Quick summary
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.
Dosing protocols
| Purpose | Route | Dosage | 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. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Aviptadil received FDA Fast Track designation for critical COVID-19 with respiratory failure. Phase 2 trials showed improved 60-day survival in some cohorts, though a Lancet Respiratory Medicine Phase 3 trial found no significant difference in the primary endpoint. Observational studies report elevated endogenous VIP plasma correlates with COVID-19 survival. Preclinical and clinical case data support a role in MCAS and long COVID neuroinflammation, though no large RCTs exist for these indications. Research into autoimmune applications (IBD, rheumatoid arthritis) continues in preclinical 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.
Preclinical and clinical case data support a role for VIP in MCAS and long COVID neuroinflammation, though no large randomized controlled trials exist for these indications. Community protocols use compounded nasal spray at 50-100 mcg, which is highly experimental.
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