VIP
Vasoactive Intestinal Peptide | Immune Regulation & Neuroprotection
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide with potent anti-inflammatory, immunomodulatory, and neuroprotective properties. Acting through VPAC1 and VPAC2 receptors, VIP regulates immune function, vascular tone, circadian rhythms, and neurological health. It has been extensively studied for chronic inflammatory response syndrome (CIRS), pulmonary conditions, autoimmune diseases, and most recently COVID-19 respiratory failure. The injectable form (Aviptadil/Zyesami) received FDA Fast Track designation for COVID-19 ARDS.
Daily dose
200-400mcg (nasal)
Frequency
2-4x daily
Cycle length
4-12 weeks or ongoing
Storage
2-8°C
Key benefits
Potent anti-inflammatory and immunomodulatory effects, neuroprotection, circadian rhythm regulation, pulmonary vasodilation, correction of CIRS inflammatory markers, cognitive and mood support. FDA Fast Track for COVID-19 ARDS (injectable form).
How it works
VIP binds to VPAC1 and VPAC2 G-protein coupled receptors, activating adenylate cyclase and increasing cAMP/PKA signaling. This cascade inhibits pro-inflammatory cytokines (IL-6, TNF-α, TGF-β1), modulates T helper cell differentiation, regulates innate and adaptive immunity, and provides neuroprotection. VIP also causes vasodilation and has bronchodilatory effects.
Dosage protocols
Goal
CIRS protocol
Dose
50mcg per spray, 4-8 sprays/day · 4x daily
Route
Intranasal
Goal
General immune support
Dose
50-100mcg · 2-4x daily
Route
Intranasal
Goal
Starting dose
Dose
50mcg · 2x daily
Route
Intranasal
Goal
COVID-19 ARDS (clinical)
Dose
50-150 pmol/kg/hr · 12-hr infusion x 3 days
Route
IV
Research indications
inflammatory
neurological
vascular
Administration
Interactions
Safety notes
First dose under medical supervision with lab monitoring
Pre/post labs: TGF-β1, Lipase at 15 minutes
Stop if abdominal pain or elevated lipase occurs
Not FDA-approved as nasal spray (compounded off-label)
CIRS patients: Complete protocol steps 1-11 first
Ensure MARCoNS eradicated and environment safe
Monitor blood pressure - VIP causes vasodilation
FDA designated Aviptadil Fast Track for COVID-19
Research studies
IV Aviptadil in Critical COVID-19 Respiratory Failure - Phase 2b/3 RCT (2022)
Humans | 196 patients | IV infusion | 60 days | 2-fold increased survival odds
Multicenter randomized controlled trial across 10 U.S. hospitals. Aviptadil showed 2-fold increased odds of 60-day survival (OR 2.0, p=0.035). Mechanically ventilated patients showed 10-fold increased survival odds. Significant reduction in IL-6 inflammatory marker.
View study →VIP Corrects Chronic Inflammatory Response Syndrome (CIRS) (2013)
Humans | CIRS patients | Nasal spray 50mcg | Multiple months | Correction of inflammatory markers
Study demonstrating VIP nasal spray corrects CIRS acquired from water-damaged buildings. Showed correction of proteomics, transcriptomics, and gray matter nuclear atrophy refractory to other therapies.
View study →IUPHAR Review: VIP and PACAP Receptor Pharmacology (2012)
Review | Comprehensive analysis of VPAC1/VPAC2/PAC1 receptors
Definitive pharmacological review of VIP receptors. Details mechanism of action through Gαs/cAMP/PKA pathway, physiological functions in CNS and periphery, and therapeutic potential for neurodegenerative, inflammatory, and autoimmune diseases.
View study →VIP Prevents Experimental Arthritis - Nature Medicine (2001)
Mice | CIA model | IP injection | 2 weeks | Complete prevention of joint destruction
Landmark study showing VIP completely prevented joint swelling, cartilage destruction, and bone erosion in collagen-induced arthritis. Therapeutic effect associated with downregulation of both inflammatory and autoimmune components.
View study →Intranasal VIP Pharmacodynamics and Toxicity (2013)
Animal model | 40-200mcg/mL | 1 week | Safe brain delivery confirmed
Demonstrated VIP can be successfully delivered to the brain via intranasal route. Higher dose (200mcg) improved spatial memory deficits in Alzheimer's model. Only minor reversible nasal irritation observed.
View study →Inhaled VIP in Pulmonary Hypertension (2008)
Humans | 20 PH patients | 100mcg inhaled | Acute study | Selective pulmonary vasodilation
Single 100mcg inhaled aviptadil caused significant selective pulmonary vasodilation, improved stroke volume and mixed venous oxygen saturation. 6 patients showed >20% pulmonary vascular resistance reduction.
View study →