Cannabidiol Oil-Associated Microscopic Colitis
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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.
H&E stain showing increased intraepithelial lymphocytes (black arrow) and subepithelial collagen band > 10 microns (red arrow) consistent with collagenous colitis.
H&E stain showing increased intraepithelial lymphocytes (black arrow) and subepithelial collagen band >10 microns (red arrow) consistent with collagenous colitis.
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.
The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.
CBD for Colon Cancer
Each day a massive process of cell destruction and repair occurs within the body. However, despite remarkable elegant systems in place to prevent errors, the body still makes tens of thousands of mistakes daily while replacing cells – either because of random errors or because there are outside pressures placed on the replacement process that promote errors. When these errors occur within the large intestine (colon), it is called colon cancer. Colon cancer is also sometimes called colorectal cancer, which is a term that refers to a combination of colon cancer and rectal cancer, in the event of the cancer also being present in the rectum.
The colon and the rectum are the final portions of the digestive system, composed of four layers, that extend from the mouth to the anus. The first is an inner layer of cells, called the mucosa, that lines the cavity through which the undigested and digesting food travels. The mucosa is attached to a thin second layer, the submucosa, that is attached to the third layer of muscle, called the muscularis. The entire tract is surrounded by fibrous tissue called the serosa.
Colon cancer typically affects older adults, though it can happen at any age. It usually begins as small, noncancerous (benign) clumps of cells called polyps that form on the mucosa, that, over time, can become colon cancers. Because these polyps are small and produce few, if any, symptoms, doctors recommend regular screening test to identify and remove these before they can turn into cancer. These screening tests usually include one of the following procedures:
- Colonoscopy is a test where a thin tube with a light on the end is put through the anus, into the rectum and colon to look closely at the inside.
- Biopsy is when a piece of any abnormal lump (mass) or growth (polyp) is found is taken and checked in the lab for cancer cells. Biopsies are the best way to test for cancer.
- CT or CAT scans are like an x-ray, but the pictures of your insides are more detailed. CT scans can also be used to help do a biopsy and can show if the cancer has spread.
- Ultrasound is when a small wand that gives off sound waves and picks up the echoes as they bounce off tissues. The echoes are made into a picture on a computer screen and is used to help find cancer and see if it has spread.
- Gene and protein tests are when the cancer cells in the biopsy tissue is tested for genes or proteins such as KRAS, BRAF, MMR and MSI. Knowing which genes or proteins your cancer has can help the doctor decide if treatments like targeted therapy or immunotherapy might help.
Symptoms of Colon Cancer
As mentioned, colon cancer might not cause symptoms right away. And because many of its symptoms can also be caused by other problems, such as infection, hemorrhoids, irritable bowel syndrome, or inflammatory bowel disease, a definitive diagnosis is often difficult without resorting to one of the above screening methods. The most common symptoms of colon and colorectal cancer include:
- A change in bowel habits, such as diarrhea, constipation, or narrowing of the stool, that lasts for more than a few days
- A feeling that you need to have a bowel movement that is not relieved by having one
- Rectal bleeding with bright red blood
- Blood in the stool which might make it look dark brown or black
- Cramping or abdominal (belly) pain
- Weakness and fatigue
- Losing weight without trying
Stages of Colon Cancer
When colon cancer is diagnosed, additional tests, called staging, are performed to determine how advanced the colon cancer has become, and ranges from stage I, the least advanced cancer, to stage IV, the most advanced cancer.
Stage I colorectal cancers involve only the innermost layers of the colon or rectum. The likelihood of cure (excellent prognosis) for stage I colorectal cancer is over 90%.
Stage II cancers exhibit greater growth and extension of the tumor through the wall of the colon or rectum into adjacent structures.
Stage III colorectal cancers manifest the spread of cancer to local lymph nodes.
Stage IV (metastatic) colorectal cancers have spread or metastasized, to distant organs or lymph nodes far from the original tumor.
With each subsequent stage of colon cancer, the risk for recurrent cancer and death due to the spread of cancer (metastasis) rises. However, depending on where cancer has spread, even in stage IV colon cancer, it can be cured.
Colon Cancer Medications & Treatments
If colon cancer develops, many treatments are available to help control it and usually consists of a combination of procedures and medications. Treatment options and recommendations and recommendations usually depend on several factors, including the type and stage of cancer, treatment side effects, and the patient’s preferences and overall health.
Systemic therapy is when medication is used to destroy cancer cells and is prescribed by a medical oncologist. It is given through the bloodstream in order to reach cancer cells throughout the body and include:
Chemotherapy destroys cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. A patient may receive 1 drug at a time or a combination of different drugs given at the same time with a chemotherapy regimen, usually consisting of a specific number of cycles given over a set period of time. Side-effects of chemotherapy include vomiting, nausea, diarrhea, neuropathy, fatigues, increased risk of infection and/or mouth sores.
Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells.
Immunotherapy, also called biologic therapy, is designed to boost the body’s natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. Different types of immunotherapy can cause different side effects. The most common side effects of immunotherapy may include fatigue, rash, diarrhea, nausea, fever, muscle pain, bone pain, joint pain, abdominal pain, itching, vomiting, cough, decreased appetite, and shortness of breath.
The most common non-pharmaceutical colon cancer treatments are surgery and radiation therapy.
During surgery, the tumor along with some surrounding healthy tissue and lymph nodes are removed during the operation. It is the most common treatment for colorectal cancer and is called surgical resection because it involves the surgical removal of part of the colon.
Radiation therapy is the use of high-energy x-rays to destroy cancer cells. Along with surgery, radiation is commonly used for treating rectal cancer because this tumor tends to recur near where it originally started. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, loose bowel movements, bloody stools from bleeding through the rectum and/or blockage of the bowel.
CBD for Colon Cancer
Research & Scientific Evidence on using CBD for colon cancer
The clinical evidence for Cannabidiol (CBD) as a viable treatment option for Colon Cancer is promising.
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer
Considering the antioxidant and intestinal anti-inflammatory as well as its inhibition of endocannabinoid enzymatic degradation, the researchers of a 2012 paper published in the Journal of Molecular Medicine, hypothesized that these mechanisms could potentially beneficial in the treatment of colon carcinogenesis (the formation of cancer cells and tumors).
Investigating cannabidiol’s (CBD) possible chemopreventive effect in the model of colon cancer induced in mice, the researchers analyzed in vivo CBD treatment and tumor evaluation in cell cultures. They found that CBD at the dose of 1 mg/kg exerted an optimal chemopreventive effect, significantly reducing polyps and tumors, by protecting DNA from oxidative damage and inhibiting FAAH, both of which are potential chemopreventive effects. Similarly, they also found that CBD reduced the spread of cancer cells via an antagonistic mechanism involving CB1, TRPV1, and PPARγ channels, all of which play a role in cancer cell proliferation.
From this the researchers concluded that CBD exerts a chemopreventive effect in vivo, and reduces cell proliferation through multiple mechanisms, making it a potentially effective treatment for colon cancer.
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol
A paper published in 2014 in the Journal of Phytomedicine investigated the role of a standardized CBD botanical drug substance (CBD BDS) that contain a high concentration of CBD along with other cannabinoids in the inhibition of colon carcinogenesis using colorectal carcinoma cells as well as in healthy colonic cells.
Previous studies have shown that pure CBD reduced cell proliferation in tumor cells and that pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. Using CBD BDS, the researchers investigated the mode of action in which it effects colorectal carcinoma cells and in-vivo murine models of colon carcinogenesis.
They found that both CBD BDS and pure CBD reduced cell proliferation in tumor cells while leaving healthy cells unaffected. In addition, they found that CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. This meant that the effect of CBD BDS was produced by selective CB1 and CB2 receptor antagonists, while pure CBD reduced cell proliferation via CB1 receptors only. In vivo, CBD BDS also reduced pre-neoplastic lesions and polyps as well as tumor growth in colon cancer cell xenographs.
The results lead them to conclude that pure CBD and CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1, and CBD BDS also via CB2 receptor activation, showing that CBD may have some clinical relevance for the use of Cannabis-based medicines in colon cancer patients.
Can cannabidiol inhibit angiogenesis in colon cancer?
In another animal study, this one from 2019 and published in the journal Comparative Clinical Pathology, researchers investigated the effects of CBD on the angiogenesis (development) and death of cancer cells in an experimental model of colon cancer.
They did this by evaluating interleukin (IL-6 and IL-8) alterations, oxidative stress parameters, and the expression of vascular endothelial growth factor (VEGF) as well as histopathological parameters, all of which are implicated in cancer cell angiogenesis.
The results showed CBD can stimulate apoptosis (cell death) and reduce tumor growth of colon cancer in mice, with a dose of 5 mg/kg CBD inhibiting tumor growth better than the 1-mg/kg dose. Similarly, they also found that CBD had a positive anti-inflammatory and anti-oxidative effects that inhibits tumor growth, cell migration, and angiogenesis by significantly reducing VEGF expression.
The researchers concluded that CBD can potentially be considered as an anti-colon cancer medicine due to the inhibitory effect it exerts on angiogenesis, tumor growth, and metastasis through reducing VEGF gene expression, decreasing cytokines, and increasing antioxidant enzyme activities.
Anecdotal Evidence on using CBD for colon cancer
Some people opt to treat their colon cancer with cannabis oil, and have done so successfully. However, when it comes to CBD and colon cancer, the anecdotal evidence centres more around CBD being used as a complementary therapy (more on that below).
CBD as a Complementary Treatment
Most of the available evidence indicates that CBD may complement colon cancer treatment, and that CBD may help people with colon cancer by helping reduce pain and inflammation. In addition, many people suffering from colon and colorectal cancer also report having other side effects from chemotherapy treatment, including sleep problems, feelings of anxiety and depression. In one large case series study investigating the effects of CBD on anxiety and sleep, the results show CBD helps improve sleep and/or anxiety in clinical populations. Similarly, CBD can further support cancer patients by reducing stress, anxiety, depression while also helping to promote REM sleep that is thought to help improve overall mood.
Scientific and anecdotal evidence both suggest that CBD can support colon or colorectal cancer patients, especially by helping to reduce chemotherapy-induced neuropathic pain, inflammation, nausea and vomiting. If you or a loved one are suffering from colon or colorectal cancer and want to try CBD, talk to your medical practitioner first. He or she can help put together a plan that includes CBD along with other treatment options to help you deal with your symptoms safely and effectively.
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