalPresent

In-vitroPresent

Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.

The hypocretins/orexins are two excitatory neuropeptides, alternately called HCRT1 or orexin-A and HCRT2 or orexin-B, that are the endogenous ligands for two G-protein-coupled receptors, HCRTR1/OX1R and HCRTR2/OX2R.

The hypocretins/orexins are two excitatory neuropeptides, alternately called HCRT1 or orexin-A and HCRT2 or orexin-B, that are the endogenous ligands for two G-protein-coupled receptors, HCRTR1/OX1R and HCRTR2/OX2R.

Hypocretin/Orexin Receptor Pharmacology and Sleep Phases. Frontiers of neurology and neuroscience · 2021 · PMID 34052813

Evidence scope. Pharmacology review; receptor-level statement, with no administered formulation or population.

Claims we could not support

No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.

Dose/route: Per protocol via Intranasal, Investigational. No checked live PubMed abstract supported this complete molecule/formulation/route/dose/frequency combination.

Primary safety claim: Nasal irritation (intranasal). No checked live abstract directly established this as the primary concern for the card's exact formulation and regimen.

Side effects & safety

Commonly reported

Nasal irritation (intranasal)
Mild stimulation

Less common & notes

Cleaner side-effect profile theoretically vs Orexin A due to OX2R selectivity.
Long-term safety not characterized.

Pharmacokinetics

Illustrative plasma concentration · 3.4 h

Half-life

~30-60 min

Plasma

Peak · Tmax

15-30 min

Intranasal

Elimination

1-3 hours

Wakefulness

Bioavailability

Intranasal for CNS access

Duration of action

1-3 hours

Per dose

Clearance

Hepatic/renal

Storage. Refrigerate. Light-sensitive. Disulfide-containing - keep cold.

Regulatory status

Not FDA-approved. Research chemical only.

Put it to work

Calculate, log & track

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Go deeper

The guide & community

The complete Orexin B walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

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