Cannabidiol Oil-Associated Microscopic Colitis
Microscopic colitis (MC) is a chronic inflammation condition of the colon characterized by watery diarrhea and normal appearing mucosa. A 75-year-old female presented with one-year history of chronic diarrhea while taking cannabidiol (CBD) for pain. Colonoscopy with random colon biopsies revealed collagenous colitis. She started budesonide and stopped CBD. At six-week follow-up, her diarrhea improved, and the budesonide dose was decreased. She restarted CBD oil twice but had diarrhea both times. Her diarrhea resolved after taking budesonide and stopping CBD. We report a case of CBD-associated MC to make clinicians aware of this potential adverse effect in patients who chronically use CBD.
Microscopic colitis (MC) is a chronic inflammation condition of the colon characterized by watery, non-bloody diarrhea and generally normal appearing colonic mucosa on colonoscopy. Colon biopsy is required to confirm the diagnosis and differentiate between the two subtypes: lymphocytic and collagenous colitis (CC) . Many drugs have been associated with MC. However, the pathophysiology is incompletely understood. Drugs that have been implicated in MC include non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, proton-pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), clozapine, and acarbose . Studies examining the etiology of MC are limited and mostly consist of case reports and observational studies. Cannabidiol (CBD) is a concentrated oily residue of the plant Cannabis sativa. Recent changes in the legality of CBD have led to an increased acceptance of its use by the medical community. The Controlled Substances Act (CSA) of 1970 made the growth of hemp and marijuana illegal in the United States, but in 2014, the Agricultural Act allowed for industrial growth of hemp . CBD and hemp are different from marijuana because they have low tetrahydrocannabinol (THC) levels . This provides patients with the medical benefits of Cannabis without the intoxicating effects of marijuana . CBD has found some popularity in the search for an alternative to opioids for the treatment of pain . CBD is not regulated by the U.S. Food and Drug Administration (FDA), and there are no determinations on appropriate dosage, safety, efficacy, or interactions with other drugs or food . There are currently no reports in the medical literature that CBD is a risk factor for the development of MC. We report a case of CBD-associated MC to make clinicians aware of this potential adverse effect in patients who chronically use CBD. The patient agreed to the use and publication of her disease process and case with her personal health information deleted.
A 75-year-old Caucasian female with a history of anemia, hypothyroidism, and migraines presented to the gastroenterology clinic with a one-year history unexplained diarrhea. The patient started taking CBD oil for lumbosacral pain about one year prior to presentation. She endorsed watery, non-bloody, nocturnal diarrhea, left lower quadrant abdominal pain, and unintentional weight loss of eight pounds. The patient also endorsed urgency, tenesmus, fecal incontinence, and a small amount of blood when wiping after bowel movements (BMs). She had already tried loperamide and bismuth subsalicylate. She also tried the BRAT (bananas, rice, applesauce, and toast) diet and probiotic yogurt, but neither diet nor over-the-counter medications were effective in reducing her diarrhea. Prior to onset of diarrhea, the patient had constipation, which required her to take metamucil to have one BM daily. However, she began to have two loose BMs daily, and then her stool frequency increased to five times daily and three to four times at night. Colonoscopy performed for polyp surveillance six months prior to presentation and symptom onset revealed decreased anal sphincter tone and multiple colon polyps; grossly, mucosa appeared normal and random biopsies were not taken. Repeat colonoscopy with random biopsies six months later (at symptom onset) revealed CC (Figures (Figures1, 1 , ,2). 2 ). She was still taking CBD oil at the time of her second colonoscopy demonstrating MC. She was not taking NSAIDs or any other agent associated with MC at the time of her second colonoscopy. Stool PCR was negative for enteric pathogens. Budesonide therapy was started, and she was advised her to continue a high fiber diet and to avoid artificial sweeteners and sugar alcohols. She was advised to avoid NSAIDs and discontinue CBD oil. During follow-up six weeks later, her diarrhea had improved. Her gastroenterologist reduced the dose of budesonide. After her six-week follow-up, the patient started taking CBD oil again at home and had a recurrence of diarrhea. She stopped CBD oil, and her diarrhea resolved. One week later, she restarted CBD oil and experienced diarrhea again. She then stopped CBD oil completely and completed a tapering course of budesonide. Eventually, diarrhea turned to constipation. She was advised to continue fiber supplements and high fiber diet. About three months after the initial presentation, she was able to stop budesonide. There was no recurrence of diarrhea after she stopped taking CBD oil and completed budesonide therapy.
The cause-effect relationship between drugs and MC is difficult to define. The patient in this case used a CBD soft gel made with hemp oil, extra virgin olive oil, vegetarian soft gel (vegetable cellulose, water), and silica. However, there are multiple different formulations of CBD oil and capsules, as well as other products including honey, vape pens, teas, gelatin snacks, baked goods, and beverages. Experimental studies on murine colitis suggest that physiologically relevant concentrations of exogenous CBD can reduce gut inflammation by stimulating CB1/CB2 cannabinoid receptors and endogenous cannabinoids N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) [5,6]. However, data are limited on dose-related adverse effects of CBD. As the popularity of CBD products increases, more research is necessary regarding their safety and efficacy in humans. The World Health Organization (WHO) has proposed a method that establishes causality based on temporal sequence, prior information on the drug, dose-response relationship, pattern of response to the drug, the re-challenge, exclusion of other alternative etiologic candidates, and exposure to concomitant drugs. The events are then classified as “certain, probable, possible, unlikely, and not assessable” (Table (Table1) 1 ) [2,7]. This case demonstrates a temporal relationship between exposure to CBD oil and onset of diarrhea, resolution of diarrhea after withdrawal of CBD oil, and reoccurrence of diarrhea with two re-challenge attempts with CBD oil while the patient was taking budesonide. Therefore, we can surmise that her CC resulted from chronic ingestion of CBD oil. The mechanism by which CBD oil induced MC in this case is unclear; however, we hypothesize that elevation of tissue levels of endocannabinoids may cause colonic inflammation by stimulating the vanilloid receptor subtype 1 (VR1) to release substance P . Based on the WHO method, we believe that this case establishes a causal link between CBD and MC that can be classified as “probable or likely”. To our knowledge there are currently no other case reports that describe such a relationship between CBD and MC. We recommend that physicians educate themselves on CBD containing products, and encourage open communication with patients regarding dietary supplements and their potential clinical adverse effects.
*WHO-UMC, World Health Organization-Uppsala Monitoring Centre
|Causality Term||Assessment Criteria|
|Certain||Plausible time relationship between event and drug intake and response to withdrawal|
|Event definitive objectively, meaning pharmacologically or phenomenologically|
|Event cannot be explained by disease or other drugs|
|Re-challenge satisfactory, if necessary|
|Probable/Likely||Reasonable time relationship between event and drug intake and response to withdrawal|
|Unlikely to be explained by disease or other drugs|
|Re-challenge not required|
|Possible||Reasonable time relationship between event and drug intake and response to withdrawal|
|Could also be explained by disease or other drugs|
|Unlikely||Improbable, but not impossible, time relationship between event and drug intake|
|Disease or other drugs provide plausible explanation|
|Conditional/Unclassified||Event occurred, but more information is required|
Multiple drugs have been implicated in the development of MC. CBD oil is a relatively new dietary supplement that is gaining popularity as an alternative to opioids for the treatment of pain. To our knowledge, there are currently no other case reports that describe such a relationship between CBD and MC. Physicians should suspect CBD-associated MC in patients taking CBD who develop diarrhea for which no other causes can be identified. We recommend that physicians educate themselves on CBD containing products and encourage open communication with patients regarding dietary supplements and their potential clinical adverse effects.
Authors P Oruganti and S Betcher contributed equally to this work and should be considered co-first authors.
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Can CBD Help Treat Microscopic Colitis Symptoms?
After being diagnosed with microscopic colitis (MC), my gastroenterologist prescribed the usual drug regimens. Some had zero effect. Others worked while I was taking the medication, but if I stopped, my symptoms quickly returned. Failing to see any lasting results from traditional prescription medications, he finally recommended I try using CBD oil, stating that other patients had seen symptoms either reduce significantly, and some experienced complete remission.
I decided to do a little research to see if and how CBD oil could help microscopic colitis. While research is still in the early phases, it indicates CBD can reduce intestinal inflammation and ease common symptoms of microscopic colitis (MC) by activating the body’s endocannabinoid system and by easing some of the more common triggers for a flare-up of symptoms.
Let’s take a look at what CBD is and how it may help treat microscopic colitis.
What is CBD?
CBD is a shortened term for cannabidiol, a compound found in plants such as cannabis and hemp. It is one of over a hundred therapeutic phytocannabinoids found in cannabis. CBD has no psychoactive effects, unlike the other common phytocannabinoid THC (tetrahydrocannabinol). In other words, CBD will not make you feel “stoned.”
The Endocannabinoid System
Cells in our bodies have cannabinoid receptors, known as CB1 and CB2, that work as highly sensitive sensors. They scan their surroundings for biochemical signals and trigger the cells to react in certain ways. These cannabinoid receptors are found in almost all areas of the body including the brain, nervous system, and most major organs. This signaling system is known as the endocannabinoid system.
CB1 and CB2 receptors are triggered by naturally occurring endocannabinoids which lock onto the receptors. When activated, these receptors cause a series of biochemical changes at the cellular level which slow excessive cellular activity. They are responsible for the retrograde signaling which tells other neurotransmitters to slow down when they are firing too fast. In other words, endocannabinoids act as the brakes to slow our cellular function down when it’s too revved up, keeping our bodies in balance.
When functioning properly, it helps regulate and balance a lot of our bodily functions such as mood, blood pressure, energy level, digestion, blood sugar levels, bone density, pain tolerance, how we handle stress, etc.
When our endocannabinoid system isn’t working properly, it can lead to a wide range of diseases. For example, when you are sick, your immune system kicks in to help fight off infection. The endocannabinoid system tells your immune system to slow back down when the illness has run its course. If the endocannabinoid system isn’t working right, your immune system will stay fired up. This dysfunction can open the door to autoimmune or inflammatory diseases.
This is where therapy with CBD comes in. The CB1 and CB2 receptors not only respond to the endocannabinoids produced by our bodies, but they can also be triggered by phytocannabinoids like CBD and THC. So if your endocannabinoid system isn’t functioning correctly, CBD may help get things going again. As a result, CBD and THC may have a therapeutic effect on a wide range of diseases, including microscopic colitis.
CBD And Symptom Relief
CBD has been shown in preliminary studies to help improve many symptoms of microscopic colitis including regulating gut function, reducing anxiety and depression symptoms, reducing inflammation by regulating immune response, and helping with fatigue.
CBD and Gut Health
Research has shown that the endocannabinoid system is found in a variety of organs, including being widely distributed throughout the gut. It is responsible for helping to regulate a variety of gut functions, many of which may be disrupted in people with microscopic colitis.
Some of the functions of gut health the endocannabinoid system can help regulate include (1):
- GI motility (movement of food through the gastrointestinal tract)
- intestinal inflammation
- nutrient absorption
- gastric secretion (release of acids and chemicals to break down food)
- gastroprotection (prevent damage to gut from gastric secretion)
- new cell and tissue production
Many of the functions of gut health that the endocannabinoid system regulate are those that are disrupted by microscopic colitis. Supplementing with CBD may help ease some of those issues.
Inflammation in the gut is the number one isssue of microscopic colitis. The word “colitis” literally means inflammation of the colon. As we said before, the endocannabinoid system has been directly linked with controlling inflammation in the body by helping to regulate the immune system.
The Central Nervous System plays an important role in regulating immune responses in the intestines. It triggers the body to produce enteric glial cells (EGC), which trigger the release of numerous chemicals, including pro-inflammatory cytokines. CBD has been shown in studies to reduce the production of EGC in the Central Nervous System, thus slowing inflammatory responses. (2)
Anxiety, Depression, and Fatigue
Anxiety and depression are two very real symptoms of microscopic colitis that many people don’t consider. Constant worry about knowing the location of bathrooms whenever you leave the house, having to take diet into constant consideration, dealing with physical symptoms and flare-ups making you sick, and the reduction in overall quality of life can quickly take its toll on the mental health of someone living with microscopic colitis.
Endocannabinoid system activity in the brain can affect feelings of anxiety and depression. CBD can help reduce those feelings. Studies have shown that CBD can reduce both the behavioral and physical symptoms of anxiety and depression, although the way in which it does so is not fully understood yet. (3)
An added bonus of reducing anxiety may be a reduction in fatigue. CBD has been shown to help people fall asleep faster and stay asleep longer. It may alter anxiety-driven sleep, which allows the body to fall into deeper sleep states and recuperate better. (4)
Types Of CBD
There are two main sources of CBD available today – CBD derived from hemp and CBD derived from marijuana. Both hemp and marijuana are from the same family of plants. Both contain CBD and THC. The difference is how much of each substance they contain. Hemp has more CBD and less THC. Marijuana has more THC and less CBD.
The chemical make-up of the CBD is the same in both plants, so the benefits are the same no matter which plant it is extracted from. The biggest difference between the two is their legal status.
In the United States, CBD extracted from hemp (which contain less than 0.3 percent THC) are legal under federal law, but may be illegal under some state laws. CBD from marijuana is illegal under federal law, but is legal in some states. Check your state’s laws regarding CBD. Also, if you are travelling, be sure to check the laws where you are going.
Choosing Quality CBD
If you decide to try CBD for your microscopic colitis, there are some things you need to look for when choosing a product.
Choose Full-Spectrum or Broad-Spectrum Products
First, look for full-spectrum or broad-spectrum extracts. These extracts contain a variety of beneficial molecules other than CBD. These are called the “entourage,” and they work together to increase the effectiveness and absorption of the CBD in the body. Some studies indicate the entourage molecule cannabigerol (CBG) might be more effective in treating colitis than CBD itself.
Check The Extraction Method
CBD oil must be extracted somehow from the plant. How that oil is extracted can alter the effectiveness of the CBD.
Avoid products that use butane to heat the plant. Instead, look for companies that use other extraction methods like CO2 or food-grade ethanol.
Look For All Natural
First, make sure the hemp used to make the products is grown organically. Pesticides can alter the CBD and can introduce toxins into your body.
Second, many CBD products come flavored to make it easier to consume. Be sure the company uses natural ingredients such as essential oils to add flavor. Avoid chemical additives.
In addition, people with microscopic colitis tend to have dietary restrictions. Check the ingredients for dietary triggers such as gluten and soy.
How your CBD is packaged is as important as how it’s made. As soon as the hemp leaf is picked, air and UV light begin to affect it, quickly causing it to lose strength and effectiveness.
Look for companies that package their products in amber-colored glass containers. Glass doesn’t hold moisture like plastic containers will. Amber-color will block UV light from penetrating the container.
Look For Third-Party Testing
The FDA doesn’t regulate CBD products, so it is important the company you purchase from has third-party testing. This testing provides you with the information you need to know regarding what exactly is in the product so you can make an informed decision about what you are putting in your body.
Check For High Bioavailability
Bioavailability is the ability of the body to absorb the product. Again, choose full- or broad-spectrum products because the entourage chemicals help with absorption. Also, look for products with nano-sized emulsions. These smaller particles help speed up the absorption process, so less product is wasted.
Money Back Guarantee
CBD is big business. Look for a company that backs the quality of their product with a money back guarantee if you aren’t satisfied. Otherwise you run the risk of buying a lesser quality product from a company solely interested in making a quick buck.
Although there needs to be a lot more research conducted in regards to CBD as a treatment option for microscopic colitis symptoms, preliminary research seems promising in its ability to reduce inflammation, regulate immune response, ease anxiety, and improve gut function.
If you decide to try CBD as a treatment option, be sure to discuss it with your doctor, especially if you are taking other medications. Look for high quality, natural products. Do your research. And most importantly, be patient. It may take some time and steady dosing to build up levels of CBD in your system and to see noticeable results.
(2) PloS one vol. 6,12 (2011): e28159. doi:10.1371/journal.pone.0028159
(4) Shannon, Scott, and Janet Opila-Lehman. “Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report.” The Permanente journal vol. 20,4 (2016): 16-005. doi:10.7812/TPP/16-005