VIP is a naturally occurring signalling molecule. Its synthetic form, aviptadil, is investigational — not approved by the FDA for any indication. This page describes what has been studied and does not describe an established treatment.
Overview
VIP is not a fringe compound: it is a 28-amino-acid neuropeptide produced throughout the human body, with a receptor system and physiological roles that have been studied since the 1970s. That solid biology is exactly what makes its therapeutic record instructive. When the synthetic form, aviptadil, was finally tested at scale — 461 patients with COVID-19-associated hypoxaemic respiratory failure — the trial was stopped for futility.
Understanding VIP means holding two things at once: the physiology is real and well mapped, and the demonstrated clinical benefit in humans is, so far, close to absent.
The physiology is genuinely well characterised
VIP signals through VPAC1 and VPAC2 receptors, raising cyclic AMP and producing smooth muscle relaxation, vasodilation, and changes in secretion. It functions as a neurotransmitter, a neurotrophic factor, and an immunoregulator, and its roles are mapped in specific tissues rather than asserted generally.
In the hippocampus, VIP controls GABAergic transmission and pyramidal cell activity. A 2020 review describes the division of labour: VPAC1 activation promotes disinhibition while VPAC2 activation enhances pyramidal excitability, with downstream effects on long-term potentiation and depression — and discusses VIP receptor ligands as targets in cognitive decline and mesial temporal lobe epilepsy (Cunha-Reis and Caulino-Rocha, Front Cell Neurosci 2020).
In immunity, VIP is produced in response to inflammation and autoimmunity as a natural endogenous route to tolerance, downregulating inflammatory and Th1 responses and inducing antigen-specific regulatory T cells and tolerogenic dendritic cells. A 2012 review notes it has been therapeutically effective in experimental models of autoimmune disorders and, more recently, in human sarcoidosis (Souza-Moreira et al. 2012).
Note what the second citation does and does not say. "Therapeutically effective in various experimental models" describes animal work; the human evidence it points to is a single rare-disease context. Strong mechanism plus thin human outcome data is the recurring shape of this literature.
The largest trial, and what it found
The most rigorous test of VIP as a medicine is TESICO, part of the NIH ACTIV-3b programme, published in The Lancet Respiratory Medicine. Hospitalised adults with COVID-19-associated acute hypoxaemic respiratory failure at 28 US sites were randomised to intravenous aviptadil or matched placebo, given as daily 12-hour infusions for three days targeting 600, 1,200, and 1,800 pmol/kg on successive days. The modified intention-to-treat population was 461 patients — 231 on aviptadil, 230 on placebo — of whom 94% were in intensive care at baseline (Brown et al., Lancet Respir Med 2023; NCT04843761).
- Primary six-category ordinal outcome at day 90: odds ratio 1.11 (95% CI 0.80–1.55, p=0.54).
- Mortality to day 90: 38% with aviptadil versus 36% with placebo (hazard ratio 1.04, 95% CI 0.77–1.41, p=0.78).
- The independent data and safety monitoring board recommended stopping the aviptadil trial for futility in May 2022.
This is the single most important fact about VIP as a therapeutic, and it is usually omitted from material promoting the peptide. A well-powered, properly randomised trial in the condition aviptadil was most loudly advocated for did not show benefit.
Smaller and more recent signals
A separate multicenter, prospective, double-blind, placebo-controlled trial in Turkey tested inhaled rather than intravenous aviptadil in 80 hospitalised patients with COVID-19 pneumonia (mean age 55.8, 33.8% female). The aviptadil group was discharged sooner (7.8 ± 4.0 versus 10 ± 5.0 days, p=0.049), reported better breathing-difficulty scores by day 7 (p=0.033), showed greater CT improvement by day 28 (p=0.028), and had lower mortality (5.1% versus 12.2%), with good tolerability (Esendagli et al., Med Princ Pract 2025).
Read carefully, this is a hypothesis-generating result, not a contradiction of TESICO. It is one-sixth the size, in a less severely ill population, by a different route, with p-values sitting just under 0.05 across several endpoints. The most defensible reading is that inhaled delivery to the lung is a different question from systemic infusion and remains open — not that VIP has been shown to work.
Where the wellness claims sit
Almost none of the above involves the uses VIP is marketed for online. Intranasal VIP is promoted for chronic inflammatory response syndrome, mould-related illness, fatigue, and general immune "modulation." None of those indications has a published randomised controlled trial. The immunoregulatory biology is real, but the distance between "induces regulatory T cells in experimental models" and "treats a chronic illness in humans" is exactly the distance TESICO demonstrates can be lost.
For how the peptide is delivered in the studies that exist, see VIP dosing and delivery.