VIP Really Is the Hormone It Says It Is. The Nasal Dose Came Off a Nebuliser
The identity check comes back clean, which is rare here. The only marketing authorisation I found is an injection into the penis, combined with a second drug, and the 50 microgram spray traces to a lung study in eight patients.
What it is
The identity check is clean, which almost nothing else in this reference manages. UniProt, the reference database for protein sequences, gives the mature chain in entry P01282 as 28 amino acids, HSDAVFTDNYTRLRKQMAVKKYLNSILN. Aviptadil, the name used in trials and on prescription labels, is a synthetic copy of that sequence, and PubChem files it at 3,326.8 daltons, a little over half the weight of insulin at 5,808. The identity trap that has caught other compounds in this reference, including Epithalon, does not apply here.
One substitution to watch. Pemziviptadil, written PB1046, is this peptide with an engineered protein tail on it, meant to make it last a week instead of a minute. The registry calls it "a Long-acting, Sustained Release Human VIP Analogue". Its two phase 2 trials, 35 people with pulmonary arterial hypertension and 54 with COVID-19, were both terminated, and neither registry record blames a bad result: one gives delayed drug resupply during COVID, the other says the company stopped pursuing the indication. (NCT03556020, NCT04433546)
The obstacle is arithmetic rather than biology. Domschke and colleagues infused the peptide into four healthy volunteers in 1978 and measured an average disappearance half-time of one minute after the drip stopped, concluding that "The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions." (PMID 730072) A minute is why every serious programme has either run a continuous drip or sprayed the peptide onto the tissue it is meant to act on.
What the human trials found
Petkov and colleagues published the founding paper in the Journal of Clinical Investigation in 2003. Eight adults with primary pulmonary hypertension, dangerously high blood pressure in the vessels between heart and lungs, inhaled "a total of 200 μg VIP in four single inhalations" a day through a nebuliser for three months, and mean pulmonary artery pressure fell 13 mmHg, from 59 to 46. (PMID 12727925) The paper calls itself controlled, which is why vendor pages do, and what it means by that is intraindividual: each of the eight was compared against their own earlier numbers. There was no placebo group. That paper also carries the finding the whole replacement idea rests on, that the peptide is deficient in the blood and lung tissue of these patients, and I found no replication of it in people. What my searches returned was mouse gene-deletion work and human gene-variant studies, none of them a measurement of the peptide in people.
The randomised version exists: EudraCT 2007-003621-24, sponsor protocol MG-101-01, double blind and placebo controlled, inhaled aviptadil in pulmonary arterial hypertension, planned for 48 subjects. The European register has it prematurely ended in six of the eight countries that ran it and completed in the other two. What it found is in a letter. Galiè, Palazzini and Manes of the University of Bologna, replying in 2012 to Sami Said, who discovered the peptide and had asked for the trial to be published in full, named it MG-101 and referred to "the negative results of the acute hemodynamic test and of the 3 months of administration". Negative on the single dose, negative at three months. Their reply carries doi 10.1164/ajrccm.185.7.786a and I found no PubMed record for it of its own. The letter does not say which endpoint, and the text is paywalled after the first paragraph, so I could not read further.
The one clean positive is mechanistic. Prasse and colleagues treated 20 patients with biopsy proven sarcoidosis, an inflammatory disease that forms clumps of immune cells in the lungs, with nebulised VIP for four weeks in an open study, and tumour necrosis factor alpha, a signal that drives inflammation, fell in cells washed out of the lungs against each patient's own starting sample, while regulatory T cells, whose job is switching other immune cells off, rose against the same baseline. (PMID 20442436) That is cells in lung washings in 20 people over four weeks, not a symptom trial and not placebo controlled.
Then COVID-19. Youssef and colleagues randomised 196 patients with respiratory failure, 131 to three days of aviptadil into a vein and 65 to placebo. The sponsor announced that the trial had met its primary endpoint; the paper says "The primary end point did not reach statistical significance", with a secondary survival analysis at 60 days that did separate. (PMID 36044317) TESICO, funded by the National Institutes of Health rather than a manufacturer, put 231 patients on the drug against 230 on matched saline and stopped for futility, with 38 percent of the treated group dead by day 90 against 36 percent on saline. Its conclusion on aviptadil is one sentence long: "aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo." (PMID 37348524) A 2025 systematic review pooling nine studies, 361 of whose 665 patients received aviptadil, put the survival odds ratio across the two randomised trials at 1.01, spanning 0.72 to 1.42, which is as close to nothing as a number gets.
Whose evidence is it
The molecule is the same. Four other things are not.
Route. A nebuliser into the lungs, a drip into a vein, or an injection into the penis, against a nasal spray and, secondarily, an injection under the skin. I found no human trial of either of the last two in PubMed or on ClinicalTrials.gov. The nasal evidence that does exist sits outside PubMed and is described below.
Population. Pulmonary hypertension, sarcoidosis, COVID-19 respiratory failure, erectile dysfunction. I found no trial in a healthy adult chasing sharper thinking or faster recovery. The nearest two are the migraine patients below, where the finding was a headache, and 12 healthy volunteers given a two hour infusion into a vein, who got a widened artery and a delayed headache.
Combination. The only licensed product I found is aviptadil plus phentolamine, and nothing in that licence is evidence about the peptide alone. This is the mismatch most likely to get dropped, because a licence number reads like a citation.
Molecule, in one case. Pemziviptadil, above.
The illness the spray is prescribed for, reported and not settled
The spray is prescribed as the last step of a numbered protocol for chronic inflammatory response syndrome. This entry is about a molecule and its evidence, not about whether anybody is ill, and people carrying that diagnosis read this site too. So both positions, attributed.
Ritchie Shoemaker's framing is that exposure to bioaerosols in water damaged buildings produces a persistent innate immune illness, treated by a numbered sequence in which the peptide comes last. His 2017 paper states that "over 300 physicians have prescribed intranasal VIP for their CIRS patients". The American College of Medical Toxicology adopted a position statement on 13 August 2025 stating that "There is no documented evidence that inhalation exposure to fungi or mycotoxins in indoor environments causes a chronic toxic encephalopathy".
What can be said without adjudicating that is what the treatment evidence consists of. Shoemaker, House and Ryan, Health 2013: open label, 20 patients, no control arm inside it. Shoemaker and colleagues, Internal Medicine Review 2017: open label, 35 enrolled of whom 31 received the spray, because the four who could not obtain the drug in the state they lived in were kept in as negative controls, so the comparison group is four people, and a co-author is listed with Hopkinton Drug, the pharmacy that compounds the product being evaluated. Neither paper came up in the PubMed searches I ran. The 2013 paper announced that "A double blinded, placebo controlled clinical trial has begun." I could not find it published or registered in the thirteen years since.
Where the 50 micrograms came from
This is the cleanest derivation chain in the batch, and it ends at a nebuliser. In 2003 Petkov's eight patients inhaled 200 micrograms a day in four doses, which is 50 a dose. In 2010 Prasse's 20 sarcoidosis patients got 50 micrograms four times daily; the abstract does not print that, but the trial's own German registry record, DRKS00000184, gives "50 microgramm Aviptadil four times daily per inhalation" through an ultrasonic nebuliser for 28 days. Same number, same frequency, same route, different disease. In 2013 Shoemaker's 20 patients "self-administered 50 mcg VIP (Aviptadil; Bachem AG, Switzerland) four times a day via nasal aerosol", and the reason the paper gives for the number is Prasse. Read that paper's own results, though, and the schedule is the protocol rather than what most patients did: 8 of the 20 used it three or four times a day consistently, 4 used it once or twice, 3 used it only before strenuous activity, and 5 stopped. The number the market inherited is the protocol as written. Today the Hopkinton Drug patient sheet reads "Each spray delivers 50mcg of VIP", one spray in a single nostril, four times daily.
An oven time worked out for a fan oven does not survive being moved to a grill unless somebody sits down and works it out again. Nobody worked this one out again. I found no study establishing that 50 micrograms into a nostril delivers anything like 50 micrograms misted into a pair of lungs, and no human study of how much of a nasal dose reaches the blood, over what time, at all.
Then it drifted upward, reported here as convention and not as a recommendation. Shoemaker's published protocol says a patient with a particular brain imaging finding "may need 12 sprays/day", which is 600 micrograms, three times the studied amount, and both that protocol and a compounding pharmacy's own patient directions escalate to two sprays four times a day, which is 400, twice the amount the 2003 study inhaled. The under the skin figure has no derivation at all that I could find: a widely mirrored guide gives 25 to 50 micrograms to start and 50 to 100 as standard, prints no frequency, calls that a research dose range and cites no study. I searched PubMed and ClinicalTrials.gov and found no human study of this peptide given under the skin.
| Study | Species | Route | Dose | How many got the drug | Duration |
|---|---|---|---|---|---|
| Petkov 2003 | Human | Inhaled, nebuliser | 200 mcg a day in 4 doses | 8 | 3 months |
| Leuchte 2008 | Human | Inhaled, nebuliser | 100 mcg once | 20 | Single dose |
| Prasse 2010 | Human | Inhaled, nebuliser | 50 mcg four times daily | 20 | 28 days |
| Youssef 2022 | Human | Into a vein | 50, 100 then 150 pmol/kg/hour | 131 of 196 randomised | 3 days |
| TESICO 2023 | Human | Into a vein | 600, 1,200 then 1,800 pmol/kg | 231 of 461 analysed | 3 days |
| Pellesi 2021 | Human | Into a vein | 8 pmol/kg/min | 21, crossover, all got both | 2 hours |
| Domschke 1978 | Human | Into a vein | 0.6 to 3.3 pmol/kg/min | 4 | 30 minutes each |
| Invicorp label | Human | Into erectile tissue | 25 mcg with 2 mg phentolamine | Licensed product | Maximum 3 a week |
Not one row of that table is a nasal spray or an injection under the skin.
What the regulators have on file
The only marketing authorisation I found for any product containing this peptide is Invicorp, and it is a combination: 25 micrograms of aviptadil with 2 mg of phentolamine mesilate in a 0.35 mL ampoule, injected into the erectile tissue of the penis. United Kingdom authorisation PL 44616/0001, held by Evolan Pharma AB of Danderyd, Sweden, first granted 21 April 2015, for one indication, "the symptomatic treatment of erectile dysfunction in adult males". Two drugs, one licence, and none of it is evidence about the peptide by itself.
I queried the FDA's own Drugs@FDA database for aviptadil and for vasoactive intestinal peptide as an active ingredient, and both queries came back empty. The agency declined an emergency use authorisation in critical COVID-19 in November 2021, and declined a second, narrower request resting on a subgroup picked out after the results were in on 1 July 2022, both according to the sponsor's own announcements.
What lets a pharmacy compound the spray is a holding position rather than an approval. The FDA's list of bulk drug substances nominated for compounding under section 503A, updated 14 May 2026, files Vasoactive Intestinal Peptide under "503A Category 1 - Bulk Drug Substances Under Evaluation". The same document keeps a second list, "503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks", holding six entries, and this peptide is not among them. Category 1 means the agency has not finished evaluating the nomination. That is not an approval, not a safety finding, and the closest thing to a regulatory document a seller of the spray can point at.
What could go wrong
The best controlled human exposures to this peptide were designed to cause a headache, and they succeeded. Pellesi and colleagues ran a randomised, double blind, placebo controlled crossover in 21 patients with migraine without aura at the Danish Headache Center, crossover meaning all 21 received both the peptide and the placebo on different days. Fifteen of 21 developed a migraine attack on the peptide against one of 21 on placebo, at a P value below 0.001, meaning a gap that size would turn up by chance less than once in a thousand runs if the peptide did nothing. That was the trial's primary endpoint, and it hit it. (doi 10.1001/jamanetworkopen.2021.18543) The infusion delivered about 224 micrograms into a vein over two hours for a 70 kilogram adult, a mid-range worked example since the trial enrolled people from 50 to 90 kilograms. The nasal convention is 200 micrograms a day. Not an equivalent exposure, since how much of a spray reaches the blood is unknown and is almost certainly a fraction, but the same order of magnitude.
What excess looks like when the body does it is a VIPoma, a rare tumour that secretes the peptide, at 0.05 to 0.2 cases per million person-years, producing watery diarrhoea, low blood potassium and no stomach acid. Domschke's four volunteers, at the top infusion rate, reached plasma levels the authors compared to that syndrome, with flushing and a raised pulse.
In TESICO the primary safety outcome by day 5 occurred in 146 of 231 patients on aviptadil, 63 percent, against 129 of 230 on placebo, 56 percent. Not a separation, not reassuring either. And the nasal route as its own protocol describes it is a supervised prescription process, ordered by a physician against a numbered sequence of prior steps, with a compounding pharmacy filling it. A vial bought online is none of that.
What nobody knows
Whether the deficiency is real. The replacement rationale, in the lung first and then borrowed into the nasal protocol, rests on that one measurement in eight patients, and the randomised trial built on it was negative.
What a spray delivers. With a blood half-life of about a minute and a mucous membrane in the way, whether 50 micrograms in a nostril produces any systemic exposure at all is genuinely open, and it cuts both ways: it is the reason the route might be harmless and the reason it might do nothing.
Why the European lung trial stopped early. No reason is given in the register record.
Batch to batch consistency of the compounded solution, which I did not examine and found no published stability data on.
What this comes down to
The clean identity is what makes this one hard, because it removes the argument that settles most entries here. This is the hormone. Not a lookalike, not an extract, not a name shifted by one letter. And then the evidence turns out to be about a nebuliser, a drip stand and a urology clinic, while the product on the shelf is a bottle you spray up your nose.
Every link in the chain from 2003 to that bottle is documented and honest on its own terms, and at no point did anybody stop to ask what a number derived for a pair of lungs means for a nostril. That is not fraud. It is a measurement carried through three studies and a pharmacy without ever being worked out again, which is a commoner failure and a harder one to see.
The randomised lung trial is the thing a seller should have to answer for. Its own investigators wrote the word negative about both the single dose and the three months, and the protocol document still lists pulmonary hypertension as an indication for the spray.
If you have bought it, open the EU Clinical Trials Register at EudraCT 2007-003621-24 and read the country records yourself. Then check whether the page that sold it to you mentioned that trial at all, or stopped at the 2003 study in eight patients.
Frequently asked
Is VIP an approved drug?
The only marketing authorisation I found for any product containing it is Invicorp in the United Kingdom, a combination of 25 micrograms of aviptadil with 2 mg of phentolamine mesilate injected into the erectile tissue of the penis for erectile dysfunction, which licenses two drugs together rather than this peptide on its own. I queried the FDA's Drugs@FDA database for aviptadil and for vasoactive intestinal peptide as an active ingredient and both queries came back empty.
Is the VIP nasal spray FDA approved?
I found no FDA approval for it. What lets a compounding pharmacy make it is that the FDA's list of bulk substances nominated for compounding files vasoactive intestinal peptide under Category 1, which the same document defines as substances under evaluation, meaning the agency has not finished deciding. That is not an approval. It is not a safety finding either: the document's separate list of substances raising significant safety risks holds six entries and this peptide is not one of them.
Does VIP nasal spray work for chronic inflammatory response syndrome?
The published evidence for the nasal route that I found is two open label studies from one research group, 20 patients in 2013 and 31 of 35 enrolled in 2017, neither with a randomised comparison group and neither coming up in PubMed. The 2017 paper's comparison group is the four patients who could not obtain the drug in the state they lived in, and one of its co-authors is listed with the compounding pharmacy that makes the product. The 2013 paper announced that a double blind placebo controlled trial had begun, and I could not find it published or registered in the thirteen years since.
Where does the 50 microgram VIP dose come from?
From a nebuliser. Fifty micrograms four times a day was an inhaled dose given to 8 human patients with pulmonary hypertension in 2003 and to 20 human sarcoidosis patients in 2010, and it was carried across to a nasal spray in 2013 without being worked out again for the new route. Reported here as convention, not as a recommendation. I found no study establishing what 50 micrograms sprayed into a nostril delivers compared with the same amount misted into the lungs.
Does VIP have side effects?
The best controlled human exposures to it were designed to answer that question. In a randomised double blind crossover trial at the Danish Headache Center, 15 of 21 patients with migraine had a migraine attack after a two hour infusion into a vein, against 1 of 21 after placebo, and that was the trial's primary endpoint. The same team reported cranial artery widening and a delayed mild headache in 12 healthy volunteers given the same two hour infusion into a vein against placebo in a crossover. For the nasal spray specifically, I found no controlled safety study.
What did the COVID-19 trials of aviptadil show?
Two randomised trials, both negative on the measure they were built around. Youssef and colleagues randomised 196 patients with COVID-19 respiratory failure, 131 to aviptadil into a vein and 65 to placebo, and the published paper reports that the primary endpoint did not reach statistical significance, although a secondary survival analysis at 60 days did separate. TESICO, funded by the National Institutes of Health, put 231 patients on the drug against 230 on matched saline and was stopped for futility, with 38 percent of the treated group dead by day 90 against 36 percent on saline.
Is VIP the same thing as aviptadil, and what about pemziviptadil?
Aviptadil is the name for synthetic vasoactive intestinal peptide, the same 28 amino acid sequence the human body makes, so on identity the two are the same molecule. Pemziviptadil, also written PB1046, is not: it is the peptide fused to an engineered protein tail meant to make it last about a week instead of about a minute, and its two phase 2 trials, in 35 people with pulmonary arterial hypertension and 54 with COVID-19, were both terminated, neither for a bad result: the registry gives delayed drug resupply during COVID for one and the company no longer pursuing the indication for the other.
This content is for educational and informational purposes only and is not medical advice. Peptides discussed are research compounds and may not be approved for human use. Nothing here should be used to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any peptide, supplement, or protocol. Individual responses vary. Do not self-administer compounds without proper medical supervision.
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