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VIP

VIP · Aviptadil · Vasoactive Intestinal Peptide

C
Animal replicated
Research chemicalNeuropeptideVasoactive Intestinal PeptideVPAC Agonist
RouteNasalGray-market only
C
Evidence grade: Animal replicated

Effect demonstrated in multiple animal studies; human data sparse or extrapolated. Grades summarize evidence quality, not whether a compound is appropriate, legal, or risk-free.

At a glance
What it is
Vasoactive Intestinal Peptide — Aviptadil — Endogenous Neuropeptide — Neuropeptide, Vasoactive Intestinal Peptide, VPAC Agonist.
Why people use it
CIRS Patients · Long-COVID · MCAS · Athletes and Performance
If you only read one thing

VIP represents the most complete immunomodulatory, anti-inflammatory, autonomic-normalizing, and neuro-regenerative mechanism in this entire book — and no one in mainstream medicine knows what to do with it. The compound has been in human clinical trials for 20+ years, treats multiple conditions through a mechanism that addresses the pathological substrate of Long-COVID, CIRS, MCAS, and dysautonomia simultaneously, and is produced endogenously by the very immune cells it regulates. It cannot be turned into a standard oral or IV drug because of its 90-second half-life. The intranasal route — developed outside the standard pharmaceutical pipeline by a clinical researcher (Shoemaker) working with a specific patient population (CIRS) — produced extraordinary results across thousands of patients. The pharmaceutical industry has not invested in scaling this approach because the compound cannot be patented effectively. The community uses it because the evidence from the CIRS program is hard to ignore, the mechanism makes complete sense for multiple inflammatory and autonomic conditions, and there is no other intervention that addresses all of these pathways simultaneously.

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Route / form

Same compound, route-specific context. Switch forms instead of opening separate pages.

Evidence fit
Route-specific

Use the route notes below to match form, goal, and evidence quality.

Route caveat
Protocol not standardized

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Protocol anchor
Full dosing section

Open the full report at the dosing chapter for protocol rows, cycle context, and administration notes.

Typical dose snapshot
See route notes
Evidence varies by use case
Published literature
2human RCTs3human studies5animal4in vitro

Human evidence includes aviptadil/VIP clinical trials and CIRS/Long-COVID clinical-program data; intranasal CIRS evidence is largely real-world/open-label rather than large blinded RCT evidence.

Evidence reality check
Human evidence
5 human studies
2 randomized; 3 observational.
Preclinical base
9 lab signals
5 animal; 4 in-vitro/mechanistic.
Risk posture
No major flags listed
Review route-specific cautions before use.
Indication map
Supported / plausible / speculative / avoid
Plausible
CIRS Patients · Long-COVID · MCAS · Athletes and Performance
Derived from the chapter quick-reference use-case line; study support varies by use case.
Categories
Cognition & MoodGut & DigestiveImmune & Thymic
Properties
Active malignancy: caution✓ Human RCT
Evidence
CAnimal replicated
The Half-Life Problem
Native VIP has a plasma half-life of approximately 60-90 seconds due to rapid degradation by plasma peptidases, DPP-4, and other proteolytic enzymes. Intravenous VIP at doses sufficient for therapeutic effect causes immediate cardiovascular side effects: hypotension, tachycardia, facial flushing — driven by the potent vasodilatory effect at VPAC2 receptors on vascular smooth muscle. This makes IV VIP impractical for most therapeutic applications except specific clinical settings (erectile dysfunction via intracavernosal injection at 25 mcg). The solution that changed VIP's clinical utility: intranasal administration via the olfactory pathway — allowing direct nose-to-brain transport that bypasses systemic circulation entirely.
The Shoemaker CIRS Protocol
Dr. Ritchie Shoemaker developed the intranasal VIP protocol for Chronic Inflammatory Response Syndrome (CIRS) — a multi-system, multi-symptom inflammatory illness acquired from biotoxin exposure (mold, Lyme, dinoflagellates). Since 2008, over 300 physicians have prescribed intranasal VIP to CIRS patients. Over 90% of prescribing physicians reported: symptom reduction; normalization of inflammatory markers (MMP9, TGF-β1, C4a reduction; VEGF increase); normalization of clotting abnormalities (including acquired von Willebrand's); restoration of pituitary axis regulation (ACTH/cortisol, ADH/osmolality). The Shoemaker protocol uses compounded intranasal VIP 50 mcg/spray, BID. This is the most extensively documented clinical use of VIP in the Western medical literature.
VIP and Long-COVID / MCAS
The Long-COVID and Mast Cell Activation Syndrome (MCAS) communities have adopted VIP based on mechanistic overlap with CIRS. Long-COVID patients frequently show dysregulated inflammatory markers overlapping with CIRS: elevated TGF-β1, elevated C4a, VIP deficiency in some, autonomic dysfunction (POTS), immune dysregulation, mast cell hyperactivation. VIP's documented actions directly address multiple Long-COVID pathological mechanisms: mast cell degranulation suppression (reducing histamine and cytokine release); autonomic nervous system regulation; pulmonary inflammation reduction; neurological inflammation. Allegra et al. 2021 pilot (n=20, inhaled VIP 20 mcg BID): rapid symptom improvement in Long-COVID. The community has extrapolated this to intranasal and SubQ use.
Aviptadil Clinical Development
Aviptadil (synthetic VIP) has an extensive pharmaceutical development history: FDA IND approval 2001 (NeuroRx); EMA approval for clinical trials 2005. Intracavernosal injection (25 mcg + phentolamine) for erectile dysfunction — established clinical use. COVID-19 ARDS trials: multiple Phase 2/3 trials (ACTIV-3b, NCT04311697, NCT04360096) evaluating IV and inhaled aviptadil for severe respiratory failure. Results mixed; some positive signals on survival and respiratory function; ACTIV-3b trials ongoing as of 2025. The COVID program established extensive Phase 2 safety data for inhaled aviptadil. This is not a research chemical with no safety data — VIP has been in human clinical trials for decades.
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Alternatives

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DSIP
C
Same class · Neuropeptide

Isolated 1977. Named for Sleep. 40+ Years of Research. No Gene Found. No Specific Receptor Identified. Half-Life 15 Minutes In Vitro — Yet Produces Multi-Night Effects. Studied for Sleep, Stress, Alcohol Withdrawal, Opiate Withdrawal, Neuroprotection, and Longevity. The Most Mechanistically Mysterious Compound in this reference.

Naltrexone / LDN
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Shared goal · cognition

FDA-Approved at 50 mg for Opioid and Alcohol Use Disorder Since 1984. Off-Label at 1.5-4.5 mg (LDN) — Two Completely Different Mechanisms at Two Completely Different Doses. TLR4 Blockade on Microglia. The Endorphin Rebound. A Lancet Rheumatology RCT in 2024. An Evidence Base Growing Faster Than Pharma Has Any Reason to Fund. The Most Favorably Tolerated Prescription Drug in Its Evidence Literature.

Gut Peptide Stack
C
Shared goal · gut

Scope appropriateness is the question: local gut peptides are being stacked for barrier integrity and inflammatory signaling, not for systemic regeneration claims.

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