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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: January 26th, 2022


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).

Please ask your veterinarian for the dose recommendation for your own specific dog and their specific condition.

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.


Leave a Comment

  1. Debbie on January 10, 2023 at 8:50 am

    Would it be better to use pepcid ac or tagament with diphenhydramine for mast cell tumors? I’m not finding alot of information on pepcid ac and diphenhydramine.. Your article is very informative. My boy is 13 yrs old. And has been on a variety of treatments. FROM prednisone to finally diphenhydramine and just added pepcid ac I question this particular drug. Would appreciate any insight you can give me..Thanks Debbie

  2. Gayle S on August 1, 2022 at 6:22 am

    If my dog mast cell tumor removed. Is this protocol also to help her from not getting any more in the future?

    • Molly Jacobson on August 2, 2022 at 12:14 pm

      Hi Gayle, yes, as Dr. Ettinger points out in her chapter on conventional treatments for mast cell tumors, if you can remove a mast cell tumor, that is priority number one. Depending upon the grade of tumor — how severe it is — you may help prevent others from popping up. Unfortunately, mast cell tumors are notorious for being sneaky and changing things up. As with all tumors, there is no guarantee that future tumors won’t arise. But it helps, for sure! Benadryl is helpful in terms of keeping histamine down. That helps to make the environment less cancer-friendly, and keeps the side effects of histamine overload at bay … but it doesn’t necessarily kill cancer cells directly.

  3. lynn summers on July 11, 2022 at 10:54 am

    we have a dog at our dog rescue that had severe mast cell tumors that were removed and she got an injection made of her cells . She was doing well up until recently she developed some diarrhea, a bit of mental status change, irritable, depression, anxiety, decreased appetite. Is it from the mast cell disease or could it be from too much benadryl , she takes 2 1/2 tabs (25mg tabs) tid.

    • Molly Jacobson on July 29, 2022 at 10:19 am

      Hi Lynn! In my experience Benadryl can cause irritability and anxiety for sure in dogs that don’t tolerate it or get too much. That said, histamine overload can ALSO cause all of those symptoms. (Mast cells secrete histamine, so when they have a tumor they can secrete a lot of it!) It’s best to check with a vet and see what’s going on.

  4. Linda Goldsmith on April 1, 2022 at 4:44 pm

    Edie Sweetie has glioma brain tumors. According the the U of florida, she he was supposed to live 5 days and we are now at 250 days. She now has diarrhea and does not want to eat. She is on Covetrus 8mg 2x daily,Phenobarbital, kepra 250 3x daily and mirtazamine daily, now. Also, she is on Cerinia…new addtion and I have to coax her to eat chicken and rice with Forta Flora probitics. Before the Diarrhea, she was on Proplan senior bright mind and the chicken one. Any ideas ? I need help. I will let her go, if I have to. I am heatr broken.
    Mama Linda

  5. Penny/Arnold Boatman on February 14, 2022 at 7:54 am

    You are wonderful Dr. Dresser!! I have my son’s dog we rescued 12 years ago . His name is Rampage, He was around a year. He was beaten and abused. . He’s had a food addiction because of this and my son has spent thousands on blood work trying to find the right dog food he was allergic to everything. Turns out he can eat deer meat.have a lalhound that is
    Full of cancer and he’s got a large mass on his rib cage and bumps all 9ver. But he’s been really good up untill a few days ago he looks like he choked like something’s in his throat. He is full of cancer I think, and we will do the human thing when it’s time , he’s been the greatest dog it’s gave us more love and got to grow up with my son . And see my son new born son. We are heart broken he’s thrown up alit and is going down hill but I think it’s because. He’s not been eating properly. I want to thank you. I’m going to cook some things up for him give him some benedryl and see if he shows any more sign of needing to go to meet his brother and sister. We’re crushed, thanks for the educational inspiration. It gave me firm feelings that I know I’ll continue to cook for my dogs. To avoid cancer I believe it’s what dog is food has in my it I’m sure can not be wait to see get your book
    Thank you again.
    Penny, Arnold, Rampage
    The Boatman’s (Twin cities Minnesota) 612-437-1412
    Your a Saint at my time of hurt I needed to guidance on helping our Rampage, Thank You Again xoxo

  6. Ruth Corbett on February 1, 2022 at 9:35 am

    Thank you! My American Bulldog has had two non-cancerous masked cell tumors removed. One was in her naval area and the second one is one of two caudal mammary glands. The first one was removed 10 days ago the second one will be removed in another week or so. I am looking forward to researching the connections between her allergies (a syringe every 2 weeks of anti allergens) and Benadryl and Pepcid.

  7. Ken baker on January 24, 2022 at 7:16 pm

    My dog just had a small mast cell low grade removed 2 weeks ago she had a full ultrasound and chest X-ray along with a full panel she was given Benadryl befor and after surgery. I was wondering how much Benadryl should I give her and every day all test came out great also what is Tkls treatment

    • Molly Jacobson on January 26, 2022 at 2:44 pm

      Hi Ken, thanks for asking. As Dr. Dressler says in the article, you may not need Benadryl if your dog isn’t experiencing histamine overload. If you think it will help your girl, please ask your veterinarian about the dose for her weight and medical condition.

  8. Helena Lam on April 21, 2021 at 5:30 am

    How much Benadryl can I give my dog who has a Histiocytomas on his paw. He is a pit bull mix breed. Weighs about 50 lbs. I found this interesting to read about. He also has allergies. Would I benefit if I simply start to give him his allergy prescription? I also read about ACV( apple cider vinegar) being applied daily helping it shrink and fall off. What is your take on that?

  9. Susan K. on March 13, 2021 at 3:00 am

    Hi Dr. D.! Is Benadryl effective for lymphoma? (I’m not sure how lymphoma compares to mast cell tumors.) Thanks in advance!

  10. Linda on February 22, 2021 at 12:39 pm

    Why do some vets recommend Loratadine 10mg instead of the Benadryl?

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