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Featuring Demian Dressler, DVM and Sue Ettinger, DVM, Dip. ACVIM (Oncology), authors of The Dog Cancer Survival Guide

Benadryl For Dogs With Mast Cell Tumors: How It Can Help

Updated: November 18th, 2019


Vets often prescribe Benadryl for mast cell tumors. Why on earth do they do that? Dr. Dressler explains how this common allergy med can help.

Benadryl for mast cell tumorsBenadryl for mast cell tumors? What on earth does an over-the-counter allergy medicine have to do with cancer?? Let’s find out.

Most of us have heard of Benadryl, the brand name for diphenhydramine hydrochloride. It’s an antihistamine, which means it reduces the effects of excess histamines in the body.

In human medicine, we usually use it for allergies: hay fever, runny eyes, sneezing, and allergic sinus congestion. It is also used for more sudden-onset allergic reactions, including hives, facial swelling and so on.

In veterinary care,  we use it to treat things like insect stings, vaccine reactions or other allergic reactions in dogs.

And we often recommend Benadryl for dogs suffering from mast cell tumors.

Dogs with cancer are not experiencing allergies. So, what’s the logic?

Dr. Dressler goes into deep detail on Mast Cell Tumors in his audio seminar.

Well, it turns out there are similarities between a dog with a high mast cell burden and a dog experiencing allergic flare-ups. And Benadryl for mast cell tumors can address those.

Mast Cells Are Weird and Cool

Mast cells are really interesting cells. They are part of the immune system, a type of white blood cell.

Mast cells help rid the body of foreign invaders or material. They also help in healing. They do this in part by generating a substance called histamine. Yup, the same histamine that we talk about when it comes to allergies.

Mast cells that are normal release histamine as part of their work. Histamine helps attract other white cells to trouble spots, like foreign bacteria, or viruses, or injuries. They’re like those red flags your car’s roadside safety kit has. Histamine “marks” an area of the body that is in trouble, so other immune cells can find the area.

Histamine also causes blood vessels to dilate (get larger), and get a little “leaky.” The increased blood flow brings more white blood cells more quickly, and the little leaks help the white blood cells slip out of the blood and into the area that needs them.

So, you see, histamine is an important part of our immune system.

Mast Cell Detects Trouble ==> Releases Histamine ==> Attracting Other Immune Cells ==> Which Kill Invaders and/or Repair Injuries

So, yay histamine, right?

Yes. Mast cells are cool, because they produce histamine. Until they produce too much.

Mast Cells Can Overdo It

As with all things, balance is needed when it comes to histamine. Too much histamine is not good for the body.

When mast cells release too much histamine, whether during an allergic reaction or by huge numbers of cancerous mast cells, bad things happen.

  • The blood vessels in the area of the mast cells dilate, bringing inflammation and swelling of body tissues. In allergic reactions, this looks like hives and abnormal swelling.
  • The excess histamine is capable of causing the lining of the stomach to produce excessive acid. This causes loss of appetite and lethargy.
  • Blood pressure can be affected if enough histamine is secreted. It can drop to truly dangerous levels as many blood vessels open up all at once.

As it turns out, when a lot of mast cells are busy releasing their contents, they secrete lots of things, not only histamine. There are other chemical signals that work in tandem with the histamine, and those get released, too.

The end result of all these mast cells releasing their chemical signals is that the dog’s body goes into a completely abnormal state.

Inflammation and swelling results, and discomfort, as well. I would imagine the sensation is like getting stung or perhaps old stings (itchy, burning). Those with allergies might be familiar with the feeling of all-0ver discomfort, a sort of panicky itchy weird feeling. I imagine it is something like that for our dogs who have a massive release of histamine.

Histamine and Mast Cell Tumors

Now, both cancerous and non-cancerous mast cell tumors are capable of releasing histamine, and both are capable of releasing too much.

If your dog has allergies, you might see a little swelling or redness, and itching. Same is true if your dog has mast cell tumors.

But NOT every mast cell tumor will release very high levels of histamine that cause terrible symptoms like those above.

So if your dog has mast cell tumors, don’t assume that you will see those symptoms.

Only the most severe cases will have these high levels of histamine release.

Why We Use Benadryl for Mast Cell Tumors

Benadryl blocks the effects of histamine in the body, which is why it’s called an “antihistamine.”

Basically, it helps the body cope with abnormally high histamine levels.

That’s why you might hear your veterinarian recommend it for your dog with mast cell tumors: it can help to block the uncomfortable-to-dangerous effects of excess histamine released by cancerous mast cells.

Benadryl can help with the side effects of excess histamine sometimes associated with mast cell tumors.

Remember how excess histamine can also affect the stomach, by causing extra stomach acid? Benadryl helps with that, too. However, sometimes veterinarians will also suggest using an antacid as well, just to be sure to protect the tummy. Cimetidine and famotidine (Tagamet and Pepcid) are often used, and ulcers (if they are present) are often treated with misoprostol (Cytotec) and sucralfate (Carafate).

Diet Matters

If you’ve read my book, you know that I recommend a low-carb, relatively high fat, moderate protein diet for dogs with cancer.

If your dog with mast cell tumors is also experiencing excess histamine release — and remember, not all do — there are special dietary considerations you should also be aware of. You can read more about special nutritional choices for dogs with mast cell tumors in this article.

Of course, diet is just one of five steps in my Full Spectrum approach to cancer care. In addition to diet, nutraceuticals, anti-metastatic supplements, and mind-body strategies, you can find an entire chapter on the conventional care for mast cell tumors in chapter 30 of The Dog Cancer Survival Guide.

All my best,

Dr D

If your dog has mast cell tumors, this book is a wealth of information. In addition to the main steps Dr. D recommends, read the extra chapter dedicated to mast cell tumors from Dr. Ettinger, his oncologist co-author.


Discover the Full Spectrum Approach to Dog Cancer

Leave a Comment

  1. Susan Joy on September 2, 2020 at 5:09 pm

    Thank you for giving pet parents this wonderful information,my lab Luke is ten and we are going through mast cell tumor problems ,the diet has made a huge difference.No more bag food,chicken ,peas and brussel sprouts are causing his itching and painful gait to dissipate.Benadral is a help ,my boy deserves the best ,the most terrific companion dog possible.

  2. Vanesa on August 12, 2020 at 9:27 am

    Ordering your bok today. Cancer is just as confusing when its us or our pets. My girl recently had surgery to remove a MCT. My vet never mentioned Benadryl, so after the fact, I’m doing the tagamet/benadryl protocol. But, it almost seems I should have her on benadryl for life. And therefore my question, should my dog be on Benadry permanently?

    • Molly Jacobson on August 13, 2020 at 10:29 am

      Hi Vanessa! The short answer is: if your dog is actively itchy a LOT, Benadryl may become a lifestyle choice for you. I’ve heard about that protocol, and the rather enthusiastic fans of it often say that no other supplements or meds should be used. I’m a big believer in doing ALL the research before choosing a method that excludes other ideas or treatments, because there is no silver bullet or one-right-way or protocol that works for every dog, in every case, every time. I also tend to trust medical professionals or researchers over anecdotes shared by other dog lovers, even those who have a lot of confusing videos about what they are promoting.

      Cancer is complex and nuanced, and absolutes, in my experience, just don’t apply. Benadryl is a very helpful OTC drug that specifically reduces histamine in the body. Since mast cell tumors are located in mast cells, which produce histamine, it can be really helpful in terms of reducing the symptom (excess histamine production) but it doesn’t “cure” the cancer itself.

      If your dog wasn’t actively itchy and didn’t have a lot of over-dosed-on-histamine symptoms, your veterinarian may not have thought it was necessary. Giving a drug — even an over-the-counter drug — when it’s not necessary can throw the body out of balance. As Dr. Dressler notes above in a couple of places, not every dog’s mast cells release massive amounts of antihistamine just because they have tumors.

      As for Tagamet, he recommends it in his book as an antacid because it was originally developed for its anti-cancer properties. But the fact is, that just because a drug is developed for one purpose doesn’t mean it’s great at it or stands alone as a perfect treatment. Viagra was originally developed as a heart disease drug, but it was a dud in the end (but it did have an interesting side effect — so they labeled it for that!).

      To me, both benadryl and tagamet are useful if your dog is too high in histamine (which the benadryl will break down) and therefore has an upset tummy (caused by the high histamines) for which Tagamet can be used because it also may have a slight anti-cancer effect.

      And I could not agree with you more — cancer is just as confusing in dogs as it is in us. We are confounded by this oldest illness known to man!

  3. Debbie on July 21, 2020 at 4:41 am

    Wouldn’t quercitin be better than actual Benadryl

    • Molly Jacobson on July 24, 2020 at 9:11 am

      Hi Debbie, Benadryl is pretty powerful as an anti-histamine, so if a dog is really in need, it can manage it well. Quercetin may or may not be as effective in a pinch.

  4. Tammy Harvester on June 27, 2020 at 11:46 pm

    My best friend Baby has has MCT since 2016. Underwent chemo them palladia. Dis nor tolerate well. She started developing more the beginning of the year 28 plus tumors. Am going to use the Holistic approach. Need help. I can’t live without her. No metastasis. But has a lot of GI upset. Diarrhea freq

  5. ISABELA on June 25, 2020 at 10:57 am

    my daughter gets angry when I tell her my 4 year old dog may have cancer as she has elevated white blood cells, she was refusing to eat, drink, and did not want to move. fever over 104.8. After caring with wet towels trying to make her favorite chicken broth and new toys, she is recovering. but please send my daughter articles in case the dog has a severe damage. I have an appointment with the Vet, although the last one charged me $1,000 for an examination and blood test with no diagnosis.

  6. Irene Burgess on May 20, 2020 at 4:15 pm

    When should you put down the dog or cat with this type of cancer?

    • Molly Jacobson on May 22, 2020 at 3:57 pm

      Aloha Irene, there is no one answer for this question. The time to euthanize depends upon about a million factors, and in the end, you are really the best one to know what to do for your own pet. Here’s an article that may help:

      Sometimes when we learn what the end of life looks like, it’s easier to recognize it when it arrives. Until then, you might not need to even think about it!

      Warm Aloha,

  7. Dawn E Stevenson on May 10, 2020 at 11:49 am

    My pit mix has had 2 surgery’s. Once in 2016 and then in 2018. The last surgery, 7 were removed and not sure how many were Mast cell but the it was low grade 2 mitotic index 0.
    About 2 weeks ago, I found a bump in her tummy. The vet wasn’t convinced it was Mast cell yet, so she put her on antibiotics. It’s still there. She is 12 and does not sneeze or exhibt any signs of allergies. She eats well, plays etc..
    I am not sure what to do. If they do a needle biopsy will that cause it to spread?
    She only gets the bumps. It has never gone into her lymph nodes. I am in a tight budget but more importantly I want what is best for her.
    If I do not have it removed, could it spread?
    Thank you.

    • Molly Jacobson on May 10, 2020 at 2:49 pm

      Hi Dawn, I’m sorry to hear about your girl 🙁

      If you haven’t read this article yet, it will help you to understand the possibilities around needle biopsy:

      As for whether this bump is cancerous or not, or whether it has spread, unfortunately it’s just unknowable without doing the testing you probably remember from before: biopsy and imaging.

      And yes, if it is cancer and you do not remove it, it could spread. However, even if you DO remove it, there could still be spread that they just don’t pick up on tests. That can happen too. Cancer is just the worst in part because there are so many unknowns.

      If you don’t have the budget to test, you might want to focus on life quality strategies like the dog cancer diet, supplements, and mind-body strategies. Even when we can’t test/treat with surgery, chemo, or radiation there is still a lot we can do for our dogs. I highly recommend you get a copy of Dr. Dressler’s book The Dog Cancer Survival Guide, and if you can’t do $9.99 for the digital edition, the diet is also found in the free PDF The Dog Cancer Diet. Sign up for our newsletter and you will get that automatically:

      And here are a few more links to articles on the site that might get you started on how to help your dog.

      This is such a tough time for all of us, with the pandemic going. But I know that even with your challenges your girl knows the most important thing: that you really love her. Take good care of yourself, so you can take care of her <3


  8. Leanne on February 23, 2020 at 7:35 am

    I’m just reaching for what to do to help my dog Remington from dying from cancer. He is 7 1/2 years old and is a French Bull dog- Beagle. He had 2 small grade II mast cell tumors on his lower right side of his torso near ribs and 1 larger subcutaneous mast cell tumor on his left knee removed 1/28/20. The Dr said per pathology report she did not get clean margins on the knee tumor and the “dirty margins” is located at the 6 o’clock area or bottom of the incision on his knee. I was giving him Benadryl twice a day am & pm all up until the surgery ( about 6 weeks ) and continued it after the surgery and the Dr added Meloxicam and Famatodine. He hasn’t been on the Meloxicam or Famatodine for weeks now. I stopped the Benadryl for a while because I felt bad making him sleepy all the time. I just started giving him Benadryl in pm again because of the literature on it helping cancer in dogs. His Dr said I could stop giving it to him if I want to. We haven’t seen Oncology yet. I’m not sure if I should be giving the Benadryl twice a day or not. If it will help or hurt. Because it is confusing, it sounds like histamines the MCT’s give off are good and not good. Prior to surgery he had x-rays of his lungs and thorax and ultrasound and aspirations of his spleen and liver and nothing was seen. But he has had a small unidentified nodule on his lungs for many many years and his recent recheck of the lungs showed 2. He started turning so gray very young and since we first noticed the tumor on his leg in November and the surgery he has turned so much more gray he looks very old. I want to do the right thing for him in caring for him right now. I’m afraid of the Oncology appointment after reading alot about subcutaneous MCT’s without clean margins on the limbs. I just want to do what I myself can do for him right now each day. I switched him to NW Naturals raw for his dinner 1/2 cup with 1/2 cup of Canidae Pure grain free Bison. In the morning I always cook eggs 1/2 cup and 1/2 cup of the Canidae. He had a lot of allergies/ ear infections and gooky eyes when younger so going with grain free has helped. I thought he might have an allergy to poultry but I’m not sure, and just avoiding it in fear it will make his histamines worse. Your advice on if it’s a good idea to give him Benadryl and Famatodine twice a day would be so appreciated. I also just read that exercise and being out in the cold causes inflammation in the area where the MCT’s are so I’m wondering if I should give him Benadryl before his walks out in the cold. I just want to understand it all better and make the right choices and I feel so lost. He had wonderful Dr. but she just says if you want to you can and doesn’t seem to have an opinion on it. I’m always afraid there’s a chance he’s dying with the cancer in him still and he has changed over the last 6 months. He gets up very late morning, eats and then goes back to sleep for several hours before wanting to go outside to walk ( or go to the bathroom ) He just holds it and sleeps..Sometimes, actually quite often he will not get up after his breakfast until 2 or 3pm. Once out he comes alive and seems to like to walk. 🙂 But he’s just not his old self and it of course worries me. Any help you can give I will appreciate so much.

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