VIP (Aviptadil)
28-amino-acid neuropeptide · relaxes blood vessels and calms immune cells in the gut, lungs and brain
VIP relaxes blood vessels, airways and gut muscle and calms immune cells. Nerves release this 28-amino-acid messenger in the gut, lungs and brain. Its human results come from infusions, inhalers, a nasal spray and an erection drug.
The short version
VIP is one of the body's own signals. Nerves release it to open blood vessels, relax airways and gut muscle, and quiet inflammation.
In people, its clearest result is an erection drug that pairs it with phentolamine. Inhaled, it eased lung pressure and inflammation in small studies, and two placebo-controlled COVID-19 infusion trials missed their main goals.
How it works
Relaxes vessels and smooth muscle. VIP widens arteries and relaxes airway, gut and erectile muscle. In its 1970 discovery it widened blood vessels and lowered blood pressure.
Works through two receptors. It binds VPAC1 and VPAC2, which raise cAMP, a messenger inside the cell. Its sibling PACAP shares both and has a third, PAC1, mostly to itself.
Calms immune cells. VIP lowers inflammation signals such as TNF-α and IL-6, raises the calming signal IL-10, and helps form regulatory T cells, which hold inflammation in check.
Gone in about a minute. Blood clears it with a half-life near one minute, so studies give it by long infusion, by inhaler, as a nasal spray or straight into the target tissue.
Sources:PMID 5450698PMID 22289055PMID 15169929PMID 22139413PMID 730072PMID 20442436PMID 36044317
Side effects and what to watch
What people notice. Flushing is the common one. It followed 40% of injections in the erection-drug trial and came with infusions, along with a faster pulse.
Headache and migraine. A 2-hour infusion set off migraine attacks in 15 of 21 people with migraine, against 1 of 21 on placebo. Healthy volunteers got delayed headaches.
Watery diarrhea. It hit 33% of patients on IV infusion, against 1.5% on placebo. VIP is the hormone behind VIPoma, a rare tumor known for it.
Skip it or take care if. You get migraines, run low blood pressure or have POTS (a racing pulse on standing). VIP widens blood vessels and can drop blood pressure.
Sources:PMID 10233493PMID 730072PMID 34357396PMID 32594760ClinicalTrials.govPMID 5450698
Common questions
How is VIP dosed?
Every human treatment dose on record came from a hospital infusion, an inhaler or nasal-spray study, or an erection-drug injection, none under the skin. So this page gives the study record rather than a schedule.
Can VIP help with POTS or brain fog?
VIP widens blood vessels, can lower blood pressure and raises the pulse, all unwelcome in POTS, where the pulse already races on standing. A 2-hour infusion set off migraine in 15 of 21 people with migraine. Neither has been studied on its own.
Why do mold-illness (CIRS) protocols use it?
Ritchie Shoemaker's protocol adds nasal VIP as its last step, after the other treatments. In his open-label study of 20 patients, symptom scores fell from 17.8 to 3.4 over 18 months on VIP.
Did VIP fail in the COVID trials?
Two placebo-controlled infusion trials missed their main goals. TESICO, with 461 patients, found no better recovery at day 90, and pooled with a trial from India, it showed no survival benefit.
Is a research vial the same molecule as the study spray?
It is if the vial holds the 28-amino-acid peptide with its amide end, the form the body makes. Product listings carry one of two CAS numbers for that same molecule. The CIRS study sprayed aviptadil, the drug form of that molecule.
Deep dive
What the studies found · Molecular identity · References
04From the researchWhat the studies found
These are the main human studies behind VIP, controlled trials first, then the open-label ones, then one animal study.
| Design | Route | Model | Outcome | Sources: |
|---|---|---|---|---|
| Randomized, placebo-controlled | IV infusion in hospital, 3 days | 461 adults with COVID-19 respiratory failure, 94% in intensive care (TESICO) | No better recovery at day 90 (odds ratio 1.11, p=0.54); deaths 38% vs 36% | PMID 37348524 |
| Randomized, placebo-controlled | IV infusion in hospital, 3 days | 196 adults with critical COVID-19 respiratory failure | Missed its main goal (alive and free of respiratory failure at day 60); its key secondary endpoint, 60-day survival, favored the drug (odds ratio 2.0) | PMID 36044317 |
| Systematic review of 9 studies, 2 trials pooled | IV infusion, in hospital | 665 patients with ARDS (severe lung injury), 361 given aviptadil | TESICO and a 150-patient trial from India, pooled, showed no survival benefit (odds ratio 1.01, 95% CI 0.72 to 1.42) | PMID 41368449 |
| Randomized, placebo-controlled | Inhaled in hospital, 7 to 14 days | 80 adults hospitalized with COVID-19 | Discharged after 7.8 days on average vs 10 on placebo (p=0.049) | PMID 39870064 |
| Randomized, placebo-controlled | Injected into the penis with phentolamine, up to 6 months | Men with erectile dysfunction of mainly physical cause (171 in the placebo-controlled phase) | 75% responded vs 12% on placebo; flushing after 40% of 1,711 injections; one priapism (a prolonged erection) | PMID 10233493 |
| Crossover, placebo-controlled | IV infusion, 2 hours | 21 people with migraine without aura | Migraine attacks in 15 of 21 on VIP vs 1 of 21 on placebo | PMID 34357396 |
| Open-label, no placebo group | Inhaled, 3 months | 8 people with primary pulmonary hypertension (high blood pressure in the lungs) | Mean lung artery pressure fell from 59 to 46 mmHg; the 6-minute walk rose 113 m at 12 weeks | PMID 12727925 |
| Single-dose study, no placebo group | Inhaled once, during heart catheterization | 20 people with pulmonary hypertension | A small, short-lived fall in lung vessel resistance; more than 20% in 6 of 20 | PMID 18978135 |
| Open-label, no control group | Inhaled (nebulized), 4 weeks | 20 people with active sarcoidosis, an inflammatory lung disease | Lung immune cells made less TNF-α, and regulatory T cells rose | PMID 20442436 |
| Open-label, no placebo group | Nasal spray, 18 months or more | 20 people with CIRS after water-damaged-building exposure | Symptom score fell from 17.8 to 3.4 on VIP; blood VIP rose from 14.4 to 16.6 pg/mL; one brief rise in lipase, a pancreas enzyme | DOI 10.4236/health.2013.53053 |
| Animal study | Injected into the abdominal cavity, once or every other day (mice) | Mice with TNBS colitis, a model of Crohn's disease | Less weight loss, diarrhea and gut inflammation, even when started after the disease set in | PMID 12671893 |
05ChemistryMolecular identity
- Molecular weight
- 3,325.8 g/mol
- Molecular formula
- C₁₄₇H₂₃₈N₄₄O₄₂S
- Monoisotopic mass
- 3,323.7561 Da
- Sequence (28 AA)
- HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH₂ (C-terminal amide)UniProt P01282
- Structure / class
- Endogenous neuropeptide of the glucagon and secretin family; aviptadil is its synthetic drug form, the same moleculeUniProt P01282; FDA GSRS
- PubChem CID
- 16140438 (amidated VIP; the record titled Aviptadil, CID 16132300, is drawn without the C-terminal amide)PubChem
- InChIKey
- HEOYHMUESMJFDC-RIWXPGAOSA-NPubChem CID 16140438
- CAS / UNII
- 40077-57-4 · A67JUW790C (aviptadil); 37221-79-7 · 6J2WVD66KR (vasoactive intestinal peptide)FDA GSRS
- Water solubility
- Water-soluble (a highly polar peptide; computed XLogP3 −14.2)PubChem CID 16140438 (XLogP3); solubility by structural inference
- Molecular target
- VPAC1 and VPAC2, receptors that raise cAMP; PAC1 is the receptor of its sibling PACAPPMID 22289055
- Half-life
- About 1 minute (human, IV); no human nasal or subcutaneous pharmacokinetics publishedPMID 730072Half-life curve →
- Regulatory status
- Not FDA-approved in any form; FDA's May 14, 2026 list puts it in 503A Category 1, for substances under evaluation; four FDA orphan designations, none approved; approved in seven European jurisdictions only with phentolamine, as an injection for erectile dysfunctionFDA 503A category list, May 14, 2026; FDA orphan designations; EMA PSUSA/00010814/202202
- Anti-doping status
- Not named on the WADA 2026 Prohibited List; aviptadil's European approvals mean the S0 catch-all for unapproved drugs does not plainly applyWADA 2026
06Primary sourcesReferences
- PMID 5450698Said & Mutt, Science 1970;169(3951):1217–8 (VIP isolated from hog small intestine; vasodilation and lowered blood pressure)
- PMID 22289055Harmar et al., Br J Pharmacol 2012;166(1):4–17 (IUPHAR review of the VPAC1, VPAC2 and PAC1 receptors)
- PMID 15169929Delgado et al., Pharmacol Rev 2004;56(2):249–90 (VIP in immune regulation, review)
- PMID 730072Domschke et al., Gut 1978;19(11):1049–53 (human IV infusion: half-life about 1 minute, flushing, faster pulse)
- PMID 37348524Brown et al., Lancet Respir Med 2023;11(9):791–803 (TESICO: IV aviptadil vs placebo in COVID-19 respiratory failure)
- PMID 36044317Youssef et al., Crit Care Med 2022;50(11):1545–54 (IV aviptadil vs placebo in critical COVID-19 respiratory failure)
- PMID 41368449Udupa et al., Indian J Crit Care Med 2025;29(11):942–53 (aviptadil in ARDS, systematic review and meta-analysis)
- PMID 39870064Esendagli et al., Med Princ Pract 2025;34(2):191–200 (inhaled aviptadil vs placebo in hospitalized COVID-19)
- PMID 10233493Dinsmore et al., BJU Int 1999;83(3):274–9 (VIP with phentolamine for erectile dysfunction, placebo-controlled)
- PMID 34357396Pellesi et al., JAMA Netw Open 2021;4(8):e2118543 (2-hour VIP infusion and migraine attacks, placebo-controlled crossover)
- PMID 32594760Pellesi et al., Cephalalgia 2020;40(11):1212–23 (2-hour VIP infusion: delayed headache in healthy volunteers)
- PMID 12727925Petkov et al., J Clin Invest 2003;111(9):1339–46 (inhaled VIP in primary pulmonary hypertension)
- PMID 18978135Leuchte et al., Eur Respir J 2008;32(5):1289–94 (a single inhaled dose in pulmonary hypertension)
- PMID 20442436Prasse et al., Am J Respir Crit Care Med 2010;182(4):540–8 (inhaled VIP in sarcoidosis, open-label)
- DOI 10.4236/health.2013.53053Shoemaker et al., Health 2013;5(3):396–401 (nasal VIP in CIRS after water-damaged-building exposure, open-label)
- PMID 12671893Abad et al., Gastroenterology 2003;124(4):961–71 (VIP in the TNBS mouse model of Crohn's disease)
- ClinicalTrials.govClinicalTrials.gov NCT04311697, posted results (IV aviptadil vs placebo: diarrhea in 43 of 131 vs 1 of 65)
- FDAFDA, Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (updated May 14, 2026). Vasoactive intestinal peptide in Category 1, under evaluation
- EMAEMA, PSUSA/00010814/202202 (2022). Nationally authorised medicines containing aviptadil / phentolamine mesilate
- WADA 2026WADA 2026 Prohibited List (vasoactive intestinal peptide and aviptadil not named)
- PMID 22139413Delgado & Ganea, Amino Acids 2013;45(1):25–39 (VIP's immune functions, review: less TNF and IL-6, more IL-10)
Research use only · Not medical advice · Updated 2026-11-05