Also known as: Vasoactive Intestinal Polypeptide, PHM-27 family
Half-life: ~2 minutes (plasma); longer functional duration via tissue distribution
Last reviewed: · Published:
Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide originally isolated from porcine intestine but now known to be widely distributed throughout the central and peripheral nervous system, the gastrointestinal tract, and the immune system. It signals through two G-protein-coupled receptors (VPAC1 and VPAC2) that activate cAMP and downstream anti-inflammatory and tissue-protective pathways. VIP has potent vasodilatory, smooth-muscle-relaxing, immunomodulatory, and circadian-rhythm-organizing effects.
In medical research, VIP has been investigated for diverse conditions including pulmonary hypertension, sarcoidosis, COPD, chronic inflammatory diseases, and chronic inflammatory response syndrome (CIRS) caused by biotoxin exposure. The Shoemaker protocol — a clinical framework developed by Ritchie Shoemaker for treating CIRS from mold and other biotoxin illnesses — uses intranasal VIP as a final restoration step in patients who have completed environmental remediation and earlier protocol stages. This off-label use has driven significant interest in VIP within the chronic-illness community.
VIP has shown promising effects in clinical trials for several inflammatory conditions but has not achieved broad regulatory approval as a therapeutic. Research-grade synthetic VIP is sold by peptide vendors for use in research and (with appropriate clinical supervision) in compounded intranasal formulations under the Shoemaker CIRS protocol. VIP is generally well-tolerated at the low doses used clinically; hypotension and flushing are the main acute concerns.
VIP was isolated and sequenced in 1970 by Sami Said and Viktor Mutt, who initially characterized it as a vasoactive substance from porcine intestine. Its broader role in neurotransmission, circadian biology, and immunomodulation was established through subsequent decades of research. The application of intranasal VIP for CIRS was developed by Ritchie Shoemaker in the early 2010s based on his clinical observations of post-treatment patients. Pharmaceutical-grade VIP analogs have been developed (aviptadil for ARDS in COVID-19) and have undergone regulatory consideration without full approval.
Intranasal VIP at the very low doses used in the Shoemaker CIRS protocol (50 mcg, 4 sprays daily) is generally well-tolerated, with most users experiencing only mild transient flushing or warmth. Higher systemic doses (IV in ARDS or pulmonary hypertension trials) have caused more pronounced hypotension and require clinical monitoring. VIP's broad receptor distribution means that off-target effects on smooth muscle and immune signaling are real possibilities, particularly for users with cardiovascular or autoimmune conditions.
Dose Range
50 mcg
Frequency
4 sprays daily
Duration
Per Shoemaker protocol; months to years for full restoration
Dose Range
Variable per protocol
Frequency
Per protocol
Duration
Per protocol
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
5 mg
Water Type
Bacteriostatic water (BAC water) — or sterile saline for intranasal formulation
Mixing Volume
2-5 mL
Half-Life
~2 minutes (plasma); longer functional duration via tissue distribution
Molecular Weight
3,326 Da
Store reconstituted vial refrigerated at 2-8°C. Use within 21-30 days. The Shoemaker CIRS protocol uses compounded intranasal VIP at 50 mcg/spray prepared by specialty pharmacies; concentrations and preservatives matter for nasal mucosal compatibility.
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FDA Status
Not FDA approved as therapeutic. VIP analog aviptadil received Emergency Use Authorization consideration for COVID-19 ARDS but not full approval.
Legal Status
Unregulated research chemical / compounded pharmaceutical depending on jurisdiction.
USA
Compounded onlyUsed off-label in CIRS protocols via compounding pharmacies; not FDA-approved
EU
Not approvedNot authorized as medicinal product
UK
Not approvedCompounded only via specialty pharmacies
Australia
Not approvedTGA has not authorized
Canada
Not approvedNot authorized for human use
Said SI
Annals of the New York Academy of Sciences (1996)
Authoritative historical and physiological review by the discoverer of VIP, providing the foundational characterization of its broad neuropeptide functions.
View Study →Delgado M, Gonzalez-Rey E, Ganea D
Annals of the New York Academy of Sciences (2006)
Comprehensive review of VIP's immunomodulatory and anti-inflammatory mechanisms, framing its therapeutic potential in autoimmune and chronic inflammatory disease.
View Study →Youssef JG, Lavin P, Schoenfeld DA, Lee RA, Lenhardt R, Park DJ, Fernandez JP, Trotman R, Sciurba FC, Wassuna KA, Magnani CW, Gianopoulos JG, Brown SAN, Goldsmith R, Smith C, Ricci K, Bansal S, Habashi NM, Andersen M, Brodbeck KC, Vetal V, Steiner M, Walker C, Marquez-Magdaleno M, Buno V, McFatridge S, Ostrelich C, Hutkin J, Wang T, Hagen P, Hopkin JD, Bhatti V, Singh A, Bahaa A, Maleksabet J, Choden S, Bagley P, Gomez CR, Lannoye S, Levine A, Smith P, Wieland S, Bahabri F, Javed Z, Boumlali A, Boyce K, Onishi M, Aroniadis O, Cooper R, Habashi C, Tate T, Boulton-Brown D, Tan K, Cervinka B, Kuriacose R, Mitchell C, Saturnino Y, Friedman D, Brewer R, Wahed AS, Hayek M, Skarboevish E, Karachi T, Kovac D, Kao G, Aldemir T, Lampotang S, Christensen S, Plowman MJ, Buckman R, Klinedinst K, Mejia D, Wright DK, Ribbons L, Mecca D, Sajjadi SS, Sabella E, Forderkunz N, Sandell A, Sahli W, Choi S, Bouchard B, Mohammadhaghighi K, Pajooh K, Garr K, McLelland T, Sabir N, Kanchapuram N, Mistry K, Eronia P, Bahrami N, Borchart J, Choi J, Yu N, Mason A, Levin J, Mahbubani K, Khalifa R, Akula S, Hassan U, Acharya S, Sneath W, Watanabe T, Lai NS, Wettstein PJ, Vandal A, Manno C, Khattab R, Frank L, Foley S, Andrews J, Yu Y, Bibawy J, Foroutan A, Hartford L, Tushir T, Ghaffari M, Lim K, Mauricio L, Patel B, Anders W, Kim S, Olarte Echenique D, Mosellie A, Toh H, Hudak F, Hudak M, Cisek J, Berkenpas M, Stevenson A, Lobato JG, Patil P, Stay D, Vinces M, Cooper J, Pavlik V, Ailawadi R, Robbins B, Reddy NK, Brettler J, Goldfarb DS, Gusev A, Hochberg L, Cushing G, Hardy R, Andron L, Tang S, Allen H, Holland T, Bonin J, Schrickel B, Faden D, McCready M, Salasen E, Mukherjee A, Jacobs J, Maurer D, Tinker E, Wright A, Atkinson L, Goldfarb DS, Marquez J, McGowan P
Critical Care Medicine (2022)
Clinical trial of inhaled aviptadil (a synthetic VIP analog) in critically ill COVID-19 patients, providing modern clinical safety and efficacy context for VIP-pathway therapeutics in acute inflammatory lung disease.
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