PACAP-38
Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP38; PACAP-38; ADCYAP1; pituitary adenylate cyclase-activating peptide 1-38)
This peptide has not been evaluated by the FDA. It is sold as a research chemical and has no regulatory status for human use.
A natural brain peptide that protects nerve cells and affects blood vessels, playing a key role in migraine biology. Researchers are actively studying it as a potential target for migraine prevention treatments.
This entry is a cited research summary, not an established treatment reference. Dosing language is included as source context, not as medical instruction.
PACAP-38 has limited human evidence; signal requires confirmation.
This peptide has not been evaluated by the FDA. It is sold as a research chemical and has no regulatory status for human use.
Safety Summary
The acute safety profile of PACAP-38 is dominated by its potent vasodilatory and headache-inducing properties. In the largest published RCT (n=38), PACAP-38 infusion at 10 pmol/kg/min over 20 minutes induced mild-to-moderate headache in ~79-84% of participants and migraine-like attacks in a majority of migraine-susceptible individuals PMC11998216. Flushing, warmth, and palpitations are near-universal during infusion. No treatment-related serious adverse events (SAEs) have been reported in PACAP-38 peptide infusion challenge studies, though these studies are small (n=6-45) PMC11998216. Mast cell degranulation mechanisms are implicated in headache responses, though cluster headache attacks induced by PACAP-38 were not associated with changes in plasma CGRP or mast cell activation markers (IHS podcast). For PACAP-pathway therapeutics (anti-PACAP antibodies, distinct from the peptide itself): isolated SAEs include one B-cell lymphoma in the LY3451838 program (causality not established, PMID 40836866) and one sympathetic posterior cervical syndrome in the Lu AG09222 Phase II study PMC10210362. No tolerance, tachyphylaxis, or withdrawal effects have been documented. No formal carcinogenicity studies exist. Long-term safety data (>6 months) are not available. PACAP-38 is an endogenous peptide with low immunogenicity risk when administered exogenously.
Clinical check-in
If real-world use or exposure is being considered, review potential interactions, contraindications, and monitoring needs with a licensed clinician rather than relying on summary copy alone.
Cited sources
Every claim on this page links to one of the 10 sources below. Identifiers are PubMed (PMID), ClinicalTrials.gov (NCT), or DOI; click through to the source of record before acting on a claim.
- 1PMID 40229719PubMed
- 2NCT05378061ClinicalTrials.gov
- 3PMID 19220306PubMed
- 4PMID 37231350PubMed
- 5NCT05133323ClinicalTrials.gov
- 6PMID 40836866PubMed
- 7NCT04197349ClinicalTrials.gov
- 8NCT03814226ClinicalTrials.gov
- 9NCT02542605ClinicalTrials.gov
- 10A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine preventionReference