VIP
A 28-amino-acid neuropeptide that binds VPAC1/VPAC2 receptors to drive potent anti-inflammatory, vasodilatory, and circadian-regulating effects across the nervous, immune, and vascular systems.
VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide of the glucagon superfamily, widely expressed throughout the central and peripheral nervous systems, gastrointestinal tract, and immune system. Acting through the Gs-coupled VPAC1 and VPAC2 receptors, it raises intracellular cAMP to produce vasodilation, bronchodilation, smooth-muscle relaxation, immune modulation, and circadian rhythm regulation via the suprachiasmatic nucleus. It has drawn research interest for neuroinflammation, neuroprotection, and contested chronic-inflammatory frameworks such as CIRS, while its synthetic analog Aviptadil advanced into late-stage trials for respiratory conditions. VIP has no FDA-approved product and is sold as a research-use-only compound.
Class
Endogenous 28-amino-acid neuropeptide (glucagon/secretin superfamily)
Half-life
~1-2 minutes (IV plasma); ~60-90 minutes (subcutaneous)
Routes
Intranasal, Subcutaneous, Intravenous
Category
Cognitive & Nootropic
Researched benefits
What it's studied for
Potent anti-inflammatory signaling
VIP suppresses pro-inflammatory cytokine production (TNF-alpha, IL-6, IL-12) through the cAMP pathway and shifts activated microglia and macrophages toward neuroprotective phenotypes. In vitro work in BV-2 microglia shows it blocks rotenone-induced increases in nitric oxide, CD11b, MMP-9, and IL-6.
Neuroprotection
VPAC receptor activation supports neuronal survival in excitotoxicity and neuroinflammation models, and VIP has been proposed as a therapeutic target for neuroinflammatory conditions including Alzheimer's disease and Parkinson's-relevant models. Evidence is preclinical.
Circadian rhythm regulation
VIP is a key neuropeptide of the suprachiasmatic nucleus (SCN), where VPAC2 signaling synchronizes the body's master clock. This underlies its research interest in irregular sleep and circadian dysregulation.
Vasodilation and blood flow
As a potent vasodilator, VIP relaxes vascular and airway smooth muscle, supporting research into peripheral vascular blood flow, bronchodilation in airway inflammation, and pulmonary arterial hypertension.
Immune modulation in chronic inflammatory syndromes
VIP is increasingly studied in CIRS (Chronic Inflammatory Response Syndrome), mast cell activation, and biotoxin illness contexts, where intranasal administration is proposed to restore VIP deficiency and reduce neuroinflammatory cytokine activity. These clinical frameworks remain contested at evidence-based-medicine standards.
GI motility and mucosal protection
VIP regulates gut motility and intestinal secretion and supports GI mucosal protection, reflecting its role as one of the few neuropeptides with simultaneous central, peripheral, and immune functions.
Mechanism
How it works
VIP is a 28-amino-acid neuropeptide of the glucagon/secretin superfamily that signals through two G-protein-coupled receptors, VPAC1 and VPAC2. Both are Gs-linked, so receptor binding stimulates adenylyl cyclase and elevates intracellular cAMP in target cells. This single second-messenger mechanism produces VIP's remarkably broad physiology: vasodilation, bronchodilation, smooth-muscle relaxation, intestinal secretion, immune modulation, and circadian regulation.
In the immune system, VIP acts as a predominantly anti-inflammatory signal. cAMP elevation in activated microglia and macrophages suppresses pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-12, and shifts microglial activation toward neuroprotective phenotypes. In vitro models show VIP prevents neurotoxin-induced rises in inflammatory injury markers, supporting VPAC signaling as a route to preserve cognitive function under inflammatory stress.
In the brain, VIP is a key neuropeptide of the suprachiasmatic nucleus (SCN), the master circadian pacemaker. VPAC2 receptor activation synchronizes SCN neuronal firing and coordinates circadian rhythm, which is why VIP is researched in the context of irregular sleep and clock dysregulation. VPAC agonism also supports neuronal survival in excitotoxicity models.
Native VIP has a very short half-life (roughly one to two minutes in plasma after IV administration, extending to about 60-90 minutes subcutaneously), so sustained-effect applications typically rely on alternative formulation strategies or analog development. The synthetic analog Aviptadil was developed to exploit VIP's VPAC1-mediated protection of alveolar epithelial cells and anti-cytokine activity in acute lung injury.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Standard
- Dose
- ~50 mcg
- Frequency
- Once or twice daily
- Timing
- No fixed protocol; intranasal dosing is often morning-weighted in circadian/CIRS contexts
- Duration
- Not standardized
- Route
- Intranasal or subcutaneous
The most commonly cited research starting point. Because of VIP's vasodilatory action, low starting doses are used to gauge tolerance to flushing and blood-pressure effects.
- No tiered beginner/intermediate/advanced protocol is established in the source material; ~50 mcg once or twice daily is the primary cited dose range.
- Intravenous VIP carries significant hypotension risk and is described as not appropriate for unsupervised use.
- Intranasal formulations have particular stability and excipient considerations that basic peptide HPLC does not address; formulation quality matters for this route.
- VIP is not approved for human consumption and dosing varies by route; the sources explicitly decline to recommend a dose and advise consulting a licensed physician.
Evidence
Research & clinical studies (2)
PACAP and VIP Mitigate Rotenone-Induced Inflammation in BV-2 Microglial Cells
In BV-2 microglia treated with the pesticide rotenone, co-treatment with VIP prevented increases in nitric oxide, CD11b, MMP-9, and IL-6, demonstrating suppression of pro-inflammatory microglial activation in a Parkinson's-relevant neuroinflammation model.
PMID 35199308Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases
This review summarizes evidence that VIP and related neuropeptides attenuate microglial pro-inflammatory cytokine release and neuroimmune activity, positioning them as candidate therapeutic targets for neuroinflammation in neurodegenerative disease.
PMID 28154473Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Low blood pressure
- Concurrent vasoactive drug interactions
- Unsupervised intravenous use (significant hypotension risk)
VIP's transient side effects stem mainly from its vasodilator activity and are more likely with intranasal or subcutaneous dosing at higher amounts. Rare bronchospasm has been described as a paradoxical effect. There is no long-term human safety data for subcutaneous research use, and CIRS-protocol intranasal use rests on community-reported experience rather than formal long-term RCT data.
FAQ
VIP — common questions
What is VIP?
VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide of the glucagon superfamily, expressed throughout the nervous system, GI tract, and immune system. It binds VPAC1 and VPAC2 receptors to raise cAMP, producing vasodilation, bronchodilation, immune modulation, circadian regulation, and neuroprotection.
What is VIP primarily studied for?
Its main research areas are neuroprotection, CNS anti-inflammatory activity, CIRS (Chronic Inflammatory Response Syndrome) contexts, and circadian rhythm regulation, along with pulmonary and vascular applications through its analog Aviptadil.
Is the CIRS / Shoemaker protocol use of VIP evidence-based?
The CIRS framework and Shoemaker-protocol use of intranasal VIP are contested within mainstream medicine. They have community and practitioner support but limited formal randomized-controlled-trial evidence, so anyone considering this use should evaluate the underlying framework critically and consult a licensed physician.
Is VIP the same as Aviptadil?
No. VIP is the native 28-amino-acid neuropeptide; Aviptadil is a synthetic VIP analog developed for formal clinical use (studied in ARDS, COVID-19 lung injury, and pulmonary arterial hypertension). They are mechanistically related but are not identical products.
What are the side effects of VIP?
The most common effects relate to its vasodilator activity: facial flushing, hypotension, nausea, headache, and tachycardia at higher doses. Intravenous use carries significant hypotension risk and long-term human safety data is lacking.
How is VIP administered and dosed?
Reported routes are intranasal, subcutaneous, and intravenous. A commonly cited research dose is around 50 mcg once or twice daily, though no standardized tiered protocol exists and dosing varies by route. VIP is not approved for human consumption.
What is the regulatory status of VIP?
VIP is not FDA-approved for any indication. No NDA has been filed for VIP itself, and its analog Aviptadil has not achieved approval despite formal clinical development. Research-grade VIP is sold as a research-use-only compound and is legal to purchase for laboratory use in most jurisdictions but not approved for human consumption.
