Intranasal Peptide Research: What Reaches the Brain and What Does Not

Two different goals: through the nose into the body, or into the brain

Absorbed through the nose into the blood. Several approved peptide sprays are meant to act in the body. The US label for calcitonin salmon nasal spray reports bioavailability of 3% to 5% relative to an injection into muscle, fast absorption through the nasal lining, and a half-life of about 18 minutes. [3] The US label for the desmopressin spray Stimate reports absolute bioavailability of 3.3% to 4.1%. [4] So even approved nasal peptides deliver a small fraction of the dose.

Reaching the brain. A review of nose-to-brain delivery of peptides says the olfactory and trigeminal nerves provide a pathway to the brain that can bypass the blood-brain barrier and minimize exposure in the rest of the body, and it also discusses the limitations of the approach. [1] That describes the proposed route. It is not proof that a given product works.

The best-studied case: oxytocin

Oxytocin is a peptide hormone, and nasal oxytocin is the most studied "nose-to-brain" peptide in people.

• A human study measured blood and spinal fluid (CSF) in 11 people given 24 IU of oxytocin and 4 given placebo, and found both rose significantly. Blood levels peaked at 15 minutes while spinal fluid took up to 75 minutes, and the two were not correlated. [5] Small study; label: promising but limited for the question "does some reach CSF?"
• A critical review argued that very little of the large amounts applied intranasally appears to reach the CSF, that blood levels rise to supraphysiologic levels with likely effects on the gut, heart and reproductive tract, and that claims need scepticism and rigor. [2] Label: mixed.
• A statistical review concluded that intranasal oxytocin studies are generally underpowered and that there is a high probability that most published findings do not represent true effects. [6]

Reaching spinal fluid, even if confirmed, would not prove that behavior or health changes. The takeaway is about method: brain delivery has to be measured, not assumed.

Another example: nasal insulin

A systematic review of 29 randomized trials (pooled N = 1,726) of intranasal insulin and cognition found improvement in global cognition in people with Alzheimer's disease or mild cognitive impairment (SMD 0.22, 12 studies) but no significant effect on global cognition in healthy people and other groups. [7] Label: promising but limited, specific to one population. We did not verify the regulatory status of any nasal insulin product.

Promoted nasal peptides

Some research peptides are sold as nasal sprays, for example those discussed on Semax and Selank. The existence of a nasal spray does not show that the compound reaches the brain or has a benefit. For those compounds proper evidence not found here for brain delivery in people; see their own pages for what we could read.

Do not assume

• That nasal means brain. Blood absorption through the nose is enough to explain effects of some medicines. [3]
• That a delivery method for one molecule works for another. The oxytocin findings above cannot be applied to other peptides.
• That the nose-to-brain path works the same in animals and humans. Treat animal results as preclinical.