• Calcitonin gene-related peptides (CGRPs) are proteins that may contribute to migraine headache pain.
• Anti-CGRP drugs represent a new class of medications specifically developed for migraine prevention.
• Anti-CGRP drugs are expensive but promising, especially for people who can’t use other treatment options.

There are new developments in the world of treating migraine, a debilitating condition that affects around 12 percent to 15 percent of people in the U.S. A new class of medications — drugs that target calcitonin gene-related peptides — has shown a lot of promise for treating the condition.

CGRPs are peptides found in the nervous system. They’re responsible for processing pain, increasing inflammation, and contributing to the development of migraine attacks. Medications that interfere with the activity of the body’s circulating CGRPs have been shown to be effective in reducing migraine attacks. These medications are called anti-CGRP medications or treatments, CGRP medications, or CGRP inhibitors.

Anti-CGRP treatments are the first preventive medications specifically developed for treating migraine.

Several members of MyMigraineTeam have asked questions to understand CGRP and anti-CGRP medications better. One member asked, “Is anyone familiar with or has experience with the CGRP family of drugs?” Others have asked, “What are the CGRP injections?” and “Would you please tell me about other CGRP drugs available?

Continue reading for a closer look at the function of CGRP in the brain and body. We’ll discuss the role of CGRP in migraine and the different preventive treatments that inhibit CGRP activity.

What’s Different About Anti-CGRP Medications?

Traditionally, migraine prevention has included medications for managing seizures, blood pressure, and depression. Anti-CGRP treatments are the first preventive medications specifically developed for treating migraine.

Anti-CGRP treatments are also well tolerated. This means they cause very few side effects. Many anti-CGRP medications are given as a shot or infusion, so reactions tend to be related to the injection site.

Some members of MyMigraineTeam have reported that anti-CGRP medications work well for them. They’ve shared comments such as these:

• “CGRP worked for me immediately. I took it for 18 months, and during those 18 months, I had six migraines that were less intense and short-lived.”
• “No other meds have helped other than CGRP.”
• “Ask your doctor about one of the new CGRP drugs; they do work.”

What Is CGRP?

Calcitonin gene-related peptide is a protein in everyone’s body that naturally helps protect the brain. CGRP is a vasodilator that helps arteries dilate (widen) to increase blood flow, aiding healing. CGRP influences the immune system by increasing or decreasing levels of inflammation. For example, when the body has nerve damage, levels of CGRP rise. Researchers believe that higher CGRP levels may be linked to the release of nerve growth factor, which supports nerve growth and health.

Recently, the American Headache Society stated that CGRP medications should be considered a first-line approach for migraine prevention and treatment.

CGRP works by activating receptors in the brain and cardiovascular systems. When the receptors are activated, the meninges (tissues surrounding the brain) become inflamed, contributing to migraine pain.

CGRP’s Role in Migraine

Research findings have shown a link between elevated levels of CGRP and migraine. An area in the brain that processes sensory information, the posterior thalamic nuclei, becomes hyper, or very sensitive, during a migraine attack. Researchers have found evidence in rodents that CGRP increases the sensitivity of the posterior thalamic nuclei.

Researchers and doctors still don’t understand exactly how migraine attacks happen. However, they know that most people prone to migraine attacks will develop a migraine within four hours if they’re given CGRP intravenously (into a vein).

How Do CGRP Inhibitors Work?

There are two classes of anti-CGRP medications: CGRP receptor antagonists and CGRP monoclonal antibodies (mAbs). Both types aim to disrupt the activity of CGRP to prevent migraine attacks. Anti-CGRP medications don't constrict blood vessels like conventional migraine medications, such as triptans. Instead, anti-CGRP medications prevent blood vessels from dilating.

CGRP Receptor Antagonists

The term “receptor antagonists” means these drugs prevent CGRP from binding to its normal receptors, which reduces its activity. Another term for CGRP receptor antagonists is “gepants.” Gepants bind to the CGRP receptors on the trigeminal ganglion (a group of neurons in the face and neck) and are more often used for acute treatment of migraine rather than prevention.

The National Headache Foundation offers a list of patient assistance programs, which help people who need financial assistance purchase necessary medications.

Four gepants have been approved by the U.S. Food and Drug Administration (FDA):

• Ubrogepant (Ubrelvy) — An acute migraine treatment taken by tablet, typically given to people with moderate to severe migraine whose headache pain isn’t relieved by common over-the-counter drugs
• Atogepant (Qulipta) — A drug taken orally for preventive use rather than acute intervention for episodic or chronic migraine
• Rimegepant (Nurtec ODT) — An acute and episodic migraine treatment taken by tablet as an acute or preventive migraine treatment
• Zavegepant (Zavzpret) — A nasal spray that’s used to treat acute migraine headaches after they’ve started

The most common side effects of gepants are fatigue, upset stomach, and dry mouth. It’s important to discuss symptoms with your doctor and, to prevent interactions between drugs, let them know about any other medications you’re taking.

CGRP Monoclonal Antibodies

Monoclonal antibodies are a type of biologic therapeutic, meaning they’re medicines that come from living cultures. Monoclonal antibodies can remain active in a person’s body for more than a month. This makes mAbs especially effective for preventing migraine attacks for a longer period.

As of 2024, the FDA has approved four CGRP monoclonal antibody medications for migraine prevention. One of them, erenumab-aooe (Aimovig), targets the CGRP receptor and is self-injected once 1 month. The other three mAbs target the CGRP protein itself:

• Eptinezumab-jjmr (Vyepti) — Administered as an IV infusion once every three months
• Fremanezumab-vfrm (Ajovy) — Self-injected every one or three months

• Galcanezumab-gnlm (Emgality) — Self-injected once a month

CGRP mAb drugs need to be injected because they’re very large molecules. They don’t cross the blood-brain barrier (a protective layer within the brain’s blood vessels), and they’re not broken down in the liver.

Is Anti-CGRP Therapy Right for You?

Recently, the American Headache Society stated that CGRP medications should be considered a first-line (preferred) approach for migraine prevention and treatment. However, more research needs to be done on some groups of people, and anti-CGRP therapy may not be the best option for everyone. Doctors don’t recommend using CGRP drugs during pregnancy or while taking vasoconstrictive medications.

A 2024 study in the journal Cephalalgia suggests that gepants are more effective for acute migraine treatment in women than in men. The authors noted that more research is needed to explore possible differences in how men and women respond to anti-CGRP therapy.

CGRP medications are expensive, which can be a significant barrier to newer treatments for people with migraine. One member of MyMigraineTeam commented, “I have been trying to get the new CGRP drugs. The problem is Medicare won’t cover them and my supplemental insurance only covers half.”

The National Headache Foundation offers a list of patient assistance programs (PAPs) that help people who need financial assistance purchase necessary medications and devices. Drug companies, government agencies, and nonprofits can help those who qualify for free or lower-cost treatment.

Talk With Others Who Understand

MyMigraineTeam is the social network for people with migraine and their loved ones. On MyMigraineTeam, more than 84,000 members come together to ask questions, give advice, and share their stories with others who understand life with migraine.

Are you living with chronic migraine and want to know more about anti-CGRP treatment? Have you tried anti-CGRP medication? Share your experience in the comments below, or start a conversation by posting on your Activities page.