Crohn Disease

Strong evidence for pain, nausea and MS spasticity, weak to absent evidence for most other therapeutic indications.

Update of the National Academies of Sciences report on therapeutic effects of cannabis (Abrams 2018); consolidates evidence for chronic pain, MS spasticity, chemotherapy-induced nausea; for Crohn's disease, limited evidence for symptomatic relief in the absence of an anti-inflammatory effect is summarized.

Systematic review of treatment recommendations for pediatric Crohn's disease; no primary effect measurement, but rather consensus-building on medical treatment options.

Canadian Association of Gastroenterology Clinical Practice Guideline for pediatric Crohn's disease; 25 statements according to GRADE methodology. Recommends against cannabis in any role in pediatric Crohn's disease. Systematic evidence assessment through an iterative consensus process.

Best evidence for herbal therapy (Plantago ovata and curcumin in UC maintenance therapy, wormwood in CD), mind-body therapy and acupuncture, but overall low number of studies and heterogeneous methodological quality.

Systematic review on complementary and alternative medicine in IBD (Crohn's disease and ulcerative colitis); k=39 studies (26 RCTs + 3 CTs on phytotherapeutics, 7 RCTs on mind/body interventions, 2 RCTs on acupuncture, 1 RCT on Trichuris suis). Evaluated cannabis, among others, as a phytotherapeutic. Best evidence for Plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy in UC, acupuncture in UC and CD. Heterogeneous methodological quality (Cochrane Risk of Bias).

Cannabinoids significantly reduced colitis severity (DAI) and myeloperoxidase activity (MPO) in animal models compared to control.

Systematic review and meta-analysis on cannabinoids in intestinal inflammation; k=53 publications (51 preclinical animal models, 2 clinical studies). Preclinical: cannabinoids reduced Disease Activity Index (DAI) vs. vehicle (SMD -1.36; 95% CI -1.62 to -1.09; I²=61%); largest effect for FAAH inhibitor URB597 (SMD -4.43; 95% CI -6.32 to -2.55). MPO reduction SMD -1.26 (95% CI -1.54 to -0.97; I²=48.1%). Cannabigerol showed the largest MPO effect (SMD -6.20; 95% CI -9.90 to -2.50). No significant difference between prophylactic and therapeutic use.

Cannabinoids showed improvements in disease activity in Crohn's disease and quality of life in both IBD forms, but no significant effects on UC activity, endoscopic findings or inflammatory markers.

Meta-analysis across k=8 RCTs on cannabinoids in IBD (4 Crohn's disease, 3 ulcerative colitis, 1 both). Crohn's disease: significant reduction in clinical disease activity, RR=-0.91, 95% CI (-1.54, -0.28), I²=71.9%. QoL improvement in Crohn's disease and UC combined, RR=1.79, 95% CI (0.92–2.66), I²=82.8%. No significant differences in endoscopic activity or inflammatory markers. Database search: PubMed, Embase, CENTRAL, CINAHL.

Cannabinoids showed a statistically significant advantage over placebo in CDAI scores, but were not superior in quality of life, full remission, or inflammatory markers.

Systematic review + meta-analysis on cannabinoids in mild-to-moderate Crohn's disease; k=4 RCTs included. Cannabinoids vs. placebo: significant CDAI reduction (SMD -0.92; 95% CI -1.80, -0.03; p<0.05). No significant differences in QoL, full remission, or CRP reduction after 8 weeks. Heterogeneity 'low' to 'substantial'; risk of bias 'low' to 'some concern'.

Cannabinoids did not induce clinical remission in IBD, but significantly improved symptoms and quality of life.

SR+MA on cannabinoids in IBD (k=20 studies: 5 RCTs + 15 non-randomised); n=146 randomised participants; clinical remission not achieved (RR=1,56; 95%-CI 0,99–2,46); however significant improvement in patient-reported symptoms (abdominal pain, well-being, nausea, diarrhoea, appetite) and quality of life.

The effects of cannabis and cannabinoids on Crohn's disease are uncertain; the evidence is very low to low and no robust conclusions can be drawn.

Cochrane review (k=3 RCTs, n=93) on cannabis/cannabis oil in active Crohn's disease. THC cigarettes: clinical response 91% vs. 40% (RR 2,27; 95% CI 1,04–4,97); remission rate 45% vs. 10% (RR 4,55; 95% CI 0,63–32,56; very low evidence quality). CBD oil (15%+4% THC): CDAI score after 8 weeks 118,6 vs. 212,6 (MD −94,00; 95% CI −148,86 to −39,14; low evidence quality); quality of life (SF-36) 96,3 vs. 79,9 (MD 16,40; 95% CI 5,72–27,08). Conclusion: effects uncertain, no robust conclusions possible; larger RCTs required.

Cannabis showed higher clinical remission rates after 8 weeks, but worse quality of life compared to placebo; reduction in CRP not significant.

Meta-analysis of RCTs (PRISMA 2020, PROSPERO-registered): Cannabis showed significantly higher clinical remission rates in Crohn's disease patients after 8 weeks versus control (MD = −67,98; 95% CI: −100,68 to −35,29; low heterogeneity). No significant difference in CRP (MD = −0,51; 95% CI: −1,05 to 0,02). Quality of life was significantly better in the placebo group (MD = 19,62; 95% CI: 14,24–25,00). Conclusion: Cannabis shows therapeutic potential in CD, larger standardized studies required.

Cannabis showed no significant benefit over placebo/standard therapy in clinical remission or response in Crohn's disease or ulcerative colitis.

Meta-analysis of cannabis in Crohn's disease; k=2 RCTs (n=40: 21 cannabis, 19 placebo); no difference in remission failure (RR 0.72, 95%CI 0.47-1.12) or response (RR 0.15, 95%CI 0.02-1.05); GRADE evidence low to very low.

CBD-rich cannabis led to significant clinical improvement (CDAI reduction) and improved quality of life, but no significant improvements in endoscopic scores or inflammation markers.

Naftali et al. 2021 — double-blind RCT, n=56 Crohn's disease patients (30 cannabis, 26 placebo); CBD-rich cannabis oil (160/40 mg/ml CBD/THC) vs. placebo over 8 weeks. CDAI reduction significant in cannabis group (median 282→166) vs. placebo (264→237), p<0.05. Quality-of-life score improved (74→91 cannabis vs. 74→75 placebo, p=0.004). NO significant change in endoscopic score (SES-CD) or inflammation markers (CRP, calprotectin, p=0.75). Clinical remission without endoscopic or inflammatory improvement; well tolerated.

Clinical response rate 90% vs. 40% (p=0,028), but primary endpoint remission not significantly achieved (45% vs. 10%, p=0,43).

n=21 active Crohn's disease, cannabis (cigarettes with THC) vs. placebo over 8 weeks; clinical response (CDAI reduction ≥100) in 45% (cannabis) vs. 10% (placebo, p=0.028), no endoscopic remission, symptomatic improvement without anti-inflammatory effect.

CBD showed no significant benefit: CDAI decreased in the CBD group from 337±108 to 220±122 and in the placebo group from 308±96 to 216±121 (p=NS); both groups improved similarly.

n=19 active Crohn's disease, CBD 10 mg 2x daily vs. placebo over 8 weeks; no significant difference in the Crohn's Disease Activity Index (CDAI: -18 vs. -30 points, p=0.6), CBD well tolerated but ineffective at this dose.

After 3 months of cannabis treatment, significant improvements were seen in quality of life (general health perception, social functioning, work ability, bodily pain, depression), weight gain (4,3 kg) and reduction in disease activity (Harvey-Bradshaw index from 11,36 to 5,72).

Prospective pilot study on inhaled cannabis in long-standing IBD patients, n=13. After 3 months: improvement in general health perception (p=0.001), social functioning (p=0.0002), work ability (p=0.0005), bodily pain (p=0.004) and depression (p=0.007). Health scale score increased from 4.1±1.43 to 7±1.42 (p=0.0002). Weight gain 4.3±2 kg (range 2-8; p=0.0002), BMI increase 1.4±0.61 (p=0.002). Harvey-Bradshaw index reduced from 11.36±3.17 to 5.72±2.68 (p=0.001).

Cannabis improves subjective IBD symptoms, but is associated with a higher risk of surgery in Crohn's disease.

Questionnaire survey of n=313 IBD patients (University of Calgary 2008–2009); 17.6% used cannabis specifically for symptom relief. Subjectively reported improvements: abdominal pain (83.9%), cramping (76.8%), joint pain (48.2%), diarrhea (28.6%). NOTE: Cannabis use >6 months was a strong predictor of surgery in Crohn's disease (OR=5.03, 95% CI 1.45–17.46) after adjustment for demographic factors. Not a predictor of hospitalization.

Cannabis showed improvements in UC and CD scores and quality of life in studies, but the authors warn of deficiencies in standardisation and call for randomised controlled trials before therapeutic recommendations can be given.

Narrative review on cannabis/cannabinoids in chronic inflammatory bowel diseases (IBD); discusses the endocannabinoid system, preclinical anti-inflammatory mechanisms and clinical pilot studies in Crohn's disease/ulcerative colitis.