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Cbd oil for intestinal inflammation

Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go?

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Introduction: Fifty years after the discovery of Δ 9 -tetrahydrocannabinol (THC) as the psychoactive component of Cannabis, we are assessing the possibility of translating this herb into clinical treatment of inflammatory bowel diseases (IBDs). Here, a discussion on the problems associated with a potential treatment is given. From first surveys and small clinical studies in patients with IBD we have learned that Cannabis is frequently used to alleviate diarrhea, abdominal pain, and loss of appetite. Single ingredients from Cannabis, such as THC and cannabidiol, commonly described as cannabinoids, are responsible for these effects. Synthetic cannabinoid receptor agonists are also termed cannabinoids, some of which, like dronabinol and nabilone, are already available with a narcotic prescription.

Areas covered: Recent data on the effects of Cannabis/cannabinoids in experimental models of IBD and in clinical trials with IBD patients have been reviewed using a PubMed database search. A short background on the endocannabinoid system is also provided.

Expert commentary: Cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines.

KEYWORDS: Cannabinoids, Crohn’s disease, dronabinol, inflammatory bowel disease, medical marijuana, nabilone, nabiximols, ulcerative colitis, Cannabis

1. Introduction

Inflammatory bowel diseases (IBDs), i.e. Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal (GI) tract with increasing prevalence in Westernized countries [1]. Although their etiology is still unknown, these diseases are thought to comprise misdirected attacks of the immune system against gut microbiota or their products [2]. Defects in the epithelial barrier function and in mucosal wound healing are of paramount importance in the progression of IBD [1,2]. The endocannabinoid system (ECS) has been recognized to play an important role in the maintenance of gut homeostasis since it quickly responds to disturbances by de novo synthesis of its effector molecules and is, therefore, of particular interest in the management of IBD [3].

The ECS consists of lipid mediators, so-called endocannabinoids, their synthesizing and degrading enzymes, and of G protein-coupled cannabinoid receptors (CBs) that mediate the endocannabinoid effects ( Figure 1 ). Components of the ECS have been found to be expressed throughout the GI tract and have been reviewed in detail elsewhere [4,5]. Briefly, the ECS has been described to comprise two CBs, i.e. cannabinoid receptor 1 (CB1) and 2 (CB2). CBs can be activated by a variety of synthetic or plant-derived cannabinoids, as well as by the endocannabinoids anandamide (arachidonoylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG). Synthesizing enzymes include N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) for AEA and diacylglycerol lipase for 2-AG, respectively.

A schematic overview of cannabinoid receptors, cannabinoid-responsive non-cannabinoid receptors, their ligands and degrading enzymes of the endocannabinoid system as described in murine IBD. 2-AG, 2-arachidonoylglycerol; AEA, anandamide; CB, cannabinoid receptor; CBD, cannabidiol; FAAH, fatty acid amide hydrolase; GPR55, G protein-coupled receptor 55; NAAA, N-acylethanolamine-hydrolyzing acid amidase; PEA, palmitoylethanolamide; PPARs, peroxisome proliferator-activated nuclear receptors; THC, Δ 9 -tetrahydrocannabinol; TRPV1, transient receptor potential of vanilloid-type 1.

Degradation of AEA is facilitated mainly by fatty acid amide hydrolase (FAAH), whereas 2-AG is degraded mostly by monoacylglycerol lipase (MGL or MAGL). However, the notion of the ECS being a confined physiological entity with CB receptors in its center has been challenged by the discovery of receptors responsive to cannabinoids other than CB1/2, such as G protein-coupled receptor 55 (GPR55), transient receptor potential of vanilloid-type 1 (TRPV1), and peroxisome proliferator-activated nuclear receptors (PPARs) [6]. Furthermore, it has been found that the ECS does not only consist of the aforementioned biosynthetic and degrading components, but also in fact shares many enzymes with other pathways, e.g. cyclooxygenase-2 which oxidizes AEA and thus provides a link between the ECS and prostaglandin synthesis [7]. While the complexity of the interactions of all molecules involved in (endo-) cannabinoid signaling represents a large obstacle in understanding the endocannabinoids’ role in (patho-)physiology, research on the ‘expanded ECS’ or ‘endocannabinoidome’ [7] may very well open doors for new treatment options. After all, it is desirable to discover cannabinoid based drugs that exert their actions without causing psychotropic effects that arise from activation of central CB1 receptors.

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2. The ECS as a therapeutic target in IBD

To investigate the role of cannabinoids in IBD, mostly animal models that rely on chemically induced mucosal inflammation are used. Dextran sulfate sodium (DSS)-induced colitis, for instance, causes the influx of macrophages, neutrophils, and a Th2-mediated immune response [8–10], whereas trinitrobenzene sulfonic acid (TNBS)-induced colitis is more dominated by a Th1-response [8,10]. Analysis of expression levels of ECS components in inflamed rodent colonic tissue revealed enhanced cannabinoid signaling under inflammatory conditions as compared to healthy tissue. Thus, CB1 and CB2 receptors, as well as AEA, were found to be upregulated in experimental IBD models [11,12]. Upregulation of AEA, however, was only found in certain layers of the colon (e.g. in the submucosa but not the mucosa) [11]. On the other hand, the AEA-degrading enzyme FAAH was expressed to a lesser extent in the initial stage of colitis but returned to control levels as the disease progressed [13]. Pharmacological strategies to enhance endocannabinoid levels in the inflamed colon of rodents through inhibition of the degrading enzymes FAAH or MGL, respectively, ameliorated the inflammation [14,15]. Accordingly, it has been reported that activation of CB1 or CB2 with synthetic agonists protected from colitis [12,16] and that treatment with Δ 9 -tetrahydrocannabinol (THC), the main psychoactive constituent of Cannabis sativa, reduced TNBS-induced inflammation as well as myeloperoxidase (MPO) activity and motility disturbances in the in rat colon [17]. These findings prompted the investigation of other nonpsychoactive components of Cannabis in IBD models. It has been shown that cannabidiol (CBD), a cannabinoid with very low affinity for CB1 and CB2, has protective effects in murine colitis as observed by a reduction of colon injury, inducible nitric oxide synthase expression, reactive oxygen species production, MPO activity, and tumor necrosis factor alpha (TNF-α) levels [17–21]. CBD has also been reported to inhibit FAAH activity [22] and could thus alter endocannabinoid levels. Other non-psychotropic cannabinoids, shown to be beneficial in colitis models, include the plant cannabinoid cannabigerol [23] and the synthetic atypical cannabinoid O-1602, which has been shown to inhibit neutrophil recruitment [24]. Cannabigerol reduced nitric oxide production in macrophages and this effect was modulated by the CB2 receptors [23]. While the molecular targets of cannabigerol and O-1602 have not been fully elucidated yet, extensive evidence exists that CBD exerts its functions, at least partly, through PPARs [21]. CBD has also been reported to act as an antagonist to GPR55, a receptor that plays a crucial role in intestinal inflammation [25]. Another molecule of interest in IBD is palmitoylethanolamide (PEA), a structural relative of anandamide that acts via multiple targets including CB1, CB2, GPR55, PPARα, and TRPV1 and that has been reported to reduce inflammation and intestinal permeability in mice [26–28]. With regard to the ECS, beneficial effects of PEA in experimental IBD involved an increase in colonic CB1 receptor expression and activation of CB2 and GPR55 [26]. Another plant cannabinoid with anti-inflammatory properties in murine colitis is cannabichromene [29] which inhibited endocannabinoid inactivation [30].

Taken together, a huge amount of preclinical data strongly support the ECS as a therapeutic target in IBD (as previously reviewed by Refs. [3,31–33]).

2.1. Components of the ECS are differentially expressed in human IBD

The altered regulation of the ECS in IBD patients has been addressed in various reports with rather contradictory outcomes (summarized in Table 1 ). Although AEA levels were found to be increased in UC patients (n = 8) [11], some studies reported an overall reduced AEA signaling in IBD patients, as observed through decreased activity and/or levels of the synthesizing enzyme NAPE-PLD [34,35], as well as through increased activity of the degrading enzyme FAAH [34,35], and through reduced levels of AEA [34]. Enhanced CB2 immunoreactivity has been observed in the colonic epithelium and some cells of the inflammatory cell infiltrate in CD and UC specimens, suggesting that CB2 might be a relevant target for IBD treatment [34–36]. In fact, activation of CB2 has shown protection in experimental models of colitis [16,37]. Also in a human colonic explant model, where colitis-like damage was induced with pro-inflammatory cytokines, activation of CB2 led to reduced damage of mucosal crypts and the epithelial lining [38].

Table 1.

Differential expression of ECS components in human IBD compared to controls as described in the literature.

Using CBD for Ulcerative Colitis

Lindsay Curtis is a health writer with over 20 years of experience in writing health, science & wellness-focused articles.

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Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.

Robert Burakoff, MD, MPH, is board-certified in gastroentrology. He is the vice chair for ambulatory services for the department of medicine at Weill Cornell Medical College in New York, where he is also a professor. He was the founding editor and co-editor in chief of Inflammatory Bowel Diseases.

Ulcerative colitis (UC) is a chronic disease that affects the large intestine (colon), causing inflammation and small sores (or ulcers). UC symptoms include diarrhea, abdominal cramps and pain, bloody stool, and the need to pass stool frequently.

There is no cure for ulcerative colitis, so treatment prioritizes symptom relief and reducing flare-ups. Many people with ulcerative colitis turn to alternative treatments, such as cannabidiol (CBD), to take control of the disease and improve their quality of life.

Read on to learn more about how CBD may be a useful supplemental therapy in the management of UC symptoms.

Tinnakorn Jorruang / Getty Images

Inflammation, CBD, and Ulcerative Colitis

Cannabis plants contain chemicals called cannabinoids, which are compounds unique to the plant. The two primary cannabinoids are:

  • Tetrahydrocannabinol (THC), which has psychoactive effects that make a person feel “high”
  • Cannabidiol (CBD), which has no psychoactive effects but can provide a number of therapeutic benefits

Both CBD and THC interact with the endocannabinoid system (ECS) in the body. The ECS is a complex biological system that regulates cardiovascular, nervous, and immune system functions.

CBD binds to and activates receptors in the brain that create a therapeutic effect in the body, helping users find relief from painful symptoms without feeling impaired.

CBD has many therapeutic properties and is a known anti-inflammatory, antimicrobial, and antioxidant. Thanks to its anti-inflammatory properties, CBD may be a potential therapeutic treatment for ulcerative colitis.

CBD for Ulcerative Colitis Symptoms

CBD has been explored in several studies as a potential treatment for ulcerative colitis. Research shows that CBD may potentially help reduce inflammation in the gastrointestinal system caused by inflammatory bowel diseases (IBD), such as ulcerative colitis.

One study found that participants with UC who took 50 milligrams (mg) of CBD oil twice a day, increasing to 250 mg per dose if needed and tolerated, experienced significant improvements in their quality of life. However, more research and follow-up studies are needed.

Another study analyzed the efficacy of CBD use in adults with ulcerative colitis. The study concluded that CBD extracts may help alleviate symptoms of IBD and UC.

Although more research is needed, current study results show promise that CBD may be beneficial for treating symptoms of ulcerative colitis.

Are There Any Side Effects?

Though CBD is generally well tolerated, you may experience some side effects. Common side effects include:

  • Changes in mood (e.g., irritability)
  • Diarrhea
  • Decreased appetite
  • Drowsiness
  • Dry mouth

CBD and Your Liver

CBD is metabolized by the liver, and large doses may lead to liver toxicity. Talk with your healthcare provider before using CBD. If you are on any prescription medications, they may recommend regularly monitoring your liver through bloodwork to ensure CBD is safe for you.

How to Use CBD for Ulcerative Colitis

While CBD won’t cure ulcerative colitis, it may help make your symptoms more manageable and help reduce flares.

There are many different forms of CBD, and you may need to try different delivery methods before finding the one that is right for you.

CBD is available in:

  • Edibles (e.g., gummies, CBD-infused beverages)
  • Plants (to be inhaled/smoked)
  • Capsules and pills
  • Tinctures and oils
  • Topicals (e.g., lotions, creams)

To date, CBD has only been approved by the Food and Drug Administration to treat epilepsy. As a result, there is no standard recommended dosage of CBD for treating ulcerative colitis.

Shopping for CBD

When shopping for CBD, you will notice different types available. These include:

  • Full-spectrum CBD: Contains all the natural components found in the cannabis plant, including terpenes, flavonoids, fatty acids, and cannabinoids. Full-spectrum CBD products contain trace amounts of THC. These compounds work in synergy in the body to obtain the desired therapeutic effects.
  • Broad-spectrum CBD: Similar to full-spectrum CBD, broad-spectrum CBD contains compounds in the cannabis plant, but with all traces of THC removed, so you will not experience any mind-altering effects.
  • CBD isolates: All other cannabinoids, terpenes, and flavonoids are removed to create a 99% pure CBD product.
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For the best results, look for broad-spectrum or full-spectrum CBD products. These may combine the effects of multiple cannabis compounds that work together in synergy, creating an “entourage effect” to offer the most health benefits.

Dosage

Because CBD is still a relatively new therapeutic option for managing different health conditions, including inflammatory bowel diseases, there is currently no recommended standard dosage.

In one study, patients with ulcerative colitis were given 50 mg of CBD oil twice a day. Some participants were able to increase to as much as 250 mg twice a day for a period of 10 weeks.

Another study also recorded dose ranges of 50 mg to 250 mg CBD capsules twice daily. Many participants were able to tolerate the higher dosage and saw improvements, though the study authors suggested that more research is needed.

As with many medications, it’s best to start with a lower dose and gradually increase the amount of CBD to determine the appropriate dosage.

Talk to Your Healthcare Provider

It’s important to talk with your healthcare provider before adding any supplemental therapy, such as CBD, to your ulcerative colitis treatment. They will be able to determine if CBD will be beneficial for your individual case and can recommend the right dosage.

How to Buy CBD

With so many different options available, it can be daunting to shop for CBD. CBD is generally safe and well tolerated, but the industry is poorly regulated, and consumers should be aware of what to look for before purchasing CBD.

You’ll want to carefully read the label of any products you are considering and look for:

  • Amount of CBD per serving
  • Suggested use/dosage
  • Type (full-spectrum, broad-spectrum, or isolate)
  • List of ingredients
  • Manufacturer and distributor name

You’ll also want to consider:

  • Cannabis source: Ensure the product you are purchasing is sourced from a company that ensures the quality and safe cultivation of their plants. Look for products that come from organic cannabis/hemp plants when possible.
  • Certificate of Analysis (CoA): CoAs are conducted by independent, accredited labels that verify third-party testing of the products.
  • Customer reviews: Testimonials from other users can tell you a lot about a product’s efficacy.

Avoid products and vendors that make broad, definitive statements or promises of a “cure” for something. If you are currently taking any other medications or supplements for your UC, speak with your healthcare provider before using CBD, as it may interact with other medications you are taking.

A Word From Verywell

People with ulcerative colitis may want to consider alternative treatments such as CBD to help manage their symptoms. It’s important to remember that while CBD may help improve your symptoms, it will not treat or cure the condition.

CBD is best used as a supplemental therapy alongside conventional treatments recommended by your healthcare provider, as well as dietary modifications. As with any supplement or medication, talk with your healthcare provider before trying CBD.

Frequently Asked Questions

Cannabinoids have anti-inflammatory properties that may make them helpful in managing symptoms of gastrointestinal diseases like ulcerative colitis. Research suggests CBD is a promising therapeutic for inflammatory bowel diseases, helping reduce mucosal lesions, ulceration, and inflammation associated with IBD. CBD may also help manage gastrointestinal pain, as well as secondary symptoms that come with IBD, such as anxiety, nausea, and sleep disturbances.

The cannabis plant (to be smoked/vaped) comes in different strains, with varying CBD and THC levels. CBD-dominant cannabis strains may provide the best relief for inflammation. These strains tend to be high in the terpene called myrcene, which helps reduce inflammation.

There are many delivery methods for CBD, including edibles (e.g., gummies), flowers, oils, tinctures, topicals, and suppositories. Finding the right one for you may require a little trial and error. The best method for you depends on personal preference and how quickly you may need relief. For example, you may get relief from painful symptoms sooner by vaping oil vs. consuming an edible. Start off with smaller doses and gradually increase the amount you use until you find the amount that offers you relief from your symptoms. Make sure to talk with your healthcare provider before you begin use.