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VIP: quick citable summary
VIP is listed by PeptaHub as a immune peptide with a research only legal-status classification. The page summarizes mechanism, research context, common routes, safety notes, and references for writers and AI answer engines.
PeptaHub. “VIP: Mechanism, Research Context, Safety.” peptahub.com, 2026. https://peptahub.com/peptides/vip. Licensed CC BY 4.0.
License: Creative Commons Attribution 4.0 International. Link back to https://peptahub.com/peptides/vip.
What is VIP?
VIP is a 28-amino acid endogenous neuropeptide that suppresses inflammatory cytokine cascades and modulates mast cell behavior. Its synthetic form aviptadil received FDA Fast Track designation for COVID-19 respiratory failure and is investigated for MCAS and long COVID.
Overview
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid endogenous neuropeptide found throughout the central and peripheral nervous systems and gut. Its synthetic pharmaceutical form, aviptadil, has been investigated for COVID-19 respiratory failure, MCAS, and autoimmune conditions. VIP suppresses inflammatory cytokine cascades and modulates mast cell behavior, making it a candidate for chronic inflammatory and post-viral syndromes including long COVID.
Mechanism of action
VIP binds to VPAC1 and VPAC2 receptors (G-protein coupled receptors), activating adenylate cyclase and elevating intracellular cAMP. This signaling cascade suppresses the release of pro-inflammatory cytokines including TNF-α, IL-6, and IL-12, while promoting regulatory T-cell differentiation. In the lung, VIP binds AT2 cell VPAC1 receptors, upregulating surfactant production, blocking apoptosis, and inhibiting cytokine-mediated lung injury. It also mediates shedding of ACE2 and TMPRSS2 surface expression via ADAM10 sheddase upregulation, reducing viral entry points. In mast cells, while VIP can trigger degranulation in isolation, within neuroimmune contexts it reprograms mast cells toward a non-degranulating phenotype, offering paradoxical anti-inflammatory protection relevant to MCAS.
Reported study ranges
| Purpose | Route | Reported range | Frequency | Notes |
|---|---|---|---|---|
| COVID-19 respiratory failure (clinical trial protocol) | intravenous | 0.166–0.498 mcg/kg/hr | escalating over 3 days | Day 1: 0.166 mcg/kg/hr; Day 2: 0.332 mcg/kg/hr; Day 3: 0.498 mcg/kg/hr. Clinical setting only. |
| MCAS / long COVID (off-label nasal, community use) | nasal | 50–100 mcg | once to twice daily | No validated human protocol exists. Community reports use compounded nasal spray. Highly experimental. |
Reported ranges are for research context only. Consult a qualified healthcare professional before using any peptide.
Convert VIP research-range units
Need to convert mg to mcg, dose volume, or U-100 syringe units? The VIP dose calculator is preloaded with these ranges, or use the general dose unit converter.
Research summary
Aviptadil, the synthetic form, received FDA Fast Track designation for critical COVID-19 with respiratory failure, and the clinical programme has now largely reported out negative. A 196-patient placebo-controlled trial missed its primary endpoint of being alive and free from respiratory failure at day 60 (odds ratio 1.6, 95 percent CI 0.86-3.11), though a secondary survival analysis favoured aviptadil (Youssef, Crit Care Med 2022). The larger TESICO trial (461 patients, Lancet Respir Med 2023) was stopped for futility: no significant difference on the primary day-90 outcome (odds ratio 1.11, p=0.54) and 90-day mortality of 38 percent with aviptadil versus 36 percent with placebo. For MCAS and long COVID there is no controlled trial evidence at all; community use is based on practitioner reports. Autoimmune work (IBD, rheumatoid arthritis) remains in animal models.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with VIP for synergistic effects.
Legal status
Aviptadil is the pharmaceutical-grade synthetic form and is not FDA-approved for any indication as of 2026. Off-label compounding and research use exist. No reclassification petition currently under FDA review for VIP.
Sourcing & access
Research compound
VIP is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
VIP (Vasoactive Intestinal Peptide) is a 28-amino acid neuropeptide found throughout the central and peripheral nervous systems and gut. Its pharmaceutical form, aviptadil, has been investigated for COVID-19 respiratory failure, MCAS, and autoimmune conditions.
VIP binds VPAC1 and VPAC2 receptors, elevating intracellular cAMP. This suppresses pro-inflammatory cytokines (TNF-alpha, IL-6, IL-12), promotes regulatory T-cell differentiation, and in the lung upregulates surfactant production while blocking apoptosis.
Side effects include facial flushing, hypotension, nausea, diarrhea, tachycardia, and transient anxiety. VIP has a very short half-life (~2 minutes IV). Aviptadil is not FDA-approved for any indication as of 2026.
There is no controlled trial evidence for VIP in either condition. The rationale is mechanistic, drawn from VIP's cytokine-suppressing effects in cell and animal work, plus practitioner reports. Community protocols use compounded nasal spray at 50-100 mcg, a route and dose no published study has evaluated.
Research references
- The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseasesPubMed
- Mechanism of Immunoregulatory Properties of Vasoactive Intestinal Peptide in the K/BxN Mice Model of Autoimmune ArthritisPubMed
- Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetesPubMed
- Understanding VPAC receptor family peptide binding and selectivityPubMed
- Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal systemReview