CGRP
The vessel-widening neuropeptide behind migraine attacks, never a treatment itself but the target of a new drug class
CGRP, calcitonin gene-related peptide, is a 37-amino-acid neuropeptide released from sensory nerves, a highly potent vasodilator. Infusing it triggers migraine-like headaches in susceptible people, which made it a drug target: antibodies against CGRP or its receptor, such as erenumab (Aimovig), now prevent migraine.
What is it?
CGRP comes from alternative processing of the calcitonin gene, in alpha and beta forms, and is released mainly from sensory nerves. It acts on an unusual receptor, the calcitonin receptor-like receptor paired with a modifying protein, RAMP1. It is a potent vasodilator with protective roles in the cardiovascular system and wound healing, and it sits in pain pathways.
Infused into six healthy people, it raised blood flow in the carotid artery to 152% of baseline and in skin to 682%, while cutting flow to the gut to 58%. In five patients with brain haemorrhage, it eased the spasm of the cerebral arteries that follows.
Its importance is migraine. In 30 people with persistent post-traumatic headache, a 20-minute CGRP infusion triggered migraine-like attacks in 70% against 20% on placebo. The same infusion triggers cluster headache attacks during an active cluster period, and aura in about a third of people with migraine with aura. Evidence like this led to drugs that block it: gepants for acute attacks, and antibodies against CGRP or its receptor to prevent them.
The provocation model keeps extending. In 2026 the same 20-minute infusion reliably triggered the typical headache of idiopathic intracranial hypertension in women without migraine, and a meta-analysis found CGRP raised in children with migraine both during and between attacks. Blocking it has not worked everywhere: pooled antibody trials in cluster headache showed no significant cut in attacks.
Because CGRP protects blood vessels, long-term blockade is watched closely. A study of 900,370 US beneficiaries linked starting a CGRP inhibitor to a higher weighted rate of cardiovascular events (hazard ratio 1.26), while a stroke comparison with onabotulinumtoxinA was reassuring but imprecise, and erenumab carries post-marketing hypertension reports. After a non-response to one antibody, switching class reduced migraine days in a controlled cohort.
CGRP itself is never given as a treatment; erenumab (Aimovig) is approved for migraine prevention in adults.
Mechanism of Action
CGRP is a sensory-nerve neuropeptide from the calcitonin gene that acts on CLR with RAMP1; it is a potent vasodilator and a key signal in migraine.
Vasodilation
Infused, it redirects blood flow to the carotid and skin and away from the gut, and eases cerebral artery spasm after haemorrhage.
Headache
A 20-minute infusion triggers migraine-like, cluster and IIH headache attacks in susceptible people.
Blocking it
Gepants and antibodies against CGRP or its receptor prevent or treat migraine; cardiovascular effects of long-term blockade are monitored.
Published Research
These are the studies that describe CGRP in people, read from their PubMed abstracts: three infusion studies and two reviews.
It provokes migraine-like attacks
30 people with persistent post-traumatic headache received a CGRP infusion or placebo, crossover. 70% developed headache with migraine-like features after CGRP against 20% after placebo.
It redirects blood flow
In six healthy people, CGRP at 80 pmol/kg/h raised carotid blood flow to 152% and skin flow to 682% of baseline while reducing gut flow to 58%; a lower dose and calcitonin had no effect.
After brain haemorrhage
In five patients after subarachnoid haemorrhage, intravenous CGRP reduced the Doppler index of cerebral artery spasm from 6.2 to 4.3 without changing blood pressure or consciousness.
It can trigger aura
In an open-label study of 34 people with migraine with aura, a CGRP infusion was followed by aura in 13 (38%) and by migraine headache in 24 (71%) within 12 hours.
Cluster headache attacks
In a double-blind crossover trial in 32 people with cluster headache, CGRP provoked attacks in 8 of 9 in an active episodic phase (1 of 9 on placebo) and in 7 of 14 with chronic cluster headache (none on placebo), but in no one in remission.
Who responds to erenumab
In 13 patients from erenumab trials, a CGRP infusion induced migraine-like attacks in 10 (77%) against none after placebo; 8 of the 10 had been strong responders to the antibody.
Headache in idiopathic intracranial hypertension
In 20 women with idiopathic intracranial hypertension and no migraine history, a 20-minute CGRP infusion reliably provoked their typical headache and raised intracranial pulse amplitude without changing mean pressure.
Switching antibody class
In patients who did not respond to a first CGRP antibody, switching between ligand- and receptor-targeting antibodies cut monthly migraine days by 3.9 more than returning to standard care.
Cross-response to eptinezumab
In 190 French patients, the 50% responder rate to eptinezumab was 76.0% in those who had responded to an earlier CGRP antibody, against 30.4% in prior non-responders.
Cardiovascular events
In 900,370 US insurance beneficiaries with migraine, starting a CGRP inhibitor was associated with a higher rate of cardiovascular events after weighting (8.77 against 6.76 per 1,000 person-years; hazard ratio 1.26).
Stroke risk versus onabotulinumtoxinA
In a cohort of migraine patients, ischaemic stroke and TIA rates with CGRP antibodies were non-inferior to onabotulinumtoxinA (hazard ratio 0.52), though the estimate was imprecise.
Blood pressure
A review of erenumab data noted 362 post-marketing hypertension reports over more than 245,000 patient-years, suggesting modest but sometimes clinically meaningful effects, especially with pre-existing hypertension.
Glaucoma risk
In 73,644 people with migraine, CGRP inhibitor users had a lower 3-year risk of glaucoma than non-users (hazard ratio 0.75) and than users of several other preventives.
From bench to migraine clinic
Drugs targeting CGRP or its receptor act specifically on the trigeminal pain system: gepants such as ubrogepant treat attacks, and antibodies against CGRP or its receptor prevent them.
Physiology and pathophysiology
CGRP is a 37-amino-acid peptide from alternative splicing of the calcitonin gene, acting on CLR with RAMP; a potent vasodilator, it protects the cardiovascular system and features in pain pathways.
Higher in children with migraine
A meta-analysis of 8 studies found CGRP levels higher in children and adolescents with migraine than in controls, both during and between attacks, with moderate- to low-certainty evidence.
Antibodies in cluster headache
Across 4 trials with 655 participants, CGRP antibodies did not significantly reduce weekly cluster attacks (−0.81 a week), with high placebo response rates clouding the responder analyses.
Adherence and long-term tolerability
A systematic review found good adherence to CGRP antibodies, constipation and injection-site reactions as the commonest side effects, and responder rates rising from 44% at 3 months to 64% at 12 months.
Dosing Data
CGRP itself is not a treatment. In research, it is infused at 1.5 µg/min for 20 minutes to provoke headache under supervision.
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Side Effects & Contraindications
Reported Side Effects
From infusion studies; it is never given as treatment.
Contraindications & Cautions
Not a treatment.
Legal Status
CGRP is not a medicine; drugs that block it are.
Frequently Asked Questions
?What is CGRP?
A 37-amino-acid neuropeptide from sensory nerves that strongly widens blood vessels and features in pain pathways.
?What does it have to do with migraine?
Infusing it triggers migraine-like attacks in susceptible people, and drugs that block it prevent or treat migraine.
?Which drugs target it?
Gepants for acute attacks, and antibodies against CGRP or its receptor, such as erenumab (Aimovig), for prevention.
?Is CGRP itself a treatment?
No. It is given to people only in research.
?Is blocking CGRP safe for the heart?
It is being watched. In US claims data, starting a CGRP inhibitor was associated with more cardiovascular events (hazard ratio 1.26), while a stroke comparison with onabotulinumtoxinA was non-inferior but imprecise, and erenumab has post-marketing hypertension reports.
?What if one CGRP antibody does not work?
Switching between ligand- and receptor-targeting antibodies reduced monthly migraine days by 3.9 more than returning to standard care, and in one series 76% of prior responders also responded to eptinezumab.
References
- [pubmed] Ashina H, et al. "Hypersensitivity to Calcitonin Gene-Related Peptide in Post-Traumatic Headache." Ann Neurol, 2020;88(6):1220-1228. PMID: 32959458.
- [pubmed] Jäger K, et al. "Calcitonin gene-related peptide (CGRP) causes redistribution of blood flow in humans." Eur J Clin Pharmacol, 1990;39(5):491-4. PMID: 2076743.
- [pubmed] Juul R, et al. "Calcitonin gene-related peptide (human alpha-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage." Neurosci Lett, 1994;170(1):67-70. PMID: 8041516.
- [pubmed] Edvinsson L, et al. "CGRP as the target of new migraine therapies - successful translation from bench to clinic." Nat Rev Neurol, 2018;14(6):338-350. PMID: 29691490.
- [pubmed] Russell FA, et al. "Calcitonin gene-related peptide: physiology and pathophysiology." Physiol Rev, 2014;94(4):1099-142. PMID: 25287861.
- [fda-pi] AIMOVIG (erenumab-aooe) injection Prescribing Information, sections 1 (DailyMed version 25, effective July 14, 2026; read September 30, 2026).
- [other] US FDA, Drugs@FDA (openFDA): no application for CGRP. Read September 30, 2026.
- [pubmed] Al-Khazali HM, et al. "Calcitonin gene-related peptide causes migraine aura." J Headache Pain, 2023;24(1):124. PMID: 37679723.
- [pubmed] Vollesen ALH, et al. "Effect of Infusion of Calcitonin Gene-Related Peptide on Cluster Headache Attacks: A Randomized Clinical Trial." JAMA Neurol, 2018;75(10):1187-1197. PMID: 29987329.
- [pubmed] Christensen CE, et al. "Migraine induction with calcitonin gene-related peptide in patients from erenumab trials." J Headache Pain, 2018;19(1):105. PMID: 30409109.
- [pubmed] Yiangou A, et al. "Calcitonin gene-related peptide induces headache attacks in people with idiopathic intracranial hypertension." Brain, 2026;149(8):2629-2642. PMID: 41989095.
- [pubmed] Zhu G, et al. "Calcitonin Gene-Related Peptide (CGRP) Levels of Children and Adolescents With Migraine: A Systematic Review and Meta-Analysis of Observational Studies." Eur J Pain, 2026;30(1):e70177. PMID: 41312882.
- [pubmed] Yuan L, et al. "Efficacy and safety of calcitonin gene-related peptide monoclonal antibodies for cluster headache: a systematic review and frequentist-Bayesian meta-analysis." J Neurol, 2026;273(7). PMID: 42249970.
- [pubmed] van Veelen N, et al. "Switching from ligand to receptor anti-calcitonin gene-related peptide (CGRP) antibodies or vice versa in non-responders: A controlled cohort study." Eur J Neurol, 2025;32(1):e16542. PMID: 39607215.
- [pubmed] Ferrao-Malheiro S, et al. "Cross-response to Calcitonin Gene-Related Peptide monoclonal antibodies in a real-world setting: analysis of prospective data collected in the French FHU InovPain registry." J Headache Pain, 2026;27(1). PMID: 42410521.
- [pubmed] Ray R, et al. "Patient Adherence and Long-Term Tolerability of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Migraine Prevention: A Systematic Review." Cureus, 2025;17(8):e91347. PMID: 41035604.
- [pubmed] Lusk JB, et al. "Calcitonin Gene-Related Peptide Inhibitors and Cardiovascular Events in Patients With Migraine: A Retrospective, Observational Cohort Study." Neurology, 2026;106(3):e214479. PMID: 41499728.
- [pubmed] Gül S, et al. "Cerebrovascular risk with calcitonin gene-related peptide monoclonal antibodies versus onabotulinumtoxinA in patients with migraine: A real-world pharmacoepidemiologic study in the National Institutes of Health All of Us Research Program." Cephalalgia, 2026;46(7):3331024261464438. PMID: 42390441.
- [pubmed] Kakde SP, et al. "Assessing the Occurrence of Hypertension in Patients Receiving Calcitonin Gene-Related Peptide Monoclonal Antibodies for Episodic and Chronic Migraine: A Systematic Review." Cureus, 2025;17(8):e90244. PMID: 40959372.
- [pubmed] Chou CC, et al. "Glaucoma Risk Associated With Calcitonin Gene-Related Peptide Inhibitor Use in Migraine: A Multinational Cohort Study." Neurology, 2026;106(11):e218035. PMID: 42090640.
Sources & Citations
Studies were read from their PubMed abstracts. Read October 7, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.