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The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information

Address correspondence to: David T. Rubin, MD, 5841 S. Maryland Ave., MC 4076, Chicago, IL 60637 ([email protected]).

Copyright © 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Abstract

There is significant interest among patients and providers in using cannabis (marijuana) and its derivatives to treat a number of chronic illnesses, including inflammatory bowel disease. Despite the Schedule I classification of cannabis by the federal government, state governments have sought ways to make cannabis available for specific medical conditions, and some states have legalized cannabis outright. This white paper summarizes the preclinical data, clinical data, safety data, and the regulatory landscape as they apply to medical cannabis use in inflammatory bowel disease. Animal models of cannabinoid chemistry and physiology give evidence of anti-inflammatory, antidiarrheal, and nociceptive-limiting properties. Human studies have found benefit in controlling symptoms and improving quality of life, but no studies have established true disease modification given the absent improvement in biomarker profiles or endoscopic healing.

Finally, this review describes the legal, regulatory, and practical hurdles to studying the risks and benefits of medical cannabis in the United States.

INTRODUCTION

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are chronic intestinal conditions characterized by uncontrolled inflammation 1 that results in gastrointestinal and extra-intestinal symptoms and, in many cases, progression to surgery or disability. 2 They are of unknown cause and have no medical cures. Therapy of these conditions has been focused on improvement of symptoms and quality of life, predominantly by control of inflammation with immune-based therapies. 3 More recently, the goal of management has included both symptom improvement and objective evidence of biochemical control, so-called “deep remission.” Deep remission has been associated with improvement in disease control over time and is associated with reductions in hospitalization and surgery. However, despite significant advances in the effectiveness of medical therapies for patients with Crohn’s disease and ulcerative colitis, there remain unmet needs and gaps in treatment options for many patients. 4, 5 In addition, despite substantial improvements in the ability to heal the bowel and even modify long-term outcomes of the disease, 6, 7 some patients with inflammatory bowel disease continue to suffer from a variety of nonspecific symptoms such as nausea, fatigue, weakness, loss of appetite, and coexisting psychosocial problems. 8

Successful management of inflammatory bowel disease involves careful review by an appropriate specialist and coordination of medical, surgical, psychological, and complimentary therapies to address the complex needs of the individual patient. 9 There has been interest in the use of cannabis as a treatment for inflammatory bowel disease, 10, 11 but there is no definitive evidence to demonstrate that currently available formulations can control inflammation. However, the use of cannabis in various forms has been associated with improvements in nausea, abdominal pain, and appetite. 12–14 Therefore, there is great interest in the possibility of this therapy for additional use and further study. The legalization of cannabis for medicinal purposes in many states, and for recreational use in a few, 15 provides unique opportunities to further explore this treatment option.

Patients have expressed great interest in understanding the full therapeutic potential of cannabis and its derivatives, 16 and providers have struggled to know how to best support their patients’ requests for authorization to use the therapy or consider it as an adjuvant therapy.

This white paper, commissioned by The Crohn’s and Colitis Foundation, summarizes the available information about medical marijuana (MMJ) and its use in IBD and provides a review of the available literature and legal status in the United States. It also provides an outline of needed research initiatives and areas for further study, emphasizing the gaps in our current understanding in order to better define the potential and future utilization of this therapy.

CHEMISTRY AND PHYSIOLOGY OF CANNABIS

Cannabis, colloquially known as “marijuana,” is a genus of flowering plant with multiple subspecies, including Cannabis sativa, 17 containing cannabinoids. Cannabis has generally been lumped into the category of “complementary and alternative medicine” when its medical application has been mentioned in the management of IBD. 18 Unlike many interventions included in this basket term, however, the effect of cannabis on the human body, which is mediated by the endocannabinoid system (ECS), has been studied in great detail.

Cannabis contains nearly 500 chemicals, the most well-known of which are cannabinoids cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC). THC is well known for its psychotropic effects, and CBD for its anti-inflammatory and immunomodulatory effects. 19–22 Broadly, the ECS system has been linked to visceral pain perception, nausea and vomiting, gastrointestinal motility, and intestinal inflammation and has been discussed elsewhere. 23

Cannabinoids act at CB1 and CB2 receptors. CB1 is mainly expressed in the brain, where it causes its well-known psychotropic effects, and the enteric nervous system. In contrast, CB2 is absent in the brain but is still found in the enteric nervous system, immune cells (macrophages and plasma cells), and gastrointestinal epithelial cells. Endogenous cannabinoids, anandamide and 2-arachydonylglycerol (2AG), are produced and released locally to act on CB1/CB2 receptors. 23, 24 THC is a partial agonist of the CB1 and CB2 receptors. Although the mechanism of action of CBD is not specific, some of its downstream effects are potentiated through the prevention of reuptake of endogenous anadamide. 25–27

Activation of the endocannabinoid receptors using CB1- and CB2-specific ligands results in decreased inflammation in animal models of colitis. 28–30 A systematic review of 24 individual cannabinoid compounds tested in murine colitis found them beneficial in reducing colonic inflammation in rats and mice. 19 A combination of THC and CBD was found to be additive in anti-inflammatory activity in a mouse model of colitis. 31

Concentrations of CB1 and CB2 receptors increase in the human gut in the settings of colon cancer, diverticulitis, and celiac disease. 23, 29, 32 There is conflicting evidence regarding changes to the expression of endocannabinoid receptors in IBD. This may be due to small heterogeneous cohorts, lack of subclassification of disease types and activity, and variable tissue sampling sites. 24 This variance may also explain the conflicting effects seen in human experiments. Contrary to some other more recent studies in patients with chronic abdominal pain, administration of synthetic THC to healthy subjects has resulted in increased visceral sensitivity. 33 Oral THC administration was not beneficial in patients with chronic abdominal pain (postop pain, pancreatitis), and this is thought to be secondary to sensitization of nociceptive pathways in the central nervous system. 34

OVERVIEW OF THE USE OF MMJ FOR THE TREATMENT OF IBD

There have been limited studies of cannabis in IBD. Prevalence studies in the United States, United Kingdom, Israel, Canada, and Spain suggest that 10%–12% of IBD patients are active cannabis users, with commonly expressed goals of mitigating abdominal pain, improving appetite, and limiting diarrhea. 12, 14, 16, 35 Nearly half of the nonusing patients in 1 study expressed interest in using cannabis to control symptoms when legally available. 14 A single-center study from Boston did not find any increase in medical use of cannabis among their IBD population over the 5 years since cannabis was decriminalized in that state. 36

Several published studies assessing cannabis use in patients with Crohn’s disease have been performed in Israel, 10, 12, 13, 37 where regulations surrounding cannabis are less restrictive ( Table 1 ) .38, 39 Although medical cannabis is increasingly available in the United States, there has been no controlled prospective evaluation of cannabis in the management of IBD in the United States.

TABLE 1.

SUMMARY OF STUDIES ON MEDICINAL CANNABIS USE IN IBD

Year/Author Ref Country Study Design Cannabis Type Patients IBD Diagnosis Outcomes
2011/Naftali 10 Israel Retrospective Inhaled and oral 30 CD Subjective improvement in symptoms
2012/Lahat 12 Israel Obsesrvational/cohort Inhaled (3 inhalations as needed for pain) 13 11 CD, 2 UC Improvements in health perception, ability to work, social activities, emotional stress, abdominal pain
2013/Naftali 13 Israel RCT Inhaled 11 treatment, 10 placebo CD Improvement in CDAI (not significant)
2017/Naftali 30 Israel RCT Oral 10 treatment, 10 placebo CD Improvement in CDAI (not significant)

MMJ Effect on IBD Symptoms and Quality of Life

There have been several studies showing improvement in symptoms associated with IBD, leading to an improvement in quality of life. Cannabis use is common among IBD patients, with the majority of patients using cannabis to control IBD-related symptoms including pain, nausea, poor appetite, and sleep disturbances. In 1 study of 292 US patients, 12.3% of IBD patients reported current cannabis use. In this study, current users noted significant improvement in abdominal pain, poor appetite, nausea, and diarrhea. 14

Lahat and colleagues performed an uncontrolled observational study of IBD patients refractory to conventional therapy. 12 Cannabis was provided as 50-g prepared cigarettes and prescribed to be used as needed for pain. Thirteen patients with Crohn’s disease were included in the study, with primary outcomes assessing quality of life and clinical disease activity indices after 3 months of treatment. Patients reported significant improvement in general health perception, social functioning, ability to work, pain, and depression. In addition, patients noted improvement in disease-specific symptoms measured through the Harvey Bradshaw Index (HBI), including general well-being, abdominal pain, and loose stools. Although there was no improvement in objective disease measures such as C-reactive protein (CRP), patients were able to gain weight from below an appropriate body mass index to normal or near-normal. There are several limitations to this prospective study, including lack of standardization of cannabis type and dosing and lack of a control group.

Naftali and colleagues performed a retrospective study of 30 patients with Crohn’s disease refractory to conventional medical management who used cannabis in the management of their IBD for management of chronic pain, for persistent clinical symptoms, or for recreational use. 10 In this small retrospective study, the duration of cannabis consumption ranged from 3 months to 9 years, with varying forms of administration including cigarettes, water pipe inhalation, and oral. In this cohort, 30% of patients had no change in their clinical symptoms, measured by the HBI, yet many discontinued steroids while using cannabis. These studies suffered from multiple limitations, including selection bias, lack of standardized dosing and route of administration, absence of blinding, recall bias, and lack of a control population.

A systematic review and meta-analysis evaluating the use of cannabinoids for other chronic medical conditions, including neuropathic pain, cancer, diabetes, fibromyalgia, multiple sclerosis, musculoskeletal problems, and chemotherapy-related pain, showed moderate-quality evidence to support the use of cannabinoids for relief of chronic pain. 40 Inflammatory bowel disease was not included.

The underlying theme of the limited available evidence is that cannabis use may offer symptomatic benefit and improved quality of life when patients have poor or incomplete response to standard therapy. However, none of the available data demonstrate improvement in biochemical or disease activity scores.

Development of Commercial Compounds

There is increasing attention by the pharmaceutical industry to therapeutic manipulation of the endocannabinoid system. 41 A peripherally restricted CB1/CB2 receptor agonist, SAB378 (Novartis Pharmaceuticals, Basel, Switzerland), inhibits gastrointestinal motility in animal models but has not shown benefit in animal models of colitis. 42 Another commercially available CB1/CB2 receptor agonist and THC analog is dronabinol (Abbvie, Chicago, IL, USA), which has been approved for appetite stimulation in AIDS patients but has not been tested in IBD patients. 43 Nabiximol (GW Pharmaceuticals, Cambridge, UK), a commercially available buccal spray, also activates CB1/CB2 receptors and is currently approved outside the United States for neuropathic pain secondary to multiple sclerosis and cancer. This has not been tested in IBD patients. 44

SAFETY AND ADVERSE EVENTS

The long-term safety profile of chronic cannabis use has not been well defined, mainly due to the heterogeneity of preparations, varying routes of administration, and the lack of controlled studies addressing safety, especially in IBD patients. In a retrospective study of more than 300 patients with Crohn’s disease, cannabis use for more than 6 months was found to be an independent risk factor for surgery (adjusted odds ratio, 5.03; 95% confidence interval, 1.45–17.46). 45 Given the retrospective nature of this study and the lack of control for other risk factors for surgery, however, it is impossible to determine a causal relationship between cannabis use and surgery. In addition, there are population-based studies that have demonstrated an increased risk for motor vehicle accidents 46 and cannabis hyperemesis syndrome. 47, 48 Despite these reported safety concerns, there have been no deaths associated with cannabis use alone.

A Canadian multicenter retrospective study of 494 patients presenting to the emergency department for vomiting found that 19.4% reported recent cannabis use, suggesting that cannabinoid hyperemesis syndrome may be an overlooked diagnosis for vomiting. 49–52 The increase in potency of THC content in cannabis, from about 3% in the 1980s to 12% in 2012, 53 may potentiate adverse effects of cannabis use. For example, cannabis ingested in an edible form is more difficult to titrate, unlike vaping or inhaling, as the effect may be delayed, and therefore higher doses may be consumed, leading to intoxication. Heavy use may cause impaired memory for at least 1 week after abstinence, hyperemesis, and withdrawal symptoms. Acute psychotic symptoms during intoxication also have been reported. 54, 55

In a separate study, Al-Shammari and colleagues evaluated the effect of MMJ legalization in the United States on trends of cannabinoid dependency (CDU) and persistent vomiting. 56 They collected hospital discharge data from the Healthcare Cost and Utilization Project before and after legalization of MMJ in 2009. Before legalization, there was an upward trend in the incidence of CDU, but the rate at which the incidence has been increasing grew by 6% after legalization. The effect is more striking in the incidence of persistent vomiting, which had a fairly stable incidence before legalization but has seen its growth rate increase by 8% since legalization. The investigators acknowledge that the defined 1-year washout period (2009) and the 5-year postlegalization period are relatively short to clearly define the legalization effect on these trends. Furthermore, the findings are based on administrative diagnosis codes and may be confounded by increased transparency in patient-reported symptoms after the legalization and decriminalization of cannabis.

Special Population: Safety in the Pediatric and Adolescent Population

The frequency of use of cannabis by adolescents in the United States has remained stable, with about 40% of 12th graders having used cannabis in the past 12 months. 57 In Colorado, a state with a robust cannabis industry, rates appear similar, with 38% of high schoolers having ever tried cannabis. 58 Both nationally and in Colorado, about 20% of adolescents report using in the past 30 days, and about 4%–6% use daily or almost daily. This suggests that 20%–25% of adolescents who use cannabis use it habitually, a trend that has been increasing over the past 10 years. Preliminary data from Colorado show that adolescents with IBD use cannabis at the same rate as their similarly aged peers without IBD, but they use it more intensely (50% weekly or more frequently vs 25% non-IBD adolescents). 59, 60 Similarly, in Connecticut, 75% of 18–21-year-olds with IBD who use cannabis do so weekly or more frequently. 61

Along with the increase in use intensity, there has been a steady decline in perception of risk with regular use. Indeed, 60% of high school seniors perceive regular use of cannabis as not having great risk, and this figure has been increasing since 2004. 57, 62 However, emerging literature supports the view of significant adverse health effects with both short-term and long-term use, mainly on neurologic, cognitive, and mental health. 63 An increase in motor vehicle accidents among adolescents combining recreational use of cannabis and alcohol has been reported but has not immediately translated to an increase in fatal crashes in states that have medical cannabis laws. Addiction risk may be higher for those beginning heavy use in adolescence, and this behavior may predict progression to harder drugs. 63, 64 Because of these short- and long-term negative effects, the American Academy of Pediatrics 65 and the Academy of Child and Adolescent Psychiatry 66 oppose cannabis legalization.

The current literature on cannabis use should be interpreted with caution, as data from heavy and/or long-term users have potential confounding factors, such as other drug use, psychiatric comorbidities, and adverse psychosocial and economic conditions. 63 These retrospective and indirect studies should not be inferred as proof of causality for adverse outcomes associated with cannabis use.

Special Population: Safety in Conception and Pregnancy and Lactation

The role of the endocannabinoid system (ECS) in reproduction has been widely investigated, with evidence suggesting that cannabis use alters the female menstrual cycle and endometrial proliferation at the cellular and molecular levels. 67–69 Limited clinical data do not suggest any decrease in fertility associated with cannabis use. A web-based prospective cohort study (Pregnancy Study Online [PRESTO]) was conducted in North America whereby women between the ages of 21 and 45 years were enrolled, and their male partners were invited to participate. 70 Couples (n = 1125) completed lifestyle and behavioral questionnaires that included frequency of cannabis use. After 1-year follow-up, fecundability rates were comparable between those who used cannabis

The American College of Obstetricians and Gynecologists does not recommend or endorse the use of cannabis in pregnant patients because observational data show that cannabis use was associated with low birth weight and preterm delivery. 71 There have been no studies looking at maternal cannabis use in IBD. However, a recent meta-analysis that compiled data from 31 observational studies looking at maternal cannabis use found no difference in rates of low birth weight, preterm delivery, or perinatal death when controlling for tobacco use and other confounding variables. The authors concluded that maternal cannabis use is not an independent risk factor for adverse fetal outcomes, citing tobacco use as the main driver for poor outcomes. 72

Analysis of breast milk from mothers using cannabis detected THC up to 6 days after last use; the concentrations were directly related to the intensity and frequency of use, and the authors suggested that this may influence brain development during this period. 73

OVERVIEW OF US STATE AND FEDERAL LAWS

As of January 2018, 30 states plus the District of Columbia have legalized medical cannabis, 74 and 16 states have legalized high-cannabidiol (CBD), low-THC forms of cannabis or hemp oil. Nine states and the District of Columbia, all with medical cannabis programs, have gone a step further and legalized recreational cannabis for adults over 21 years of age ( Fig. 1 ).

Inflammatory Bowel Disease — Indications for Cannabis Use

Inflammatory bowel disease (IBD) is an inflammatory condition affecting the gastrointestinal tract. This condition comprises both ulcerative colitis (UC) and Crohn’s disease (CD). In 2015, it was estimated that 1.3% of US adults—nearly 3 million people—reported having been diagnosed with IBD.1 Management of IBD can become frustrating for patients and practitioners alike when the few known conventional therapy options offer little relief or cause adverse side effects.

Compared with the cannabis consumption rates of the American population at large, a substantially greater percentage of IBD patients report using cannabis as a complementary alternative medicine to manage their symptoms.2 These patients report perceiving cannabis use to be effective for relief of abdominal pain, poor appetite, nausea, and frequency of bowel movements. Researchers, health care practitioners, and patients alike are encouraged by the anecdotal reports of improved symptom control, but many wonder whether cannabis use helps resolve the inflammatory response within the body or simply masks the symptoms of ongoing inflammation in active IBD.

Preliminary evidence supports the theory that cannabis may be effective in treating IBD and suggests that exogenous cannabinoids such as CBD and THC may help improve many of the symptoms associated with IBD. It’s for this reason that physicians and other health care practitioners must be familiar with the evidence surrounding cannabis therapy for IBD in order to advise their patients on safe use.

The Endocannabinoid System and IBD
One of the main barriers to finding an appropriate treatment for IBD is that the pathophysiology of the disease has yet to be fully established, although it’s clear that an inappropriate inflammatory response paired with a dysregulated immune system leads to relapsing episodes of inflammation in the gastrointestinal tract. To date, therapies for IBD include anti-inflammatory drugs, immune system suppressors, antibiotics, and other medications, followed by eventual surgery if needed.3

While these therapies are available, IBD patients often express frustration over their ineffectiveness or their associated adverse side effects, prompting them to seek complementary and alternative therapies such as cannabis consumption.4 Based on years of anecdotal reports of cannabis helping to alleviate symptoms in IBD patients, researchers have begun to explore the relationship between IBD, the endocannabinoid system (ECS), and gastrointestinal physiology, homeostasis, and inflammation.

The ECS—made up of receptors and endogenous cannabinoids found throughout the body—has been shown to play a role in the pathogenesis of IBD in animal studies.1 The ECS produces its own endogenous cannabinoids, anandamide and 2-arachidonoylglycerol, and also interacts with exogenous cannabinoids such as CBD and THC. Through the CB1 and CB2 receptors of the ECS, cannabinoids are able to exert their anti-inflammatory and immunosuppressive effects. The gastrointestinal system contains both CB1 and CB2 receptors in all layers of intestinal sections. The activation of CB1 receptors has been shown to “modulate several functions in the [gastrointestinal] tract, including gastric secretion, gastric emptying, and intestinal motility.”5 Several mouse studies have demonstrated the relationship between the ECS and the regulation of gut inflammation.1

While there’s still a need for more clinical studies in humans to reveal a possible role for cannabinoids in the management of IBD, in rodent studies, the ECS appears to protect the gastrointestinal tract by modulating the inflammatory response. This suggests that the ECS may serve as a “potentially promising therapeutic target against different [gastrointestinal] disorders” such as IBD.5

Medical Cannabis and CD: Review of the Literature
CD is a chronic IBD characterized by inflammation of the digestive tract. With CD, inflammation can occur at any point in the digestive system, from the mouth to the anus, most commonly manifesting in the small intestine.

While the symptomatic relief associated with cannabis use in CD patients remains largely anecdotal, a few studies point to the promise of cannabis being used as a potential therapeutic tool in the treatment of IBD.

In an animal study published in the Journal of Clinical Investigation, it was found that “the endogenous cannabinoid system is physiologically involved in the protection against excessive inflammation in the colon, both by dampening smooth muscular irritation caused by inflammation and by controlling cellular pathways leading to inflammatory responses.”6 These results strongly suggest that drugs targeting the ECS have the potential to be promising therapeutic agents in the treatment of Crohn’s disease and point to the need for further study.

Another study published in the Inflammatory Bowel Diseases Journal found that cannabis use provides
symptom relief in patients with IBD but was associated with worsening disease prognosis in Crohn’s patients. Results gathered in this study via anonymous questionnaire showed that of the 313 IBD patients surveyed, nearly 18% were using cannabis to relieve symptoms of IBD. Ninety-seven percent of those patients reported consuming cannabis via inhalation methods. Eighty-four percent reported that cannabis improved their perception of abdominal pain, 77% reported an improvement in abdominal cramping, 49% reported an improvement in joint pain, and 29% reported an improvement in diarrhea.7 While these self-reported statistics are encouraging, it was noted that the use of cannabis for more than six months “was a strong predictor of requiring surgery,” although the Crohn’s and Colitis Foundation reports that 75% of people with CD will eventually require surgery, regardless of cannabis use.8

In the first observational study of its kind to evaluate cannabis therapeutics for CD in humans, 21 of 30 subjects studied reported their symptoms improved “significantly after treatment with cannabis” as measured by the Harvey-Bradshaw index and a reduction in the need for other medications.9

In the first prospective, observational, single-arm pilot trial with human subjects, 13 long-standing IBD patients were prescribed cannabis inhalation treatment. After three months of cannabis treatment, patients reported an improvement in their perception of their general health, social function, ability to work, physical pain, and depression. The authors concluded that three months of cannabis treatment vastly improved “quality of life measurements, disease activity index, and caused weight gain and rise in BMI in longstanding IBD patients.”10

Finally, in the first prospective, randomized, double-blind, placebo-controlled trial to evaluate cannabis use in patients with CD, complete remission was achieved by 5 of 11 subjects in the cannabis group compared with 1 of 10 in the placebo group. A clinical response was observed in 10 of 11 subjects in the cannabis group compared with 4 of 10 in the placebo group. Three patients in the cannabis group were weaned from steroid dependency and the subjects receiving cannabis reported improved appetite and sleep with no significant side effects. The authors concluded that “a short course (eight weeks) of THC-rich cannabis produced significant clinical, steroid-free benefits to 10 of 11 patients with active Crohn’s disease, compared with placebo, without side effects.”11

Inherent flaws in human studies, small sample sizes, and a relatively limited number of preliminary studies point to the need for larger, standardized, placebo-controlled, and blinded trials of the use of cannabis in the management of CD.

Medical Cannabis and UC: Review of the Literature
UC is a chronic inflammatory disease of the large intestine in which the lining of the colon becomes inflamed; tiny, painful sores or ulcers develop and cause frequent bowel movements. There’s no known cure for UC, so the aim of treatment is to manage symptoms. Given the limited therapy options, patients are turning to alternative methods such as cannabis use to find relief, despite the lack of clinical evidence to support its efficacy. While there are studies that examine the relationship between IBD and cannabis, and studies that demonstrate the beneficial effect of cannabis for intestinal inflammation, there are few studies that have specifically looked at the relationship between UC and cannabis use.

A Cochrane review conducted in 2018 assessed the efficacy and safety of cannabis for the treatment of patients with UC. It examined only randomized controlled trials specific to cannabis use in UC and found that “the effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.”11

Emerging evidence published in Medicine Journal in 2019 noted a promising correlation between cannabis use and outcomes in hospitalized ulcerative colitis patients. In this retrospective cohort study, it was found that “cannabis use may mitigate some of the well described complications of UC among hospitalized patients.” This study showed that hospitalized UC patients who self-reported cannabis use had less need for partial or total colectomy, a lower prevalence of a bowel obstruction, and an overall shorter hospital length of stay compared with cannabis nonusers.12

These findings point to the need for more studies and large clinical trials to explore the relationship between cannabis use and UC patient outcomes.

Does Cannabis Simply Mask the Inflammation?
Cannabinoids are known to play a critical role in gut pathology and appear to be a potential positive target for drug interventions aimed at the treatment of IBD. While preliminary evidence suggests that cannabis use and cannabinoid therapy many play a beneficial role in the management of IBD, the fact remains that cannabis is still classified as a Schedule I controlled substance, thus there have been no randomized controlled trials evaluating the effects of cannabis in IBD patients in the United States.

There’s a significant need to study the potential role of cannabinoids in the treatment of IBD. Most needed are human studies designed to determine whether cannabinoids have true therapeutic anti-inflammatory effects on the disease process or cannabis use is simply masking the debilitating symptoms caused by the disease. Understanding this is critically important in helping clinicians decide how to treat their patients. While cannabis use may cause a perceived improvement in symptoms, the concern is that cannabis could mask ongoing inflammation, leading patients to perceive that their disease is in remission when it isn’t. This could be harmful to patients if they stop seeing their physicians for routine care or choose to forego other treatment options.

Practical Recommendations for Clinicians
While there’s a lack of clinical evidence to recommend the use of cannabis in the management of CD or UC, the fact remains that there’s a large unmet need in the treatment of IBD with conventional medical therapy and cannabis use remains a popular alternative choice for many patients. Surveys on cannabis use in US and Canadian IBD patients published in the Journal of Gastroenterology & Hepatology in 2018 found that approximately 15% to 20% of patients use cannabis, and up to 40% have tried cannabis to relieve IBD symptoms.

In a January 2014 article published in the Inflammatory Bowel Disease Journal, of 313 respondents to a questionnaire, 47% reported trying cannabis because they thought it would help with their symptoms, 42% said they were frustrated by their disease, 38% said they wanted to try a different approach, and 27% said they tried cannabis because the medications prescribed by their doctors didn’t help.

Of these 313 respondents, only 39% reported discussing cannabis use with their doctors and 82% said their doctors were “indifferent or not supportive of the use of marijuana for IBD treatment.”7

With rapidly expanding medical and adult use cannabis programs, consumers are gaining access to cannabis products faster and more easily than ever before. This presents a significant opportunity for clinicians to step in and talk with their patients about their perceptions or current use of cannabis for the symptom management of their IBD and the benefits and the risk of using cannabis to treat IBD symptoms.

Anecdotal and some preliminary evidence suggest that cannabis use can help relieve abdominal pain, abdominal cramping, poor appetite, and nausea, and improve quality of life, increase body weight and BMI, and improve clinical disease activity as a result of the analgesic, anti-inflammatory, antimotility, and additional effects of cannabinoids.7

While long-term effects haven’t been well studied in an IBD population, the New England Journal of Medicine has identified several general long-term risks associated with cannabis use that are worth discussing with patients. These include a higher risk of motor vehicle accidents, chronic bronchitis symptoms, psychiatric disturbances, depression, and anxiety.13

Taking into account state laws and regulations, clinicians should be open to a discussion with their patients about their current or potential cannabis use for the management of IBD symptoms and should work with their patients to meet them where they are in order to maximize their treatment benefits and minimize harm.

Conclusion
Before cannabis can be recommended as an IBD treatment option, there’s a significant need for more research and clinical trials on the efficacy of cannabinoid therapeutics specifically as it relates to IBD. However, given the limited therapy options for IBD, cannabis use remains common among IBD patients for symptom relief. Physicians and other health care practitioners should be familiar with the potential benefits and the potential risks of using cannabis therapy for IBD in order to be able to advise their patients on safe use.

— Emily Kyle, MS, RDN, CDN, CLT, HCP, is a certified holistic cannabis practitioner.

References

1. Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. Prevalence of inflammatory bowel disease among adults aged ≥18 years — United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(42):1166-1169.

2. Ahmed W, Katz S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12(11):668-679.

4. Lal S, Prasad N, Ryan M, et al. Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011;23(10):891-896.

5. Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med (Berl). 2005;83(12):944-954.

6. Massa F, Marsicano G, Hermann H, et al. The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest. 2004;113(8):1202-1209.

7. Storr M, Devlin S, Kaplan GG, Panaccione R, Andrews CN. 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;20(3):472-480.

8. Crohn’s & Colitis Foundation of America. Surgery for Crohn’s disease and ulcerative colitis. https://www.crohnscolitisfoundation.org/sites/default/files/legacy/assets/pdfs/surgery_brochure_final.pdf. Accessed March 1, 2020.

9. Naftali T, Lev LB, Yablecovitch D, Half E, Konikoff FM. Treatment of Crohn’s disease with cannabis: an observational study. Isr Med Assoc J. 2011;13(8):455-458.

10. Lahat A, Lang A, Ben-Horin S. Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study. Digestion. 2012;85(1):1-8.

11. Kafil TS, Nguyen TM, MacDonald JK, Chande N. Cannabis for the treatment of ulcerative colitis. Cochrane Database Syst Rev. 2018;11(11):CD012954.

12. Kinnucan, J. Use of medical cannabis in patients with inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2018;14(10):598-601.

13. Volkow ND, Compton WM, Weiss SRB. Adverse health effects of marijuana use. N Engl J Med. 2014;371(9):879.

CBD Oil, NOW in HONEY.

The other day a mother came into the store and asked for another bottle of CBD oil for her autistic son. I asked her how that was working for him and she replied, her son has not had a tantrum since she put him on it. She said this has been a lifesaver because his psychotropic medication was not working for him. Another mom told me CBD oil is the only thing that works for her daughters seizures. Our very own Kendal Stewart, M.D. a leading Neurotologist / Neuroimmune Specialist has recommended CBD oil to many of his patients to stabilize and improve nervous and immune system functions. So what is CBD oil and what does it do?

CBD is extracted and separated from specific varieties of cannabis, often known as hemp. The most abundant constituent of cannabis is the cannabinoid known as THC, an intoxicating and illegal substance that is responsible for causing the “high” in marijuana use. There is a lot of misinformation surrounding CBD, partially because of its close resemblance to THC. It’s important to know that CBD is completely separated and isolated from THC and CBD cannot get you “high”. CBD is non- psychoactive because it does not act on the same pathways as THC. Therefore, unlike THC, CBD is considered a legal cannabinoid and is safe to consume in any amount and concentration.

… But what is CBD exactly?

Let’s start with a little history: in 1992 a report by Devane et al discovered the existence of specific receptors in mammalian cells known as the endocannabinoid system which is closely interconnected with the nervous and immune system. Since CBD has been shown to boost just about every function of our cannabinoid receptors, it is proven to have an extensive soothing and relaxing effects. But research is showing CBD is far more valuable than just for relaxation. Studies have shown CBD to:

  • Reduce nausea and vomiting
  • Suppress seizure activity
  • Combat psychosis disorders
  • Combat inflammatory disorders
  • Combat neurodegenerative disorders
  • Combat tumor and cancer cells
  • Combat anxiety and depression disorders
  • Combat cigarette addiction
  • Used in the treatment of acne
  • Prevent the production of IL-12 the cytokine that plays a huge role in many autoimmune diseases such as diabetes.
  • Reduction of pain due to inflammation from fibromyalgia.
  • Have anti-anxiety effects caused by PTSD
  • Be used in treating Schizophrenia
  • Control gut function and could be an effective treatment for bowel diseases like Crohn's Disease.
  • Have the potential ability to reduce various aspects of MS.

WOW, sounds too good to be true? … Possibly, but Mother Nature can be very benevolent and perhaps she has graced us with one of her many miracles. I know this much — CBD is well tolerated and safe even at high doses, and seems to be effective for many conditions. Many of our patients are grateful to have it available. It comes in 1mg, and 3mg peppermint, vanilla and unflavored oral spray, 10mg and 25mg capsules, as well as a topical balm.