VIP Peptide Dosage & Injection Protocol: What the Trials Actually Show

VIP at a glance

What it is

Vasoactive intestinal peptide — a 28-amino-acid endogenous neuropeptide, HSDAVFTDNYTRLRKQMAVKKYLNSILN, amidated at the C-terminal asparagine. The synthetic pharmaceutical form is aviptadil (CAS 40077-57-4)

Researched for

COVID-19 respiratory failure and ARDS (phase 3, failed), sarcoidosis (open-label phase 2), erectile dysfunction (as Invicorp, with phentolamine), and migraine/cluster-headache provocation research

Commonly reported range

Community intranasal protocols report 50 mcg per nostril up to 4x daily (~400 mcg/day); subcutaneous examples of 25-100 mcg once daily. The only approved-medicine reference dose that has ever existed for aviptadil is 25 mcg intracavernosally

Route reported

Intranasal metered spray in community protocols; subcutaneous injection less commonly; continuous intravenous infusion and nebulisation in every controlled trial

Reported frequency

Intranasal 1-4x daily; subcutaneous once daily. Trials used a 12-hour daily infusion (TESICO) or 4 weeks of nebulisation (sarcoidosis) rather than bolus dosing

Reported cycle

Community examples of ~30 days with biomarker retesting, sometimes extended to 1-3 months. No trial has ever tested a cycled regimen

Plasma half-life

Consistently described as very short, which is why every trial infused it rather than injecting a bolus. The widely repeated "under 2 minutes" figure has no primary pharmacokinetic citation we can trace — see the half-life section

Regulatory status

No FDA approval and no US product: DailyMed returned zero labels for aviptadil and Drugs@FDA no match. EMA orphan designation EU/3/07/473 for sarcoidosis exists but is not an authorisation. Research use only

Reported ranges from research/community — examples, not recommendations.

What it is / mechanism

VIP is an endogenous 28-residue neuropeptide of the secretin/glucagon superfamily, and its identity is worth stating precisely because the research market is loose about it. UniProt entry P01282 annotates the mature peptide as residues 125-152 of the prepro-VIP precursor, sequence HSDAVFTDNYTRLRKQMAVKKYLNSILN, with a modified residue at position 152: the C-terminal asparagine is amidated. The same precursor also yields PHM-27 and PHV-42, which are different peptides sharing the same gene. The synthetic pharmaceutical form is aviptadil, CAS 40077-57-4, UNII A67JUW790C, PubChem CID 16132300. That PubChem record lists the molecular formula as C147H237N43O43S with a molecular weight of 3,326.8, and its systematic name terminates in free L-asparagine — that is, the free-acid form. The biologically produced peptide UniProt describes is the C-terminal amide, which differs by one oxygen replaced with an NH group: C147H238N44O42S, about one mass unit lighter. This is not a pedantic distinction on a certificate of analysis. Two vials both labelled "VIP" can be different molecules, and mass spectrometry on a COA will separate them by roughly one dalton if anyone is looking. If you are reading a COA for this compound, the question worth asking is whether the reported mass corresponds to the amide or the acid, and our page on reading a peptide certificate of analysis covers what else that document should carry. Pharmacologically, VIP signals through two class B G-protein-coupled receptors, VPAC1 and VPAC2, which respond with high affinity to both VIP and the related peptide PACAP; a third receptor, PAC1, is selective for PACAP. That receptor arrangement is set out in IUPHAR Review 1 (Harmar et al., British Journal of Pharmacology, 2012, PMID 22289055), which is the authoritative reference for this family rather than a secondary summary. Receptor engagement raises intracellular cyclic AMP and activates protein kinase A, and the same review documents VIP's roles in circadian rhythm, immunity and inflammation, pancreatic insulin secretion, and autonomic and sensory neurotransmission. VIP is also a potent smooth-muscle relaxant and vasodilator, which is the property that put it into pulmonary, vascular and erectile-dysfunction research in the first place — and, as the headache section below sets out, the property that produces its most reliably demonstrated human effect.

Researched effects

There are two honest ways to describe what VIP does in humans, and they point in different directions. The first is what controlled trials measured. A randomised, double-blind, placebo-controlled crossover study showed that a two-hour intravenous infusion of VIP provoked migraine attacks in 15 of 21 patients with migraine without aura, against 1 of 21 on placebo (JAMA Network Open, 2021, PMID 34357396, NCT04260035). A separate provocation programme showed VIP infusion triggering cluster headache attacks in up to half of episodic patients in their active phase (Cephalalgia, 2022, PMID 34822741, NCT03814226). In sarcoidosis, four weeks of nebulised VIP significantly reduced TNF-alpha production by cells from bronchoalveolar lavage and raised regulatory T-cell numbers in an open-label study of 20 patients (American Journal of Respiratory and Critical Care Medicine, 2010, PMID 20442436). And in the largest randomised trial ever conducted on this molecule, intravenous aviptadil did not improve clinical outcomes in COVID-19 respiratory failure and the trial was stopped for futility. The second is what community protocols report: improvements in inflammation-related symptoms within CIRS (chronic inflammatory response syndrome) frameworks, delivered intranasally. Those reports are not controlled and, as the evidence section documents, there is no published randomised trial of intranasal VIP in humans to compare them against. Setting those two lists side by side is the most useful thing this page can do. The immunological findings are real but mechanistic rather than clinical — they measured cytokines and cell counts, not whether patients got better. The headache findings are clinical, replicated, placebo-controlled, and are adverse effects. And the one clinical-outcome trial that was properly powered was negative. Nothing here is a guaranteed outcome, and none of it is medical advice.

Dosage — reported ranges (overview)

The queries that bring people to this page are about a VIP peptide injection dosage and a VIP peptide dosage protocol, so it is worth being direct: there is no established human dose for VIP, and the figures in circulation come from three sources of very different quality. The community intranasal protocol is the most-repeated one. It describes 50 mcg per nostril — 100 mcg per administration — up to four times daily, for a total near 400 mcg/day, commonly starting at 50 mcg per nostril once or twice daily and running roughly 30 days before reassessment, sometimes extended to one to three months. This is the figure that appears in CIRS protocol summaries. What does not exist behind it is a controlled trial: see the evidence and half-life sections below. The subcutaneous figures are smaller and less consistent — community reports cluster around 25 to 100 mcg once daily. A VIP peptide subcutaneous injection dosage has never been tested against placebo for any indication in any published trial we can locate; every controlled human study of this molecule delivered it by continuous intravenous infusion, by nebulisation, or by intracavernosal injection. That gap between the route people report using and the route the evidence used is the single most important thing on this page. The trial regimens are the third source, and they are not translatable into a self-administered protocol, which is precisely why they are worth reading. TESICO targeted 600, then 1,200, then 1,800 pmol/kg delivered as a 12-hour infusion on each of three consecutive days. At roughly 3,326 g/mol, 1,800 pmol/kg in an 80 kg adult is on the order of 0.5 mg spread across twelve hours — a larger total amount than any community figure, delivered over a period no injection can reproduce. The cluster-headache provocation study used 8 pmol/kg/min for 20 minutes. The sarcoidosis study nebulised VIP daily for four weeks. Whatever the correct way to give this peptide is, the researchers who studied it in humans concluded it was a slow one. A final honest note on the relationship between amount and effect: the 71% migraine provocation rate came from lengthening an infusion from 20 minutes to 2 hours, not from raising the dose. For a compound whose defining property is vasodilation, exposure time appears to be the variable that matters, and community protocols are silent on it because nobody has studied it.

A printable protocol sheet with a reconstitution reference and an injection log comes with All-Access Lifetime.

Reconstitution — bac-water math

VIP is supplied lyophilised, usually as 5 mg or 10 mg vials, and dosed in micrograms, so reconstitution is pure concentration arithmetic. Add bacteriostatic water and the concentration in mcg/mL is the vial's milligrams multiplied by 1,000 and divided by the millilitres of water. On a U-100 insulin syringe, 100 units is 1 mL, so units to draw = dose in mcg divided by concentration in mcg/mL, times 100. Worked example: a 5 mg vial (5,000 mcg) with 2 mL of bacteriostatic water gives 2,500 mcg/mL, so a 50 mcg example is 50 / 2,500 x 100 = 2 units. Every row in the table below draws well under 100 units, so no example needs a second draw. The intranasal arithmetic is where reported protocols most often go wrong, and it is worth doing explicitly because it is arithmetic rather than advice. A metered nasal spray pump delivers a fixed volume per actuation, commonly 0.1 mL. Load that pump with the 2 mL reconstitution above at 2,500 mcg/mL, and each actuation delivers 250 mcg — five times the 50 mcg the protocol describes, and two and a half times the whole 100 mcg administration in a single spray. To make one 0.1 mL actuation equal 50 mcg you need a concentration of 500 mcg/mL, which for a 5 mg vial means reconstituting into 10 mL of bacteriostatic water, or into 20 mL for a 10 mg vial. That is an unusually large diluent volume for a peptide, and it is the reason a 30 mL bacteriostatic water vial is the practical size here rather than a 10 mL one — a single 10 mL vial leaves nothing for a second preparation. Check your spray pump's stated delivery volume before assuming 0.1 mL; the figure is a property of the pump, not a convention. All of the above is concentration math for handling research material, not a dosing instruction. Add water slowly down the vial wall and swirl rather than shaking.

This is concentration math, not a dose recommendation.

Injection / administration basics

A VIP peptide injection protocol has to start with an admission: no controlled trial has administered this peptide subcutaneously. The human studies used continuous intravenous infusion (TESICO, the migraine and cluster-headache provocation studies), nebulisation (sarcoidosis), or intracavernosal injection (Invicorp). Subcutaneous injection is a community route, and the general handling notes below are handling notes rather than a validated regimen. In practice, reported subcutaneous use follows the same pattern as other microgram-dosed research peptides: a small-gauge insulin syringe, a reconstituted solution kept refrigerated, and rotation between sites such as the abdomen and thigh. Because VIP is a potent vasodilator, the effects most consistently reported around administration — flushing, warmth, a transient drop in blood pressure, lightheadedness, headache — are pharmacologically expected rather than idiosyncratic, and they arrive fast: in the provocation studies the vascular response was measurable within the infusion period. The intranasal route dominates community protocols, and the practical points are the pump and the concentration rather than the technique. The reconstituted solution is transferred to a sterile metered spray bottle; the mcg delivered per actuation is set entirely by the concentration and the pump's fixed delivery volume, which is why the arithmetic in the reconstitution section matters more here than in almost any other guide in this library. Nasal irritation is the commonly reported local effect, and an animal toxicity study of a VIP nasal spray reported minor irritation of the nasal mucosa that resolved within a week of stopping (Pharmazie, 2013, PMID 23444784) — an animal study, on cilia morphology and mucosal pathology, not a human safety trial. None of this is instruction for human use, and the absence of any tested subcutaneous regimen is the reason.

Half-life & frequency rationale

This page previously stated that VIP's plasma half-life is "under about 2 minutes in blood." That figure is repeated across the peptide market and we cannot trace it to a primary pharmacokinetic study in humans, so it is withdrawn here rather than repeated with more confidence than it has earned. What follows is what is actually documented. The qualitative claim is well supported. Reviews of VIP's therapeutic development treat its short half-life and wide tissue distribution as the central obstacle to using it as a drug — for example, a 2022 review of VIP and VPAC2 in type 2 diabetes states plainly that the clinical application of VIP is limited by its short half-life and wide distribution in the human body (Frontiers in Endocrinology, PMID 36204104), and the sustained interest in VPAC2-selective agonists, lipidated analogues and delivery vehicles exists because unmodified VIP does not persist. The strongest evidence, though, is in how the trials chose to give it. TESICO did not inject aviptadil; it infused it for twelve hours a day, three days running. The migraine and cluster-headache studies infused it continuously for two hours and twenty minutes respectively. The sarcoidosis study nebulised it daily for four weeks. Investigators with pharmacokinetic data in hand, designing trials for regulatory scrutiny, consistently chose continuous administration over bolus dosing — which is a stronger statement about persistence than any number repeated without a citation, and it is the reason the migraine study's central finding was that a longer infusion, not a larger dose, changed the outcome. One further piece of pharmacokinetic evidence is unusually clean: a phase I study in people with cirrhosis is not available for VIP, but the cluster-headache study measured plasma CGRP, tryptase and histamine at fixed timepoints during and after infusion and found the provoked attacks were not accompanied by changes in any of them, which at least establishes that the effect tracks the peptide's own receptor signalling rather than a downstream mediator that would outlast it. The practical reading: treat VIP as a peptide with no systemic persistence, understand that this is why every serious study infused or nebulised it, and treat any specific half-life figure you encounter — including the one this page used to publish — as unsourced until someone names the study.

Stacking — overview

VIP appears in community CIRS and immune-support protocols as a late or final step, described as being used after other interventions have reduced inflammatory burden, and it is often paired with peptides reported to support gut or tissue repair. Those pairings are examples of what is reported, not recommendations. Two things are worth keeping in view: no combination involving VIP has been studied in any controlled trial, and the compound's documented vasodilatory and headache effects do not disappear because it is combined with something else. Our cross-compound stacking guide covers where pairings are redundant rather than additive, and where interaction risk is documented versus merely unstudied — for VIP, it is comprehensively the latter.

For how combinations are grouped by research context, the named blends, and why a pre-mixed blend vial cannot be calculated from its total milligrams, see the peptide stacks guide.

Storage & handling

• Lyophilized (powder): store sealed and refrigerated at 2-8°C, protected from light and moisture; long-term storage is commonly at -20°C or below. Handle as a fragile peptide.
• Reconstituted (liquid): refrigerate at 2-8°C, protect from light, avoid freeze-thaw cycles and vigorous shaking. Reconstituted solution has a limited stable window commonly described as a few weeks.
• Reconstitute with bacteriostatic water rather than sterile water where the vial is to be entered more than once — the benzyl alcohol is what makes a multi-dose vial multi-dose. Note the volumes involved: the concentration needed for a 50 mcg metered nasal actuation is 500 mcg/mL, which for a 5 mg vial means 10 mL of diluent for one vial.

Evidence File

The VIP Evidence File

ClinicalTrials.gov holds more registered human studies of this peptide than the free guide lists. This module reads the rest of them: a pulmonary programme that ran for two decades before COVID-19 existed, a long-acting analogue a company took into two indications and terminated in both, a headache-provocation programme with more registered arms than the ones usually cited, and a set of stop reasons recorded in the registry verbatim - some of them two words long. It also runs down the half-life figure the free guide withdrew as untraceable. Registry text is quoted as written, typographical errors included, because that is what the record says.

• 1 half-life figure the free guide withdrew, traced to its 1978 primary source
• 6 registry records terminated, withdrawn or no longer available
• 0 posted results across the 6 registry records checked for them
• 0 studies now recruiting anywhere to administer VIP

Sourcing File

Sourcing and Certificate Analysis: VIP

The free guide notes that the PubChem record for aviptadil describes the free acid rather than the amidated peptide. This module follows that thread all the way down: what the named database entry actually contains, which records the amidated peptide does have and which identifiers none of them carries, what a mass spectrum can and cannot settle for this sequence, and what a published analytical study using aviptadil as its model substance found when it compared two purity methods on the same material. It ends with the salt arithmetic that decides whether a nasal actuation contains what the label implies, and a line-by-line read of a certificate for this specific peptide.

• 15 impurities by CE-MS versus 2 by RP-HPLC, on aviptadil itself, with no overlap
• 0.984 Da separates the acid the identifiers sit on from the amide the biology is about
• 80.6% to 94.9% net peptide across plausible salt forms
• 5 database records carry the amide's InChIKey; the INN, CAS and UNII sit on none of them

Benefit & Outcome Review

Benefit and Outcome Review: VIP

Fifteen claims are made for this peptide across research summaries and community protocols. This module grades each one on the same four questions: what was measured, in what species and system, against what comparator, and whether any human ever got better rather than merely showing a changed number. Where responder and non-responder splits exist they are given, and where they do not exist that is stated rather than filled in. Only a minority of the fifteen clear the bar for human, controlled and replicated - and two of the ones that do are descriptions of side effects rather than of benefits. One claim is graded contradicted. The rest divide between a real measured effect on the wrong kind of endpoint and nothing located at all, with the searches behind each absence named.

• 15 claims graded; 4 reach supported, and 2 of those are side effects
• 1.01 pooled survival odds ratio across the randomised evidence
• 6 of 20 patients: the only clean responder split on record
• 1 patient and 4 simultaneous interventions for the flagship claim

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