VIP

VIP (vasoactive intestinal peptide) is a natural signaling molecule the body makes throughout the gut, lungs, nerves, and immune system, best known for relaxing blood vessels and airways and calming inflammation. Its synthetic version, aviptadil, has been tested in humans for severe COVID-19 lung failure, pulmonary hypertension, and erectile dysfunction, with mixed results. It is not FDA-approved for any use.

VIP (vasoactive intestinal peptide), as the drug aviptadil, has been studied for lung and circulatory conditions. Its core biology — relaxing blood vessels and airways, protecting lung cells, dampening inflammation — is well established, but human evidence for the drug is limited and mixed. It reached a Phase 3 program as an inhaled therapy for pulmonary arterial hypertension and has a long history as an injectable (with phentolamine) for erectile dysfunction. During the pandemic it was studied IV for critical COVID-19 under FDA expanded access, but the randomized TESICO trial found no significant day-90 benefit and that arm was stopped early for futility, and a 2025 review found no survival benefit. The drug is not approved, and the research-community uses of VIP are not supported by controlled human trials.

Not FDA-approved for any indication in the United States. The synthetic form, aviptadil, has been investigated (Phase 2/3) for critical COVID-19 respiratory failure, pulmonary arterial hypertension, and erectile dysfunction, and has held FDA trial/expanded-access authorizations — but it has not received US marketing approval, and its COVID-19 program did not demonstrate the primary benefit sought. WADA status: not specifically named on the Prohibited List; as an endogenous peptide the research-supply form is best treated with caution — athletes should verify with their anti-doping organization. Not DEA-scheduled.

VIP/aviptadil is not FDA-approved. Its most prominent effect is vasodilation, so the main acute concern is a drop in blood pressure, flushing, and diarrhea; IV infusion in trials was done with monitoring. It is not specifically named on the WADA Prohibited List, but as an endogenous peptide the research-supply form warrants caution in regulated sport — verify with your anti-doping organization. The research-community "CIRS"/wellness uses are not backed by controlled trials. VialWise is a research and educational reference, not medical advice.

⚠️ For research and educational purposes only. VIP (vasoactive intestinal peptide), including the synthetic form aviptadil, is not FDA-approved for any indication in the US. Information here is informational, not medical advice. Always confirm any dose calculation with the in-app calculator and consult appropriate professional guidance.

⚠️ Human evidence is limited and mixed — and the popular "CIRS" use is not trial-supported. VIP's endogenous biology (vasodilation, airway relaxation, anti-inflammatory signaling) is well established. But the synthetic drug's clinical record is incomplete: an inhaled Phase 3 program for pulmonary arterial hypertension,[²] a long-standing injectable use for erectile dysfunction,[³] and an intravenous COVID-19 program under expanded access that produced case reports of recovery[¹] but did not establish its primary endpoint in randomized trials.[⁴][⁵][⁶] The research-community use of intranasal VIP for "chronic inflammatory response syndrome (CIRS)" is not supported by controlled human trials.

⚠️ Potent vasodilator. VIP's defining acute effect is widening blood vessels. The main acute risks are hypotension (low blood pressure), flushing, and diarrhea. IV infusion in trials was performed with hemodynamic monitoring for this reason.

VIP (vasoactive intestinal peptide) is a naturally occurring 28-amino-acid signaling peptide first identified in the gut but produced throughout the body — in the nervous system, lungs, cardiovascular system, and immune cells. It belongs to the secretin/glucagon peptide family and acts through the VPAC1 and VPAC2 receptors. Its best-characterized actions are vasodilation (relaxing blood vessels), bronchodilation (relaxing airways), and broad anti-inflammatory and immunomodulatory signaling. The synthetic, manufactured form used clinically is called aviptadil.[¹][²]

Mechanism and rationale. In the lung, VIP binds the VPAC1 receptor on alveolar type II cells — the same cells implicated in severe viral pneumonia — where it is described as protecting against injury, supporting surfactant, and dampening cytokine signaling.[¹] Systemically, VIP relaxes vascular smooth muscle (lowering pulmonary pressures) and modulates immune activation. These properties underpin the several distinct clinical directions VIP has been taken.

Human evidence (mixed, by route). According to PubMed: - Critical COVID-19 respiratory failure (IV). Under an FDA-approved expanded-access protocol, IV aviptadil was given as escalating 12-hour infusions (50/100/150 pmol/kg/hr) to critically ill patients; a published case report described rapid clinical recovery in a pregnant patient, consistent with the alveolar-protection hypothesis.[¹] Case reports are hypothesis-generating, and the randomized evidence that followed was negative. In the NeuroRx/Zyesami Phase 2b/3 randomized controlled trial (Youssef et al., *Crit Care Med* 2022; NCT04311697, n=196), the primary endpoint — alive and free from respiratory failure at day 60 — did not reach significance (OR 1.6; 95% CI 0.86–3.11), though a secondary 60-day survival signal was reported (OR 2.0; 95% CI 1.1–3.9; p=0.035).[⁵] In the larger Phase 3 TESICO trial run by NIAID (Brown et al., *Lancet Respir Med* 2023; NCT04843761, n=471 for the aviptadil comparison), the primary ordinal endpoint at day 90 showed no benefit versus placebo (OR 1.11; 95% CI 0.80–1.55; p=0.54) and 90-day mortality was 38% versus 36% (HR 1.04; 95% CI 0.77–1.41; p=0.78); the data and safety monitoring board stopped the aviptadil arm for futility on May 25, 2022.[⁴] A 2025 systematic review and meta-analysis pooling the randomized trials reported a survival odds ratio of 1.01 (95% CI 0.72–1.42; p=0.93), concluding there was no significant survival benefit.[⁶] Aviptadil was not approved, and the FDA declined Emergency Use Authorization for Zyesami. - Pulmonary arterial hypertension (inhaled). Inhaled aviptadil advanced into a Phase 3 program as a candidate PAH therapy, reflecting VIP's pulmonary vasodilatory action.[²] - Erectile dysfunction (injection). Injectable aviptadil combined with the alpha-blocker phentolamine has a long development history as an intracavernosal therapy for erectile dysfunction, approved in a small number of countries (e.g., historically in New Zealand and the UK) but not in the US.[³]

Evidence quality. VIP's endogenous physiology is solid, but the synthetic drug's clinical efficacy is limited and, where randomized, negative — no US approval, two randomized COVID-19 trials that missed their primary endpoints, and a pooled meta-analysis showing no survival benefit.[⁴][⁵][⁶] Importantly, the popular research-community use — intranasal VIP for "chronic inflammatory response syndrome (CIRS)" — rests on a specific clinician's protocol and open-label reports, not controlled trials, and should be regarded as unproven.

Regulatory status (US). VIP/aviptadil is not FDA-approved for any indication and is not DEA-scheduled. Investigational aviptadil has held FDA trial and expanded-access authorizations, but that is not marketing approval.

Regulatory status (sport — WADA). VIP is not specifically named on the WADA Prohibited List. As an endogenous peptide hormone, the research-supply synthetic form is best treated cautiously in regulated sport; verify current status via the WADA Prohibited List and your National Anti-Doping Organization before any use.

Common research interests. Anti-inflammatory and immune modulation (including the unproven CIRS use), pulmonary conditions (PAH, acute lung injury), and — via the injectable phentolamine combination — erectile dysfunction. Most of these are extrapolated from endogenous biology or incomplete trials, not established human uses.

Commonly reported

• Hypotension (low blood pressure) and flushing — direct consequences of vasodilation; the main reason IV infusion is monitored
• Diarrhea — a well-known VIP effect (VIP is the mediator of "VIPoma"-associated watery diarrhea)
• Tachycardia / palpitations
• Additive hypotension with other vasodilators or antihypertensives
• Route-specific reactions — local irritation with intranasal use; injection-site or cavernosal effects with injectable use
• Unknown long-term safety for any non-medical protocol

Hypotension / hemodynamic instability — VIP's vasodilation makes it a specific concern for anyone with low blood pressure or on blood-pressure-lowering drugs

Concurrent vasodilators (nitrates, PDE5 inhibitors) — theoretical additive hypotension; caution

Pregnancy and lactation — no established safety; the COVID-19 case report was an exceptional expanded-access circumstance, not evidence of general safety[¹]

Pediatric use — no data; should not be used in researchers under 18

Known hypersensitivity — contraindicated

Regulatory note (US): Not FDA-approved; available only as research-supply material outside the FDA-recognized supply chain. Not DEA-scheduled.

Regulatory note (sport): Not specifically named on the WADA Prohibited List, but as an endogenous peptide the synthetic form warrants caution; verify with your anti-doping organization.

Vasoactive

Acting on blood vessels — VIP causes them to relax and widen (vasodilation), which is part of how it lowers pressure in the lungs.

Aviptadil

The synthetic, manufactured form of human VIP used in clinical trials.

Anti-inflammatory

Reducing inflammation. VIP dampens immune signaling, which is the basis for interest in it for inflammatory lung and immune conditions.

Alveolar type II cell

A lung cell that makes surfactant (which keeps air sacs open). VIP binds a receptor on these cells, part of the rationale for testing it in severe lung injury.

Expanded access

An FDA pathway that lets patients receive an investigational drug outside a formal trial when no approved option fits — how some patients received IV aviptadil during COVID-19.

1. Youssef JG, Bitar MZ, Zahiruddin F, Al-Saadi M, Elshawwaf M, Yau S, Goodarzi A, Javitt JC. (2022). Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide. Critical Care Explorations, 4(1):e0607.(PMID 35018346)
2. Mucke HAM. (2008). Pulmonary arterial hypertension: on the way to a manageable disease. Current Opinion in Investigational Drugs, 9(9):957–962.(PMID 18729002)
3. Keijzers GB. (2001). Aviptadil (Senatek). Current Opinion in Investigational Drugs, 2(4):545–549.(PMID 11566015)
4. Brown SM, et al. (2023). Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. The Lancet Respiratory Medicine, 11(9):791–803.(PMID 37348524 · NCT04843761)
5. Youssef JG, et al. (2022). The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Critical Care Medicine, 50(11):1545–1554.(PMID 36044317 · NCT04311697)
6. Udupa AA, et al. (2025). Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis. Indian Journal of Critical Care Medicine, 29(11):942–953.(PMID 41368449)

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