Sifting through the weed: Crohn’s and Cannabis

With the growing number of states legalizing medical and/or recreational marijuana there has been a similarly increasing trend of people championing its use within the IBD community. While cannabis has known benefits, and is used, in certain clinical situations, people seem to think that it’s legalization and subsequent acceptance by the medical community will just about solve all the world’s problems. I think that it’s legalization and broader medical acceptance is more likely to induce another potato famine on account of world wide munchies than to solve all our problems, but hey that’s just me. Buy your Doritos stock now, it will be sky high. Okay lame joking aside lets take a look at studies investigating  cannabis use in patients with Crohn’s disease.

Reefer Madness

This will not be a reefer madness kind of discussion. Just a review of studies.

Now keep in mind this is no where near a scientific literature review! I’m not marketing it as that, rather its really just intended to give me an impression whats been done and summarizing quickly for you all. I won’t describe all the details of every study rather give you some bare bones basic information. Also if a study has so many methodological problems I’ll just say so and not really waste everyone’s time. The really interesting mechanistic data can be found in the animal model studies looking at peripheral cannabinoid receptors and anti-inflammatory properties of cannabis but these are a bit beyond our discussion today.

Undoubtedly I am going to be accused of cherry picking publications discouraging the use of marijuana in folks with Crohn’s. Here’s my disclaimer. I don’t use marijuana, nor do I have any intention of trying it as a complementary medication.  My motivation is/has been to give my mind something to do, learn more about IBD and write something up. If you object to what I say or interpret from the data that’s great! Please comment-that is how scientific discourse moves forward!  So here’s what I’ve got when it comes to human data.

I searched “cannabis and crohn’s disease” and “marijuana and Crohn’s disease” resulting in 14 and 16 publications respectively on  March 11, 2015. There was a lot of overlap between these two queries. Several of these publications are review articles or replies which I’m not going to cover. I will start with the most recent studies and work my way back. Also just an FYI I looked up “cannabis and inflammatory bowel disease” and that resulted in like 242 publications but I just want to show you that this field is being actively investigated.

A. Storr M et al. Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease. Inflamm Bowel Dis. 2014 Mar;20(3):472-80

Adult patients at University of Calgary, Canada were invited to complete voluntary/anonymous questionnaire. Patients were asked whether they used cannabis for IBD or not, whether cannabis use was for recreational or medical reasons, motives for it’s use, how they obtained the cannabis and cost. Three hundred and nineteen of 461 questionnaires were completed and returned. 56/319 (17.6%) reported current or past cannabis use for IBD, the remaining never used cannabis for IBD. Overall 141/319 (44%) reported using cannabis at any time in their life.

IBD severity was self assessed in ratings of activity, most troublesome symptoms, history of hospitalizations for IBD, surgical history for IBD, number of flares in last 12 months. In the cannabis using group 19/56 (34%) smoked cigarettes. So what about the outcomes? Click the pictures to enlarge.

Table 4 in the above pictures shows the self reported benefits from cannabis use.  Basically what we see is that cannabis use is the highest among those patients with chronic abdominal pain and a decent proportion of patients who use cannabis ~20% (1/5) are able to decrease medications for Crohn’s. Interestingly, the rates of previous surgery were highest among patients who use cannabis and this held true even when the analysis was adjusted for other factors known to increase surgical risk (increased duration of disease, tobacco use, use of biologics and socio-economic factors).

Thinking biologically you could argue that while masking or improving the symptoms (see a central nervous system effect by THC) the cannabis is not decreasing the underlying inflammation which continues to cause problems. This situation is analogous to taking an opiod pain killer for a long time and never going to the doctor to see what the problem was. Rather then treating the root cause you are just masking the pain with the drug. Prolonging the time it takes to actually figure it out increase the chances of a more severe problem developing. Get the idea? Here, self reported cannabis and tobacco use were both independently associated with over 5x increased odds of previous surgery.

If they had more patients who used cannabis it would have been interesting to create a further sub group of cannabis users only versus cannabis+tobacco. With this you would be able to get some indication if the smoking tobacco was driving more of the surgical history. More patients and studies needed! There are definitely methodological concerns and unanswered questions here but we move on!

B. Naftali T et al. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1276-1280.

This is the best study out there so most of our focus will be given to this study. It was the first prospective trial

This is an interesting study from Tel Aviv, Israel evaluating 21 adults with active disease (Crohn’s Disease Activity Index [CDAI] >200) who had failed steroids, immunomodulators (6MP, AZA) or anti-TNF therapies. Patients were randomized to smoke cannabis containing cigarettes or cannabis flowers with the THC extracted (placebo). The primary endpoint was complete remission defined by CDAIClick here for description of CDAI and Harvey Bradshaw Index.

The study group (cannabis smokers) were similar to the placebo group with regard to relevant medical history (i.e. family history of IBD, tobacco use, time since diagnosis, disease phenotype, previous surgery, concomitant medications and other variables. The placebo group was significantly older. Baseline (pre-cannabis use) CDAI levels were 330 in study and 373 in placebo groups. Five patients in study group  and 1 in the placebo reached full remission (CDAI<150, not statistically significant) at the end of 8 weeks. At 8 weeks, a response rate (CDAI decrease of >100 pts) was seen in 10/11 study patients versus 3/10 in placebo. Mean reductions for study and placebo groups were 177 and 66 respectively. At the end of the 2 week wash out period, the CDAI for the study group and placebo were 331 and 280, respectively. The treated group had significant increases in quality of life. Patients in the study group had less pain, more appetite, and higher satisfaction.

This study did not observe a statistical difference in remission rates, defined by mean reduction in CDAI, between the groups likely because it was under powered due to estimations of effect sizes. Buried in the data they present (yet don’t address in the discussion) is that the CRP levels are essentially unchanged over the course of the experiment. Why is this important? Well if you clicked and read that link above you will see that the CDAI is a self reported symptom based questionnaire that measures things like general well being and body weight. There are some other issues with it but these are the most obvious. While general well being and body weight are important, they arguably don’t really reflect inflammatory processes. We know that inflammation is the driver of IBD and you could certainly argue that the variables considered in the CDAI are not reflective of disease activity. I highlighted the CRP levels in Table 3 to show that while the reported symptoms are better the inflammatory markers seem unchanged. To me, this is a very important point that cannot be lost when you are interpreting response rates based on changes in CDAI level.

As the first prospective trial examining cannabis use I think these are impressive results but they should be interpreted cautiously. Its a small study that used a subjective outcome (CDAI) as its primary outcome while the more reliable (and objective) CRP levels did not change significantly. I suspect that this Naftali author has a larger follow up study in the works that hopefully includes more objective data on disease activity like pre/post endoscopy, histology, possibly imaging studies, serial CRPs, ESRs. This is a good study that would have been much stronger with more objective endpoints.

C. Ravikoff Allegretti J et al. Marijuana use patterns among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013 Dec;19(13): 2809-14. 

This study, performed at Brigham and Women’s Hospital, set out to determine the prevalence, demographic data and perceived benefits of cannabis use in patients with IBD (Crohn’s, ulcerative colitis, indeterminate colitis) in the United States. It’s not terribly informative so I’m just going to briefly summarize. 310 patients were given a survey and 292 completed them (an impressively high response rate). 12% were active cannabis users, almost 40% were previous users. Among people who had ever used marijuana, 16% used it for relief of abdominal pain, nausea and diarrhea. Not surprisingly younger age and and chronic abdominal pain were predictive of current use and medicinal use. Interestingly, 50% of the people who had never used marijuana expressed interest in using it for abdominal pain.

D. Naftali T et al. Treatment of Crohn’s disease with cannabis: an observational study. Isr Med Assoc J. 2011 Aug;13(8): 455-8

This was the study (I suspect) that served as the impetus for the 21 patient trial (study B). It was a retrospective observational study that estimated disease activity before and after cannabis use by the Harvey Bradshaw index. I’m not sure how exactly you retrospectively assess disease severity in the past for anyone let alone this cohort. They say that when possible medical documents were reviewed for signs of disease (number of hospital admissions and use of steroids). Its just a really unusual design for a study. Thirty patients were interviewed and 15 had an operation before cannabis use. Essentially all the patients reported that cannabis use had a positive effect on their disease activity (which was measured by estimated decreases in Harvey Bradshaw index and visual analog scales). The methods used to determine disease activity are just simply not reliable enough for an interpretation of this study, this is the kind of data that should be collected internally and then a study drawn up for, not reported.

And there you have it folks…thats the data in humans. At least the stuff I could find on pubmed and I’m tired of sorting through studies. The jury is still out on whether cannabis is effective in Crohn’s disease. From what I can tell there is the one study that is good quality (the prospective Naftali study from Israel) that suggests it helps with symptoms without increasing side effects. Also the first study I described was probably the second best and I am sure that more such information is being gathered. This being said, the clinical trials evaluating cannabis in patients with IBD are clearly in their infancy. I think that there is room for investigation in this area however I don’t think anyone should be too impressed with the data to this point.

My take away: From the current data, it seems more likely that the benefits of symptom improvement during marijuana use in Crohn’s disease seem to be tetrahydrocannabinol (THC) central nervous system mediated effects versus a true anti-inflammatory drug for IBD. 

So you tell me? Have you considered using cannabis to improve symptoms? Have you tried it? How were your results? What do you think of the data? You can comment anonymously!

4 thoughts on “Sifting through the weed: Crohn’s and Cannabis

  1. I suspect as with most natural compounds, the active ingredient that would lower the systemic inflammation, and thus affect CRP, can not be achieved with conventional use (no, really, no matter how much you smoke ). So what you end up getting is a palliative effect. This, however does not mean that it should not be studied further, both in terms of isolating the effective compound and perhaps in finding more oprimal delivery method.

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    • AB- good points about the active ingredient. Its interesting that since its a natural compound I’m not sure if a pharmaceutical could patent it unless they grew a modified strain that say had like high THC low CBD or the reverse kind of set up. for now it seems effects in humans linked to the brain rather then the guy. i agree that it should be studied further, in both of those cases assuming there is a single effective compound and effects are not synergistic or additive

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  2. Great post. I asked my doctor about this in passing at my last appointment just to see what she thought, and she was a little taken aback. I had to clarify I wasn’t looking for an excuse to take up a new hobby, just to hear what she had to say. I hope they will continue to study it especially as it becomes approved for medical use in more states. In MA you can obtain it for Crohn’s but they’re still not quite sure what it does (other than stimulate appetite).

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    • very interesting Margaret. I think this is something that patients are far more curious about then they are comfortable about discussing with their doctors. I’m not encouraging anyone to pick up new extra curricular activities by any means but I thought that a review of some current data could help settle a few questions for many patients. thanks for reading

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