Cognitive & neuro

Orexin A (hypocretin-1)

The hypothalamic peptide that keeps the brain awake; studied intranasally for alertness, not available as a drug.

Limited evidenceInvestigationalAdd to compare

What it is

Orexin A, also called hypocretin-1, is a 33-amino-acid peptide made by a small group of hypothalamic neurons. Those neurons stabilise wakefulness: their loss causes narcolepsy type 1. Interestingly the pharmacology that reached the clinic points the other way - orexin receptor blockers are approved for insomnia - while orexin itself has only been given experimentally.

How it works

1
Activates OX1 and OX2 G-protein coupled receptors.
2
Excites histaminergic, noradrenergic and cholinergic arousal systems.
3
Stabilises the sleep-wake switch so wakefulness does not collapse into sleep.
4
Links metabolic state to alertness, rising with fasting and activity.
5
Poor brain penetration from the blood limits any practical delivery.

What it's studied for

Alertness and vigilance under sleep deprivation

Narcolepsy research

Cognition during sleep loss

Reward and motivation circuits

Reported and studied effects

Small intranasal trials reported improved vigilance or reduced sleepiness in some measures
Results are inconsistent and samples tiny
Peripheral effects such as raised blood pressure appear before brain effects

Research protocol notes

Research context only

Research context only - investigational. Human intranasal studies used single doses in the region of 0.3 to 1 mg and measured vigilance and sleepiness for several hours; animal work used central injections in the nanomole range. No repeated-dose human protocol exists.

These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.

Possible side effects and contraindications

Safety profile

Possible side effects

Insomnia and difficulty sleeping
Raised blood pressure and heart rate
Anxiety at higher exposure
Nasal irritation

Contraindications and cautions

Hypertension or cardiac disease
Insomnia or anxiety disorders
Pregnancy - untested
No approved use outside narcolepsy research

A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.

Evidence assessment

Limited evidenceSmall human studies or animal data only

Small human studies or animal data only

A few very small intranasal studies in humans, alongside strong mechanistic and genetic evidence from narcolepsy research.

References

References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.

Compare Orexin A (hypocretin-1) with another peptide →

Related peptides

Other entries in Cognitive & neuro.

All Cognitive & neuro peptides →

Cognitive & neuro

ACTH 4-10 (Org 2766)

The nerve-acting fragment of ACTH, developed as a drug candidate for nerve damage and cognitive decline, and abandoned.

Limited evidenceInvestigational

Cognitive & neuro

BDNF (brain-derived neurotrophic factor)

The brain's main growth factor for plasticity: essential, widely measured, and not something a supplement can deliver.

Anecdotal evidenceNot approved

Cognitive & neuro

Cerebrolysin

A porcine brain peptide mixture licensed in parts of Eastern Europe and Asia for stroke and dementia, without EMA or FDA approval.

Limited evidenceInvestigational