CGRP: A new era for migraine treatment

Update: In early 2019, the FDA approved three CGRP monoclonal antibody drugs for the treatment of migraines. The medications are known by the brand names Aimovig, Ajovy, and Emgality.

Migraine is a common medical condition, affecting as many as 37 million people in the US. It is considered a systemic illness, not just a headache. Recent research has demonstrated that changes may begin to occur in the brain as long as 24 hours before migraine symptoms begin. Many patients have a severe throbbing headache, often on only one side of the head. Some people are nauseated with vomiting. Many are light sensitive (photophobic) and sound sensitive (phonophobic), and these symptoms can persist after the pain goes away.

There are a variety of migraine subtypes with symptoms that include weakness, numbness, visual changes or loss, vertigo, and difficulty speaking (some patients may appear as if they are having a stroke). The disability resulting from this chronic condition is tremendous, causing missed days of work and loss of ability to join family activities.

It is sometimes possible for people to use an “abortive” medication, which, when taken early, can arrest the migraine process. For many patients, a preventive medication can decrease both the frequency and the severity of the migraines. But to date, many of the medications available for migraines have been developed primarily for other causes: seizures, depression, high blood pressure, and muscle spasms, for example. Researchers have been working for decades to develop a “targeted” preventive therapy specifically for migraine, and now we are finally close to having an exciting new treatment.

What does “targeted” therapy mean?

Calcitonin gene-related peptide (CGRP) is a molecule that is synthesized in neurons (nerve cells in the brain and spinal cord). It has been implicated in different pain processes, including migraine, and functions as a vasodilator — that is, it relaxes blood vessels. Once scientists identified this target molecule, they began trying to develop ways to stop it from being activated at the start of migraines, as a kind of abortive treatment. An agonist makes a molecule work more efficiently, and an antagonist blocks or reduces the molecule’s effect. The CGRP antagonist did work to decrease migraine pain based on certain measures, but there were some serious side effects including liver toxicity.

Back to the drawing board.

Monoclonal antibodies: Cutting-edge translational science

You have likely seen ads for monoclonal antibody (mAb) cancer and autoimmune therapies. There are lots of different types of mAbs, and while some harness a person’s own immune system to block replication of cancer cells, others stop a reaction in the body by binding to a target molecule or receptor and inhibiting it, thus preventing the reaction from continuing. The CGRP mAbs have this effect, and because they have a long duration of action (called a half-life), they can be administered much less frequently than typical migraine medications that are taken daily (with the exception of botulinum toxin, which is injected every 90 days). These new migraine medications are injected under the skin monthly, and have thus far demonstrated a statistically significant decrease in days of migraine. Four different drug companies are developing these new molecules, with two versions already sent to the FDA for approval.

What’s next?

If you think you may be a candidate for this new type of migraine medication, talk with your doctor, and perhaps ask for a consult with a neurologist or headache specialist who can help you understand more about the medication. Monoclonal antibody therapy is expensive, and there will likely be regulations about for whom s the treatments are appropriate. Much more research needs to be done about who is the best candidate for this therapy. But for many migraine patients who have not responded to the standard treatments, or who have had intolerable side effects such as cognitive dysfunction, low blood pressure, weight loss or gain, or other issues, CGRP monoclonal antibodies are safe and well tolerated, and are an exciting new development for migraine therapies.


  1. Nancy

    I have had migraine headaches since the age of 12, I am 71. I have been on every drug for prevention as the current neurologist would advise, also muscle relaxers, and any other Meds to combat pain, nausea, light sensation, dizziness, aura, neck tightness & pain. Many, many trips to hospital ERs & admissions to try to alleviate pain. I currently receive Botox injections which have been life altering, however after 8 weeks I am back in Migraine hell & taking Sumatriptan daily. The proplem I receive 11 pills monthly.! I also take preventive Topamax. Not sure what I can do, however will consult my neurologist.

  2. Polo

    Anyone knows if this (CGRP) might be useful for post traumatic headache after a concussion? Because I have chronic pain after a concussion in a boxing Match and it’s doesn’t go away, is there 24/7. Is like a burning type headache.

  3. Elizabeth Tyurikov

    I suffer from almost daily migraines. I was told by a migraine specialist that I am allergic to gluten, so I went off gluten. After 3 months I still had no relief. That was two years ago. Last year I read about people getting migraine relief from going off gluten and casein, so I gave it a try. Now this is a really difficult diet to follow. I lasted 3 weeks on it before giving up because I had no relief. The strange thing was that after I began eating gluten and casein again, I went an entire month without a migraine. The migraines eventually trickled back, but I wonder if gluten and casein were acting like some type of drug. Going off of them caused withdrawal, and reintroducing them caused relief? Not sure what to think about this.

  4. Trini S.

    My daughter has had migraines since she developed a seizure disorder at the age of 24. She has at least 15-22 a month and is under the care of a headache neurologist. She has taken over the counter meds, prescription meds, Magnesium, B-2. She has had botox treatments and just got her 4th round. it is not helping. The only thing that relieves the headache is Zomig which works 95% of the time. We are waiting the FDA approval of the CPRG therapy which seems to be a panacea for those in the clinical trials. Hope this will be life changing.

  5. Rebecca Danis

    Anyone having migraines should try daily supplementation with magnesium citrate. (Solgar is a well working brand that I use)
    Also avoid foods and supplements high in calcium and sulfur and phosphorus since excess calcium in the cells will raise electrical firing and can thus cause pain (sulfur and phosphorus helps pull excess calcium into nerve cells to cause pain)

    Also avoid Vitamin D supplementation as Vitamin D makes a person absorb more phosphorus and calcium from their foods and these excesses will get into the nerves and raise the electrical firing of those nerves to a too high level which can cause pain.

    And also avoid all aspartate (aspartame) and glutamate chemicals because these cause nerve oversensitivity on a chemical level, so they too will upset the nerves and cause pain.

    So basically,
    supplement daily with a well absorbed form of magnesium like magnesium citrate or magnesium malate (Source Naturals capsules are good) or even CALM magnesium citrate powder by Natural Vitality that you dissolve in water is good as well

    And avoid all foods and supplements high in calcium, sulfur, phosphorus, and vitamin D
    (Get your genes mapped to to see if you have CBS or SUOX mutations which will make you more sensitive to these substances)

    And avoid all aspartate and glutamate chemicals (including hydrolyzed soy protein, “natural enzymes” , “autolyzed yeast extract”, etc that are actually just alternative names for MSG that food mfrs use to trick customers. They might have different names, but will still cause headaches.

    Look up neurosurgeon Dr. Russell Blaylock on the Health Ranger on youtube talking about the dangers of Aspartate and glutamate and how toxic they are for the brain.

    And check out Dr. Robert Thompson on youtube and his book “The Calcium Lie: What Your Doctor Doesn’t Know Could Kill You”.

    And check out all the youtube videos with Dr. Carolyn Dean, the author of “The Magnesium Miracle” to learn more about how magnesium is natural calcium channel blocker and how magnesium helps prevent migraines and all headaches by keeping excess calcium out of soft tissue cells like brain and nerve cells.


    This blog and the comments have given me so much hope! Thank you.

  7. Lisa Lane

    Hi Emma, I was on amitriptyline, which is quite similar to nortriptyline. They are very similar, both in the same drug classes and bith tricyclic antidepressants that can also be used to treat nerve pain and migraine. Although my headaches didn’t respond, I do know of many people that get relief from these types of drugs. The side effects were quite severe, I experienced revounf headaches and frequent nightmares. The drug increases your appetite, which is why many people gain weight, however, if you don’t overeat and regulate your diet with healthy snacks for when you do get cravings, you should not gain weight.

  8. Rita barbano

    I have migraine since I had 11 years old ,I am 61 every week
    I did all kind treatments Botox profilática medication
    And I still with doing
    I have 2 migraines for week I also be treated with Botox at Stanford
    I hope the medicine helps

  9. Colleen

    My neurologist has me on 500 mgs of magnesium every day and 400 mgs of Vitamin B2 every day. definitely makes a difference. I don’t respond to painkillers for migraines, so I’m so hoping the new meds due out in May 2018 and June 2018 will help me and others like me.

  10. Ann miller

    My headaches are caused by severe bilateral neurons foraminal stenosis at C4-5, 5-6 in other words- osteophytes pressing on nerves. Headaches totally debilitating- PT etc which worked for stenosis in rest of spine- no good with this. Verydepressed as activity is EXTREMELY curtailed by headaches. Hope new treatment might work for this type of headache and is affordable – how much btw?? Thanx!

  11. Tara

    Hi Emma,
    First question – are you seeing a family practice doc or a headache specialist/neurologist. Things changed for me in a big way when I finally got to a neurologist and she is a headache specialist as well.
    Second – I’ve done botox and it didn’t have the full effect after the first injections. I would give it at least 2 rounds, maybe 3 before deciding it does or doesn’t work. It has helped me a lot and I think sometimes we give up too soon when we don’t get the relief we need. I’ve had chronic daily migraine for a long time and between botox and a daily preventive (topomax) they’ve been under control for a while now…until recently when some intense family stress blew the top off the pressure cooker of my head. Now I’m back to researching everything I can find but there’s no way I’ll stop botox in the mean time. It keeps my headaches at a manageable level so I can function. There was a time I couldn’t leave my bed. I don’ know much about nortripilyne (sorry about the spelling) but I’m also on cymbalta – similar drug in that it’s an anti-depressant that is also supposed to help with migraine and nerve pain. I’ve been on it for so many years I couldn’t say whether it’s helping or not but I’d like to assume it is. Those kinds of meds need 4-6 weeks to kick in and you can’t just stop and start them with awful side effects so give it a try if your doctor thinks it a good fit. With that said – ITS YOUR BODY. If you are opposed to the drug for whatever reason, ask to try something else. Personally between a little weight gain and debilitating migraine I’d work on my weight another way. I hope at least some of this is helpful. I feel like I’ve been through it all…I’m sure I haven’t but quite a bit. Good luck!!

  12. Tara

    Michael – I know some people, friends of mine included, have had success with acupuncture. I however, have not. It is simple, but it doesn’t work for everyone. 🙂

  13. Tara

    In reply to Michael…
    Why no mention of acupuncture? It’s simple and it works.

    Hi Michael,

    Please see this post from January 25, 2018 Acupuncture for Headache”

    I know I have friends who had success with acupuncture but it hasn’t worked for me. It is simple but unfortunately it doesn’t ALWAYS work. 🙂

  14. Emma

    i’ve been suffering from debilitating migraines all my life. I’ve just been prescribed nortrptyline i’m worries for the side effects mainly the weight gain. Has anyone tried this stuff? did it work? I’ve been administered Botox injection and not a fan but will try the second treatment soon and hope that will do the trick. I’ve been on alot of preventive medications but none have worked. The doctors say that i use to many rescues like triptans but all i want is relief. Any advice on nortrptyline will be greatly appreciated.

  15. Michael

    Why no mention of acupuncture? It’s simple and it works.

    Hi Michael,

    Please see this post from January 25, 2018 Acupuncture for Headache

  16. Mary T.

    I too have suffered from migraines all my life.
    Has anyone tried Botox? I am in the process of appealing a denial from my insurance co.

    • Elizabeth

      I did botox for almost three years after a coworker swore it helped her. It definitely changed my headaches – I felt they were as frequent but less painful and more likely to respond to triptans. The injections are painful and made me feel headache-y and sore for a day or two afterwards. In the end, I decided the benefits didn’t outweigh the negatives for me. I still got headaches, I was injecting poison into my head and I felt I was getting some facial freezing in spots that I worried would become permanent 🙂 I’m middle aged and want my face to age evenly!

  17. Antonie Slabbert (South Africa)

    A different approach by a Professor in Physiology with a private practice in Cape Town cured my chronic headaches and migraines. (I suffered for more than 30 years.) A comprehensive food intolerance test indicated all the foods I should avoid. This was the first step in improving GUT wall impermeability and integrity, whilst taking daily probiotics (of human origin), Vitamin D and Omega 3 supplements. A daily exercise routine was also prescribed and I have been headache and migraine free ever since, provided I stick to this regime!

  18. Rosa magliola

    I am currently suffering from Migraines, your report gives me new hope. Usually started with dizziness, h/a, sensitive to bright colors, nausea, vomiting, after n/v it is usually a relief, but miserable, disfunction, no interest in activities or people, 5 days at least for the demon to leave, for easy way to explaine to people it is indeed like being possessed by demon. SOS ASAP, thank you, and I pray for your speedy success. Rosa

  19. Iceni

    99% of the time I don’t have a headache,just the aura, visual disturbances ,nausea, photophobia and phonophobia. Tiredness and numbness in a limb. These symptoms usually have an aftermath of several days.
    I have been keeping a diary and sometimes the day before an attack, I am irritable or weepy and yawn alot.
    Glare from snow, water or sand and dark cnocolate can also trigger an attack.
    I would love something to stop thes disabling attacks the day before.
    I have a magnesium deficiency which I get treatment for.

    • Francis

      My migraines have diminished since I started taking 500mg of Magnesium, Riboflavin 50mg, and Cod liver. I do have a pattern of the same triggers of yours. Now I get them twice or less at month.

  20. Richard Pizzoferrato

    Once I was on, 1 tablespoon to lemon flavored Cod Liver Oil per day my migraines stopped completely, it took 30 days, it has been eight years now.. eight years migraine free…… thanks to my Primary Care Physician at San Diego VA Health Care…… I got friends to treat their migraines they same way with the same results……. believe

  21. Marie Grenier

    MANY people who suffered from debilating migraines were healed with a CHANGE OF ATTITUDE!!! Migrainers are all about control, a lot of the times. Sometimes, they are due to allergic reactions to certain food …

    • Arlene

      If it was MIND OVER MATTER, I’d be healed!!
      I have a Traumatic Brain Injury which causes my
      Extreme Migraines (worst than before the accident)
      And you are just the kind of person I avoid!!
      One who does not, will not , and won’t try to understand another’s pain!!!

  22. Fred

    What helped my wife with migraines is Magnesium-B2 riboflavin-CoQ10. Most people are low in these especially magnesium. Magnesium Gel rubbed on left side of neck should help . Have your levels checked to see if you are deficient. Also if you are low Vitamin D3. 40% of migraine sufferers are low in D (less than 20). A good level is between 40-70 . Probiotics are crucial for good health in general including migraines.

    • Mary

      I eliminated virtually 95% of migraines with 400 mg. of magnesium citrate nightly. It took over a month before I realized that I rarely had migraines. Now I make sure to never run out of magnesium.

    • Rik Ehmann

      Fred, thanks so much for sharing this. We so often forget the basics, such as most headaches (80%) are caused by dehydration. You are absolutely right about the magnesium, it is crucial to our health, it participates in over 325 processes in the body, including softening viens and arteries and most of us are magnesium deficient.
      Rik Ehmann LAc

  23. Patti Shaffner

    I hope this is useful. Interestingly…for years I told my Doctors that I believed the migraines to be related to hormones and was always shut down. This past year an acupuncturist recommended I get a saliva test done for cortisol and hormone levels. The results led me to using CorticoB5/6 and DHEA supplements and within two weeks my migraines were reduced significantly. I hope that Docs are beginning to listen to patients who listen to their bodies. It is waaay past time for that.

  24. Rakesh Gupta

    Delighted. Hopefully, my son gets an access along with capability for its affordability.

  25. Anita

    But WHEN????

    • Cathy

      I was in one of the studies for this antibody – and it worked. Gave me my life back (no exaggeration) I have been following this on the internet ever since. As I understand it, there are 4 companies trying to get this to market and all have had similar results: a dramatic lessening of occurrence, duration and intensity with varying degrees among the study participants. The first company is set to go before the FDA on May 17th – all signs point to approval as there have not been any significant side effects. So hopefully by the 3rd quarter of this year, we’ll see it on the market.
      To all my fellow migraneurs – hang in there – there is hope

  26. Joyce

    Wow, so amazing how medication is changing today’s world. So sad that it is expensive but let’s hope that it will be affordable in the future. I for one would really appreciate it 🙂

  27. Ebin V Thomas

    Good Read 🙂

  28. Jay Morgan

    exciting new development for migraine therapies. – YES

    affordable – NO

    Thanks again pharmaceutical companies.

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