Quick summary
CGRP is a 37-amino acid neuropeptide, one of the most potent endogenous vasodilators, and central to migraine pathophysiology. Multiple FDA-approved drugs (erenumab, fremanezumab, gepants) validate it as a top pain target.
Overview
CGRP (Calcitonin Gene-Related Peptide) is a 37-amino acid neuropeptide produced by alternative splicing of the calcitonin gene. It is one of the most potent endogenous vasodilators known and plays a central role in migraine pathophysiology, nociception, and cardiovascular regulation. Two isoforms exist: α-CGRP (neuronal) and β-CGRP (enteric).
Mechanism of action
CGRP binds to the CLR/RAMP1 receptor complex (CGRP receptor), activating adenylyl cyclase and increasing intracellular cAMP. This triggers smooth muscle relaxation and potent vasodilation, particularly in cranial blood vessels. During migraine, CGRP is released from trigeminal nerve terminals, activating the trigeminovascular system and promoting neurogenic inflammation and peripheral sensitization. Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and CGRP receptor antagonists (gepants) block this cascade.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| vasodilation research (in vitro/animal) | intravenous | 0.1–10 nmol/kg | single dose per experiment | |
| nociception model (animal) | subcutaneous | 1–100 nmol | per experimental protocol |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
CGRP's role in migraine is among the best-validated therapeutic targets in pain neuroscience. Plasma CGRP levels rise during spontaneous migraine attacks and normalize with triptan treatment. Multiple FDA-approved drugs targeting CGRP or its receptor have demonstrated efficacy in migraine prevention and acute treatment. Preclinical studies show CGRP also regulates bone metabolism, wound healing, and cardiac function. Research-use peptide is employed in vasodilation and nociception models.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with CGRP for synergistic effects.
Legal status
Endogenous CGRP peptide is available for research use only. Therapeutic monoclonal antibodies targeting CGRP/its receptor (erenumab, fremanezumab, galcanezumab) are FDA-approved prescription medications. The raw peptide is not approved for human administration.
Sourcing & access
Research compound
CGRP is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
CGRP (Calcitonin Gene-Related Peptide) is a 37-amino acid neuropeptide produced by alternative splicing of the calcitonin gene. It is one of the most potent endogenous vasodilators known, with two isoforms: alpha-CGRP (neuronal) and beta-CGRP (enteric). It plays a central role in migraine and nociception.
CGRP binds to the CLR/RAMP1 receptor complex, activating adenylyl cyclase and increasing cAMP. This triggers smooth muscle relaxation and potent vasodilation, particularly in cranial blood vessels. During migraine, CGRP released from trigeminal nerve terminals activates the trigeminovascular system and promotes neurogenic inflammation.
CGRP itself is a research compound with side effects including flushing, headache, hypotension at high doses, and tachycardia. The FDA-approved anti-CGRP drugs (monoclonal antibodies and gepants) have well-characterized safety profiles used in migraine prevention and treatment.
Multiple drugs targeting CGRP are FDA-approved for migraine: monoclonal antibodies erenumab, fremanezumab, and galcanezumab block CGRP or its receptor, while small-molecule gepants (ubrogepant, rimegepant, atogepant) antagonize the CGRP receptor for acute and preventive migraine treatment.
Research references
- Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effectsReview
- The Vascular-Dependent and -Independent Actions of Calcitonin Gene-Related Peptide in Cardiovascular DiseasePubMed
- Advances in CGRP Monoclonal Antibodies as Migraine Therapy: A Narrative ReviewReview
- A narrative review of the calcitonin peptide family and associated receptors as migraine targets: Calcitonin gene-related peptide and beyondReview
- Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysisPubMed