The nasal route

Two questions, routinely merged

"Works nasally" gets used to mean two different things. One is pharmacokinetic: does a useful fraction cross the nasal mucosa and reach circulation or the brain. The other is clinical: does the compound produce the effect it is sold for, by any route at all.

Merging them produces the characteristic error of nasal peptide lists — a compound with real absorption data but no efficacy data gets filed as "proven", because the absorption study is read as proof of benefit. It is not. A molecule can cross the mucosa perfectly well and still do nothing measurable.

The nose-to-brain claim

Most nasal peptide marketing rests on direct nose-to-brain transport: molecules travelling along olfactory and trigeminal nerve pathways into the central nervous system, bypassing the blood-brain barrier entirely. The pathway is real and it is well demonstrated in rodents.

In humans it is on much softer ground. The olfactory epithelium occupies a far smaller share of the nasal cavity in people than in rats, most of a spray lands somewhere else, and measuring what actually reaches human brain tissue is close to impossible without invasive sampling. Cerebrospinal fluid studies give mixed results. So statements that a nasal peptide "delivers directly to the brain" are typically extrapolating from animal work, and should be read that way.

Compound by compound

Molecular masses are approximate and given to make the size pattern visible. Absorption verdicts describe the nasal route; evidence grades describe the compound's headline claim by its best-supported route.

Size explains most of it

Nasal absorption falls away sharply as molecules get bigger. Below roughly a thousand daltons a peptide has a reasonable chance of crossing the mucosa; above two or three thousand, without an absorption enhancer, very little does.

That single fact accounts for most of the table. Semax, Selank and DSIP are small and absorb. Semaglutide and tirzepatide are four to five times heavier, which is why they are injected and why the oral version needed a dedicated absorption enhancer rather than a spray.

But size is a guide, not a law, and two entries show where it breaks. NAD⁺ is small and still absorbs poorly, because it carries charge and membranes resist that. Ipamorelin is small and absorbs reasonably, yet nasal administration still does not produce meaningful growth hormone release — getting in is necessary, not sufficient.

Where nasal is genuinely the established route

Semax and Selank are the strongest cases, and for a specific reason: they were developed as nasal sprays and are registered that way in Russia. The nasal route is not an improvisation for them, it is the intended one.

The caveat is that the trial base is almost entirely Russian, with little independent replication elsewhere. That is why both sit at Grade C rather than higher — not because the research is dismissed, but because a body of work from one research tradition, largely unreplicated abroad, is exactly what Grade C describes. The specific claim that nasal outperforms injection for these is not well supported by head-to-head data.

Oxytocin deserves separate treatment because it is genuinely the most-studied compound here. Hundreds of intranasal trials exist. What those trials show is far less settled: effect sizes are small, replication has been poor, and there is active dispute about how much reaches the brain at all. It is also worth correcting a common claim — the intranasal oxytocin product formerly sold in the US was withdrawn, so there is no current FDA-approved nasal oxytocin there. Large literature, contested conclusions.

Where the needle wins

• PT-141. A nasal formulation was developed and abandoned. Absorption varied between individuals, and — the part usually left out — the nasal route was associated with blood pressure increases. The approved product is injectable for both reasons.
• BPC-157 and TB-500. Nasal data is effectively non-existent for the first and unpromising for the second. Describing injection as the "gold standard" overstates it: there is no established standard for either, because the human evidence is near-absent by any route.
• Epithalon. Claims that nasal needs two to three times the injectable dose imply a dose-response relationship nobody has established in humans.

Practical problems with nasal dosing

Even where the route works, it is the least controllable one available, and that matters more than lists usually admit.

• You cannot verify the delivered dose. Some runs down the throat and is swallowed, some lands where it cannot absorb. Unlike an injection, there is no volume in a barrel telling you what went in.
• Congestion changes everything. A cold, allergies or rhinitis can substantially reduce uptake, which turns a stable protocol into an erratic one without any obvious signal that it has.
• Technique alters the result. Angle, depth, whether you sniff hard, and which nostril all shift where the spray lands.
• Repeated use irritates. Dryness, burning, crusting and nosebleeds are common with frequent sprays, and chronic irritation itself reduces absorption.
• Preservatives matter more here. The nasal mucosa is not skin. Anything not formulated for nasal use should not be sprayed up a nose.

Where this differs from the usual list

This page was built from a widely circulated three-tier list, and departs from it in several places. The grading above is this site's own, and the main differences are these: NAD⁺, GHK-Cu, DSIP and VIP are graded D rather than "proven", because absorption claims are being read as efficacy claims; oxytocin is described as heavily studied but contested rather than confirmed; and the PT-141 and Melanotan II entries carry the safety context that the original omitted.

The part of the original list that holds up best is its last section. That the GLP-1 agonists and the growth hormone secretagogues do not work nasally is straightforwardly correct.

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