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Vasoactive Intestinal Peptide (VIP) research
Healing

Vasoactive Intestinal Peptide (VIP)

Also known as: VIP, vasoactive intestinal polypeptide, PHM-27

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VIP is a research compound. Not approved for human use beyond specific investigational applications.

📚 Content aggregated from:2 peer-reviewed sources·r/Peptides community·PubMed / NCBI

Overview

28-amino acid neuropeptide found throughout the CNS, gut, and immune system. Functions as a potent anti-inflammatory, vasodilator, and neurotrophic factor. Research applications include CIRS (Chronic Inflammatory Response Syndrome), pulmonary arterial hypertension, autoimmune conditions, and gut motility disorders. Intranasal administration is most studied for CIRS and neuroinflammatory conditions.

Research Summary

VIP activates VPAC1 and VPAC2 receptors coupled to cAMP, suppressing pro-inflammatory cytokines while promoting Th2 regulatory immune responses and Treg differentiation. In the CIRS/biotoxin illness framework pioneered by Shoemaker, VIP intranasal formulation demonstrates normalization of inflammatory markers and improvement in TGF-β, MSH, and VIP deficiency seen in CIRS patients. Pulmonary vasodilation effects have been studied for PAH.

Dosing Range

low

25mcg

moderate

50mcg

high

100mcg

Units: mcg · Frequency: Daily intranasal or 1–2x weekly subcutaneous

Dosing ranges are aggregated from preclinical research and community protocols. Not medical dosing guidance.

Administration Routes

Intranasal spraySubcutaneous injectionInhalation (nebulized)

Reconstitution Notes

Reconstitute with sterile saline or bacteriostatic water. For intranasal use: dilute to 50mcg/mL in sterile saline using preservative-free nasal delivery devices. Highly sensitive to temperature — store at -20°C. Intranasal solution should be used within 30 days once prepared.
Step-by-step reconstitution guide →

Supplies you'll need

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Reported Side Effects

  • Facial flushing
  • Transient hypotension
  • Nasal irritation (intranasal route)
  • Tachycardia
  • Headache
  • Dizziness (positional, from vasodilation)

Research Papers

2 peer-reviewed sources
Proceedings of the National Academy of Sciences2007
Annals of the New York Academy of Sciences2009

Community Experiences

Aggregated from public forums. Anecdotal — not clinical evidence.

r/CIRS

CIRS patient community sharing experiences with intranasal VIP in Shoemaker protocol.

View original thread
r/Peptides

Community research discussion on VIP for neuroinflammation and anti-inflammatory applications.

View original thread

Overview

Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily. It was first isolated from porcine intestine in 1970 by Said and Mutt, hence "vasoactive intestinal" — though its distribution and roles extend far beyond the gut.

VIP is found throughout the nervous system (CNS and ENS), immune tissues, respiratory tract, and reproductive system. It acts as a neuromodulator, vasodilator, immunomodulator, and circadian rhythm regulator. Its receptors (VPAC1 and VPAC2) are expressed on immune cells, smooth muscle, gut epithelium, and neurons.

Mechanism

Receptor System

VIP acts through two G-protein coupled receptors:

  • VPAC1: Expressed on T-cells, dendritic cells, gut epithelium, liver, lung; Gs-coupled → cAMP elevation
  • VPAC2: Expressed on smooth muscle, brain, T-cells; Gs-coupled → cAMP elevation; responsible for circadian SCN effects

Both receptors drive cAMP-PKA signaling cascades with anti-inflammatory outcomes.

Anti-Inflammatory Cascade

  1. cAMP elevation in dendritic cells → inhibited IL-12 and TNF-α production
  2. Promotion of Th2 over Th1 polarization
  3. Induction of T regulatory cells (Tregs) via tolerogenic dendritic cell maturation
  4. Inhibition of NFκB-mediated transcription of inflammatory genes
  5. Upregulation of IL-10 (anti-inflammatory cytokine)

Vasoactive Effects

VIP is one of the most potent endogenous vasodilators known. It relaxes vascular smooth muscle throughout the body but especially in pulmonary vasculature — the basis for its research in pulmonary arterial hypertension.

CIRS / Biotoxin Illness Context

Dr. Ritchie Shoemaker's Chronic Inflammatory Response Syndrome framework identifies VIP deficiency as a late-stage marker of biotoxin illness. VIP levels are measurable by blood test; deficiency correlates with elevated TGF-β1, upregulated VEGF, and ongoing inflammatory pathway dysregulation. Intranasal VIP is used as the final step in the Shoemaker protocol to normalize these markers.

The CIRS application requires prerequisite steps (mold avoidance, cholestyramine, addressing MMP-9, VCS testing) before VIP introduction, as VIP in an active biotoxin environment may not be effective.

Pulmonary Hypertension Research

Early studies showed VIP inhalation reduced pulmonary arterial pressure in PAH patients, providing preliminary evidence for nebulized delivery. While not advancing to approval in that indication, these studies confirmed pulmonary VIP activity and established the inhalation route as viable.

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