Neuro & cognitive
Orexin A
The natural wake-promoting neuropeptide; two small crossover studies tested intranasal dosing in narcolepsy. Not the same as approved orexin receptor drugs.
- How settled this rating is:
- low confidence in the current evidence rating
- Routes studied:
- Nasal
- Also known as:
- Hypocretin-1, hcrt-1, orexin-A peptide
- Last reviewed:
- 2026-09-26
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Evidence passport
Orexin A
A one-screen evidence identity for this compound. These fields describe research maturity, confidence and legal status. They are not a safety guarantee, efficacy percentage or recommendation.
- Evidence level
- L2Animal / lab studies
- Confidence
- Low confidence in rating
- Regulatory status
- Not approved for this use
- Development status
- Unclear
Evidence strength
Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.
The 0-100 values rate the strength and maturity of evidence, not how effective or safe the compound is.
- Evidence base
- Includes human studies
- Furthest established stage
- Not established
- Human research maturity
- Small human research studies (narcolepsy), not a development programme
- Source curation
- Sources fully curated
Routes recorded
Overview
Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.
Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.
How to read these scores
Every number here rates the evidence, not the compound. They are editorial 0-100 strength ratings, not percentages, and not a rating out of five stars.
- Human efficacy evidence strength — Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
- Preclinical evidence strength — Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.
- Human safety evidence strength — Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number. A score of 80 does not mean “80% safe”.
- Evidence level (L0-L5) — the strongest type of study behind the compound, from anecdote (L0) to large replicated human trials (L5). It is a description of the study evidence, not a quality, safety or recommendation rating.
- Confidence — how likely we think it is that this rating changes as new research lands. Low confidence means the picture is unsettled, not that the compound is bad.
None of these ratings is medical advice, a safety guarantee, or a recommendation to use anything. How we grade evidence.
How far human research has progressed: Small human research studies (narcolepsy), not a development programme
Routes & formulations
Studied / approved routes
Intranasal administration was studied only in small research crossover trials in narcolepsy with cataplexy. This is not an approved route or use.
Route availability is not evidence of efficacy, and evidence from one route does not transfer to another. The Registry never provides dosing or sourcing information.
Peptide lifecycle
Discovery
Preclinical
Phase I
Phase II
Phase III
Approved
What it is
An endogenous 33-amino-acid hypothalamic neuropeptide that activates the orexin receptors OX1R and OX2R. Loss of orexin neurons causes narcolepsy type 1. Orexin B (hypocretin-2) is a separate peptide.
What people claim
- Wakefulness and focus
- Narcolepsy treatment
- Appetite or metabolism effects
What the evidence actually says
The biology of orexin A is well established. Two small double-blind crossover studies of intranasal orexin A in narcolepsy with cataplexy (8 and 14 participants) reported changes in REM sleep and some attention measures. These were research studies, not efficacy trials, and they do not support general 'wakefulness' or 'focus' use.
Related evidence
Useful next reads based on this compound — not recommendations.
- Related compound
HDAP2 evidence profile
A short mitochondria-targeted research peptide that binds cardiolipin. Evidence is cell and mouse work, including 2026 optic-nerve injury data.
- Compare
Compare Orexin A vs HDAP2 evidence
Same questions, same fields, side by side — including how much human evidence exists.
- Context
Research Desk
How to read animal, early-phase and controlled human studies without over-reading them.
- Context
Safety Centre
What approved, investigational and unapproved actually mean for documented human safety.
Human evidence
- Baier et al. 2011: 8 people with narcolepsy with cataplexy; reduced REM sleep quantity, no significant effect on nocturnal wakefulness (PMID 22036605).
- Weinhold et al. 2014: 14 people with narcolepsy with cataplexy; fewer wake–REM transitions and fewer false reactions on divided attention (PMID 24406723).
- No study in healthy people supports use for focus, alertness or performance.
Preclinical evidence
- Extensive animal literature establishes orexin A's role in sleep–wake regulation (not individually curated here).
Animal and cell findings are Level 1–2 evidence.
Mechanism and pathways
- Agonist at OX1R and OX2R; excitatory influence on arousal-related neurotransmitter systems.
- Orexin receptor agonist drugs under development are distinct small molecules and are not this peptide.
Safety and unknowns
- The two small studies were not powered to characterise safety.
- Material sold online is unregulated: identity, purity, sterility and labelled quantity are separate questions from what the published molecule does.
Cancer relevance
This section covers questions raised by how the compound works in the body, plus anything regulators and trial teams keep an eye on. It is not a statement that this compound causes cancer — for most compounds here, no human data exist in either direction.
No concern identified
Regulatory status
Regulatory decisions apply to specific jurisdictions, products, formulations and indications. An approval elsewhere is not automatically an approval in your country.
Check the regulatory note and linked primary sources for jurisdiction-specific details.
Orexin A itself is not an approved medicine. Approved drugs that act on the orexin system (for example the insomnia medicines suvorexant, lemborexant and daridorexant) are small-molecule receptor BLOCKERS — the opposite action — and their approvals say nothing about orexin A peptide products.
Evidence grade
Documented compound-specific animal or laboratory outcome findings, without qualifying human evidence for the assessed benefit.
What would change our rating?
- Larger, registered trials with clinically meaningful outcomes.
- Published human safety and nasal-delivery pharmacokinetic data.
References and sources
Source transparency
A provenance snapshot of this profile. Counts show what kinds of sources are cited, not how much scientific weight each source deserves.
- Last editorial review
- 2026-09-26
- Recently reviewed · 20 days ago
- Linked curated sources
- 2
- Sources still pending
- 0
- External specialist reviews
- 0
- None recorded for this profile
Review provenance
Registry editorial review: Colin Jackson-White, creator and editor, who is not a doctor or clinician. External specialist review is credited only when a named reviewer has completed a review of this exact profile.
Literature-discovery and AI tools may help locate or challenge candidate evidence, but they are not counted as evidence sources here. Registry judgements are tied to the underlying papers, trial records, regulator documents and official study records.
- Peer-reviewedBaier et al. Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. Sleep Med 2011 (PMID 22036605)PMID: 22036605
- Peer-reviewedThe effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. 2014 (PMID 24406723)PMID: 24406723
Source hierarchy: regulatory documents and trial registries first, peer-reviewed work next, sponsor material flagged as non-independent. We never use supplier or clinic marketing as evidence, and where a verified source has not yet been curated we say so rather than inventing one.
Evidence change history
These entries record changes to our assessment of the published evidence — not changes to the compound itself.
No recorded changes yet. Baseline position set on 2026-09-26.