# Orexin-A (intranasal)

Wake-promoting neuropeptide; tiny narcolepsy studies, no consumer track record.

- Page: https://peprank.xyz/peptides/orexin-a
- Category: Focus & memory (Research peptide)
- Also known as: Hypocretin-1
- Routes: Nasal
- Sequence: EPLPDCCRQKTCSCRLYELLHGAGNHAAGILTL (N-terminal pyroglutamate, C-amide, two disulfides (C6-C12, C7-C14))
- Safety tier: Strict: Avoid · Balanced: Caution · Evidence only: Caution
- Risk axes (0 none to 3 severe): Seen harm 0, Mechanism 2, Data gap 2, Silent harm 2, Product 2
- Researcher estimate: 1/10 (no graded reports yet)
- Rank: #61 of 61 research peptides
- Evidence: Small human studies — Narcolepsy, n of about 10 per study
- Access: Grey market
- Onset: In the narcolepsy studies a single nasal dose changed sleep architecture the same night or day; there are no consumer reports.
- Lasts: Unknown; only single-dose studies exist.
- Cost per month: No reliable product or price.
- Updated: 2026-10-30

**Why Avoid under the strict bar:** Essentially untested, with sympathetic activation and no reliable product.

## What users report

No real user reports for intranasal orexin-A; Reddit orexin threads are about prescription orexin antagonists (sleep) or trial orexin agonists in narcolepsy.

**Effects:** in narcolepsy studies: normalised REM, slightly better attention

**Downsides:** unknown

**Risks:** almost no human safety data (studies of ~10 narcolepsy patients); orexin activation raises sympathetic tone (heart rate, blood pressure); the orexin-agonist drug class has shown insomnia, urinary urgency and visual effects, and one candidate (TAK-994) caused liver toxicity; no pharmaceutical-grade source

**Typical use:** No community dose; narcolepsy studies used single intranasal research doses.

**Getting it:** No approved orexin-A product. Some nootropic vendors have sold 'orexin-A' sprays of unverified identity; the approved route to the same target is the oral orexin-2 agonist oveporexton, for narcolepsy type 1.

## Risk profile

- **Seen harm 0/3:** The two intranasal studies (single doses in 8 and 14 narcolepsy patients) report no serious adverse events, and almost nobody uses it outside them, so this zero means no exposure rather than reassurance.
- **Mechanism 2/3:** Orexin receptor activation raises sympathetic tone: the approved orexin agonist oveporexton (Orzeyful, 2026) raised systolic pressure over 20 mmHg on day one in 22% vs 13% on placebo, and an earlier agonist, TAK-994, was stopped for liver injury.
- **Data gap 2/3:** Only single-dose narcolepsy studies of 8 and 14 patients; the class data come from different, oral molecules.
- **Silent harm 2/3:** Raised blood pressure and heart rate are silent without measurement, though insomnia would be obvious.
- **Product 2/3:** No pharmaceutical source; the rare products are grey-market nasal research peptides.
- **Never if:** Uncontrolled hypertension or heart disease; Pregnancy or breastfeeding (no human reproductive data)

## Studies

- [Baier et al. 2011: intranasal hypocretin-1 (orexin-A) on sleep in narcolepsy with cataplexy](https://pubmed.ncbi.nlm.nih.gov/22036605/) (controlled, n=8, 2011): A single 435 nmol nasal dose before bed did not change night-time wakefulness but reduced and stabilised REM sleep (fewer wake-to-REM transitions).
- [Weinhold et al. 2014: intranasal orexin-A on sleep, wakefulness and attention in narcolepsy](https://pubmed.ncbi.nlm.nih.gov/24406723/) (controlled, n=14, 2014): A morning 435 nmol nasal dose reduced wake-to-REM transitions and REM duration, and patients made fewer errors on a divided-attention test.
- [Deadwyler et al. 2007: systemic and nasal orexin-A reduces the effects of sleep deprivation in monkeys](https://pubmed.ncbi.nlm.nih.gov/18160631/) (animal, 2007): Nasal orexin-A restored short-term memory performance in sleep-deprived rhesus monkeys, more effectively than IV, with no effect in rested animals.
- [Dauvilliers et al. 2023: oral orexin-2 receptor agonist TAK-994 in narcolepsy type 1](https://pubmed.ncbi.nlm.nih.gov/37494485/) (rct, n=73, 2023): Not orexin-A itself: the agonist sharply improved wakefulness and cataplexy, but the trial was stopped early for liver toxicity.
- [Dauvilliers et al. 2026: oveporexton for narcolepsy type 1, two phase 3 trials](https://pubmed.ncbi.nlm.nih.gov/42714024/) (rct, n=273, 2026): Not orexin-A itself: this oral orexin-2 agonist improved wakefulness and cut cataplexy by about 80-89%; urinary frequency and transient insomnia were common.

## Sources

- [Baier et al. 2011: intranasal hypocretin-1 in narcolepsy with cataplexy](https://pubmed.ncbi.nlm.nih.gov/22036605/)
- [Weinhold et al. 2014: intranasal orexin-A on sleep, wakefulness and attention in narcolepsy](https://pubmed.ncbi.nlm.nih.gov/24406723/)