CGRP is a protein that helps control blood vessel expansion. It has functions all over the body but is of particular interest to people seeking treatment for migraine.

Some migraine medications called CGRP monoclonal antibodies (mAbs) block CGRP due to its direct links to headache activity. These can help prevent migraine attacks. CGRP mAbs are the only preventive medications specifically for migraine.

This article discusses CGRP and how mAbs work to help prevent migraine symptoms.

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CGRP is a protein that occurs throughout the body. It has different actions and effects depending on its location.

CGRP has a range of important functions. For example, a 2018 review suggests it is crucial for:

However, in the brain, CGRP links to the feeling of pain and how the tissues and blood vessels react. It plays an important role in migraine pain.

For this reason, researchers have developed two classes of medications to treat migraine that interfere with how CGRP works. These are small molecule CGRP receptor antagonists (gepants) and mAbs that target CGRP or the receptors it connects to in the brain and nervous system. These block the action of CGRP, preventing migraine pain.

Monoclonal antibodies (mAbs) are a type of synthetic medication that act like cells in the immune system. Antibodies are proteins in the immune system that attach to another protein called an antigen. This tells the immune system to attack or block it.

Researchers make antibodies in a lab and tailor them to a specific antigen. They then produce copies of the antibody, which becomes a mAb.

CGRP antagonists are a type of mAb that targets CGRP. A 2022 systematic review of 26 randomized, controlled trials found that CGRP mAbs were significantly effective for treating migraine.

Erenumab (Aimovig)

This was the first mAb for migraine to gain approval from the Food and Drug Administration (FDA). Aimovig binds to the receptor in place of CGRP, blocking the action of CGRP and preventing migraine pain.

People can inject Aimovig themselves using a prefilled syringe or autoinjector. It is available in 70 milligrams (mg) and 140 mg.

Fremanezumab (Ajovy)

Ajovy binds to the CGRP protein itself rather than the receptor. However, this still prevents CGRP binding to its receptor and has similar preventive effects against migraine pain.

People can either receive Ajovy through monthly injections of 225 mg or a 675 mg dose every 3 months that consists of three injections, one after the other.

Galcanezumab (Emgality)

As with Ajovy, Emgality binds directly to the CGRP protein to prevent it from joining a receptor and triggering a migraine reaction. Emgality has also reduced how much blood vessels expand due to the actions of CGRP in studies.

Emgality is available as monthly 120-mg injections with a starting dose of 240 mg.

Eptinezumab (Vyepti)

Vyepti also binds to CGRP, blocking its ability to connect to receptors and cause pain.

All the other mAbs for migraine are subcutaneous, meaning that a person injects this just under the skin. However, Vyepti is the only CGRP antagonist doctors deliver as an intravenous (IV) infusion directly into the blood vessels. This may mean that it acts quickly and the body absorbs all of it.

Physicians will often recommend 100 mg of Vyepti every 3 months. Certain people might benefit from a triple dose to last the same length of time.

Gepants are available as oral pills or dissolvable tablets, instead of injections such as mAbs. They are also known as small molecule CGRP receptor antagonists.

As this name suggests, gepants bind to CGRP receptors and block their effect. Additionally, unlike some other medications, they do not constrict blood vessels but prevent them from dilating. This makes them a safer alternative for people with heart or cardiovascular disease.

There are three gepants available in the United States, with more in development. The current ones are:

According to a 2017 review, the side effects of CGRP mAbs have been rare and mild to moderate in studies. The listed side effects include:

CGRP also helps manage how food moves through the gut, which means that blocking CGRP may lead to side effects like constipation or diarrhea in some people.

In a 2020 review of the FDA’s Adverse Event Reporting symptom, 17% of the 24,573 side effects reported involved gut disorders. The same review estimates that constipation accounts for around 3–4% of reports for CGRP mAb side effects.

Evidence notes the most common side effects of gepants include:

Treatment for migraine revolves around reducing how often attacks happen and the severity of pain when they do.

Acute treatments for migraine

The following medication may help relieve migraine pain after an episode starts:

  • pain relief medications, such as nonsteroidal anti-inflammatory drugs and acetaminophen
  • antisickness medications (antiemetics), including metoclopramide and domperidone
  • triptans, which are prescription medications that can help both moderate to severe pain and sickness during a migraine episode
  • ergot derivative drugs, which reduce how many pain messages travel along nerve fibers and have the greatest effect early on in a migraine attack
  • ditans, such as lasmiditan, which can treat moderate to severe migraines, but can cause drowsiness

Preventing migraine episodes

Reducing the frequency of migraine attacks may involve CGRP mAbs and gepants, as well as:

Lifestyle measures for reducing migraine episodes

Treatment may be necessary for severe migraine. However, taking measures at home can help people with migraine maintain comfort during attacks. These might involve:

  • lying down in a quiet, dark room to take a nap
  • placing a cool cloth or ice pack on the forehead
  • consuming regular fluids, especially if the individual is also vomiting

A person can help reduce the number of attacks by:

CGRP is a protein that has links to several processes in the body. One of these processes causes pain sensations in people with migraine. The first preventive migraine medications — CGRP mAbs — are one of two drugs that target CGRP or its receptors in the brain.

These injectable or infusible medications are multiple synthetic copies of immune system proteins. They block the activity of CGRP by binding to the protein or the receptor. CGRP mAbs may cause side effects given CGRP’s role in other body functions, such as heart health or food movements through the gut.