Vasoactive neuropeptide; investigational intranasal and pulmonary therapy

Vasoactive intestinal peptide

aka VIP · aviptadil (synthetic VIP)

Evidence grade
Grade C: Preliminary human data
for intranasal VIP for CIRS / chronic inflammation
User score too few reports (9) needs ≥ 10 reports
US FDA Not approved checked 2026-11-13
WADA 2026 Not named no clearance either · checked 2026-11-13
EU Aviptadil/phentolamine combination medicines have national European authorizations; this does not authorize nasal VIP for CIRS. EMA granted aviptadil an ARDS orphan designation on February 23, 2026, which is not a marketing authorization. · checked 2026-11-13

Goals: Immune Compare with another peptide →

User reports

approximate — combined from two independent Reddit reads

Men 45–60

0 men aged 45–60

No reports in this group yet.

All men

0 men

No reports in this group yet.

Everyone

9 people

small sample · n = 9

Outcome mixed 4 of 9 · positive 2 of 9 · negative 1 of 9 · no effect 1 of 9 · unclear 1 of 9

Benefits focus / cognition 2 of 9 · other 2 of 9 · energy 1 of 9 · mood / anxiety 1 of 9

Side effects other 2 of 9 · anxiety 1 of 9 · blood pressure 1 of 9 · fatigue 1 of 9 · gi upset 1 of 9 · low mood 1 of 9

Stopped 0 of 9 Used with other compounds 1 of 9

User reports are anecdata, not evidence: self-selected, unverified, often combined with other compounds.

In their words

  • “It has been a game changer for me.”

  • “It was about 4-5 months before I noticed small improvements.”

  • “Yes feeling so much better thank you 6 weeks in”

  • “I do not notice a difference.”

Read summaries and method notes

Read 1. No VIP thread was accessible (the five r/CIRS seed threads could not be read), so n=0 everywhere. Nothing reported rather than reconstructed from memory.

Read 2. No explicitly male user. Nine users: 2 positive, 4 mixed, 1 negative, 1 no effect, 1 unclear. Improvement was often delayed — one "game changer" took 4–5 months; another felt much worse at first and much better by six weeks. Two reported cognitive gains (one also depressive/irritable mood). Other adverse effects: anxiety, bloating, energy setbacks, low blood pressure/faintness during titration. Mostly CIRS/Lyme patients, so heavy confounding.

Note 1. No VIP threads could be opened; zero counts reported.

Note 2. No usable male age data. CIRS/Lyme populations and long titration create heavy confounding. The '100mg' nasal dose is preserved as written and may be a unit error.

Each read counted people independently. Overlap between the two reads is estimated from shared threads and removed; counts are approximate. How we count.

Summary

28-amino acid neuropeptide. MW: ~3,326 Da. Widely distributed — gut, brain, lung, immune cells. Endogenous production.

Proposed mechanism

VIP has biological regulatory functions; the proposed mechanisms below do not establish treatment outcomes in nasal CIRS, MCAS or general inflammation.

  1. Context-dependent mast-cell responses — human skin mast cells can release histamine in response to VIP. Uniform stabilization and clinical MCAS benefit are not established. Experiment.
  2. Anti-inflammatory — suppresses TNF-α, IL-6, IL-12 production from macrophages and dendritic cells. Promotes regulatory T-cell differentiation (Treg)
  3. Gut barrier integrity — maintains intestinal epithelial tight junctions, reduces intestinal permeability
  4. Pulmonary effects — an acute inhalation study showed modest temporary vasodilation; durable pulmonary-hypertension protection and equivalent nasal delivery are unestablished.
  5. Neuroprotective — anti-apoptotic in neurons, promotes neuronal survival via VPAC1/VPAC2 receptors
  6. Circadian regulation — VIP is a key signaling molecule in the suprachiasmatic nucleus (master clock)

Comparison with KPV and LL-37: mechanistic descriptions do not establish VIP’s clinical superiority or a comparative safety ranking. No controlled comparison supporting those preferences was found.

Safety

  • IV trial: hypotension, diarrhea, flushing and tachycardia were more frequent than placebo
  • Small nasal studies cannot establish uncommon or long-term risks
  • Historical FDA review raised uncertain immunologic and peptide-quality concerns
  • VIP is not a uniformly mast-cell-stabilizing substance: human skin mast cells can release histamine in response to it
  • Route-specific trial doses are not interchangeable

From labels, regulators and trials. No signal in small studies ≠ safe.

Evidence C intranasal VIP for CIRS / chronic inflammation

C stands. One 20-person open-label study without controls. The failed 471-patient IV COVID-19 trial and the small inhaled trial are different routes and uses and do not move the grade.

Human trials · 4

  1. No PMID2013Open-label, 18-month study with healthy reference values, not randomized controls; DOI 10.4236/health.2013.53053; PMID/NCT not found 20 people

    Previously treated patients classified as having CIRS after water-damaged-building exposure

    Symptoms and selected biomarkers improved, but attribution to VIP is limited by lack of blinded concurrent controls.

  2. PMID 189781352008Acute open-label inhalation during right-heart catheterization 20 people

    Pulmonary hypertension of several causes

    Small, temporary pulmonary vasodilation; no evidence of durable clinical benefit from this single-dose study. Source

  3. NCT04843761; PMID373485242023Multicenter randomized placebo-controlled trial; 461 received study infusion 471 people

    COVID-19-associated acute hypoxemic respiratory failure

    No improvement in day-90 ordinal clinical outcome (OR 1.11, 95% CI 0.80–1.55); mortality 38% versus 36%. Source

  4. NCT04844580; PMID398700642025Double-blind randomized placebo-controlled trial 80 people

    Hospitalized COVID-19 pneumonia, initially outside intensive care

    Inhaled treatment shortened mean discharge time (7.8 versus 10 days; p=0.049); mortality difference was not significant; 11 ICU transfers discontinued study treatment. Source

Bar length = trial size on a log scale.

Dose ranges

Reported ranges from labels and studies, with context. Not a recommendation.

  • Clinical study, intranasal CIRS protocol
    50 micrograms by nasal aerosol four times daily initially, with subsequent titration; the paper does not specify 50 micrograms per nostril Source on a non-primary host — not linked
  • Clinical study, pulmonary hypertension
    Single 100-microgram inhaled dose during catheterization Source
  • Clinical trial, hospitalized COVID-19 pneumonia
    200 micrograms/day nebulized, delivered as two 1-mL portions of 100 micrograms/mL solution 30 minutes apart, for 7–14 days Source

Editorial ratings EDITORIAL

Editors’ judgement, 0–5. Opinion, not data; separate from grade and user score.

Not rated yet.

Sources

  1. pubmed.ncbi.nlm.nih.gov/18978135/
  2. pmc.ncbi.nlm.nih.gov/articles/PMC10527239/
  3. pmc.ncbi.nlm.nih.gov/articles/PMC11936437/
  4. fda.gov/media/94155/download
  5. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
  6. ema.europa.eu/en/medicines/human/orphan-designations/eu-3-26-3200
  7. pubmed.ncbi.nlm.nih.gov/37348524/
  8. pubmed.ncbi.nlm.nih.gov/39870064/
  9. pubmed.ncbi.nlm.nih.gov/2464382/
  10. fda.gov/media/100283/download
  11. accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=142001
  12. fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-c
  13. ema.europa.eu/en/documents/psusa/aviptadil-phentolamine-mesilate-list-nationally-authorise

Reddit threads read · 3

3 further sources on commercial or non-primary hosts not listed.

Research checked 2026-11-13.