CBD Oil for Ulcerative Colitis - April 2024

Research on CBD for Ulcerative Colitis

Inflammatory bowel disease, or IBD, has two major subtypes: ulcerative colitis and Crohn’s disease⁽⁵⁾. Patients with IBD may have various symptoms depending on the location of inflammation in the gastrointestinal tract. 

For instance, an individual with inflammation that affects most of their colon may experience diarrhea, rectal bleeding, and urgency. 

Also, constipation may be a sign of ulcerative colitis, especially in patients with the left-sided disease (the inflammation is only on the left side of the large intestine)⁽⁶⁾.

In the U.S., recreational use of cannabis is regarded as the most common type of drug used by individuals with inflammatory bowel disease⁽⁷⁾. The Cannabis sativa plant has around 100 phytocannabinoids composed of various compounds such as flavonoids and terpenes.

According to a study published in NIH, cannabis terpenes may alleviate chronic pain (offer pain relief) and contribute to the “entourage effect”⁽⁸⁾. 

The “entourage effect” refers to the favorable impact that terpenes provide to cannabinoids⁽⁹⁾.

Also, research showed that flavonoids may block regulatory enzymes or transcription factors that are crucial for modulating inflammatory mediators⁽¹⁰⁾.

These compounds are utilized by the endocannabinoid system, which is an endogenous system that regulates various factors such as energy balance, immune regulation, memory, mood, and homeostasis⁽¹¹⁾. 

The most common type of phytocannabinoid is delta-9-tetrahydrocannabinol, which is responsible for the psychoactive effects of medical marijuana. 

Also, cannabidiol or CBD has putative anti-inflammatory properties⁽¹²⁾.

Cannabidiol (CBD) has potential anti-inflammatory characteristics that may reduce inflammatory bowel disease activity⁽¹³⁾. A proof-of-concept trial evaluated the effectiveness, safety, and tolerability of a botanical extract high in CBD in patients with ulcerative colitis.

In the study, the phytocannabinoids exert their action through the endocannabinoid system. 

The primary clinical response was negative; remission rates after therapy were comparable for CBD-rich botanical extract (28%) and placebo (26%).

Meanwhile, in another study, the effects of cannabinoids on gut motility may potentially have a substantial impact on visceral pain perception⁽¹⁴⁾. Abdominal pain and other symptoms may be linked to altered levels of gut motility.

CBD, the primary nonpsychoactive cannabinoid, also inhibited GI motility in a rodent model of croton oil-induced intestinal inflammation. In other trials, IBD patients, also cannabis users, reported a reduction in diarrhea and abdominal pain due to cannabis use.

Thus, the effects of cannabis on GI motility may have significant improvement in the abdominal discomfort experienced by these patients.​​

The Endocannabinoid System (ECS)

In inflammatory bowel disease, the endocannabinoid system modulates several physiological processes, including intestinal homeostasis, regulation of gastrointestinal motility, visceral feeling, and immunomodulation of inflammation⁽¹⁵⁾.

The ECS comprises cannabinoid receptors: CB1 and CB2⁽¹⁶⁾. These are the main targets of this system and are responsible for synthesizing anandamide and 2-arachidonoylglycerol. 

Anandamide (N-arachidonylethanolamine) is a brain lipid that binds to cannabinoid receptors and mimics the euphoric effects of cannabinoid medicines produced from plants⁽¹⁷⁾.

Also, 2-Arachidonoylglycerol (2-AG) is an endogenous ligand of the cannabinoid receptors (CB1 and CB2), which are members of the GPCR family best recognized for mediating the effects of the active compounds in marijuana⁽¹⁸⁾.

Determining CB1 and CB2 receptors’ significance in IBD was validated mainly by increased expression in a dextran sulfate sodium–produced mice model of colitis or increased mRNA expression in dinitrobenzene sulfonic acid–induced colitis⁽¹⁹⁾.

CB1 receptors are prevalent in neural tissue and the central nervous system. Meanwhile, CB2 receptors mediate immunity-related actions.

In a study, researchers wanted to determine whether cannabis therapy affects the number of endocannabinoids (eCBs) and the clinical symptoms of IBD patients⁽²⁰⁾.

Thirteen individuals with Crohn’s disease (CD) and nine patients with ulcerative colitis (UC) received cannabis⁽²¹⁾. About 17 CD patients and 10 UC patients served as placebo groups. ECB levels were unchanged during the therapy period in all individuals with CD.

Cannabis usage modifies ECB “tone” in UC patients. According to this research, cannabis may positively impact illness symptoms in UC patients⁽²²⁾.

What Is CBD?

CBD is a compound present in cannabis. CBD does not include tetrahydrocannabinol (THC), the psychoactive component of marijuana that causes a high⁽²³⁾. 

CBD is often sold as oil, although it is also available as an extract, a vaporized liquid, and capsules. Food, beverages, and cosmetic goods are among the many online CBD-infused products accessible.

Different Forms of CBD

There might be hundreds of distinct varieties of CBD oil. However, the three most common CBD extracts are as follows: 

• CBD Isolate: CBD Isolate is considered the purest form of CBD oil since it does not include any other cannabinoids or natural substances derived from the cannabis plant. 
• Full-spectrum CBD: Full Spectrum CBD oil is a CBD-rich oil containing trace levels of THC (up to 0.3%). This CBD variant also has terpenes, flavonoids, essential oils, and other cannabinoids. 

Due to the entourage effect, some individuals prefer full-spectrum CBD oil to CBD isolate. This idea asserts that taking CBD, THC, and other cannabis components together may work better than CBD alone.

• Broad-spectrum CBD: Broad–spectrum CBD oil falls midway between CBD isolate and full-spectrum CBD oil. The broad-spectrum CBD variant includes mainly cannabidiol and trace levels of other cannabis compounds except for THC. 

As with full-spectrum CBD, this type of CBD may provide enhanced effects due to the presence of other compounds that interact with each other. Cannabinol (CBC) and terpenes, such as limonene, myrcene, and pinene, are among the compounds that are often added.

CBD Usage

Although CBD products such as gummies, vape pens, capsules, and lotions are available, CBD oils are the most common application method. CBD may be administered in many ways, such as directly ingesting a tincture or putting a few drops of oil into the next meal.

If users do not like swallowing CBD oil, there is always the option of mixing it with the meal. Individuals may benefit from adding CBD oil to their smoothies, coffee, tea, and other favorite beverages. CBD oils come in several flavors, making them an ideal component for many foods and beverages.

In addition, CBD oil may be taken sublingually or under the tongue for a more straightforward method. 

Lastly, there are various CBD-infused lotions and balms meant for topical administration. However, CBD oils may also be utilized to create DIY topicals. Users may be able to tailor their CBD topical to their skin and preferences.

CBD Dosage 

There is no standard CBD dosage prescribed for ulcerative colitis to improve the quality of life. 

However, one study focused on the dosing and method of intake, side effects, usage, and long-term effects of medicinal cannabis in 127 patients with inflammatory bowel disease⁽²⁴⁾.

Cannabis usage by individuals with inflammatory bowel disease is connected with clinical improvement, decreased pharmaceutical use, and slight weight gain. Most patients react well to a dosage of 30g per month or 21mg of THC and 170mg of CBD every day.

Users may note that CBD oil’s effects may last up to 8 hours upon the liquid’s ingestion. CBD oil has an onset time of 30 to 90 minutes⁽²⁵⁾.

Safeness

No strong conclusions can be formed about the effectiveness and safety of cannabis or cannabidiol in individuals with active UC⁽²⁶⁾. Cannabis or cannabinoids are not shown to maintain UC remission. 

To examine the effects of cannabis on active and quiescent UC, more extensive trials are needed. Assessing cannabis dosages, modes of delivery, and long-term safety is also imperative.

Interactions of CBD With Other Medications

Fish oil is one of the sources of omega-3 fatty acids, which have anti-inflammatory qualities and other health advantages⁽²⁷⁾. Some individuals utilize omega-3 fatty acids to alleviate Crohn’s disease and ulcerative colitis-related intestinal inflammation.

However, CBD has a complicated pharmacokinetic and pharmacodynamic profile comparable to that of any other drug with the potential to interact with other medications and medical conditions⁽²⁸⁾. 

Additionally, healthcare professionals should be aware of the possibility of DDIs (drug-drug interactions) and ADEs (​​adverse drug events) with CBD. 

Therefore, healthcare providers should monitor their patients’ regimens wisely and take note of individual preferences when it comes to complementary and alternative medicines. 

Side Effects 

Although CBD is generally considered safe, it may cause various side effects. These include nausea, dry mouth, and drowsiness⁽²⁹⁾.

Meanwhile, two randomized controlled trials (RCTs) were conducted to evaluate the effects of cannabidiol on participants’ behavior⁽³⁰⁾. One study compared the effects of cannabidiol with that of placebo on the behavior of mild to moderate UC participants.

A study conducted on eight weeks of therapy showed that two cannabis cigarettes daily provided equivalent to 23mg of THC to a placebo in patients with UC who did not respond to standard medical treatment. On the other hand, no studies were conducted on the use of cannabis in quiescent UC.

The first study was regarded as having a low risk of bias. In contrast, the second study was considered to have a high risk of bias for the personnel and participants. These two small studies could not be combined due to the differences in the drugs used.

Risks

Note that inhaled CBD enters the bloodstream the quickest, reaching high concentrations within 30 minutes and increasing the likelihood of experiencing acute adverse effects⁽³¹⁾. 

Edibles need more time to absorb and are less likely to generate a high concentration peak. However, they may ultimately reach sufficient concentrations to pose a problem or interact with other drugs.

Topical formulations like creams and lotions may not enter the blood in sufficient amounts to interfere with other drugs. However, it is unknown how much CBD ultimately enters the blood. 

None of the CBD items are regulated or tested for purity, concentration, or safety. Hence, it further complicates the situation.

Legality

A modification in the law in December 2018 boosted the FDA‘s safety monitoring efforts involving CBD use⁽³²⁾. In the 2018 Farm Bill, hemp is no longer considered a controlled substance.

Additionally, medical cannabis and its derivatives with less than 0.3% delta-9-tetrahydrocannabinol by dry weight are no longer deemed as controlled substances.

Still, FDA-regulated products containing hemp must nevertheless adhere to the applicable standards of the Federal Food, Drug, and Cosmetic Act.

What Is Ulcerative Colitis?

Mayo Clinic defines ulcerative colitis as an inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive system⁽³³⁾. The lining of the large intestine (colon) and rectum are affected by ulcerative colitis. 

If an individual has inflammation that primarily affects the small intestine, they may have symptoms of diarrhea, abdominal pain, or weight loss⁽³⁴⁾.

This disorder is the outcome of an excessive immune response⁽³⁵⁾. Although ulcerative colitis may develop at any age, the average age of diagnosis is in the mid-30s. Men and women are susceptible to this condition, although older men are more likely to get a diagnosis than older women.

UC may be debilitating and can lead to life-threatening problems⁽³⁶⁾. Therefore, individuals need to get proper medical attention. Even though there is no known cure, therapy may significantly lessen symptoms and bring about long-term remission of the condition.

Causes of Ulcerative Colitis

Although the actual etiology of ulcerative colitis is uncertain, it is believed to result from an immune system issue⁽³⁷⁾.

1. Autoimmune condition

The immune system fights infection. Experts believe ulcerative colitis is autoimmune⁽³⁸⁾. The immune system fights infections by releasing white blood cells to eradicate the source of infection. Infected tissue swells and becomes red (inflamed).

In ulcerative colitis, the immune system mistakes “friendly bacteria” that promote digestion for a hazardous infection, inflaming the colon and rectum. Some experts think a viral or bacterial infection initiates the immune system. However, the infection does not “switch off” afterward and causes inflammation.

No infection may be present, and the immune system may merely fail, or there may be an imbalance of healthy and harmful bowel bacteria.

2. Genetics and environmental factors

Ulcerative colitis likely has genetic and environmental causes⁽³⁹⁾. Variations in hundreds of genes may be connected to ulcerative colitis, but their significance is unclear. Researchers believe this illness may be caused by genetic differences in the intestinal lining’s protective role or an abnormal immune response to normal bacteria. 

Several of the genes associated with the development of ulcerative colitis are also involved in protecting the intestines. The intestines’ inner surface is a barrier that helps keep the body’s tissues from getting infected by harmful bacteria.

However, researchers believe that a breakdown of this barrier could lead to an immune response that can trigger chronic inflammation. The breakdown could also cause gastrointestinal problems, such as ulcerative colitis.

Treatments for Ulcerative Colitis

Having IBD like ulcerative colitis may need dietary and lifestyle adjustments to control symptoms and avoid flare-ups. However, treatments may be necessary to manage the medical condition. 

Endoscopic procedures involving tissue biopsy diagnose ulcerative colitis. Further testing may rule out complications or other forms of IBD, like Crohn’s disease⁽⁴⁰⁾.

The doctor may recommend blood tests to check for anemia, a disease with insufficient red blood cells to provide enough oxygen to the tissues, or look for infection.

Ulcerative colitis is diagnosed by the presence of white blood cells or specific proteins in the stool. Taking a stool sample may also help rule out other conditions, such as bacterial, virus, and parasitic infections.

Meanwhile, endoscopic procedures may involve colonoscopy or flexible sigmoidoscopy. Both procedures are used to screen for colon cancer⁽⁴¹⁾. 

One of these procedures is a flexible sigmoidoscopy, allowing the healthcare provider to visualize the lower part of the colon. During a colon cancer screening, the healthcare provider can remove polyps growing in the lower colon. If they detect cancer, they can remove them immediately.

Colonoscopy

A colonoscopy is an examination performed to detect abnormalities in the large intestine (colon) and recta, such as swollen, irritating tissues, polyps, and cancer⁽⁴²⁾.

A physician inserts a flexible, long tube (colonoscope) into the rectum during a colonoscopy. A video camera at the tip of the tube enables the doctor to view the inside of the colon.

Polyps and other abnormal tissue forms may be removed using a scope during a colonoscopy. Throughout the procedure, tissue samples (biopsies) may also be collected.

The surgical treatment of ulcerative colitis is reserved for individuals whose medicinal treatment fails or develops severe bleeding, perforation, or malignancy⁽⁴³⁾. 

A higher risk of colon cancer is related to persistent ulcerative colitis. Eight years after pancolitis and 12 to 15 years after the onset of left-sided illness, patients should have an initial screening colonoscopy. Further colonoscopies should be performed every two to three years.

Flexible Sigmoidoscopy

A gastroenterologist or gastrointestinal specialist conducts a flexible sigmoidoscopy to examine the lower (sigmoid) portion of the colon and rectum⁽⁴⁴⁾. The doctor uses a sigmoidoscope, a flexible, illuminated tube equipped with a camera. The process aids in diagnosing and sometimes treating bowel disorders and cancer.

Meanwhile, imaging procedures are also alternative treatments for ulcerative colitis, such as the following⁽⁴⁵⁾:

• Computerized tomography (CT), enterography, and magnetic resonance (MR) enterography: The doctor may offer a noninvasive test to rule out small intestinal inflammation. These techniques detect intestinal inflammation more sensitively than traditional imaging. MR enterography avoids radiation.
• X-rays: If the patients have significant symptoms, the doctor may perform an abdominal X-ray to rule out the perforated colon.
• CT scan: If the doctor suspects ulcerative colitis complications, an abdominal or pelvic CT scan may be conducted. A CT scan may measure intestinal inflammation⁽⁴⁶⁾.

Medication and Combination Therapy

Ulcerative colitis medication may reduce inflammation and repair tissues⁽⁴⁷⁾.

In some cases, a healthcare provider may decide to add a combination therapy to improve the effectiveness of the initial treatment. This type of therapy could involve using a biological or an immunomodulator. Although this type of therapy has risks and benefits, it is still considered a safe and effective treatment option.

Combining multiple treatments can help improve the effectiveness of IBD therapy. However, it can also lead to additional side effects and toxicities. The healthcare provider will then determine the appropriate treatment for the patients.

When to See a Doctor

While ulcerative colitis is not lethal, it may produce life-threatening consequences.

Individuals may need to see a doctor if patients have persistent bowel changes or symptoms such as⁽⁴⁸⁾:

• Blood in feces
• Nonstop diarrhea 
• Diarrhea that can awaken individuals
• Fever lasting longer than a day

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1. Cannabis for Treating IBD: Hope or Hype?
   https://healthblog.uofmhealth.org/digestive-health/cannabis-for-treating-ibd-hope-or-hype
2. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis
   https://pubmed.ncbi.nlm.nih.gov/29538683/
3. Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease – A Systematic Review
   https://www.frontiersin.org/articles/10.3389/fimmu.2021.790803/full
4. Cannabis for the treatment of ulcerative colitis
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516819/
5. Cannabis for Treating IBD: Hope or Hype?
   https://healthblog.uofmhealth.org/digestive-health/cannabis-for-treating-ibd-hope-or-hype
6. Constipation and Incomplete Bowel Emptying
   https://inflammatoryboweldisease.net/symptoms/constipation-and-incomplete-bowel-emptying
7. Cannabis for the Treatment of Inflammatory Bowel Disease: A True Medicine or a False Promise?
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000156/
8. Study shows Cannabis terpenes provide pain relief, contribute to ‘entourage effect’
   https://www.sciencedaily.com/releases/2021/07/210714110455.htm
9. The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324885/
10. Anti-inflammatory effects of flavonoids
    https://pubmed.ncbi.nlm.nih.gov/31288163/
11. Cannabis for the Treatment of Inflammatory Bowel Disease: A True Medicine or a False Promise?
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000156/
12. Antioxidative and Anti-Inflammatory Properties of Cannabidiol
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
13. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis
    https://pubmed.ncbi.nlm.nih.gov/29538683/
14. Cannabis and Cannabis Derivatives for Abdominal Pain Management in Inflammatory Bowel Disease
    https://www.karger.com/Article/FullText/517425
15. Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease – A Systematic Review
    https://www.frontiersin.org/articles/10.3389/fimmu.2021.790803/full
16. Ibid.
17. Anandamide
    https://www.sciencedirect.com/topics/neuroscience/anandamide
18. 2-Arachidonoylglycerol
    sciencedirect.com/topics/neuroscience/2-arachidonoylglycerol
19. Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease – A Systematic Review
    https://www.frontiersin.org/articles/10.3389/fimmu.2021.790803/full
20. Endocannabinoid Levels in Ulcerative Colitis Patients Correlate With Clinical Parameters and Are Affected by Cannabis Consumption
    https://www.frontiersin.org/articles/10.3389/fendo.2021.685289/full
21. Ibid.
22. Ibid.
23. What are the benefits of CBD — and is it safe to use?
    https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700
24. Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects
    https://pubmed.ncbi.nlm.nih.gov/31567639/
25. Healing with CBD. page 191
    https://drive.google.com/file/d/1AGlxnhS2SoFeOXEuysv75bd_C9pEnwsU/view
26. Cannabis for the treatment of ulcerative colitis
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516819/
27. Vitamins, Minerals, and Supplements
    https://www.crohnscolitisfoundation.org/complementary-medicine/supplements
28. Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/
29. CBD and other medications: Proceed with caution
    https://www.health.harvard.edu/blog/cbd-and-other-medications-proceed-with-caution-2021011121743
30. Cannabis for the treatment of ulcerative colitis
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516819/
31. CBD and other medications: Proceed with caution
    https://www.health.harvard.edu/blog/cbd-and-other-medications-proceed-with-caution-2021011121743
32. Better Data for a Better Understanding of the Use and Safety Profile of Cannabidiol (CBD) Products
    https://www.fda.gov/news-events/fda-voices/better-data-better-understanding-use-and-safety-profile-cannabidiol-cbd-products
33. Ulcerative colitis
    https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326#
34. Cannabis for Treating IBD: Hope or Hype?
    https://healthblog.uofmhealth.org/digestive-health/cannabis-for-treating-ibd-hope-or-hype
35. What is Ulcerative Colitis?
    https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis
36. Ulcerative colitis
    https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326#
37. Causes -Ulcerative colitis
    https://www.nhs.uk/conditions/ulcerative-colitis/causes/
38. Ibid.
39. Ulcerative colitis
    https://medlineplus.gov/genetics/condition/ulcerative-colitis/#causes
40. Ulcerative colitis
    https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/diagnosis-treatment/drc-20353331
41. Flexible Sigmoidoscopy
    https://my.clevelandclinic.org/health/diagnostics/4953-flexible-sigmoidoscopy
42. Colonoscopy
    https://www.mayoclinic.org/tests-procedures/colonoscopy/about/pac-20393569
43. Ibid.
44. Flexible Sigmoidoscopy
    https://my.clevelandclinic.org/health/diagnostics/4953-flexible-sigmoidoscopy
45. Ulcerative colitis
    https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/diagnosis-treatment/drc-20353331
46. Ibid.
47. Complications-Ulcerative colitis
    https://www.nhs.uk/conditions/ulcerative-colitis/complications/
48. Ulcerative colitis
    https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326

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