What Is CGRP and Why Does It Matter for Migraine Treatment?

CGRP appears alongside a growing number of migraine treatments, including injections, infusions, tablets, and even a nasal spray. The name sounds technical, but the idea behind it is fairly simple.

CGRP stands for calcitonin gene-related peptide. It is a natural signaling molecule found in the nervous system and involved in several processes throughout the body. Researchers became particularly interested in CGRP because of the role it can play during a migraine attack. That research led to treatments that block either CGRP itself or the receptor it attaches to: some taken when an attack starts, others used regularly to help prevent attacks.

CGRP is one part of the migraine pathway

Migraine is a neurological condition involving several systems in the brain and nervous system. One of them is the trigeminovascular system, a network of nerves and blood vessels associated with migraine symptoms. When this system becomes active, trigeminal nerve fibers can release signaling molecules, including CGRP.[1] CGRP is thought to contribute to pain signaling and can affect nearby nerve and blood vessel activity, and changes in its activity during migraine attacks helped researchers identify it as a possible treatment target.

This does not mean CGRP alone causes migraine. Migraine involves several biological processes, and people can experience the condition very differently — CGRP is one part of the migraine pathway, not the whole story.

What does it mean to block CGRP?

A signaling molecule like CGRP needs somewhere to deliver its message. That’s the job of a receptor: a docking site on the surface of a cell that CGRP attaches to in order to trigger its effects, like pain signaling and changes in nearby blood vessels. CGRP-targeting treatments interfere with that process in one of two ways. Some attach directly to the CGRP molecule itself, stopping it from reaching a receptor at all. Others attach to the receptor instead, blocking CGRP from activating it even when the molecule is nearby.

One way to picture this is to think of CGRP as a message and the receptor as the place where the message is received. One treatment may capture the message before it arrives; another may block the receiver. Both approaches aim to reduce CGRP-related signaling involved in migraine.

Two types of CGRP-targeting treatment

There are two main groups of CGRP-targeting treatment: monoclonal antibodies and gepants.

Monoclonal antibodies

Monoclonal antibodies are larger molecules that attach either to CGRP or to its receptor. They are mainly used for migraine prevention, administered by injection or infusion, and tend to stay in the body longer than tablets, depending on the treatment, they may be given monthly or less often.

Gepants

Gepants are smaller molecules that block the CGRP receptor. They usually come as tablets, although other forms also exist. Some are used as acute treatments, meaning they’re taken when a migraine attack begins; others are used regularly for prevention; and some may be approved for both, depending on the country, in the United States, for example, rimegepant is approved for both acute and preventive treatment.[2]

Acute vs. preventive: An acute treatment is used during an attack, to reduce symptoms and help restore function. A preventive treatment is taken regularly, to reduce how often attacks happen, how severe they are, or how much they interfere with daily life.

What does the evidence show?

CGRP-targeting treatments now have more than a decade of clinical trial and real-world evidence behind them. In a 2024 position statement, the American Headache Society recognised CGRP-targeting therapies as a first-line option for migraine prevention.[3] The statement supports considering these treatments earlier in preventive care, rather than automatically reserving them until several older options have failed. However, access rules still vary insurance requirements, national healthcare systems, local approvals, and individual medical circumstances can all affect which treatments are available.

One pivotal trial studied 955 people with episodic migraine. Around half of the participants receiving the higher dose of erenumab, a CGRP monoclonal antibody, had their monthly migraine days reduced by at least 50%, compared with around one-quarter of those receiving placebo.[4] That is a meaningful response for many people, but it also shows why expectations need to remain realistic: CGRP-targeting treatments can help many people, but they do not work equally well for everyone.

What about side effects?

No treatment is risk-free, and side effects vary between medications. Injection-site reactions are commonly reported with CGRP monoclonal antibodies, and constipation has been reported with some treatments in this group.[5] For gepants, reported side effects can include nausea, although the exact side-effect profile differs by medication.[5]

Warnings, interactions, and side effects can all differ by medication. A healthcare professional can explain the risks and precautions that apply to the specific treatment you are considering.

Why did CGRP change migraine treatment?

Many older migraine preventive treatments were originally developed for other conditions, including high blood pressure, epilepsy, and depression. Doctors later found that some of these medicines could also help prevent migraine, and these treatments still have good evidence behind them and may work very well for some people. They may also be more affordable or easier to access.

CGRP-targeting treatments were developed around a pathway linked more specifically to migraine. This gave people another group of acute and preventive options, particularly when previous treatments did not help enough or caused difficult side effects.

Newer does not automatically mean better. The right treatment depends on the person: cost, access, other health conditions, treatment goals, side effects, and preferred method of taking medication can all affect the choice. For some people, an older or more accessible treatment may still be the best fit; for others, a CGRP-targeting treatment may be worth discussing. As with any change to your treatment plan, it is worth talking it through with a healthcare professional first.

What can CGRP treatment realistically do?

CGRP-targeting treatments do not cure migraine, and they do not work the same way for everyone.

For preventive treatment, success may mean:[6]

• fewer monthly migraine days
• less severe migraine attacks
• fewer associated symptoms
• less disruption to work, family life, or daily plans

For acute treatment, success may mean:[7]

• relief from pain or other disabling symptoms
• fewer associated symptoms
• being able to return to normal activity sooner

Whether a treatment “worked” is not the only useful question. What matters is whether it helped with the specific symptoms, frequency, or disruption that migraine causes in your life. For one person, the main goal may be fewer attacks; for another, it may be reducing nausea, brain fog, or missed days at work. Treatment goals are personal, and it helps to identify yours before speaking with a healthcare professional.

What to discuss with your healthcare professional

A treatment conversation is easier when you can clearly describe what is happening now. Before an appointment, it may help to bring information about:

• how many migraine days you have each month
• which acute and preventive treatments you have tried
• how often you use acute medication
• which symptoms affect you most
• which side effects you have experienced
• how migraine affects your work, studies, family life, or daily plans

A migraine diary can make this easier, especially when attacks are frequent or difficult to remember accurately. Logging in Migraine Buddy can also help you compare your migraine pattern before and after starting a new treatment. You may want to ask:

Could a CGRP-targeting treatment fit my goals, and how would it compare with the options I have already tried?

Do not stop or change medication without medical guidance. Treatment approvals and availability differ between countries, so a healthcare professional can explain which options are relevant where you live.

 

References

[1] Russo AF. (2017). Overview of Neuropeptides: Awakening the Senses? Headache: The Journal of Head and Face Pain, 57(Suppl 2), 37-46. https://doi.org/10.1111/head.13084 

[2] US Food and Drug Administration. (2025). Prescribing information for NURTEC ODT (rimegepant). https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/212728s028lbl.pdf

[3] Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey AD. (2024). Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache: The Journal of Head and Face Pain, 64(4), 333-341. https://doi.org/10.1111/head.14692 

[4] Goadsby PJ, Reuter U, Hallström Y, et al. (2017). A Controlled Trial of Erenumab for Episodic Migraine. New England Journal of Medicine, 377(22), 2123-2132. https://doi.org/10.1056/NEJMoa1705848 

[5] Messina R, Huessler EM, Puledda F, Haghdoost F, Lebedeva ER, Diener HC. (2023). Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis. Cephalalgia, 43(3). https://doi.org/10.1177/03331024231152169 

[6] McGinley JS, Houts CR, Nishida TK, Buse DC, Lipton RB, Goadsby PJ, Dodick DW, Wirth RJ. (2021). Systematic review of outcomes and endpoints in preventive migraine clinical trials. Headache: The Journal of Head and Face Pain, 61(2), 253-262. https://doi.org/10.1111/head.14069 

[7] Diener HC, Tassorelli C, Dodick DW, et al. (2019). Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia, 39(6), 687-710. https://doi.org/10.1177/0333102419828967