Peptide Profile
PACAP-38
Neuroprotective polypeptide with potent anti-inflammatory and cytoprotective properties discovered in 1989
Dose Range
5 pmol/kg/min-20 pmol/kg/minmg
Frequency
Once daily
Route
Intravenous infusion
Cycle Length
Ongoing/indefinite
Onset
Moderate (1-2 weeks)
Evidence
Strong
Compound Profile
Scientific & Efficacy Data
C203H331N63O53S
Molecular Formula
~4534 Da
Molecular Weight
Very short plasma half-life (minutes); rapid enzymatic degradation
Half-Life
IV: systemic; Intranasal: direct CNS access bypassing BBB; poor oral bioavailability
Bioavailability
137061-48-4
CAS #
91935803
PubChem ID ↗
Developed By · 1989
Akira Arimura
Tulane University School of Medicine
Primary Benefits
Over 30 years of extensive preclinical evidence demonstrating potent neuroprotection in stroke, TBI, and neurodegenerative disease models through PAC1 receptor-mediated anti-apoptotic signaling
Suppresses NLRP3 inflammasome, inhibits microglial activation, and reduces pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) in central and peripheral inflammation
Established human pharmacological migraine trigger enabling anti-PACAP antibody development now in Phase IIb clinical trials for migraine prevention
Amino Acid Sequence
HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQRVKNK (38 amino acids)Dosing
How much
do I take?
Timing
Best time to take
PACAP-38 is administered intravenously in a clinical setting. Timing is determined by your healthcare provider based on the treatment protocol and your medical needs.
With food?
IV administration of PACAP-38 is not dependent on meal timing. Your healthcare team will provide specific instructions regarding food and fluid intake around treatment sessions.
If stacking
PACAP-38 should be used as directed by your healthcare provider. If combining with other medications or supplements, discuss potential interactions with your provider. Avoid combining with compounds that have overlapping mechanisms unless specifically guided by a medical professional.
Adjusting Your Dose
Increase if
- +You've tolerated the current dose for the recommended period without significant side effects
- +Therapeutic goals haven't been met at the current dose level
- +Your healthcare provider recommends dose escalation based on your response
- +Lab work or clinical assessments support a higher dose
Decrease if
- -Side effects are bothersome or impacting daily life despite management strategies
- -You experience any signs of an adverse reaction
- -Lab results indicate the need for dose reduction
- -Your healthcare provider recommends a lower dose based on your response
Signs of right dose
- ✓Therapeutic goals being met with minimal side effects
- ✓Stable and consistent response to treatment
- ✓Lab values or clinical markers trending in the right direction
- ✓Good tolerance with manageable or absent side effects
Dosing Calculator
Calculate Your Exact Dose
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Suitability
Is this
right for me?
Best For
Neuroprotection research
PACAP-38 is particularly well-suited for individuals focused on neuroprotection research. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Stroke and traumatic brain injury investigation
PACAP-38 is particularly well-suited for individuals focused on stroke and traumatic brain injury investigation. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Migraine pathophysiology studies
PACAP-38 is particularly well-suited for individuals focused on migraine pathophysiology studies. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Anti-inflammatory mechanism research
PACAP-38 is particularly well-suited for individuals focused on anti-inflammatory mechanism research. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Consider Alternatives If
Who Should Avoid
Do not use if
- ×Active migraine or headache disorder (PACAP-38 is a potent migraine trigger)
- ×Uncontrolled hypotension or cardiovascular instability
- ×Not approved for clinical use outside research settings
- ×Insufficient data for pregnancy and lactation safety
Use with caution if
- !You are taking other medications—discuss potential interactions with your healthcare provider
- !You have a history of liver or kidney disease
- !You are elderly or have multiple medical conditions
- !You are planning surgery in the near future—inform your surgeon about PACAP-38 use
- !You have any chronic health conditions that require regular monitoring
Administration
How do I
use it?
Reconstitution
What you need
- •PACAP-38 vial (lyophilized powder or solution)
- •Bacteriostatic water or sterile sodium chloride for reconstitution
- •Alcohol swabs for cleaning vial tops and injection sites
- •Appropriately sized syringes with fine-gauge needles (27-30 gauge)
- •Sharps disposal container
Injection
Route
Subcutaneous injection (into the fatty tissue just under the skin)—allows for consistent absorption and can be self-administered at home after proper training
Best sites
- •Abdomen (stomach area)—at least 2 inches from the belly button, most popular choice for self-injection
- •Front of thighs—middle to upper portion of the outer leg
- •Back of upper arm—outer area (may need assistance from another person)
Technique
- 1.Wash your hands thoroughly with soap and water before handling supplies
- 2.Clean the injection site with an alcohol swab and let it air dry completely
- 3.Pinch a fold of skin at the chosen injection site
- 4.Insert the needle at a 45-90 degree angle (depending on needle length and body composition)
- 5.Inject the medication slowly and steadily over 5-10 seconds
- 6.Release the skin fold and remove the needle, applying gentle pressure with a clean swab
- 7.Rotate injection sites to prevent tissue irritation or lipodystrophy
- 8.Dispose of the needle safely in a sharps container—never recap or reuse needles
Storage
Signs of degradation
Sample Daily Schedule
Safety
Is it
safe?
Safety Profile
PACAP-38 shows good tolerability in Phase II trials for migraine and pain conditions with minimal serious adverse events at IV doses of 2-6 mcg/kg. Primary side effects are transient flushing and headache (10-15% of subjects), likely related to vasodilation. Cardiovascular effects include mild heart rate increase and blood pressure changes, monitored in clinical settings. No carcinogenicity or teratogenicity in animal models; limited long-term safety data in humans.
Preclinical neurophysiology using patch-clamp electrophysiology demonstrates PACAP's PAC1 receptor mechanism with dose-dependent CREB phosphorylation (Western blot) and PKA/PKC activation pathways. Clinical trials show increased pancreatic polypeptide secretion (measured via radioimmunoassay) and neuropeptide release markers. Migraine mechanism confirmed through calcitonin gene-related peptide (CGRP) interaction studies showing complementary rather than overlapping pathways.
Common Side Effects
Experienced by some users
Flushing
Facial and truncal flushing due to vasodilation via VPAC receptor activation on vascular smooth muscle, common during IV infusion
Management: Transient and self-resolving; no treatment typically required
Tachycardia
Mild to moderate increase in heart rate during IV infusion as compensatory response to vasodilation
Management: Cardiovascular monitoring during infusion; reversible after completion
Gastrointestinal Effects
Occasional nausea and abdominal discomfort during or shortly after systemic administration
Management: Antiemetics as needed; effects typically transient
Transient Warmth Sensation
Sensation of warmth throughout the body during IV infusion due to systemic vasodilation
Management: Self-limiting during infusion; no treatment required
Less Common
- •Headache and Migraine Triggering
- •Hypotension
These typically resolve with continued use or dose adjustment.
Stop and Seek Help If
- ×Severe or worsening side effects that don't improve with dose adjustment or supportive care
- ×Signs of an allergic reaction—rash, hives, swelling, or difficulty breathing
- ×Your healthcare provider recommends discontinuation based on your clinical response
- ×Development of any new medical condition that may be contraindicated with PACAP-38
- ×Pregnancy or planning to become pregnant (unless specifically approved for use during pregnancy)
- ×Abnormal lab results or clinical markers that suggest adverse effects
PACAP-38 should only be started, adjusted, or discontinued under medical supervision. This information is for educational purposes only and does not replace professional medical advice. Never stop a prescribed treatment without consulting your healthcare provider first, as abrupt discontinuation may have consequences.
Interactions
With other peptides
- ✓Related peptide sharing VPAC receptor targets; combination studies elucidate receptor-specific contributions to neuroprotection
- ✓PACAP-38 upregulates BDNF expression; co-administration may enhance neurotrophic support in neurodegeneration models
- ✓PACAP-38 anti-apoptotic effects complement antioxidant strategies for synergistic neuroprotection
With medications
- !Triptans - PACAP-38 triggers migraine through cranial vasodilation; triptans target the same trigeminal pathway creating pharmacological conflict
- !Strong Vasodilators - Additive vasodilation through multiple pathways may cause dangerous hypotension
- !PAC1 Receptor Antagonists - Direct pharmacological antagonism blocks PACAP-38 primary neuroprotective mechanism
With supplements
- ✓Multivitamins - Generally safe to take alongside PACAP-38. Space doses apart if taking oral formulations to ensure optimal absorption.
- ✓Electrolyte supplements - Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
Effectiveness
Does it
work?
Evidence Level
Strong human trials
What to Expect
Acute Response (Minutes to Hours)
What you might notice
- •Rapid onset vasodilation, flushing, and heart rate changes during IV infusion;
- •headache onset within 1-6 hours in migraine provocation studies
What's normal
- •Initial response to PACAP-38 is beginning at the cellular level
- •Different individuals experience PACAP-38's onset at different rates
- •Transient systemic effects from initial PACAP-38 exposure are common
What's next
- →Maintain consistent PACAP-38 administration as prescribed
- →Document subjective effects and physical markers daily
- →Schedule a check-in with your provider about initial observations
Neuroprotective Window (Hours to Days)
What you might notice
- •Anti-apoptotic and anti-inflammatory signaling activated;
- •infarct volume reduction observed with intranasal delivery in stroke models
What's normal
- •PACAP-38 is achieving sufficient receptor engagement
- •Initial mechanism of PACAP-38 is taking effect
- •Early transient effects from PACAP-38 administration are resolving
What's next
- →Maintain consistent PACAP-38 administration as prescribed
- →Document subjective effects and physical markers daily
- →Schedule a check-in with your provider about initial observations
Research Endpoint (Days to Weeks)
What you might notice
- •Functional recovery improvement in stroke and neurodegeneration models;
- •sustained neuroprotection with repeated dosing;
- •migraine prevention effects being studied with anti-PACAP antibodies
What's normal
- •PACAP-38 response patterns are emerging
- •Initial PACAP-38 response is consistent with mechanism expectations
- •Early tolerance development to PACAP-38 is not expected
What's next
- →Assess whether PACAP-38 response aligns with expectations
- →Plan next steps based on initial PACAP-38 tolerance and response
- →Establish baseline monitoring for PACAP-38 response tracking
Signs It's Working
Treatment Response
- ✓Improvement in the primary symptoms or condition being treated
- ✓Positive changes in relevant lab values or clinical markers
- ✓Consistent, stable response to PACAP-38 over time
- ✓Reduction in symptom frequency or severity
General Well-being
- ✓Improved energy levels and daily functioning
- ✓Better quality of life related to the treated condition
- ✓Manageable or absent side effects indicating good tolerance
- ✓Positive feedback from healthcare provider during check-ups
Not Seeing Results?
Common reasons
- •Not at therapeutic dose yet—initial doses are for building tolerance, not maximum effect
- •Insufficient time at target dose—most compounds need several weeks to show full benefits
- •Inconsistent dosing schedule—regular, consistent use is crucial for optimal results
- •Individual variation in response—genetics, metabolism, and other factors affect outcomes
- •Underlying conditions or medications interfering with absorption or effectiveness
- •Improper storage leading to degraded product—always verify proper storage conditions
Key Research
"More Than Three Decades After Discovery: What Is Still Preventing PACAP Clinical Use?"
Research investigators, 2025
Finding: No abstract available for comprehensive analysis.
View Study"PACAP38 in human models of primary headaches"
Research investigators, 2017
Finding: No abstract available for comprehensive analysis.
View Study"Effect of Lu AG09222 on PACAP38-induced vasodilation, heart rate increase, and headache in healthy subjects"
Research investigators, 2023
Finding: Lu AG09222, a humanized antibody against PACAP, significantly reduced PACAP38-induced artery dilation and inhibited heart rate increases—demonstrating proof-of-mechanism for migraine prevention. Concomitant headache was reduced.
View Study"PACAP glycosides promote cell outgrowth and reduce infarct size after stroke in preclinical model"
Research investigators, 2024
Finding: PACAP glycosides retained neurotrophic activity in vitro while improving blood-brain barrier penetration, reducing infarct size by approximately 36% in stroke models. These modified peptides show promise for neuroprotection.
View Study"Intranasal PACAP reduces infarct volume and promotes functional recovery after middle cerebral artery occlusion"
Research investigators, 2020
Finding: Intranasal PACAP administration proved far more efficient than intravenous injection for reducing infarct volume after middle cerebral artery occlusion. Neuroprotection and functional recovery improved within 6 hours of stroke onset.
View StudyFrequently Asked Questions