Is VIP (aviptadil) approved anywhere?

Yes, in a narrow indication: aviptadil combined with phentolamine (Invicorp) is approved in the UK and EU for erectile dysfunction via intracavernosal injection since 2000. For respiratory or inflammatory conditions, aviptadil is not approved by the FDA, EMA, or MHRA. India granted a conditional approval for severe COVID-19 ARDS in 2022. The FDA declined emergency use authorisation twice for the COVID-19 indication.

Did aviptadil work for COVID-19?

No, in the definitive trial. The TESICO Phase 3 RCT (n=461, Lancet Respiratory Medicine, 2023) found no benefit on the primary endpoint (patient status at day 90) and was stopped early for futility. An earlier smaller trial had suggested a survival benefit in a subgroup, but this was not confirmed. The FDA rejected emergency use.

What is VIP's half-life and why does it matter?

VIP has a plasma half-life of approximately 1–2 minutes, degraded by DPP-4 and NEP. This means continuous IV infusion is required to maintain systemic levels during therapy, and inhaled or intranasal routes deliver primarily local effects with rapid systemic clearance. This short half-life is the key pharmacokinetic limitation for therapeutic use.

What is intranasal VIP used for in the community?

Anecdotally, intranasal VIP is used by some individuals for chronic inflammatory response syndrome (CIRS), mould-related illness, and general anti-inflammatory purposes, primarily associated with clinician-led protocols (Shoemaker CIRS protocol). These uses have no controlled trial support and are not FDA-approved uses.

Is VIP on the WADA prohibited list?

VIP is an endogenous neuropeptide and as a vasodilator/anti-inflammatory it is not primarily a performance-enhancing compound in the traditional sense. Its WADA status is not as clearly defined as for EPO or anabolic steroids. Athletes should consult WADA guidance and their anti-doping authority, as non-approved peptides may fall under general prohibited categories.

Is synthetic VIP safe to use outside clinical trials?

Short-duration inhaled or intranasal use at low doses appears relatively well tolerated based on available data, but high-dose IV infusion causes significant vasodilatory side effects (hypotension, diarrhoea) at high rates. Research-grade synthetic VIP is unregulated for quality and purity. Clinical trial use outside of a supervised protocol is inadvisable.

Recovery

VIP

Also known as: Vasoactive Intestinal Peptide, Aviptadil, RLF-100, ZYESAMI

A 28-amino-acid endogenous neuropeptide with pleiotropic vasodilatory and anti-inflammatory effects; aviptadil (synthetic VIP) has been evaluated in Phase 2/3 human trials for...

Last updated July 11, 2026

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Overview

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide belonging to the secretin/glucagon superfamily. It was isolated and identified by Sami Said and Victor Mutt in 1970 and is widely expressed throughout the central and peripheral nervous systems, gastrointestinal tract, lungs, cardiovascular system, and immune tissues. It functions simultaneously as a neurotransmitter, vasodilator, bronchodilator, exocrine secretagogue, and immunomodulator. Synthetic human VIP, known commercially as aviptadil, has been investigated in clinical trials across several indications. Its most established approved use is a niche intracavernosal injection for erectile dysfunction (Invicorp, approved in the UK and EU since 2000), in combination with phentolamine. Inhaled aviptadil has been studied in a small but encouraging pilot trial for primary pulmonary hypertension. Intravenous aviptadil (branded as RLF-100/ZYESAMI) attracted significant attention during the COVID-19 pandemic as a potential lung-protective agent, but a definitive Phase 3 randomised controlled trial (the TESICO trial, n=461) reported no benefit on the primary endpoint, and the FDA declined emergency use authorisation twice. Because VIP is an endogenous peptide, it is also studied in the context of its endogenous role in sarcoidosis, inflammatory lung disease, and autoimmune conditions, where VIP deficiency has been detected. Research-use-only synthetic VIP peptide is available from laboratory suppliers; its use outside clinical trial contexts carries uncharacterised risks. This entry is for research and educational purposes only.

How it works

VIP acts primarily through two class-B G-protein-coupled receptors, VPAC1 and VPAC2, which are broadly expressed on smooth muscle, neurons, immune cells, and glandular tissue. Both receptors couple principally to Gs, activating adenylyl cyclase and raising intracellular cAMP, which drives smooth muscle relaxation (producing vasodilation, bronchodilation, and gut motility effects), regulates airway secretions, and modulates circadian rhythms. The anti-inflammatory and immunomodulatory effects are mediated largely through VPAC1 on resting immune cells (T cells, monocytes, neutrophils, dendritic cells), suppressing pro-inflammatory cytokine production (including IL-6 and TNF-α) while promoting regulatory T-cell (Treg) generation and secretion of anti-inflammatory mediators such as IL-10 and IL-1Ra. VPAC2 is preferentially expressed on activated T cells and contributes to immune tolerance signalling. In lung physiology, VIP upregulates surfactant production by type II pneumocytes and protects alveolar cells from cytokine-mediated injury, which was the rationale for trials in ARDS. VIP's plasma half-life of approximately 1–2 minutes — due to rapid degradation by DPP-4 and neutral endopeptidase (NEP) — is a major pharmacological constraint, requiring continuous IV infusion, repeated inhalation, or formulation modification for any sustained therapeutic effect.

Researched effects

Clinical Selective pulmonary vasodilation and improved functional capacity in primary pulmonary hypertension (small pilot, n=8, inhaled 200 µg/day)
Clinical Approved combined intracavernosal injection (with phentolamine) for erectile dysfunction (Invicorp, UK/EU)
Clinical Improved 60-day survival signal in a subgroup of COVID-19 patients with hypoxaemic respiratory failure in a Phase 2b/3 trial; not confirmed in subsequent larger trial
Preclinical Anti-inflammatory effects: suppresses IL-6, TNF-α, and COX-2; promotes IL-10 and Tregs in preclinical and in-vitro models
Preclinical Airway protective and surfactant-promoting effects in lung injury models
Anecdotal Anecdotal use for chronic inflammatory respiratory syndrome (CIRS) and mould-illness related conditions, intranasal route

Evidence levels: Clinical (human trials) · Preclinical (animal/lab) · Anecdotal (community-reported).

Dosing reference

For research reference only — not a recommendation.

Clinical / studied dosing

Inhaled aviptadil for pulmonary hypertension: 200 µg/day in four inhalations in the Petkov et al. 2003 pilot (n=8, 12–24 weeks). Intravenous aviptadil for COVID-19 respiratory failure (TESICO and earlier trials): escalating 12-hour infusions over 3 days — 50 pmol/kg/hr (Day 1), 100 pmol/kg/hr (Day 2), 150 pmol/kg/hr (Day 3). Intracavernosal (Invicorp): aviptadil 25 µg plus phentolamine 2 mg, on-demand for erectile dysfunction. All dosing figures from published trials; no approved dosing for research use.

Community-reported dosing (anecdotal)

Anecdotal and research-reference only; not medical advice. Community use of synthetic VIP peptide is primarily reported in the context of intranasal self-administration, typically 50–100 µg per dose, in patients or individuals exploring treatment for mould-related illness (CIRS) or inflammatory conditions. These protocols are derived from clinician-prescribed off-label intranasal use, most associated with the Shoemaker CIRS protocol, and are not supported by controlled trials. Subcutaneous research-use protocols are also reported but uncommon. Dosing ranges are not standardised and should be treated as reference points only.

Half-life: Approximately 1–2 minutes in plasma (human pharmacokinetic data), due to rapid enzymatic degradation by dipeptidyl peptidase-4 (DPP-4) and neutral endopeptidase (NEP). VIP concentrations fall to undetectable levels within 5–7 minutes of stopping intravenous infusion. This very short half-life necessitates continuous IV infusion for sustained systemic levels, repeated inhalation for respiratory delivery, or use of modified/stabilised analogues for other routes.
Routes: intravenous, intranasal, inhaled, intracavernosal

Safety & side effects

VIP's rapid degradation limits systemic side effects from brief exposure, but sustained dosing (as in IV infusion) produces vasodilation-related effects. In the TESICO Phase 3 trial (n=461), infusion reactions were substantially more common in the aviptadil arm: any adverse infusion reaction 86.6% versus 57.4% for placebo; diarrhoea 39.8% vs 11.3%; hypotension 58.4% vs 41.3%. These adverse event rates at the high IV doses used in ARDS treatment substantially exceeded those in the inhaled pulmonary hypertension studies. Inhaled administration at 100–300 µg/day has generally been well tolerated in small trials. The intracavernosal combination product (Invicorp) has an established safety record in its approved indication. VIP is an endogenous peptide and synthetic versions appear physiologically benign in short exposures, but high-dose or sustained IV use carries haemodynamic risk. Research-grade synthetic VIP for non-clinical routes (intranasal, subcutaneous) has not been evaluated in controlled safety studies. It is not approved for research self-use and should be regarded as an experimental compound.

Research summary

VIP's endogenous biology and pharmacology are among the best characterised of any research peptide — the VPAC1/VPAC2 receptor system, cAMP signalling, vasodilatory effects, and anti-inflammatory properties are established at the Grade A level in peer-reviewed literature. The clinical translation story is more complicated and ultimately cautionary. The strongest clinical signal remains the 2003 Petkov et al. pilot (n=8) in primary pulmonary hypertension, which showed striking haemodynamic and functional improvements with 200 µg/day inhaled VIP. This small open-label study has not been followed by a larger RCT with published results, leaving the pulmonary hypertension indication unconfirmed at scale. The COVID-19 ARDS programme generated early excitement when a Phase 2b/3 trial (NCT04311697, n=196) reported a secondary survival benefit and subgroup improvements in patients on high-flow nasal cannula. This attracted FDA Fast Track designation and media coverage. However, the subsequently powered TESICO trial (NCT04843761; Brown et al., Lancet Respiratory Medicine, 2023; n=461) was definitively negative on its primary endpoint (ordinal outcome at day 90: OR 1.11, 95% CI 0.80–1.55, p=0.54), and the FDA declined emergency use authorisation twice. TESICO was stopped early for futility. The COVID-19 programme illustrated how compelling early-phase signals can fail in adequately powered confirmatory trials — a lesson relevant to interpreting all research-peptide evidence. Intranasal VIP for CIRS and inflammatory conditions has a community following but essentially no RCT evidence. The honest summary: VIP's mechanism is real, its approved use is narrow (intracavernosal ED), its best clinical application (PAH) remains pilot-level, and its highest-profile recent trial (COVID-19 ARDS) failed.

FAQ

Is VIP (aviptadil) approved anywhere?: Yes, in a narrow indication: aviptadil combined with phentolamine (Invicorp) is approved in the UK and EU for erectile dysfunction via intracavernosal injection since 2000. For respiratory or inflammatory conditions, aviptadil is not approved by the FDA, EMA, or MHRA. India granted a conditional approval for severe COVID-19 ARDS in 2022. The FDA declined emergency use authorisation twice for the COVID-19 indication.
Did aviptadil work for COVID-19?: No, in the definitive trial. The TESICO Phase 3 RCT (n=461, Lancet Respiratory Medicine, 2023) found no benefit on the primary endpoint (patient status at day 90) and was stopped early for futility. An earlier smaller trial had suggested a survival benefit in a subgroup, but this was not confirmed. The FDA rejected emergency use.
What is VIP's half-life and why does it matter?: VIP has a plasma half-life of approximately 1–2 minutes, degraded by DPP-4 and NEP. This means continuous IV infusion is required to maintain systemic levels during therapy, and inhaled or intranasal routes deliver primarily local effects with rapid systemic clearance. This short half-life is the key pharmacokinetic limitation for therapeutic use.
What is intranasal VIP used for in the community?: Anecdotally, intranasal VIP is used by some individuals for chronic inflammatory response syndrome (CIRS), mould-related illness, and general anti-inflammatory purposes, primarily associated with clinician-led protocols (Shoemaker CIRS protocol). These uses have no controlled trial support and are not FDA-approved uses.
Is VIP on the WADA prohibited list?: VIP is an endogenous neuropeptide and as a vasodilator/anti-inflammatory it is not primarily a performance-enhancing compound in the traditional sense. Its WADA status is not as clearly defined as for EPO or anabolic steroids. Athletes should consult WADA guidance and their anti-doping authority, as non-approved peptides may fall under general prohibited categories.
Is synthetic VIP safe to use outside clinical trials?: Short-duration inhaled or intranasal use at low doses appears relatively well tolerated based on available data, but high-dose IV infusion causes significant vasodilatory side effects (hypotension, diarrhoea) at high rates. Research-grade synthetic VIP is unregulated for quality and purity. Clinical trial use outside of a supervised protocol is inadvisable.

References

All content is for research and educational use only and is not medical advice. Products are sold for laboratory research only and are not for human consumption.