Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide (MW ~3326.8 g/mol) widely distributed in the central and peripheral nervous systems, lungs, and gastrointestinal tract. It is a potent vasodilator, bronchodilator, and immunomodulator. The synthetic form aviptadil (RLF-100) was investigated for COVID-19-associated acute respiratory distress syndrome (ARDS) and has been studied in pulmonary arterial hypertension. VIP is also used diagnostically in VIPoma identification.
Category: Neuropeptide / Reference. Evidence rating: B (meaningful human data).
Clinical status: Aviptadil (synthetic VIP) received FDA Emergency Use Authorization consideration for COVID-19 ARDS. Phase II/III trials for ARDS completed. Not FDA-approved for any indication. Investigational for…
VIP binds with high affinity to VPAC1 and VPAC2 receptors (Gs-coupled GPCRs), activating adenylyl cyclase and increasing intracellular cAMP. This produces smooth muscle relaxation (vasodilation, bronchodilation), stimulation of water and electrolyte secretion in the gut, modulation of immune cell…
Research base: 0 registered clinical trials and 17 indexed publications reference VIP (Vasoactive Intestinal Peptide).
Safety considerations: Very short plasma half-life (~1-2 minutes) limits systemic effects but requires continuous infusion; Hypotension is the primary dose-limiting adverse effect due to potent vasodilation; Diarrhea and flushing reported at higher doses, consistent with VIP physiology.
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-08-12.
Related peptides: Substance P, Neuropeptide Y, PACAP.
Compare: VIP (Vasoactive Intestinal Peptide) vs Substance P, VIP (Vasoactive Intestinal Peptide) vs Neuropeptide Y, VIP (Vasoactive Intestinal Peptide) vs PACAP.
Aviptadil (also known as RLF-100) is the synthetic form of human VIP developed as a drug by NeuroRx/Relief Therapeutics. It was investigated primarily for COVID-19-associated ARDS based on VIP lung-protective properties, but did not receive FDA approval or Emergency Use Authorization.
Some practitioners prescribe intranasal VIP for chronic inflammatory response syndrome (CIRS), based on the work of Dr. Ritchie Shoemaker. This use is not FDA-approved, lacks rigorous controlled trial evidence, and is not endorsed by mainstream medical organizations.
VIP has a plasma half-life of only 1-2 minutes due to rapid enzymatic degradation, requiring continuous IV infusion for systemic effects. This limits practical therapeutic use. Researchers are developing longer-acting VIP analogs and alternative delivery methods (inhaled, intranasal) to overcome this limitation.
Preclinical research shows VIP has potent anti-inflammatory and immunomodulatory effects, with promising results in animal models of rheumatoid arthritis, multiple sclerosis (EAE), and inflammatory bowel disease. However, no controlled human trials have demonstrated efficacy for autoimmune diseases. The extremely short half-life of native VIP remains a major barrier to clinical translation.
Compounding pharmacies prepare VIP nasal spray by reconstituting lyophilized VIP in bacteriostatic water and dispensing it in metered-dose spray bottles. The Shoemaker CIRS protocol typically uses 50 mcg per spray, administered once daily. VIP nasal spray must be refrigerated at 2-8°C and used within 30 days of compounding. This is an off-label compounded product without FDA approval.