VIP

A natural hormone found in the gut, lungs, brain and blood vessels, part of the glucagon/secretin family. Its synthetic form, aviptadil, was developed for lung and erectile-dysfunction research.

VIP binds VPAC1 and VPAC2 receptors and raises cAMP. It strongly relaxes airway and blood-vessel smooth muscle and has anti-inflammatory effects, including promoting regulatory T cells. In the gut it drives water and salt secretion.

IV aviptadil was tested in two randomized trials in COVID-19 respiratory failure; neither met its main goal, though one reported a day-60 survival signal that FDA called hypothesis-generating. NIH stopped its trial arm for futility, and inhaled trials were stopped or paused. Small, short studies of inhaled VIP looked at pulmonary hypertension and sarcoidosis. An aviptadil plus phentolamine combination is approved abroad for erectile dysfunction, with UK case series reporting about 59–63% success. Its use in the CIRS ('mold illness') protocol rests on a small study by the protocol's originator, with no independent controlled trial.

In the IV COVID-19 trial, diarrhea (33% vs 2%) and low blood pressure were more common than on placebo, and there were more slow heart rates and cardiac arrests in critically ill patients, cause unclear. With the erectile-dysfunction combination, facial flushing occurred in about 20–30%, and priapism was rare. Its half-life in blood is about 2 minutes.

Not FDA-approved; FDA declined emergency use authorization for COVID-19 in 2021 and development was later suspended. It is in FDA's 503A Category 1 (under evaluation), so 503A pharmacies may compound it on prescription under FDA's interim policy. Approved abroad as an ED combination and in India for severe COVID-19; not named on the 2026 WADA list.