vip

Q: What is VIP?

Vasoactive intestinal peptide is a 28-amino-acid signaling peptide isolated from hog small intestine in 1970 by Said and Mutt. It acts at the VPAC1 and VPAC2 receptors, dilates blood vessels and relaxes smooth muscle. The synthetic form carries the International Nonproprietary Name aviptadil. It is not FDA-approved for any indication.

Q: What does VIP do?

It dilates vessels and relaxes smooth muscle, which is the effect it was named for and the first thing that appears in every human infusion study. It also has a documented immune role: VIP induces regulatory T cells in animal models of arthritis, and in a 20-patient open-label sarcoidosis study nebulized VIP lowered TNF-alpha and raised regulatory T cells in lavage fluid. For acute respiratory distress syndrome and COVID-19, where it has been tested hardest, the randomized evidence is null: a 2025 meta-analysis of 9 studies and 665 patients pooled survival across the only two randomized trials in it, 611 patients, at an odds ratio of 1.01 (95% CI 0.72 to 1.42), and the largest and only independently run trial was stopped for futility.

Q: How is VIP administered in the trials that studied it?

By continuous intravenous infusion, by nebulizer, or by intracavernosal injection, depending on the trial. TESICO used a 12-hour intravenous infusion daily for 3 days. The sarcoidosis and COVID-19 inhalation studies used a nebulizer. The erectile-dysfunction trials used direct intracavernosal injection with phentolamine. The reason is pharmacokinetic: the human plasma disappearance half-time is about one minute, and a granted patent from a company that spent a decade engineering around that number describes native VIP as impractical as a pharmaceutical agent. The intranasal route that dominates community protocols does not appear in any registered trial this sweep could reach.

Q: What are the side effects of VIP?

The reported effects read like the vasodilator it is. In TESICO, hypotension during infusion was recorded in 135 of 231 on drug (58.4%) against 95 of 230 on placebo (41.3%), p<0.001, flushing in 34 against 14, and mean arterial pressure ran 5 to 7 mmHg lower on drug on days 2 and 3 (p<0.001); infusions were paused in 31% of the drug arm against 15% of placebo, and the authors wrote that this suggests a higher dose would not be well tolerated. In the sponsor-run COVID-AIV trial, diarrhea occurred in 32.8% on drug against 1.5% on placebo (p<0.0001). The 1978 human infusion study recorded flushing, raised pulse and raised blood-pressure amplitude at the top dose. In the intracavernosal erectile-dysfunction trial, transient facial flushing accompanied 40% of 1711 injections and one priapism episode was recorded. Long-term exposure has not been characterized in any controlled human study.

Q: Is VIP FDA approved?

No. There are zero Drugs@FDA records for aviptadil, Zyesami or Invicorp, and zero EMA centralized authorizations across 1,982 register records. An emergency use authorization was applied for on 31 May 2021 and the FDA declined it in November 2021 on insufficient data, noting it had reviewed 131 randomized patients; breakthrough therapy designation was also denied. Four FDA and four EU orphan designations issued between 1993 and February 2026 have produced no approval. The only marketing authorizations anywhere are national ones for the aviptadil plus phentolamine combination in erectile dysfunction, by intracavernosal injection, held in the UK, Denmark and New Zealand.

Q: Is intranasal VIP studied for CIRS or mold illness?

Not in any registered trial. A ClinicalTrials.gov sweep on 25 July 2026 returned zero entries for intranasal VIP in chronic inflammatory response syndrome, mold illness or water-damaged-building exposure. The two supporting papers sit outside the indexed literature: a 2013 open-label report of 20 patients in a Scientific Research Publishing journal, with no placebo and no control arm, and a 2017 imaging paper in Internal Medicine Review whose abstract states no patient count and describes no control group. A PubMed search for that author on VIP returns zero records, while the same author is indexed for other work on the syndrome. WHO ICTRP registries were outside this sweep, so a non-US trial would not have appeared.

four randomized trials in COVID-19 respiratory failure, a 665-patient meta-analysis, and a plasma half-time of about one minute. the biggest trial was stopped for futility, and the one clearly positive trial is for an indication nobody researches it for.

tier D · healing · phase 3 TESICO · stopped for futility 2022

verdict

does it work: not for lungs, and that is a finding rather than a gap. a 461-patient NIH-run phase 3 halted for futility, a pooled survival odds ratio of 1.01 across the two randomized trials in the 2025 meta-analysis (611 patients), and one genuinely positive randomized trial in erectile dysfunction by intracavernosal injection.

on whether VIP works for ARDS, COVID or lung inflammation — on the randomized evidence, no. TESICO, the only large independently run trial (NIAID, 471 randomized and 461 analyzed, 28 US sites), missed every outcome: day-90 ordinal odds ratio 1.11 (95% CI 0.80 to 1.55, p=0.54), 86 of 231 deaths on drug against 83 of 230 on placebo, hazard ratio 1.04. the data monitoring board stopped the arm for futility on 25 May 2022, at 471 of a planned 640, with conditional power down to 12.4%. a 2025 meta-analysis of 9 studies and 665 patients pools survival across the only two randomized trials in it, 611 patients, at an odds ratio of 1.01 (0.72 to 1.42); its seven uncontrolled case series contribute 54 patients and nothing to that estimate. the sponsor-run 196-patient trial quoted as a survival doubling missed its own primary endpoint, and its primary and secondary endpoints were reversed in February 2021 while it was running.

on intranasal VIP, CIRS and mold illness — there is no registered trial. a ClinicalTrials.gov sweep returns zero entries for intranasal VIP in chronic inflammatory response syndrome, mold illness or water-damaged-building exposure. the two papers the protocol rests on sit outside the indexed literature: an open-label 20-patient report in a Scientific Research Publishing journal with no control arm, and a 2017 imaging paper whose abstract states no patient count and describes no control group. separately, the molecule clears human plasma with a half-time of about one minute, so whatever a nasal spray produces is not the exposure the randomized trials produced.

on why this is not an F — because VIP is unmistakably active in people, and one randomized trial is clearly positive. injected into the corpus cavernosum with phentolamine, it produced a response in 75% of men against 12% on placebo (n=171, p<0.001) and carries national marketing authorizations as Invicorp. F is for a compound that is fake, a scam, or actively harmful beyond reasonable doubt. a real positive trial and a real regulatory decision rule that out.

based on published trials, trial registries and regulatory records. VIP is not FDA-approved for any indication. not medical advice.

why D-tier

D, and the volume of human data is not the reason. VIP carries more human evidence than most compounds on this board: four randomized trials in COVID-19 respiratory failure, a placebo-controlled randomized trial in erectile dysfunction, a 665-patient meta-analysis, five decades of human pharmacology since Said and Mutt isolated it in 1970, and national marketing authorizations in three countries. the direction of that evidence is the problem. pooled across the only two randomized trials in the 2025 meta-analysis, 611 patients, survival gives an odds ratio of 1.01 (95% CI 0.72 to 1.42). TESICO, the only large independently run trial, missed every outcome and was stopped for futility on 25 May 2022, at 471 of a planned 640 with conditional power at 12.4%. large, well run, and conflicting is exactly what D describes. one distinction the tier depends on: respiratory failure is a failed indication, tested adequately and negative. intranasal use for chronic inflammatory response syndrome is an unmeasured one. those are opposite findings, not two flavours of thin. why not C: C is the mostly-preclinical slot. the base here is human, and randomized trials in two indications plus five decades of infusion pharmacology disqualify a preclinical grade. why not F: VIP is unmistakably active in people. injected into the corpus cavernosum with phentolamine it produced a response in 75% of men against 12% on placebo (n=171, p<0.001) and carries national authorizations as Invicorp. F would have to erase a genuine positive trial and a real regulatory decision. why not B: B implies the randomized record supports the compound and is only incomplete. the best-powered trial is null. the positive COVID-19 trial is a sponsor-run 196-patient study whose primary endpoint missed and whose primary and secondary endpoints were reversed while it ran. the route the community literature describes has never been entered into a trial registry this sweep could reach, and the molecule survives about a minute in blood.

the core tension

the one indication where VIP clearly beats placebo in a randomized trial is erectile dysfunction, by injection directly into the corpus cavernosum, combined with phentolamine, authorized in three countries and sold by nobody in this market. the indication it is actually researched for, intranasal anti-inflammatory and neurological use, has never been entered into a trial registry this sweep could reach. sitting between those two facts is a 461-patient phase 3 that found nothing on any endpoint and a molecule with a one-minute plasma half-time, which means a nasal spray is not the exposure any of the trials produced.

what it is

A 28-amino-acid signaling peptide the body makes in gut, lung and nerve tissue. Sami Said and Viktor Mutt isolated it from hog small intestine and published it in Science in 1970 while chasing a vasodilator, and the name is a description of what they found. It sits in the secretin and glucagon superfamily alongside PACAP and acts at two receptors, VPAC1 and VPAC2. The synthetic version carries an International Nonproprietary Name, aviptadil. It has been trialed as Zyesami and, combined with phentolamine mesilate, is sold as Invicorp. It is not FDA-approved for any indication.

what it does

It dilates vessels and relaxes smooth muscle. That is the effect it was named for and the effect that shows up first in every human infusion study: the 1978 pharmacokinetic work recorded flushing, a raised pulse and a widened blood-pressure amplitude at the top dose. The anti-inflammatory case is largely animal and cell work. VIP shifts T-cell populations toward a regulatory phenotype in collagen-induced arthritis in mice, and damps inflammatory signaling in cultured human cells. In a 20-patient open-label sarcoidosis study, nebulized VIP lowered TNF-alpha in bronchoalveolar lavage fluid and raised regulatory T cells there, with no lung-function or symptom endpoint reported.

origin

Said and Mutt published the isolation in Science in 1970, and Said spent decades on the lung biology that followed. The COVID program grew out of that line: VPAC receptors are dense on lung epithelium, plasma VIP was found to be elevated in severe COVID-19 and to correlate with survival, and VIP protected SARS-CoV-2-infected cells in culture. NRx Pharmaceuticals and Relief Therapeutics turned that into Zyesami and took it to the FDA. The erectile-dysfunction line ran separately, and is the one that ended in an actual approval.

why researchers are interested

Two unrelated audiences arrived at the same molecule. During COVID the ARDS program drew heavy coverage and a widely repeated survival headline. Independently, an intranasal protocol for chronic inflammatory response syndrome built a following in the mold-illness world on the strength of a real animal anti-inflammatory literature. Neither audience is reading the trial record. The ARDS headline came from a secondary endpoint in a sponsor-run study that missed its primary. The intranasal protocol has never been entered into a trial registry.

does it work

Three different answers, and the difference between them is the point. For ARDS and COVID-19 it was tested properly and it failed. TESICO, NIH-run and triple-masked, missed its day-90 primary at an odds ratio of 1.11 (0.80 to 1.55, p=0.54) and ran a hair the wrong way on death, 86 of 231 against 83 of 230, hazard ratio 1.04. Pooled across the two randomized trials that exist, 611 patients, survival sits at an odds ratio of 1.01 (0.72 to 1.42). For erectile dysfunction by intracavernosal injection with phentolamine, yes: 75% response against 12% on placebo in 171 men, p<0.001, and marketing authorizations in three countries. For intranasal anti-inflammatory or neurological use, nobody has measured it. No trial is registered anywhere this sweep could reach. That is untested, not failed, and the two must not be blurred.

claims vs the data

VIP doubles survival in critical COVID-19 — overreach — that figure is a secondary endpoint in a sponsor-run 196-patient trial whose primary endpoint missed (odds ratio 1.6, 0.86 to 3.11), and whose primary and secondary endpoints were reversed in February 2021 while the trial was running. the 461-patient independent phase 3 found a hazard ratio of 1.04 for death and was stopped for futility. pooled across the only two randomized trials in the 2025 meta-analysis, 611 patients, survival odds ratio 1.01 (0.72 to 1.42).
intranasal VIP treats CIRS and mold illness — unverified — never measured, which is a different answer from the lung result and has to be read as one. zero registered trials in any registry this sweep could reach. the published support is one open-label 20-patient report in a non-indexed journal with no control arm, and one 2017 imaging paper whose abstract gives no patient count and describes no control group. a one-minute plasma half-time also makes nasal exposure a separate question from anything the infusion trials measured. the failed phase 3 does not refute this claim and the absence of a trial does not support it.
VIP on its own produces an erection — contradicted — the licensed result belongs to the combination. a placebo-controlled study of 24 men given VIP alone by intracavernosal injection recorded statistically significant dose-dependent increases in penile length and diameter and states that none of the patients achieved rigidity adequate for intromission. every approved product pairs it with phentolamine, and the 75% against 12% figure comes from that pairing.
VIP is an approved drug — partially true — true for one combination in one indication. aviptadil with phentolamine holds national marketing authorizations as Invicorp for erectile dysfunction by intracavernosal injection, the UK authorization dated 21 April 2015, with approvals also in Denmark and New Zealand. zero Drugs@FDA records and zero EMA centralized authorizations exist for aviptadil, Zyesami or Invicorp.
VIP is a proven anti-inflammatory — weak — the immune data is mostly animal and cell work: regulatory T-cell induction in collagen-induced arthritis in mice, cytokine suppression in culture. the one human immunology readout is a 20-patient open-label sarcoidosis study that measured lavage cytokines and lavage T cells, with no lung-function or symptom endpoint and no control arm. real, and thin.
inhaled VIP treats pulmonary hypertension — weak — one uncontrolled 8-patient study in 2003 reported a fall in mean pulmonary artery pressure and a gain in 6-minute walk distance at 12 and 24 weeks. no control arm, and never replicated in a randomized trial. the long-acting analogue built to carry that idea forward ran two pulmonary-hypertension trials and both were terminated.
VIP is well tolerated — contradicted — it is a vasodilator and the trial record reads like one. TESICO recorded hypotension during infusion in 135 of 231 on drug (58.4%) against 95 of 230 on placebo (41.3%), p<0.001, mean arterial pressure 5 to 7 mmHg lower on days 2 and 3 (p<0.001), and infusions paused in 31% of the drug arm against 15% of placebo; the authors wrote that a higher dose would not be well tolerated. the sponsor-run trial recorded diarrhea in 32.8% against 1.5%. VIP-secreting tumors produce a named human syndrome of watery diarrhea, hypokalemia and achlorhydria.
a nasal or subcutaneous dose reproduces the trial evidence — contradicted — the human plasma disappearance half-time is about one minute, and every randomized efficacy trial used continuous intravenous infusion, a nebulizer, or direct intracavernosal injection. a granted PhaseBio patent on modified VIP calls the native molecule impractical as a pharmaceutical agent for exactly this reason, and the engineered long-acting version built to fix it ran 234 participants across seven registered trials and ended with no efficacy readout.
FDA category 1 means the FDA endorses VIP — contradicted — category 1 on the 503A bulk drug substances list means a substance was nominated with enough information for the FDA to evaluate it and is under evaluation, and that the agency does not currently intend to act against a compounder using it. it is enforcement discretion. it is not approval, it is not placement on the 503A bulks list, and it is not a finding about the compound.
the FDA blocked a working COVID-19 drug — contradicted — the emergency use authorization was applied for on 31 May 2021 and declined in November 2021 on insufficient data, with the FDA noting it had reviewed 131 randomized patients; breakthrough therapy designation was also denied. the independently run phase 3 that read out afterwards found nothing on any endpoint.

key facts

molecular formula: C₁₄₇H₂₃₈N₄₄O₄₂S
molecular weight: ~3325.8 g/mol
amino acids: 28
half-life: ~1 minute plasma disappearance half-time (IV, human, n=4)
type: secretin/glucagon-family neuropeptide; VPAC1 + VPAC2 agonist
CAS: 40077-57-4 (aviptadil, synthetic VIP)
461 analyzed in TESICO, arm stopped for futility
1.01 pooled survival odds ratio, 611 randomized
~1 min plasma disappearance half-time, n=4
0 registered trials of intranasal VIP

frequently asked questions

What is VIP?

Vasoactive intestinal peptide is a 28-amino-acid signaling peptide isolated from hog small intestine in 1970 by Said and Mutt. It acts at the VPAC1 and VPAC2 receptors, dilates blood vessels and relaxes smooth muscle. The synthetic form carries the International Nonproprietary Name aviptadil. It is not FDA-approved for any indication.

What does VIP do?

It dilates vessels and relaxes smooth muscle, which is the effect it was named for and the first thing that appears in every human infusion study. It also has a documented immune role: VIP induces regulatory T cells in animal models of arthritis, and in a 20-patient open-label sarcoidosis study nebulized VIP lowered TNF-alpha and raised regulatory T cells in lavage fluid. For acute respiratory distress syndrome and COVID-19, where it has been tested hardest, the randomized evidence is null: a 2025 meta-analysis of 9 studies and 665 patients pooled survival across the only two randomized trials in it, 611 patients, at an odds ratio of 1.01 (95% CI 0.72 to 1.42), and the largest and only independently run trial was stopped for futility.

How is VIP administered in the trials that studied it?

By continuous intravenous infusion, by nebulizer, or by intracavernosal injection, depending on the trial. TESICO used a 12-hour intravenous infusion daily for 3 days. The sarcoidosis and COVID-19 inhalation studies used a nebulizer. The erectile-dysfunction trials used direct intracavernosal injection with phentolamine. The reason is pharmacokinetic: the human plasma disappearance half-time is about one minute, and a granted patent from a company that spent a decade engineering around that number describes native VIP as impractical as a pharmaceutical agent. The intranasal route that dominates community protocols does not appear in any registered trial this sweep could reach.

What are the side effects of VIP?

The reported effects read like the vasodilator it is. In TESICO, hypotension during infusion was recorded in 135 of 231 on drug (58.4%) against 95 of 230 on placebo (41.3%), p<0.001, flushing in 34 against 14, and mean arterial pressure ran 5 to 7 mmHg lower on drug on days 2 and 3 (p<0.001); infusions were paused in 31% of the drug arm against 15% of placebo, and the authors wrote that this suggests a higher dose would not be well tolerated. In the sponsor-run COVID-AIV trial, diarrhea occurred in 32.8% on drug against 1.5% on placebo (p<0.0001). The 1978 human infusion study recorded flushing, raised pulse and raised blood-pressure amplitude at the top dose. In the intracavernosal erectile-dysfunction trial, transient facial flushing accompanied 40% of 1711 injections and one priapism episode was recorded. Long-term exposure has not been characterized in any controlled human study.

Is VIP FDA approved?

No. There are zero Drugs@FDA records for aviptadil, Zyesami or Invicorp, and zero EMA centralized authorizations across 1,982 register records. An emergency use authorization was applied for on 31 May 2021 and the FDA declined it in November 2021 on insufficient data, noting it had reviewed 131 randomized patients; breakthrough therapy designation was also denied. Four FDA and four EU orphan designations issued between 1993 and February 2026 have produced no approval. The only marketing authorizations anywhere are national ones for the aviptadil plus phentolamine combination in erectile dysfunction, by intracavernosal injection, held in the UK, Denmark and New Zealand.

Is intranasal VIP studied for CIRS or mold illness?

Not in any registered trial. A ClinicalTrials.gov sweep on 25 July 2026 returned zero entries for intranasal VIP in chronic inflammatory response syndrome, mold illness or water-damaged-building exposure. The two supporting papers sit outside the indexed literature: a 2013 open-label report of 20 patients in a Scientific Research Publishing journal, with no placebo and no control arm, and a 2017 imaging paper in Internal Medicine Review whose abstract states no patient count and describes no control group. A PubMed search for that author on VIP returns zero records, while the same author is indexed for other work on the syndrome. WHO ICTRP registries were outside this sweep, so a non-US trial would not have appeared.

related peptides

kpv — anti-inflammatory tripeptide, thinner human record but the same immune lane
thymosin α-1 — immune-modulating peptide with approvals abroad and a narrow indication
larazotide — the other clean mechanism on this tier that failed its pivotal
pt-141 — the sexual-function peptide with an FDA approval, different mechanism entirely

reptides grades the research record and cites the literature behind every call. research reference only; not medical advice.