Vasoactive Intestinal Peptide (VIP)

Overview

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide of the secretin/glucagon family, widely distributed in the CNS and peripheral nervous system. It is a potent vasodilator, bronchodilator, and immunomodulator. Synthetic VIP (aviptadil) has been investigated in clinical trials for COVID-19-associated acute respiratory failure; it is NOT FDA-approved. Intranasal compounded VIP is used off-label in the controversial 'CIRS' (Chronic Inflammatory Response Syndrome) / mold-illness protocol popularized by Ritchie Shoemaker — CIRS is not a mainstream medical diagnosis.

Mechanism of Action

VIP binds the Gs-coupled VPAC1 and VPAC2 receptors expressed on immune cells, neurons, and smooth muscle, elevating cAMP. It suppresses pro-inflammatory cytokines (TNF-α, IL-6, IL-12) and iNOS, promotes Th2-polarized and regulatory T-cell responses, and relaxes vascular and airway smooth muscle (potent vasodilator/bronchodilator).

Research Summary

Delgado, Pozo, and Ganea's 2004 Pharmacological Reviews paper (PMID 15169929) is a foundational review of VIP's immunomodulatory actions via VPAC receptors. For COVID-19 ARDS, the Youssef et al. 60-day RCT of IV aviptadil (Crit Care Med 2022, PMID 36044317) reported improved survival in a secondary analysis but did not meet its primary endpoint. The larger NIH-sponsored TESICO trial (Lancet Respir Med 2023, PMID 37348524) was stopped for futility and found no benefit. The FDA granted Fast-Track designation to aviptadil in 2020 but DENIED the Breakthrough Therapy designation request and DECLINED an Emergency Use Authorization; aviptadil is NOT FDA-approved. Intranasal VIP for CIRS/mold illness lacks peer-reviewed RCT evidence and is used via compounding pharmacies only.

Dosing Information

Reported Side Effects

• Transient hypotension (dose-limiting with IV)
• Flushing
• Diarrhea / increased GI motility
• Nasal irritation (intranasal route)
• Headache

Research References

• The significance of vasoactive intestinal peptide in immunomodulation (Delgado, Pozo, Ganea, Pharmacol Rev) (2004)
• The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial (Youssef et al., Crit Care Med) (2022)
• Intravenous aviptadil and remdesivir for COVID-19-associated hypoxaemic respiratory failure (TESICO): a randomised, placebo-controlled trial (Lancet Respir Med) (2023)