VIP peptide (vasoactive intestinal peptide) is a natural 28-amino-acid signaling molecule first isolated from pig intestine in 1970.[2] It is made by nerves and immune cells throughout the body and widens blood vessels, relaxes smooth muscle and calms some immune responses.[3] A synthetic version, aviptadil, failed a large NIH-funded COVID-19 trial,[6] but in combination with phentolamine it is authorized in some European countries for erectile dysfunction.[12][13] In the US it is not FDA-approved, though compounded VIP nasal spray is used off-label, mainly for chronic inflammatory response syndrome (CIRS).[1][15]

What is VIP peptide?

VIP belongs to the secretin family of peptides. It acts on two receptors, VPAC1 and VPAC2, and relaxes smooth muscle in blood vessels and airways.[3][19] Nerves and immune cells release it, and many cell types, including immune cells, carry VIP receptors.[3] Its main jobs include:

  • Blood flow: relaxing blood vessel walls, which is why it causes flushing.[2][4]
  • Gut: triggering fluid secretion; tumors that overproduce VIP cause severe watery diarrhea.[3][16]
  • Immune system: dampening inflammatory signals from immune cells in lab and animal studies.[3]
  • Brain: acting as a neurotransmitter in the central nervous system.[3]

VIP breaks down very fast. In healthy volunteers given IV VIP, blood levels fell by half in about one minute after the infusion stopped.[4] That short life, and the difficulty of delivering it, have limited its use as a medicine.[19]

Aviptadil and COVID-19

During the pandemic, NeuroRx (later NRx Pharmaceuticals) and Relief Therapeutics developed IV aviptadil, branded Zyesami (also called RLF-100), for COVID-19 respiratory failure.[8]

  • NeuroRx trial: in 196 patients, aviptadil missed its primary endpoint (alive and free of respiratory failure at day 60). The company pointed to a secondary survival analysis as a positive sign.[5]
  • FDA decision: in November 2021, FDA reportedly declined to grant an emergency use authorization. According to trade-press coverage, regulators said there was not enough data on benefits and risks, having reviewed safety data on only 131 randomized patients treated with the drug.[7]
  • TESICO (NIH): in 461 patients, the trial was stopped for futility in May 2022. Aviptadil did not improve recovery, and 90-day deaths were 38% with aviptadil and 36% with placebo. Serious problems in the first five days occurred in 63% vs 56%, a difference that was not statistically significant.[6]
  • Aftermath: in its quarterly report for mid-2022, NRx told investors it had suspended development of Zyesami after the NIH trial was stopped and had no plans to invest further in it.[8]

A smaller 80-patient trial of inhaled aviptadil in Turkey reported shorter hospital stays (7.8 vs 10 days),[9] and an older study found a small, short-lived drop in lung blood pressure after a single inhaled dose in pulmonary hypertension.[17] Neither has led to approval.

VIP for erectile dysfunction (Invicorp)

Invicorp combines aviptadil (25 micrograms) with phentolamine, injected into the penis.[10] VIP mainly helps trap blood in the penis, while phentolamine increases blood flow in.[10]

  • Head-to-head trial: in 187 men, VIP/phentolamine and alprostadil produced similar erection rates in the second phase (in the first, dose-finding phase alprostadil worked in more men, 83% vs 73%), but injection pain occurred with 3% of VIP/phentolamine injections vs 28% for alprostadil. Facial flushing was more common with VIP/phentolamine (16% to 17% vs 3%).[11]
  • UK experience: in a 2025 London series of 308 men who had failed or could not tolerate alprostadil, 59% found it effective. Facial flushing affected 22.5%, and one man (0.3%) had priapism.[14]
  • Regulators: Scotland’s medicines body accepted it for restricted NHS use in December 2017, for men who had failed oral tablets and other non-injected treatments.[12] France’s health authority, while noting it is authorized there, judged in 2019 that its clinical benefit was too low to justify reimbursement.[13]

It is not FDA-approved. For a US-approved melanocortin drug in sexual health, see PT-141.

VIP nasal spray for CIRS (the Shoemaker protocol)

CIRS (chronic inflammatory response syndrome) is a diagnosis used by some clinicians for multi-symptom illness after exposure to water-damaged, moldy buildings. Nasal VIP is the last step in a treatment protocol developed by Dr. Ritchie Shoemaker.[15]

The main published study, written by Shoemaker and colleagues, treated 20 patients whose illness had not responded to the earlier steps with 50 micrograms of nasal VIP four times a day at first, with the dose then adjusted, and followed them for 18 months. The authors reported that symptoms and several blood markers returned toward normal, with no dropouts for side effects; levels of the pancreatic enzyme lipase, which they monitored, did not rise.[15]

VIP peptide dosage

The only dose with a regulatory review behind it is Invicorp: 25 micrograms of aviptadil with 1 or 2 mg of phentolamine, injected into the penis, used as needed.[10] The CIRS protocol used 50 micrograms per nasal spray, up to four times a day.[15] The COVID-19 trials used 12-hour IV infusions in hospital.[6] None of these has been tested for long-term use as an immune or brain supplement. For general vial math, see our peptide calculator.

VIP side effects

  • Flushing and fast heart rate: seen in volunteers given IV VIP,[4] and the most common side effect with Invicorp.[11][14]
  • Low blood pressure: VIP was first described as a potent blood vessel widener that lowers blood pressure.[2]
  • Priapism and penile scarring: rare but serious risks with penile injection.[13][14]
  • Diarrhea and low potassium: seen in people with VIPomas, rare tumors that pour out VIP continuously, which shows what sustained high levels can do.[16]
  • US: not FDA-approved. VIP is listed in Category 1 of FDA’s 503A compounding list (“under evaluation”), updated May 14, 2026.[1] That is an interim status, not approval, and FDA has not decided whether to add it to the permanent list.
  • Europe: aviptadil with phentolamine is authorized for erectile dysfunction in some countries, including France and the UK.[12][13]
  • Sports: VIP is not named on WADA’s 2026 list. The S0 category covers substances with no government approval for human use; because aviptadil is approved in some countries, it is unclear in our reading whether S0 applies. Athletes should check with their anti-doping agency.[18]

This is general information, not legal advice. For other immune peptides, see thymosin alpha-1, KPV and our immune peptides page.