Should you snort your peptides? The ones that are made for the nose

Semax: the peptide that is sold as nose drops

Semax is a short peptide of 7 amino acids, built from a piece of the stress hormone ACTH. It is one of 14 peptide drugs registered in Russia, and it comes as nose drops, put in with a dropper.

Russian doctors use it after strokes. The Russian product information lists the 1% drops for the acute phase of an ischemic stroke and the 0.1% drops for the recovery period after a stroke. A review of Russian peptide drugs puts it plainly: "The Semax peptide is used to treat ischemic stroke".

The human studies behind that use are Russian and small. In one, 110 stroke patients were followed during rehabilitation, and those who also got Semax had higher BDNF in their blood and recovered movement faster. We found no approval for Semax in the US or the EU.

Why the nose: a shortcut to the brain

Your brain sits behind the blood-brain barrier, a tight wall that keeps most molecules in the blood out. The nose is different. It is the one place where nerves from the brain end right next to the outside world, and researchers think some molecules can travel along those nerves straight to the brain. A 2022 review describes it as a "shortcut" from the nose to the brain that bypasses the barrier.

That is the idea behind Semax drops. How well it works in people is less clear. A 2020 review warns that results in animals are "not readily transferable to humans" because our noses and brains are built differently.

The BDNF study: what it really showed

BDNF (brain-derived neurotrophic factor) is a protein that helps brain cells grow and connect. It matters most in the hippocampus, the part of the brain that stores memories.

In 2006, researchers gave rats a single dose of Semax, 50 micrograms per kilo of body weight. In the hippocampus, BDNF protein went up by as much as 1.4 times, about 40%. The gene for BDNF was switched on about 3 times more, and the treated rats did better on a learning task. A second study from the same team that year put Semax into the nose and saw BDNF rise within 3 hours in another part of the rat brain.

The honest version: the 40% is real, it is the peak value, and it was measured in rat brains. Nobody has measured BDNF inside a human brain after Semax. The human data is BDNF in the blood of stroke patients.

Other peptides made for the nose

Semax is not the only one. These peptides are, or were, approved as nose sprays or drops:

Note that only Semax and Selank are given by nose to reach the brain. Glucagon, calcitonin and desmopressin go up the nose simply because it is easier than a needle, and they work through the blood.

Two that are only research. Insulin up the nose has been tested for memory. A small 2012 trial in people with early memory loss saw a benefit, but a bigger 2020 trial of 289 people found "no cognitive or functional benefits" over 12 months. Nasal oxytocin is widely used in behaviour studies, but researchers point out that "very little" of it reaches the fluid around the brain.

Used by nose with little or no proof

Some peptides are taken as nose sprays even though they were never approved that way. Here is what the studies behind them actually show.

Orexin A. Orexin A (also called hypocretin-1) is the brain's own "stay awake" signal. People with narcolepsy lose the cells that make it. Of all the peptides on this list, it has the most nose data, and it is still small:

• In rhesus monkeys kept awake for 30 to 36 hours, orexin A sprayed into the nose improved their memory test scores. The nose spray worked better than the highest dose given into a vein.
• In 7 people with narcolepsy, a nose dose brought their sense of smell back toward normal.
• In 8 people with narcolepsy, it cut REM sleep and made sleep more stable, but didn't make them more awake at night. In 14 people, it stabilised REM sleep and they made fewer mistakes on an attention test.
• In 10 healthy men, a nose dose raised the nerve activity that tightens blood vessels, without changing blood pressure or heart rate.

All of these are pilot studies with a handful of people. None tested orexin A as a stay-awake or focus aid in healthy people.

Orexin B. The second orexin, made by the same cells. We found no study that gave orexin B through the nose, in animals or people. Using it that way is theory: it is a short peptide with the same job, so it might travel the same route.

DSIP (delta sleep-inducing peptide). Sold as a sleep peptide and often used as a nose spray. In its one double-blind sleep trial, 16 people with chronic insomnia got DSIP into a vein for three nights. The effects were weak, and the authors concluded it "is not likely to be of major therapeutic benefit". By nose, there is only one short 2001 report in people, which measured a brain wave signal and not sleep. Using DSIP by nose for sleep rests on user reports.

Why most peptides don't go up the nose

Two reasons: size and how little gets through.

The nose lining lets small molecules through far better than big ones. Absorption through it drops off for anything heavier than about 1,000 daltons. Semax and Selank, at 7 amino acids, are under that line. Most peptides people use are bigger.

Even the approved sprays don't get much in. Only 3.3 to 4.1% of a desmopressin nose dose reaches the blood. For salmon calcitonin it is 3 to 5% of what a shot into the muscle delivers. That is why those drugs use much bigger doses in the nose than in a shot.

So should you snort your peptides? Only the ones that were made for it. A peptide that was built and tested as a shot has no study showing it works the same way up the nose, and for most of them the nose lets through only a small share of the dose.

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