VIP
Vasoactive Intestinal Peptide
VIP (vasoactive intestinal peptide; drug name aviptadil) is a naturally occurring 28-amino-acid neuropeptide, not an anabolic or performance-enhancing drug. It is a potent vasodilator and immunomodulator that has been studied medically as an inhaled/nebulized agent for pulmonary hypertension and sarcoidosis, as an intracavernosal injection (combined with phentolamine, brand Invicorp) for erectile dysfunction, and as an intravenous infusion (aviptadil) for COVID-19 respiratory failure. It is also promoted in "biohacking"/wellness circles (often as a compounded intranasal spray) for chronic inflammatory or "CIRS" complaints, a use with no adequate human data. Because VIP is a systemic vasodilator, intravenous or absorbed dosing can cause flushing, a rapid heart rate, and a fall in blood pressure; supraphysiologic exposure reproduces some metabolic features of VIP-secreting tumors (Verner-Morrison/WDHA: watery diarrhea, transient rises in glucose, free fatty acids and calcium). Human efficacy evidence is limited and mixed: intracavernosal VIP/phentolamine has positive placebo-controlled data for ED, but the large intravenous COVID RCT (TESICO) was stopped for futility with no survival benefit. There is essentially no evidence supporting the systemic-wellness or intranasal uses for which it is most often sold online.
Mechanism of action
Pharmacokinetics
Very short. In healthy volunteers given IV VIP, plasma levels fell by first-order kinetics with a disappearance half-time of about 1 minute (Domschke 1978); a separate infusion study found bi-exponential elimination with half-lives of roughly 2 and 21 minutes (Holm-Bentzen 1981).
Brief for systemic dosing (minutes) given rapid clearance; effects of a single inhaled dose in pulmonary hypertension were described as modest and short-lived. Intracavernosal VIP/phentolamine produced erections with a median duration of about 56 minutes in a placebo-controlled trial. Sustained systemic exposure requires continuous infusion.
Studied routes: intravenous infusion (aviptadil), inhaled/nebulized aerosol, and intracavernosal injection (combined with phentolamine). Compounded intranasal use is marketed for wellness indications but has no adequate human pharmacokinetic or efficacy data.
Rapidly degraded by peptidases in plasma and tissues; not a hepatically metabolized small molecule. Reported apparent metabolic clearance rates were ~9 mL/kg/min (Domschke 1978) and ~42 mL/kg-min (Holm-Bentzen 1981), with a small volume of distribution (~14–135 mL/kg). Radiolabeled 123I-VIP showed high first-pass lung uptake and predominant urinary (renal) excretion, indicating the lungs and kidneys are major sites of handling/elimination.
For monitoring and washout planning, not drug-test evasion.
Physiological & performance effects
- Systemic vasodilation with increased heart rate and cutaneous flushing after intravenous dosing (healthy-volunteer studies)
- Selective but modest and short-lived pulmonary vasodilation after a single inhaled dose in pulmonary hypertension, reducing right-ventricular workload without lowering systemic blood pressure
- Immunomodulation in sarcoidosis: 4 weeks of nebulized VIP reduced bronchoalveolar TNF-alpha production and increased regulatory T cells (phase II, open-label)
- Facilitation of penile erection via the veno-occlusive mechanism when injected intracavernosally with phentolamine; ~66–82% of men achieved erections sufficient for intercourse in trials
- Transient metabolic changes during IV infusion: small rises in blood glucose, free fatty acids, and calcium
- No demonstrated clinical benefit in COVID-19 hypoxaemic respiratory failure in a large randomized trial (aviptadil arm stopped for futility)
Adverse effects by system
Systemic VIP is a vasodilator: IV dosing in healthy volunteers increased pulse rate and blood-pressure amplitude/heart rate and lowered diastolic blood pressure, i.e., tachycardia and hypotension risk. By contrast, a single inhaled dose in pulmonary hypertension caused selective pulmonary vasodilation without systemic blood-pressure effects, and intracavernosal dosing has minimal systemic hemodynamic impact.
No hepatotoxicity signal reported. VIP is a peptide cleared by peptidases and renal/pulmonary routes rather than undergoing hepatic small-molecule metabolism; liver injury has not been described in the human trials retrieved.
Not a sex steroid, androgen, or SERM; no evidence of hypothalamic-pituitary-gonadal suppression. During IV infusion VIP transiently raised glucose, free fatty acids and calcium. Supraphysiologic/endogenous VIP excess (VIPoma / Verner-Morrison syndrome) causes a distinct secretory-diarrhea endocrine syndrome; therapeutic exogenous use has not been shown to cause endocrine disease.
Used therapeutically to induce erection by intracavernosal injection with phentolamine; priapism was very rare (about 0.06% of injections, one episode) and injection pain was notably low compared with other intracavernosal agents. No human data on effects on fertility, spermatogenesis, or pregnancy.
No established human psychiatric adverse effects and no adequate data; neuropsychiatric consequences of exogenous dosing have not been characterized.
No nephrotoxicity reported. The kidney is a major elimination route (predominant urinary excretion of radiolabeled VIP); no direct renal injury described in the human data retrieved.
No clinically significant hematologic toxicity reported in the retrieved human studies; no adequate data on effects on blood counts or coagulation with exogenous use.
Cutaneous flushing is the most common effect of systemic/absorbed VIP (vasodilation). In intracavernosal ED trials, transient facial flushing occurred in roughly 40–53% of patients, with truncal flushing and injection-site bruising also reported.
HPTA suppression & recovery
Suppression: None expected / not applicable. VIP is a neuropeptide, not an androgen, anabolic steroid, or SERM, and no hypothalamic-pituitary-gonadal axis suppression has been demonstrated with exogenous use.
Because VIP is not androgenic and no meaningful HPTA suppression mechanism is established, post-use hormonal 'recovery' protocols are not indicated on current evidence. SERM-based recovery is not relevant to this compound (and any SERM use should in any case be single-agent only). Anyone with concerns about hormonal effects (or symptoms such as changes in libido, menstrual pattern, or galactorrhea) should have hormones evaluated and managed by an endocrinologist rather than self-treating.
Monitoring
Cadence: Clinical hemodynamic monitoring (heart rate, blood pressure) during and after any systemic/inhaled dose; lab checks at baseline and if symptoms (diarrhea, palpitations, lightheadedness) develop. Any ongoing use should be under a physician who orders bloodwork rather than self-monitoring.
- Lightheadedness, fainting, or palpitations (hypotension/tachycardia)
- Persistent watery diarrhea, dehydration, or muscle weakness/cramps (possible hypokalemia)
- Chest pain or shortness of breath
- For intracavernosal use: an erection lasting more than ~4 hours (priapism) — seek emergency care
- Marked or persistent flushing, rash, or signs of allergic reaction
Contraindications
- Hemodynamic instability, hypotension, or clinically significant cardiovascular disease where vasodilation, tachycardia, or a drop in blood pressure would be dangerous (systemic/IV dosing)
- Known hypersensitivity to VIP/aviptadil or excipients
- For intracavernosal use: conditions predisposing to priapism (e.g., sickle cell disease, myeloma, leukemia), anatomical penile deformity/fibrosis, and concurrent use of other vasoactive erectile agents
- Concomitant vasodilators/antihypertensives or alpha-blockers that could compound hypotension
- Active severe diarrheal or volume-depleted states (VIP promotes secretory GI effects)
- Pregnancy/breastfeeding and pediatric use — not studied; avoid
- Use for undiagnosed inflammatory or 'CIRS'-type conditions in place of evaluated medical care; no adequate evidence supports this
Interaction profile
- ContraindicatedWith DNP: Additive cardiovascular strain
Check a specific combination in the interaction checker.
Reducing harm & when to stop
- VIP is not an anabolic or performance-enhancing agent; there is no evidence it builds muscle, strength, or leanness, and it should not be used for those purposes.
- The compounded intranasal/systemic 'wellness' and 'CIRS' uses commonly marketed online have no adequate human efficacy or safety data. Do not substitute them for evaluated medical care of an inflammatory or chronic illness.
- Because systemic VIP is a vasodilator, expect flushing and be alert for lightheadedness, palpitations, or fainting; sit or lie down and stop if these occur, and avoid combining with other blood-pressure-lowering drugs.
- Watery diarrhea, weakness, or cramping could signal fluid/potassium loss — stop and seek medical evaluation with electrolyte testing.
- For intracavernosal ED use, this should be done under a clinician's guidance with a proper starting dose and technique; an erection lasting more than ~4 hours is a medical emergency (priapism) requiring immediate care.
- Any ongoing use should be supervised by a physician who orders baseline and follow-up bloodwork (electrolytes, glucose, renal function) rather than self-monitoring.
- Seek urgent care for chest pain, severe shortness of breath, signs of an allergic reaction, or a prolonged erection.
- Hormonal or endocrine concerns (e.g., changes in libido, menstruation, or galactorrhea) should be evaluated and managed by an endocrinologist, not self-treated.
Citations (11)
Every clinical claim above is tied to a primary source. Overall evidence grade B — graded to the best available evidence for its core claims.
- 01
VIP given IV to healthy volunteers is cleared with a disappearance half-time of about 1 minute, with a low metabolic clearance rate and small volume of distribution, and causes increased pulse rate, increased blood-pressure amplitude, cutaneous flushing, and small rises in glucose, free fatty acids and calcium mirroring Verner-Morrison syndrome.
CohortPMID 730072 ↗
- 02
After IV VIP infusion, elimination is bi-exponential with half-lives of about 2 and 21 minutes and a metabolic clearance rate of ~42 mL/kg-min; VIP did not significantly change gastric acid secretion.
- 03
Intravenous VIP in healthy volunteers significantly increased heart rate and decreased diastolic blood pressure and had a potent vasodilating action; it has a short half-life.
- 04
A single 100-microgram inhaled dose of aviptadil (VIP) in pulmonary hypertension produced modest, short-lived selective pulmonary vasodilation, improved stroke volume and mixed venous oxygen saturation, reduced right-ventricular workload, caused no side effects, and did not affect systemic blood pressure.
- 05
In a phase II open-label study, 4 weeks of nebulized VIP in 20 sarcoidosis patients was safe and well tolerated, reduced bronchoalveolar TNF-alpha production, and increased regulatory T cells.
- 06
Intracavernosal VIP 25 microg plus phentolamine (Invicorp) in a double-blind placebo-controlled trial produced erections suitable for intercourse in the majority of men (75% vs 12% placebo for VIP/phentolamine-1), with a median erection duration of ~56 minutes; the principal adverse event was transient facial flushing (~40% of injections), with no post-injection pain and a single priapism episode (0.06%).
- 07
In 70 men with ED resistant to other agents, intracavernosal VIP/phentolamine produced erections sufficient for intercourse in 67%, with transient facial flushing (53%), truncal flushing (9%), bruising (20%), and injection-needle pain (11%), and no priapism or serious adverse events.
- 08
Invicorp is a combination of VIP 25 microg and phentolamine for intracavernosal injection whose components have complementary actions (VIP on the veno-occlusive mechanism, phentolamine on arterial inflow), associated with a very low incidence of penile pain and negligible priapism risk.
- 09
Intracavernosal injectables for ED show efficacy in roughly 54-100% of patients but have high discontinuation rates and a moderate side-effect profile; approval is mainly limited to alprostadil with recent addition of aviptadil/phentolamine in select regions.
- 10
In the randomized, placebo-controlled TESICO trial of 471 patients with COVID-19-associated hypoxaemic respiratory failure, intravenous aviptadil (VIP) did not improve the primary ordinal outcome or 90-day mortality (38% vs 36% placebo); the aviptadil arm was stopped for futility and the early safety-event rate was numerically higher (63% vs 56%, not significant).
- 11
Radiolabeled 123I-VIP administered IV shows high first-pass lung uptake (40% of dose at 0.7 h) and is predominantly excreted in urine (93% within 24 h), indicating major pulmonary and renal handling.
CohortPMID 7562036 ↗
Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice