VIP (vasoactive intestinal peptide)

Summary

VIP (vasoactive intestinal peptide) is a 28 amino acid neuropeptide, a signaling peptide made by nerve cells, that relaxes smooth muscle, widens blood vessels, and dampens inflammation. Its synthetic form, aviptadil, has been tested in small pulmonary hypertension (high blood pressure in the lung arteries) studies and in two randomized COVID-19 respiratory failure trials, the largest of which (TESICO, 461 patients in the aviptadil comparison) found no improvement in recovery. It is not FDA approved for any indication; it sits in FDA 503A Category 1 (nominated compounding ingredients still under evaluation), which means compounding is currently tolerated while FDA decides, and it is sold as a compounded nasal spray for chronic inflammatory conditions without trial evidence.

What is VIP (vasoactive intestinal peptide)?

VIP (vasoactive intestinal peptide) is an endogenous 28 amino acid neuropeptide of the secretin/glucagon family. It is also known as Vasoactive intestinal polypeptide, Aviptadil, VIP nasal spray, RLF-100, Zyesami.

How does it work?

VIP binds the G protein coupled receptors VPAC1 and VPAC2, raising intracellular cyclic AMP. This relaxes vascular, airway, and gut smooth muscle, stimulates surfactant production by type II alveolar cells, and shifts macrophages and T cells toward anti inflammatory profiles by lowering TNF alpha, IL-6, and IL-12. It is degraded within minutes in plasma, which is why inhaled, intranasal, and continuous intravenous forms are used.

What does the evidence say about VIP (vasoactive intestinal peptide)?

Small human studies exist, and the randomized ones are negative or inconclusive. Petkov 2003 reported hemodynamic improvement in 8 patients with primary pulmonary hypertension after inhaled VIP, but Leuchte 2008 found only modest acute effects and limited chronic benefit in 20 patients. In COVID-19 respiratory failure, a 196 patient 60 day RCT (Youssef 2022) did not meet its primary endpoint, and the NIH sponsored TESICO trial (Brown 2023) found no benefit of intravenous aviptadil on recovery. No randomized trial supports the intranasal VIP used for chronic inflammatory response syndrome or mold illness.

Human evidence

Petkov 2003: 8 patients with primary pulmonary hypertension, inhaled VIP 200 ug daily, open label, reduced pulmonary artery pressure and improved 6 minute walk over 3 months. Leuchte 2008: 20 patients with pulmonary hypertension of various causes, single inhalation produced a small acute fall in pulmonary vascular resistance; chronic treatment in 9 patients produced modest changes. Youssef 2022: 196 patients with critical COVID-19 respiratory failure randomized to intravenous aviptadil or placebo; the primary endpoint (alive and free of respiratory failure at day 60) was not significantly different. Brown 2023 (TESICO): 461 patients randomized to aviptadil versus placebo within the ACTIV-3b platform; aviptadil did not improve recovery and the trial stopped for futility.

Animal evidence

In rodent and sheep models VIP reduces lung injury from endotoxin and hydrochloric acid, lowers pulmonary artery pressure, and protects against sepsis. VIP knockout mice develop pulmonary hypertension and airway inflammation. VIP also reduces disease severity in mouse models of colitis, rheumatoid arthritis, and experimental autoimmune encephalomyelitis, which underlies its immunology interest.

Key studies

Conditions studied

Is VIP (vasoactive intestinal peptide) legal in the United States?

FDA and compounding status

Not an FDA approved drug in the United States. An aviptadil and phentolamine combination is approved in some European countries for erectile dysfunction, and aviptadil was studied under FDA authorized COVID-19 trials but never authorized or approved. Vasoactive intestinal peptide appears on the FDA 503A bulk drug substances list as Category 1 (nominated and under evaluation), so 503A pharmacies may compound it while FDA finishes its review; it has not been placed on the bulks list and was not part of the April 2026 Category 2 removals or the July 2026 advisory committee recommendations.

WADA status

WADA status unclear. The current prohibited list does not name this compound explicitly and its class status is not settled. Athletes should ask their anti-doping organization before use.

Regulatory timeline

No regulatory events recorded.

Full tracker for VIP (vasoactive intestinal peptide) or the category-wide tracker.

What published studies of VIP (vasoactive intestinal peptide) used

Ranges below are reported from published studies and labeling only. PeptideAgent does not recommend doses or protocols.

Inhaled VIP about 200 ug per day in four divided inhalations for 3 months (Petkov 2003, primary pulmonary hypertension) or a single inhalation of 100 ug (Leuchte 2008). Intravenous aviptadil in COVID-19 trials was infused at escalating rates of 50, 100, and 150 pmol/kg/hour over 12 hours on three successive days (Youssef 2022). No dose for intranasal VIP in chronic inflammatory conditions has been established in a randomized trial.

Routes reported

What are the side effects and interactions of VIP (vasoactive intestinal peptide)?

Side effects

Interactions

Contraindications

How do people access VIP (vasoactive intestinal peptide) legally?

Typical cost: Roughly 150 to 400 USD per month for compounded intranasal VIP through a prescribing clinic, plus consultation fees. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.

• Rules by state
• Verified provider directory

What's actually offered, and what that means for you

Licensed compounding pharmacies, clinics, and telehealth prescribers openly offer many unapproved peptides, and prescribers write prescriptions for them. VIP (vasoactive intestinal peptide) is not FDA approved. It is a nominated bulk substance FDA has not finished evaluating, and pharmacies compound it under FDA's interim policy where state boards permit, without any FDA finding on its safety or quality. [5] [8]

Enforcement is uneven. FDA mostly acts through warning letters to compounders and online sellers, Category 2 safety listings, and import alerts that let it detain shipments, rather than stopping every pharmacy. State pharmacy boards oversee pharmacies day to day, and their rules differ. [9] [10] [11] [12] [13]

What changes for you

• No FDA review of the product: FDA does not check a compounded drug's safety, effectiveness, or quality before it is sold. [13]
• Identity, purity, sterility, and dose accuracy can vary from batch to batch. [11]
• Insurance rarely covers it, so you usually pay cash.
• For tested athletes, WADA status is unclear; ask your anti-doping organization before any use. [7]

What to check

Before you accept a compounded product, check for:

• A 503A pharmacy licensed in your state (your state board of pharmacy publishes license lookups). [13]
• A real evaluation by a licensed prescriber, not just an online form.
• A certificate of analysis for the specific batch.

Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.