Cannabidiol (CBD) and the Gut: Exploring Therapeutic Potential in GI Disorders
Cannabidiol (CBD) is a non-psychoactive constituent of the Cannabis sativa plant that has garnered increasing attention for its potential therapeutic applications across a range of medical conditions, including gastrointestinal (GI) disorders.
Preclinical data strongly suggests that CBD is beneficial for improving gut function via several mechanisms. Human studies are beginning to reveal CBD’s benefit in certain GI conditions, although more studies are needed to confirm effective dosing regimens.
The Endocannabinoid System (ECS) in the Gut
The GI tract is equipped with cannabinoid receptors (CB1 and CB2) and their endogenous ligands (endocannabinoids) to maintain gut function and homeostasis. CB1 is located in the enteric nervous system and epithelial cells, while CB2 receptors are expressed in immune cells and a smaller amount in the enteric nervous system.1,2
The gut-brain axis also plays a role, and accounts for regulation of gut motility and other functions by cannabinoids.3 Cannabinoids interact with non-CB1/CB2 receptors that influence gut function, including opioid receptors, GPR55, 5-HT1a (serotonin 1A receptor), and others.1
The ECS affects GI pain modulation, intestinal barrier function, inflammation, microflora balance, gastric acid secretion, and gastric and colonic motility.2,4-7
Cannabidiol (CBD) and Gut Function
Cannabidiol (CBD) acts as a CB1 receptor antagonist and CB2 receptor agonist which beneficially impacts gut function. Preclinical cell culture models show that CBD:1
- Prevents intestinal cell apoptosis
- Decreases reactive oxygen species
- Inhibits proinflammatory cytokines
- Beneficially modulates the gut microflora
- Increases certain tight-junction proteins, decreasing intestinal permeability
These mechanisms are beneficial in treating many GI conditions.
CBD even protects the gut lining during infections. It decreases Clostridium difficile toxin A-induced intestinal cell death and decreases intestinal inflammation caused by the SARS-CoV-2 spike protein in cell studies.1
Irritable Bowel Syndrome (IBS)
Irritable bowel syndrome (IBS) is the most frequent diagnosis in gastroenterology practices, with prevalence of 10–15%.11 Cannabis use to relieve IBS symptoms is common in this population.12 Endocannabinoid deficiency is thought to underlie GI problems like IBS as well as other comorbid problems including headaches and fibromyalgia.11
IBS patients, especially IBS-D, may have genetic polymorphisms and/or epigenetic influences such as stress, affecting the endocannabinoid system (ECS). CBD has been suggested as a useful therapeutic intervention because of the ability to influence the mechanisms involved in IBS pathophysiology.7
A chewing gum containing 50 mg CBD was given to 32 female IBS patients in an 8-week double-blind, placebo-controlled, crossover study. Patients were instructed to chew gum only when they experienced pain 4/10 or greater on a visual analogue scale. There was no significant effect on pain scores or quality of life using the IBS-36 questionnaire which assesses other IBS symptoms.13 More human studies are needed using different delivery methods, doses, and more consistent dosing regimens versus symptom-driven dosing of CBD.
Inflammatory Bowel Disease (IBD)
Cannabis use among ulcerative colitis (UC) and Crohn’s disease (CD) patients is common for symptom relief.14 CBD is worthy of investigation, especially for patients who are refractory to standard IBD therapies.
Mouse models of colitis show mixed findings with CBD. Some studies show that CBD reduces swelling, reverses colonic injury, corrects abnormal cytokine levels, and reduces intestinal permeability. One study found that CBD was only effective when administered with fish oil.1
A randomized, double-blind, placebo-controlled 10-week study using CBD observed symptom reduction in 39 UC patients. Remission rates were similar between the placebo and study groups. The CBD group had improved illness severity, global impression of change, and patient-reported quality of life. Although it did not reach statistical significance, in the CBD group, there was a trend towards improvement in total and partial Mayo scores which correlate with disease severity. Also, there was a trend towards lower circulating concentrations of inflammatory cytokines and improved endoscopic scores in the CBD group.15
A randomized, placebo-controlled trial on 19 patients with CD received 10 mg CBD BID for 8 weeks. CBD was shown to be safe, but not beneficial for symptom relief or disease activity compared to placebo.16 This is a relatively low dose, possibly explaining the lack of effect.
Gastroparesis and Functional Dyspepsia
A randomized, double-blinded, placebo-controlled study of CBD in patients with nonsurgical gastroparesis showed symptom relief and improved tolerance of liquid nutrient intake. Patients were given CBD for 4 weeks starting at 2.5 mg/kg/day and increasing up to 20 mg/kg/day.17
Another 4-week study evaluated CBD in patients with functional dyspepsia (FD). This randomized, double-blinded, placebo-controlled study used CBD starting at 2.5 mg/kg/day and increasing up to 10 mg/kg/day. FD symptom relief in general was not observed, but in a subset of patients who have a genetic variation in CNR1 (gene for CB1) there may be benefits for postprandial distress (nausea, fullness, bloating, and pain).18
CBD: A Beneficial Adjunctive Therapy for Improving Gut Health
CBD is worthy of consideration as part of a comprehensive GI therapeutic protocol. Research suggests CBD increases beneficial microbes, alleviates gut inflammation, positively influences intestinal permeability, and improves symptoms of gastroparesis, IBD, and other gastrointestinal disorders.
References:
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