Evidence Review: Inflammatory Bowel Disease

Hello! Dr. Lee here. I’m here to talk about some of the research and evidence we have regarding marijuana and Inflammatory Bowel Disease.

We promise three things with these articles (which is maybe why they take so damn long). We always cite (nerd alert), we only use actual research (peer-reviewed, published evidence) and we highlight the people and scientists that have contributed to the body of evidence we have on marijuana.

Takeaways on IBD and Cannabis

  1. A ton of people, in many countries, use marijuana to treat IBD

  2. Marijuana products have been shown to improve pain scores, symptom scores, and quality of life for IBD patients and high-quality clinical research dates back to 2011.

  3. CBD alone appears to be useful for the treatment of IBD, although the doses that have been best studied (up to 500 mg/day) are prohibitively expensive in the current United States market.

  4. Until we know that marijuana is disease-modifying (prevents progression of cellular markers of illness), we shouldn’t really be replacing traditional IBD meds with marijuana. But, it has clear value as an adjunct treatment.

Background

Two separate conditions, ulcerative colitis and crohn’s disease, are considered inflammatory bowel diseases. IBD is found on nearly every state’s qualifying condition list for medical marijuana. Symptoms of IBD include abdominal pain, rectal bleeding, weight loss, diarrhea, cramping, and occasional ‘flare-ups’ that can be truly debilitating. Many patients require surgery and hospitalization at some point in their lives.

Inflammatory Bowel Disease is a fairly common illness affecting around 1.3% of adults in the United States. IBD has a strong genetic component and often runs in families. Increasingly, we are realizing that environmental triggers- like stress, a sugar- and fat-rich die are also involved in IBD. IBD is typically treated by immunosuppressant medications like methotrexate and (gasp) hydroxychloroquine.

Immunosuppressant medications decrease inflammation and IBD symptoms- they literally suppress your immune system. They’re useful for many patients! BUT these medications also cause issues for the patient- patients are more prone to infection, and experience bone marrow issues and increased incidences of cancer.

That’s why there is interest in marijuana to treat IBD- it’s well known that it helps manage symptoms, and the other treatments for IBD are problematic.

IBD and Marijuana- Patient Stats

Many patients with IBD turn to marijuana, and many report a positive outcome. In a study conducted in 2018 (1), a little over 25% of IBD patients at a large American center reported using marijuana for IBD. Even American children and adolescents are using marijuana products to treat IBD- 18% of IBD patients at an American children’s hospital reported cannabis use to manage symptoms in 2019 (2).

Interestingly, many patients seek marijuana outside of legalized structures. In the same 2018 study mentioned above, 80.7% of patients with inflammatory Bowel Disease described a positive effect on their symptoms. The same study shows that marijuana is rarely prescribed- only 4% of these patients had marijuana prescribed by a physician, and 21% had ever discussed it with a physician. Big-picture wise, this study says that IBD patients find marijuana helpful, and doctors aren’t great about talking about marijuana. Room for improvement! That’s what we’re here for!!

Patients with IBD in several countries have described marijuana use to manage pain, appetite, symptoms of reflux and diarrhea, and to go to sleep (2).

History of IBD Research

Let’s look at the history of research into IBD! In each research article we highlight at least one actual human being that is involved in the history of marijuana research! As the idiotic war on drugs has raged in the USA for decades, much of the initial research on marijuana has come from international sources- Israel, the United States and the Netherlands.

Below you will see a picture of Dr. Timna Naftali, an Israeli gastroenterologist. In medical terms, Dr. Naftali is an O.G. At a time with virtually no mainstream acceptance of cannabis, she realized that her patients, some of whom had been tried on numerous other medications, were benefiting greatly from marijuana. Instead of ignoring this information, she designed a research study and showed the world that IBD patients benefit from marijuana.

Most of the original research on marijuana and IBD occurred in 2011 and 2012 by Dr. Naftali in Israel. The first was in 2011 (4). In this study, 30 participants were instructed to use a “marijuana cigarette” when they noted pain. 21/30 participants noted a significant improvement in symptoms, and participants were seen to require far less surgery in the years after starting treatment.

Dr. Naftali’s follow-up study in 2013 (5) was placebo-controlled and showed that marijuana was effective as a treatment vs a control. It would be another 4-5 years before additional high quality research was published. These two studies are landmarks in early marijuana research!

An amusing excerpt from this 2013 study:

“However, it is difficult to maintain the blindness of the study, as psychotropic effects are noted in the group that received the intervention, even if the recruited patients were laymen to the compound, most patients were able to report which group they were allocated.”

Or, in plain English: “You can’t design a study with a placebo for marijuana, because research subjects get high when they smoke weed. That shit slaps.”

Why We Need Research!

Like with many things involving marijuana, we seem to have plenty of ‘observational’ data that patients with IBD like marijuana. But, we have little in terms of hard-hitting research that changes the way that physicians in the USA will practice.

As physicians, we really like fancy research studies called DBRCT (double-blinded, randomized, controlled trials). In a perfect world, we’d like them to be MC (multi-center) and conducted on an American population. That’s just hard to do without federal legalization.

“But Dr. Lee, we have all this information that it helps so many patients with IBD, why does that matter? Why do we need these expensive-ass, complicated-ass studies?”

The issue is that IBD is an immune-mediated disease. With these illnesses, your body’s immune system attacks your own body- other common immune diseases are asthma, psoriasis and lupus.

For many immunological diseases, the best treatments are what we call disease-modifying. This term implies that the disease process itself is slowed down- the way it changes your bodies’ cells and organs. Marijuana can make an IBD patient feel better and live a better life- that is clear. My big question is- should IBD patients that use marijuana still be taking another medication?

We know that, for all their issues, immunosuppressant meds are indeed disease-modifying. They save lives, and that’s why we use them! Patients that are good about taking disease-modifying medications (and can tolerate them) have fewer hospitalizations and fewer surgeries. Until we have proof that marijuana is truly disease-modifying, doctors really shouldn’t be suggesting it as a replacement for a traditional medication. It can be an adjunct- it shouldn’t be a replacement.

What we know about marijuana and IBD

We know that it helps patients! There’s a lot of jargon in this article but the big takeaway is that it helps, we know it helps, and it should be available to continue helping people. That is the #1 thing for sure!

From a research perspective, we do have some actual data examining marijuana use for IBD management. It’s not as much of a slam-dunk as some other things (like seizures, or chronic pain for instance). There are some things about IBD, particularly the fact that it’s immune-generated, that make it difficult to definitely make a judgment on. When you’re dealing with pain, if you have less pain, we call it a win. When you’re dealing with IBD, we also have to think about what’s happening to your cells and organs, and you can’t always tell that simply based on how good you feel.

To date, there have only been five randomized controlled trials performed- 3 for Crohn’s Disease and 2 for Ulcerative Colitis studies, 185 participants total (7). That’s…not a lot, and none of them are American studies. Two of these trials were negative, meaning that they did not reach their designed endpoints- patients using marijuana or marijuana products did not achieve remission (absence of disease). However, all five trials DID note an increased quality of life for patients using cannabis to treat IBD. That matters!

While some of these trials examined whole flower, two examined CBD alone for treatment of IBD symptoms. The largest of these studies did show that CBD alone had positive benefits for patients- but, it started patients at 50 mg twice a day, gradually increasing to 250 mg twice a day (8). In developed markets, that would just be a slightly-expensive nuisance, but in Illinois and Michigan, that amount of CBD sourced from a dispensary would be a few hundred dollars a month.

Further research has examined the link between marijuana use and biochemical markers of inflammation. Some of these include C-reactive Protein, TNF-a and fetal calprotectin. These markers are elevated in patients with immune-mediated diseases, and go down when the disease is well controlled. If marijuana was a gold-standard treatment for IBD, we’d see these markers go down- and we haven’t. YET!

However, we do know enough to at least make a case that marijuana may be disease-modifying. It has been shown to decrease the incidence of surgery and hospitalization in patients with advanced crohn’s disease (9). This is one of the hallmarks of a successful disease-modifying treatment. However, knowing more about how marijuana changes individual cells and organs over time is key.

A Fantasy Research Scenario for IBD and Marijuana

  1. We legalize marijuana, design rigorous domestic MC-DBRCT, and find a specific dose of CBD or THC or whole flower oil or whatever magic terpene in marijuana that appears to be most effective for treating IBD

  2. We make a bunch of this medication then give it to patients for years and years and go into their colons and get tissue samples and look at them with a histological microscope.

  3. We say, “Bro/sis, wow, this colon looks AMAZING. Just incredible. One of the best colons.” The cells are as healthy as if you were taking a disease-modifying medication. We have now established non-inferiority of marijuana as a treatment compared to the gold-standard!

  4. We publish said information in several journals of high repute, going through the peer-review process and sustaining all criticism.

  5. Thanks to research, pharmaceutical interest develops and a company produces a product that can be prescribed and sold

    1. And hopefully be available through medicare for all because american pharmaceutical companies are bull shit

    2. And also american health insurance is also bullshit

    3. Ok and where is our pharmaceutical price regulator? You know, the thing that every other developed nation has?

    4. Dont @me

  6. Patients begin taking medication and report efficacy and side effects in a general population

Conclusions

We have enough evidence and consensus to say that IBD patients live better lives with marijuana. Whether or not marijuana is effective as a gold-standard treatment for IBD will require a lot more effort and research.

What is for sure…is that we should all be critically evaluating our relationship with marijuana.

Constantly!! If you have ever been certified by me, you know I will talk your ear off about finding ways to not inhale or smoke. If you do not accept that smoking marijuana is bad for you, you are as bad as people that don’t wear masks. You are a straight-up science denier- Period, point blank, end of story!! (I used to smoke every day. It’s hard for all of us.)

I would like to point out that the research also proves that marijuana users amongst IBD patients were seen to have higher rates of mental illness such as depression and anxiety. This is a distressing trend that is unfortunately, NOT isolated. Marijuana has clearly been shown to prevent or prolong patient recovery from depression and anxiety if it is misused or overused.

It is not dope to be overly dependent on anything. These are facts.

Peace

Dr. Lee

P.S. WHAT SHOULD WE COVER NEXT? I have this thing on ADD that I have been working on forever (ironic sentence). EMAIL ME @ greenmindphysicians@gmail.com!

NERD CITATIONS

  1. Kerlin AM, Long M, Kappelman M, Martin C, Sandler RS. Profiles of Patients Who Use Marijuana for Inflammatory Bowel Disease. Dig Dis Sci. 2018;63(6):1600-1604. doi:10.1007/s10620-018-5040-5

  2. Hoffenberg EJ, McWilliams S, Mikulich-Gilbertson S, Murphy B, Hoffenberg A, Hopfer CJ. Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2019;68(3):348-352. doi:10.1097/MPG.0000000000002189

  3. Picardo S, Kaplan GG, Sharkey KA, Seow CH. Insights into the role of cannabis in the management of inflammatory bowel disease. Therap Adv Gastroenterol. 2019;12:1756284819870977. Published 2019 Sep 3. doi:10.1177/1756284819870977

  4. Naftali T, Lev LB, Yablecovitch D, Half E, Konikoff FM. Treatment of Crohn’s disease with cannabis: an observational study [published correction appears in Isr Med Assoc J. 2011 Sep;13(9):582. Yablekovitz, Doron [corrected to Yablecovitch, Doron]]. Isr Med Assoc J. 2011;13(8):455-458.

  5. Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013;11(10):1276-1280.e1. doi:10.1016/j.cgh.2013.04.034

  6. Kafil TS, Nguyen TM, MacDonald JK, Chande N. Cannabis for the treatment of ulcerative colitis. Cochrane Database Syst Rev. 2018;11(11):CD012954. Published 2018 Nov 8. doi:10.1002/14651858.CD012954.pub2

  7. Kafil TS, Nguyen TM, MacDonald JK, Chande N. Cannabis for the Treatment of Crohn’s Disease and Ulcerative Colitis: Evidence From Cochrane Reviews. Inflamm Bowel Dis. 2020;26(4):502-509. doi:10.1093/ibd/izz233

  8. Irving PM, Iqbal T, Nwokolo C, et al. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis. Inflamm Bowel Dis. 2018;24(4):714-724. doi:10.1093/ibd/izy002

  9. Carvalho ACA, Souza GA, Marqui SV, et al. Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse. Int J Mol Sci. 2020;21(8):2940. Published 2020 Apr 22. doi:10.3390/ijms21082940