VIP (vasoactive intestinal peptide)

BLicensed narrowly (ED, some countries); other uses unapprovedImmune, antimicrobial and repair-signal peptides →aviptadilvasoactive intestinal peptideZyesami
In one paragraphVasoactive intestinal peptide is a natural hormone that relaxes smooth muscle and blood vessels and dampens inflammation, made throughout the gut, lungs and nervous system. As the drug aviptadil it is licensed in the UK and some other countries — combined with phentolamine as an injection into the penis — for erectile dysfunction. Its pandemic moment came as an intravenous treatment for COVID-19 respiratory failure: the NIH-run TESICO trial of 461 patients was stopped for futility, with no improvement in outcomes or survival. The nasal-spray use promoted for 'chronic inflammatory response syndrome' from mould exposure has never been tested in a controlled trial.
Schematic 3D structure of VIP (vasoactive intestinal peptide)
28 residues · amphipathic helix, secretin family · schematic
Overall gradeB Probable
Human trialsTESICO RCT (n=461) + earlier sponsor RCT; small trials in ED and pulmonary hypertension
Outcomes graded6
Last reviewed10 September 2026
EvidenceWhat it isHow it worksUnknownsMolecule & PKRegulationQuestionsReferences

What the human research shows

A real hormone with one narrow licence, one large clean negative, and a popular use with no evidence at all — the grades below track exactly that split.

MetabolicCardioMuscleHealingNeuroImmuneSexualSkinAgeing

Evidence profile0–5

  • Metabolic & weight—0.0
  • Cardiovascular—0.0
  • Muscle & growth—0.0
  • Healing & repair—0.0
  • Neuro & sleep—0.0
  • Immune & inflammationA0.0
  • Sexual & hormonalB2.3
  • Skin & appearance—0.0
  • Ageing & longevity—0.0
Each score is confidence × effect size, taken from the best-evidenced benefit in that domain: the grade (A–D) sets the confidence, the measured effect sets the size. Hover a domain to see the outcomes behind it. Adverse effects are excluded and listed separately below.
OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
COVID-19 respiratory failure (intravenous)AEstablishedNot measurable1 large RCT (n=461) — stopped for futilityIn the NIH-funded TESICO trial, three days of intravenous aviptadil did not improve the 90-day outcome or survival; the safety monitoring board stopped it for futility. An earlier, smaller sponsor-run trial had reported benefit in some analyses.12
Survival in COVID-19 respiratory failureAEstablishedNot measurableTESICODeaths by day 90 were 38% on aviptadil and 36% on placebo.1
Erectile dysfunction (intracavernosal, with phentolamine)BProbableModerateLicensing trialsThe combination injection produces erections sufficient for intercourse in a majority of men in the trials behind its UK and Danish licences; a niche option where PDE5 inhibitors fail or are unsuitable.3
Pulmonary hypertension (inhaled)CWeakSmallSmall studiesInhaled VIP lowered pulmonary pressures acutely in small open studies; a development programme did not reach approval.4
'Mould illness' / CIRS (nasal spray)DNo human evidenceNot measurableNone controlledThe use it is most sold for online. No randomised trial exists; the diagnosis itself is not recognised by mainstream medicine. Claims rest on a single practitioner's uncontrolled case series.5
Adverse effectsadverseAEstablishedSmallTESICO + licensing dataFlushing, low blood pressure, diarrhoea and fast heart rate with systemic doses; in TESICO the composite safety outcome was numerically worse on aviptadil without reaching significance. Intracavernosal use: pain and prolonged erection.13
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 10 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

Registered trials

ClinicalTrials.gov lists 8 interventional studies naming VIP (vasoactive intestinal peptide) as an intervention — 4 completed, and 3 with results posted to the registry.

A registration is not a result. Anyone can register a study, and many never report — so this list shows what has been attempted, not what has been shown. The graded evidence above is the answer to whether something works.

StudyPhaseStatusParticipantsSponsorResults
ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19NCT04843761 · started Apr 2021Phase 3Completed473National Institute of Allergy and Infectious Diseases (NIAID)Posted
Aviptadil for Severely Ill Inpatients With COVID-19 (An ACTIV-3b/TESICO Treatment Trial)NCT06729606 · started Apr 2021Phase 3Completed471National Institute of Allergy and Infectious Diseases (NIAID)Posted
Intravenous Aviptadil for Critical COVID-19 With Respiratory FailureNCT04311697 · started May 2020Phase 2Completed203APR Applied Pharma Research s.a.Posted
Inhaled ZYESAMI (Aviptadil Acetate) for Treatment of Severe COVID-19NCT05137795 · started Dec 2021Phase 3Withdrawn0APR Applied Pharma Research s.a.None
I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill PatientsNCT04488081 · started Jul 2020Phase 2Active not recruiting1,500*QuantumLeap Healthcare CollaborativeNone
Inhaled ZYESAMI™ (Aviptadil Acetate) for the Treatment of Severe COVID-19NCT04360096 · started Feb 2021Phase 2Terminated144APR Applied Pharma Research s.a.None
Inhaled Aviptadil for the Treatment of COVID-19 in Patients at High Risk for ARDSNCT04536350 · started May 2021Phase 2Terminated83Prof. Dr. Jörg LeuppiNone
A Clinical Study Evaluating Inhaled Aviptadil on COVID-19NCT04844580 · started Mar 2021Phase 2Completed80Centurion PharmaNone

Participant counts marked * are the sponsor's estimate, not a final enrolment. Source: ClinicalTrials.gov, read directly from the registry and refreshed weekly.

What it is

VIP was isolated from pig gut in 1970 and turned out to be one of the body's most widely distributed neuropeptides — a vasodilator, a bronchodilator, a regulator of gut secretion and an anti-inflammatory signal in the lung. Aviptadil is the synthetic drug form.

Its licensed niche is small: Invicorp, aviptadil with phentolamine, injected into the penis for erectile dysfunction in the UK, Denmark and a few other countries. Its widest exposure was in 2020–22, when a company promoted intravenous aviptadil for COVID-19 under the name Zyesami; the FDA declined emergency authorisation and the NIH trial then found no effect.

How it is thought to work

It binds VPAC1 and VPAC2 receptors, raising cyclic AMP in smooth muscle and immune cells: vessels and airways relax, and in the lung it protects type 2 alveolar cells and suppresses cytokine release in animal models — the rationale for the COVID trials, which the human results did not support.

What is still unknown

  • Whether any inhaled or intranasal formulation delivers a meaningful dose — the peptide is degraded in minutes.
  • Whether the 'mould illness' use does anything; it has never been tested.

The molecule and how long it lasts

Identity
Formula
C147H237N43O43S
Molecular weight
3326.8 g/mol
CAS number
40077-57-4
PubChem
CID 16132300

PubChem record, read 23 September 2026.

Pharmacokinetics
Route
Intravenous infusion (healthy volunteers); intracavernosal in the licensed product
Half-life
About 1 minute (intravenous)

From a published human pharmacokinetic study: Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut 1978;19:1049

Regulatory status

European Union
Authorised in some member states (ED, with phentolamine)

Invicorp is licensed nationally in Denmark and others for erectile dysfunction; no authorisation for any other use.

United States
Not approved

Emergency authorisation for COVID-19 was sought and not granted; no approved aviptadil product.

United Kingdom
Licensed, prescription-only (Invicorp, ED)

Licensed for erectile dysfunction as an intracavernosal injection with phentolamine. Nasal VIP is unlicensed.

Australia
Not registered

Not on the ARTG.

Canada
Not authorised

No Health Canada authorisation.

Sport (WADA)
Not prohibited

Not on the Prohibited List.

Questions people actually ask

Did VIP work for COVID-19?
No. The NIH-funded TESICO trial of 461 patients with respiratory failure was stopped for futility: no improvement in recovery and no survival benefit. A smaller sponsor trial had suggested otherwise.
Does nasal VIP treat mould illness or CIRS?
There is no controlled trial, and the diagnosis is not recognised by mainstream medicine. The claims come from one practitioner's uncontrolled patient series.
Is VIP approved anywhere?
Yes, narrowly: as an injection into the penis, combined with phentolamine, for erectile dysfunction in the UK, Denmark and a few other countries. Not in the US, and not for any inhaled or nasal use.

One page per claimed effect

References

  1. 1
  2. 2
  3. 3
    Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.MHRA / emc, UKLicensed use in erectile dysfunction.
  4. 4
  5. 5

Change log

  • 2026-09-10Initial publication. COVID rows carry a high-certainty null (A, effect none); ED graded B on licensing data; CIRS use D.