Introduction

Crohn’s disease and ulcerative colitis comprise the two chronic inflammatory bowel conditions that fall under the collective umbrella of inflammatory bowel disease (IBD). Crohn’s disease is characterised by so-called “skip lesions”, in which there are patches of inflammation interspaced by unaffected gut mucosa and inflammatory lesions which can affect the whole of the gut thickness (transmural lesions). Crohn’s disease can affect any part of the alimentary canal (from the mouth to the anus). Typically, the symptoms of Crohn’s disease are diarrhoea, nausea and vomiting, abdominal pain, and weight loss. Crohn’s disease exists in 3 physical forms: inflammatory (with patchy gut inflammation alone), structuring (in which fibrosis and narrowing of the gut lumen occur), and penetrating (in which the gut wall is breached, causing the formation of a fistula). These different forms may exist alone or in combination, depending on the severity of the disease. Usually, the disease manifests with acute flare-ups of inflammation, interspaced with periods of remission. Estimates of the incidence of Crohn’s disease vary from 3 to 20 cases per 100,000.¹

Overview of symptoms and treatment

Loss of appetite and weight loss are frequently found in Crohn’s disease. This may occur as a direct result of gut inflammation (causing pain and suppressing appetite), malabsorption of nutrients from food, side effects from the medications used to treat Crohn’s disease, or be as a result of sufferers reducing their oral intake because of symptoms such as diarrhoea or fear of inducing abdominal pain.

The mainstay of treatment for Crohn’s disease is with drugs that modify the body’s inflammatory response, such as thiopurines, methotrexate, natalizumab, corticosteroids, and anti-TNF drugs. In recent years, newer drugs have been developed, including antibodies to interleukin-12 and interleukin-23. However, although these drugs may be useful in controlling some of the inflammation in Crohn’s disease, none represent a definitive cure, and they are associated with significant adverse effects. Ultimately, the vast majority of patients with Crohn’s disease will undergo at least one surgical procedure to resect the diseased bowel. Unsurprisingly, therefore, there is interest in any potential treatments that may improve the course and symptoms of Crohn’s disease. The use of the cannabis sativa plant to alleviate symptoms in many refractory diseases, such as multiple sclerosis and chronic pain, has prompted interest in its possible applications in other conditions, including Crohn’s disease.¹

Surveys of cannabis use in patients suffering from inflammatory bowel disease report usage of between 10-12% in Europe and the US, although one recent study in Australia reported 25.3% of respondents reported regular cannabis use, claiming improvements in symptoms of discomfort, diarrhoea and appetite loss.² There is currently a relatively small body of clinical research into the application of medical cannabis to inflammatory bowel disease, including Crohn’s disease.  

Cannabis and its mechanisms of action

Cannabis contains almost 500 active compounds, of which the most widely studied are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Within the body, there is a system of cannabis receptors and endogenous (made by the body itself) compounds that activate these receptors, known collectively as the endocannabinoid system. THC and CBD interact with this system. Two types of cannabinoid receptors have been identified: 

• CB1 - present in the central nervous system 
• CB2 - present in peripheral nerve cells and immune and gastrointestinal cells. 

In addition, the endocannabinoid system interacts with other receptors such as peroxisome proliferator-activated receptors (PPAR) and the orphan GPR55 receptor, amongst others. THC binds to the CB1 receptor in the central nervous system, which leads to the release of so-called “feel-good chemicals” - dopamine and serotonin, and a decrease in GABA, the brain’s inhibitory neurotransmitter. The effect of the endocannabinoid system with respect to the symptoms of Crohn’s disease is to modify pain perception, modify gut motility, stimulate appetite, reduce nausea and vomiting, and modify immune response.³ Historically, cannabis has been thought to stimulate appetite in studies dating back to the 1970s, and anecdotally recreational cannabis users frequently describe appetite stimulation (“the munchies”).⁴

Crohn's disease and nutritional challenges

The nutritional challenges of Crohn’s disease are complex and are not simply related to a lack of food intake. Nevertheless, it is estimated that rates of malnutrition in Crohn’s disease vary in the range 20-85%. This may be due to the following factors:

• Anorexia - reduced appetite for food
• Hypercatabolism - increased metabolic activity due to the metabolic demands of active disease
• Malabsorption - particularly when the disease affects the terminal ileum, where many important nutrients are absorbed
• Drug side effects - drugs used in the treatment of Crohn’s disease may result in nausea or affect appetite
• Protein-losing enteropathy - a condition associated with Crohn’s disease in which protein leaks into the gut
• Patients associate food intake with unpleasant symptoms eg, diarrhoea, and therefore avoid eating⁵

Nutritional deficiencies are common in Crohn’s disease, particularly:

• Iron deficiency anaemia, affecting 36-88% of patients
• B12 deficiency occurs in up to 20% of patients
• Folate deficiency affects up to 28% of patients

Deficiencies of vitamins A, D, E and K (fat soluble vitamins) are generally the result of malabsorption, rather than inadequate oral intake, but may require supplementation. For most patients with Crohn’s disease, oral supplementation of nutrients is sufficient, however, some patients may require enteral tube feeding, in which feeds are given via a nasogastric tube, or in long-term cases, a tube inserted through the abdominal wall directly into the stomach (gastrostomy feeding tube).⁵

Medical cannabis as a treatment for appetite and weight gain

Medical cannabis has been advocated as a treatment for appetite and weight gain for a number of other conditions, namely HIV/AIDS, weight and appetite loss associated with cancer, and anorexia nervosa. However, the evidence from scientific studies of medical cannabis in these conditions does not strongly support its effectiveness. 

A systematic review (a type of study comparing the results of several different studies) conducted by Whiting et al in 2015 appeared to show minimal improvement in weight gain in patients with HIV/AIDS related weight loss, but these findings have not been reproduced in other studies.⁶ Additionally, there have been studies that may suggest that the effect is dependent on the dose of cannabis given (both oral cannabis extract and inhaled cannabis have been studied), raising the possibility that patients were under-dosed in some of these trials.⁷ In a document reviewing the evidence for medical cannabis in a variety of conditions, “The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research”, the authors concluded that there was only limited evidence for the effectiveness of medical cannabis in HIV/AIDS and did not find sufficient evidence to support the use of medical cannabis in either cancer-associated weight loss or anorexia nervosa.⁸

Whilst anecdotally cannabis is used by many Crohn’s sufferers, high-quality clinical evidence is sparse. The first randomised, controlled clinical trial of cannabis in Crohn’s disease was undertaken in 2013, with subsequent trials in 2017.^9,10 In 2020, two Cochrane reviews (a type of systematic review conducted to rigorous academic standards) were performed on the available evidence for the use of cannabis in Crohn’s disease and ulcerative colitis. Whilst the trials studied in the Cochrane review were primarily interested in whether cannabis could bring about a clinical remission of Crohn’s disease, other outcomes, such as quality of life, which included pain and appetite, were also measured. Whilst these trials did report an improvement in symptoms and in quality of life scores in the cannabis group, the overall finding of the Cochrane review was that the evidence was uncertain, finding the quality of the evidence produced in the trials to be “low to very low” based on their scoring system for clinical evidence. They pointed to a number of problems with these studies, including but not limited to: low study numbers, short duration of treatment, high risk of bias, poor data on adverse events, and difficulty maintaining “blinding” due to the psychoactive effects in the cannabis group.¹¹ Nevertheless, there is certainly scope for further, better-quality research in the future.

With regards to the specific effect cannabis has on appetite and weight gain, there are even fewer studies. A 2022 meta-analysis of the effects of cannabis on appetite and weight gain, which included 11 clinical trials, mainly in patients receiving medical cannabis for other conditions, actually found that the overall effect was to reduce appetite and body weight, although the authors point out that many of the participants were also taking other medications known to have this effect.¹² However, a 2023 study in Israel looked specifically at the effects of cannabis on appetite and weight gain in people with Crohn’s disease and ulcerative colitis. Whilst it found that cannabis improved appetite in some patients, this was not associated with any significant weight gain or increased intake of food. Given the complexity of the nutritional challenges in Crohn’s disease, the authors could only recommend that cannabis might be a useful adjunct to a full nutritional assessment and that it perhaps prevents further weight loss in patients with reduced appetite.¹³ Nevertheless, in an Australian survey of Crohn’s and ulcerative colitis, 60% of sufferers who used recreational cannabis regularly said they felt it improved their appetite.²

Risks and side effects

Of course, like any other treatment, cannabis is not without risk of side effects, which must be balanced against any potential benefits. In the doses used in the 2013 trial mentioned earlier, 82% of the cannabis-treated group experienced side effects, compared with 20% of the control group. In studies of cannabis in Crohn’s disease, side effects were less prevalent in patients treated with oral cannabis oil compared to those with inhaled smoked cannabis.⁹ Typical side effects included:

• Nausea
• Confusion
• Dizziness
• Concentration difficulties
• Memory loss
• Sedation

The longer-term use of cannabis is associated with deficiencies in cognitive function, particularly affecting attention, memory, concentration, and decision making, some of which may persist for a period after the drug has been withdrawn. In addition, some users are at risk of developing dependence on cannabis after long-term use. Therefore, there is a need for careful dosing and supervision of patients treated with medical cannabis.¹⁴

Summary

Crohn’s disease is an inflammatory bowel disease characterised by episodic flare-ups of diarrhoea, nausea, abdominal pain, and weight loss. Whilst the symptoms may be controlled by various medications that modify the immune system, ultimately most patients require at least one surgical procedure to resect diseased bowel. Poor appetite, weight loss and malnutrition are common features of Crohn’s disease. The issues surrounding nutrition in Crohn’s disease are complex and not simply related to reduced intake of food, but also to the disease process and medication side effects. Medical cannabis has been used in other conditions characterised by loss of appetite and weight loss, sparking interest in its potential for use in Crohn’s disease. Additionally, cannabis has been studied in the management of other symptoms of Crohn’s disease and its use as a treatment to induce remission. Whilst there have been reports from some studies that medical cannabis improved some of the symptoms of Crohn’s disease, the consensus from expert medical bodies is that there is currently no high-quality evidence for its effectiveness, and studies that have shown improvements in appetite have not demonstrated associated weight gain. Nevertheless, there is scope for further research, and surveys of Crohn’s disease sufferers report that many patients find the use of recreational cannabis helpful in controlling their symptoms, including poor appetite and improving overall quality of life.