VIP peptide (vasoactive intestinal peptide): what the trials found, what is licensed and what is unknown

VIP peptide is the abbreviation for vasoactive intestinal peptide, a 28-amino-acid chain the body makes itself. In 1970 Sami Said and Viktor Mutt isolated a polypeptide from hog small intestine that lowered blood pressure, increased cardiac output, stimulated breathing and raised blood sugar, and showed it was chemically distinct from the kinins, substance P, glucagon and secretin ^[1]. Four years later Mutt and Said published its full amino-acid sequence ^[2]. In 1977 Fuxe and colleagues showed by immunohistochemistry that VIP is also present in central and peripheral neurons, including cortical interneurons, which is why it is classed as a neuropeptide as well as a gut hormone ^[3].

VIP belongs to the same structural family as glucagon, secretin, the GLP-1 peptides and growth-hormone-releasing hormone, and it acts through two G-protein-coupled receptors, VPAC1 and VPAC2, which it shares with the related peptide PACAP ^[4]. Those receptors are found on blood vessels, airway and gut smooth muscle, the pancreas and immune cells, which explains why one peptide has so many actions.

The synthetic version of VIP used in medicine has the international non-proprietary name aviptadil. Aviptadil and VIP have the same sequence. Research peptide stores sell the same molecule under the names VIP, VIP peptide or vasoactive intestinal peptide, usually as a freeze-dried vial, and sometimes as a pre-made nasal spray. PepFinder lists only vials. VIP is grouped on this site with other neuropeptides such as Semax, Selank and oxytocin, although its physiology is closer to the incretin hormones than to the Russian nootropic peptides.

VIP relaxes smooth muscle in blood vessels, airways and the gut, and it does so partly by raising cyclic AMP inside cells after binding VPAC1 or VPAC2 ^[4]. In the lungs it is one of the main relaxing neurotransmitters of the airways and pulmonary vessels. In a study of six healthy volunteers, intravenous VIP raised heart rate and lowered diastolic blood pressure, and increased forearm blood flow when infused into an artery, while the related peptide PHV had a longer half-life but weaker vasodilating action; the authors noted that VIP itself has a short half-life in circulation ^[5].

VIP is also an immunoregulatory peptide. It is made by immune cells as well as neurons, and those cells carry VIP receptors. A 2015 review from Temple University summarised evidence that VIP reduces production of inflammatory cytokines by macrophages and T cells, promotes regulatory T cells, and improves outcomes in animal models of inflammatory and autoimmune disease ^[6]. The IUPHAR review adds roles in circadian rhythm, learning and memory, stress responses, insulin secretion and catecholamine release ^[4].

These properties explain the range of conditions VIP has been studied in: pulmonary hypertension, because it dilates pulmonary vessels; sarcoidosis and acute lung injury, because it dampens macrophage activity; and erectile dysfunction, because it relaxes penile smooth muscle. They also explain the side effects seen when it is given systemically, which are flushing, a faster heart rate and a fall in blood pressure ^[5].

Claims about VIP peptide benefits online tend to draw on its natural physiology, and on animal work summarised in the immunology reviews ^{[4] [6]}, rather than on treatment trials. The clinical evidence, which is unusually rich for a peptide sold by research stores, is set out below by condition.

Pulmonary hypertension: in a 2008 study, 20 patients with pulmonary hypertension of mixed causes inhaled a single 100 µg dose of aviptadil during right-heart catheterisation. It produced a small, temporary but significant selective pulmonary vasodilation, improved stroke volume and mixed venous oxygen saturation, and reduced pulmonary vascular resistance by more than 20% in six patients, without side effects or a fall in systemic blood pressure. The effect was modest and short-lived ^[7].

Sarcoidosis: in an open-label phase 2 study, 20 patients with active sarcoidosis inhaled nebulised VIP for four weeks. Treatment was well tolerated, significantly reduced TNF-alpha production by cells washed from the lungs, and increased the number of regulatory T cells in the airways. The authors described it as the first demonstration of an immunoregulatory effect of VIP in humans ^[8]. There was no placebo group.

Erectile dysfunction: aviptadil combined with the alpha-blocker phentolamine is a licensed intracavernosal injection (Invicorp) in the UK, discussed under Regulatory status. In the largest published series, 308 men at a London centre who had failed or could not tolerate alprostadil injections were taught to self-inject aviptadil with phentolamine; 59% found it effective at three months, rising to 76% among men referred because alprostadil was painful. The most common adverse event was facial flushing (22.5%), and ischaemic priapism occurred in one patient (0.3%) ^[9].

COVID-19 respiratory failure: this is the most heavily studied use and is covered in the next section. In short, one trial was positive on survival but not its primary endpoint, and a larger independent trial found no benefit.

VIP peptide for CIRS, mould illness or chronic fatigue: VIP nasal spray is widely promoted for chronic inflammatory response syndrome. We found no randomised trial of VIP in that setting indexed in PubMed, and no published trial of VIP nasal spray at all. The sarcoidosis study is the closest human evidence for an anti-inflammatory effect, and it used a nebuliser in a hospital, not a nasal spray at home ^[8].

The first randomised trial was run by NRx Pharmaceuticals at ten US hospitals and registered as NCT04311697 ^[10]. It randomised 196 patients with critical COVID-19 respiratory failure 2:1 to three days of intravenous aviptadil or placebo. The primary endpoint, being alive and free of respiratory failure at day 60, did not reach statistical significance (odds ratio 1.6, 95% CI 0.86 to 3.11). The trial did report a statistically significant two-fold odds of survival at 60 days (odds ratio 2.0), a reduction in interleukin-6 by day 3, and no drug-related serious adverse events ^[11]. An accompanying editorial in the same journal used the trial as a case study in the difficulties of drug research during a pandemic, pointing to the negative primary endpoint and the weight placed on secondary analyses ^[12].

The US FDA declined the company’s request for emergency use authorisation of aviptadil, under the name Zyesami, on 4 November 2021, citing insufficient data on the known and potential benefits and risks in patients with critical COVID-19; the FDA had reviewed safety data in 131 randomised patients at that point ^[13]. A second EUA request for a subgroup was declined in July 2022.

The definitive test was TESICO (ACTIV-3b), a randomised, placebo-controlled trial run by the US National Institutes of Health at 28 sites and registered as NCT04843761 ^[14]. It enrolled 473 patients with COVID-19 acute hypoxaemic respiratory failure, of whom 461 received at least part of an infusion of aviptadil (231) or placebo (230). Aviptadil was given as a 12-hour infusion on each of three days, at 600, 1,200 and 1,800 pmol/kg. The independent monitoring board stopped the aviptadil arm for futility in May 2022. At day 90 the odds ratio for a better outcome with aviptadil was 1.11 (95% CI 0.80 to 1.55, p = 0.54), and 38% of the aviptadil group had died compared with 36% of the placebo group. The composite safety outcome up to day 5 occurred in 63% of aviptadil patients and 56% of placebo patients, a difference that was not statistically significant ^[15].

Taken together, the aviptadil COVID story is a clear example of why secondary endpoints in a company-run trial need an independent replication. The larger, NIH-run trial found no benefit. A separate trial of inhaled aviptadil for severe COVID-19 (NCT04360096) was terminated after enrolling 144 patients, and inhaled aviptadil has since been reported for post-COVID lung damage in a small study ^[18], but no randomised result supports it.

In the human studies, VIP acted within minutes when given into a vein or inhaled: the pulmonary vasodilation after inhaled aviptadil was measured during the same catheterisation session and was short-lived ^[7], and intravenous VIP changed heart rate and blood pressure during the infusion itself ^[5]. The peptide is cleared from blood quickly ^[5], which is why the COVID trials gave it as a continuous 12-hour infusion ^[15] and why the immune effects in sarcoidosis were assessed after four weeks of daily inhalation ^[8]. These timelines apply to intravenous, inhaled and intracavernosal use in trials; no published study has measured how quickly, or whether, a nasal spray or subcutaneous injection of VIP bought online does anything.

The doses below are what studies used. They are not recommendations, they were given under medical supervision by routes that are not the ones sold to consumers, and the largest trial found no benefit. Inhaled: a single 100 µg dose of aviptadil in pulmonary hypertension ^[7], and nebulised VIP daily for four weeks in sarcoidosis ^[8]. Intravenous: 12-hour infusions on three consecutive days at 600, 1,200 and 1,800 pmol/kg in TESICO ^[15], which for a 70 kg adult works out at roughly 140, 280 and 420 µg per day based on a molecular weight of about 3,327 g/mol. Intracavernosal: 25 µg aviptadil with 2 mg phentolamine per injection in the licensed product ^[16]. Intra-arterial and intravenous infusions in the 1990 volunteer study produced measurable cardiovascular effects at circulating concentrations far below those achieved with the related peptide PHV ^[5].

Vendor protocols for VIP nasal spray, typically quoted as a fixed number of micrograms per spray several times a day, do not come from any of these studies. There is no published dose-finding study for nasal VIP. Our peptide calculator converts vial contents to concentration for record-keeping, and the VIP calculator page is pre-set for this peptide, but neither implies a dose.

Every human study of VIP used one of three routes: intravenous infusion ^{[5] [11] [15]}, inhalation as an aerosol or nebulised solution ^{[7] [8]}, or injection into the penis ^{[9] [16]}. We found no published human study of VIP given subcutaneously or as a VIP peptide nasal spray, which are the two forms most often sold. VIP is broken down quickly in blood ^[5], and there are no published data on how much of a nasal dose reaches the bloodstream or the brain. The oral route is not used because the peptide would be digested.

Research peptide stores sell VIP as a freeze-dried powder in vials, usually 2 mg, 5 mg or 10 mg, for reconstitution with bacteriostatic water. Some also sell pre-mixed nasal sprays. PepFinder lists only vials, because a pre-mixed spray cannot be matched against a certificate of analysis for the powder it was made from.

VIP is a vasodilator, so its expected effects are also its side effects. In healthy volunteers, intravenous VIP raised heart rate and lowered diastolic blood pressure ^[5]. In the erectile dysfunction series, facial flushing affected 22.5% of men and one man in 308 had ischaemic priapism ^[9]. Inhaled aviptadil in pulmonary hypertension caused no side effects at 100 µg ^[7], and nebulised VIP was well tolerated over four weeks in sarcoidosis ^[8].

In the COVID-19 trials, the NRx trial reported no drug-related serious adverse events ^[11], while in TESICO the composite of death, serious adverse events, organ failure, serious infection or grade 3 to 4 adverse events by day 5 was numerically higher with aviptadil (63% versus 56%), a difference that did not reach statistical significance but does not support the idea that intravenous VIP is free of risk in very sick patients ^[15]. VIP also raises blood sugar, as Said and Mutt noted in the original description ^[1], and it stimulates insulin release ^[4], so its net effect on glucose in a given person is not predictable.

The safety of long-term nasal or subcutaneous VIP has not been studied. Because VIP has receptors on immune cells and can shift immune responses ^[6], the effect of chronic dosing on infection risk or autoimmunity is unknown. VIP receptors are also expressed on some tumours, including breast and lung cancers, and have been proposed as a drug and imaging target for that reason ^[17]; no study has examined whether giving VIP affects tumour growth in people.

In the UK, aviptadil is an approved medicine only in combination with phentolamine mesilate as Invicorp, a 25 µg/2 mg intracavernosal injection for erectile dysfunction. The Scottish Medicines Consortium accepted it for restricted use in NHS Scotland in December 2017, for men who have failed oral PDE5 inhibitors and other non-injectable treatments ^[16]. That authorisation does not extend to VIP sold as a research peptide, to nasal sprays or to any other indication. See our UK legal status page.

In the US, aviptadil is not an approved drug. The FDA declined emergency use authorisation for COVID-19 in November 2021 ^[13] and again in July 2022, and the NIH trial that followed was negative ^[15]. VIP does not appear on the FDA’s list of compounding bulk substances that were nominated and withdrawn, nor in its category 2 list, as of the page current in 2026, so it has no compounding status either way. See the US legal status page and our legal status overview for Canada, Australia and Europe.

VIP is supplied as a freeze-dried powder. It contains a methionine residue, which can oxidise, so it should be kept cold, dry and away from light, and reconstituted solution should be refrigerated and used within a limited period. See how to store peptides and what research peptides are for general handling.

VIP is a 28-residue peptide, long enough that synthesis errors and truncated sequences are a real risk, so a certificate of analysis matters. A COA for VIP should report a measured mass close to 3,327 g/mol and a purity figure from HPLC; our guide to reading a peptide COA explains what to look for, and the third-party testing guide covers why a vendor’s own certificate is not enough.

You can compare VIP prices, including VIP in the UK, VIP in the US and VIP in Australia, and see our list of third-party tested suppliers. Prices are compared per milligram; our guide to peptide prices explains how. A listing is not a statement that a product is legal to buy or appropriate to use.