VIP (Vasoactive Intestinal Peptide)

What it is

Vasoactive intestinal peptide (VIP) is a naturally occurring 28-amino-acid signaling peptide in the glucagon/secretin superfamily that acts through the class II G-protein-coupled receptors VPAC1 and VPAC2 S1. The body produces it in the gut, nervous system, and other tissues, where it functions in vasodilation, smooth-muscle relaxation, regulation of secretions, and circadian timekeeping in the brain's suprachiasmatic nucleus S1. Because it is an endogenous molecule with wide-ranging receptor activity, it has attracted both legitimate research interest and unregulated wellness marketing.

Marketed as

In gray-market and compounding-pharmacy channels, VIP is most often sold as a nasal spray promoted for "CIRS" (chronic inflammatory response syndrome), a construct associated with water-damaged-building exposure, along with broader immune, lung, and anti-inflammatory claims S6. This use traces largely to a single practitioner-led body of work and small, uncontrolled reports rather than independent randomized trials, and CIRS is not a diagnosis recognized by mainstream regulatory or specialty bodies S6. These are best understood as marketing and advocacy positions, not validated medical outcomes.

Regulatory status (US)

There is no FDA-approved VIP product for the wellness uses under which it is marketed S4S1. Material sold for these purposes generally comes from compounding pharmacies operating under Section 503A, and the FDA has been actively re-examining which peptide bulk drug substances may be used in compounding S4. The synthetic VIP analogue aviptadil was studied in humans only under investigational (IND/expanded-access) pathways and has not received FDA approval for any indication S5S3.

Around the world

VIP itself is an endogenous human peptide rather than a globally approved drug, and no major regulator has approved a VIP or aviptadil product for the marketed inflammation or immune uses S1S3. Investigational programs for the synthetic analogue were centered in the United States S5S3.

Evidence

The most substantial clinical evidence concerns the synthetic analogue aviptadil (RLF-100/ZYESAMI) in COVID-19 respiratory failure — a disease setting distinct from the wellness marketing S2S3. A 60-day randomized controlled trial did not reach statistical significance on its primary endpoint of being alive and free of respiratory failure, though it reported a secondary survival signal S2. The definitive NIH-sponsored ACTIV-3b/TESICO pivotal trial was stopped for futility and showed no survival benefit (about 37% mortality with aviptadil versus 36% with placebo) S3. For the inflammation and immune claims made for VIP nasal spray, there is no comparable body of adequately powered, independent randomized evidence S6.

Anti-doping

VIP is not listed by name as an example substance on the current WADA Prohibited List S1. Athletes and support staff should nonetheless verify current status directly with their anti-doping authority, because peptide and metabolic-modulator categories are worded broadly and are revised annually S1.

Safety

Across the COVID-19 trials, reported effects of intravenous aviptadil included manageable diarrhea and low blood pressure (hypotension), with no new safety signals flagged by monitors S3. However, VIP's mechanism includes potent vasodilation and blood-pressure lowering, so effects can differ by route and setting S1. Gray-market nasal-spray products are unapproved and compounded, meaning purity, dose accuracy, and manufacturing quality are not FDA-verified S4.

What's changing

The FDA's ongoing review of peptide bulk drug substances — including Pharmacy Compounding Advisory Committee meetings scheduled through 2026–2027 — could alter whether VIP remains available through compounding pharmacies S4. On the drug-development side, the pivotal aviptadil program for COVID-19 respiratory failure has failed, leaving no active late-stage indication as of mid-2026 S3.