Irritable Bowel Syndrome

Medical cannabinoids show variable therapeutic effects depending on substance and indication: CBD effective for epilepsy (high evidence) and parkinsonism (moderate evidence); dronabinol and nabiximols effective for chronic pain, spasticity and other indications (moderate evidence); many other effects with low or very low evidence.

Comprehensive pharmacology-based SR of k=152 RCTs (n=12.123) on medical cannabinoids; for irritable bowel syndrome the evidence is rated as 'insufficient' — no significant therapeutic effects demonstrated.

Phytotherapeutics show varying levels of evidence for different gastroenterological diseases: strong recommendation for peppermint oil in irritable bowel syndrome, recommendations for further phytotherapeutics in constipation and ulcerative colitis, but insufficient data for Crohn's disease and a need for further methodologically high-quality studies.

Systematic review of phytotherapeutic recommendations in medical guidelines for gastroenterological diseases. For irritable bowel syndrome (IBS): 'strong recommendation' for peppermint oil (particularly for pain and flatulence); 'recommendation' for STW-5, Tibetan Padma Lax, and warm caraway oil compresses for symptom relief. Cannabis-based medicines may be considered for abdominal pain and clinically relevant loss of appetite when standard therapy is ineffective or contraindicated; should not be used for acute inflammation in active Crohn's disease. Safety and tolerability of the phytotherapeutics were predominantly rated as 'very good' to 'acceptable'.

Systematic review on cannabinoids in gastroenterology; k=1 RCT in Crohn's disease (n=21) identified, NO RCTs found for irritable bowel syndrome. For IBS only a qualitative statement: cannabis might be helpful for symptoms such as pain, nausea and loss of appetite, but sufficient studies are completely lacking.

Narrative review on the endocannabinoid system (ECS) in irritable bowel syndrome and cannabis as a potential therapy. Emphasizes the role of the ECS in GI physiology and in functional disorders such as IBS; concrete clinical efficacy data for cannabis in IBS are NOT reported. Conclusion: further research on ECS-based IBS therapies required.

Primary endpoint not met (no significant difference vs. placebo), but significant improvement in subgroup with baseline AAPS ≥6.5 under olorinab 50 mg.

Phase 2b RCT CAPTIVATE, n=273 IBS-D/IBS-C patients, olorinab (CB2 full agonist) 10/25/50 mg 3× daily vs. placebo over 12 weeks. Primary endpoint (change in average abdominal pain score up to week 12) not met. Pre-specified subgroup with moderate-severe pain (baseline score ≥6,5): olorinab 50 mg (n=35) significantly more effective than placebo (n=30), p=0,014. Tolerability comparable to placebo, no serious adverse events.

Dronabinol reduced fasting proximal and distal left colonic motility compared with placebo, especially in diarrhea-predominant or alternating IBS; colonic compliance was increased.

Pharmacogenetic RCT, n=75 IBS patients (35 IBS-C, 35 IBS-D, 5 IBS-A), dronabinol (2,5 mg/5 mg) vs. placebo. Dronabinol reduced fasting proximal colonic motility index (MI) overall p=0,05 (5 mg: p=0,046) and increased colonic compliance (p=0,058). Largest effects in IBS-D/IBS-A: proximal MI p=0,022, compliance p=0,03. CNR1 rs806378 (CC vs. CT/TT) influenced fasting proximal MI (p=0,075).

Dronabinol 2,5 or 5 mg twice daily for 2 days showed overall no effect on gastrointestinal transit in IBS-D, although a possible genotype-specific delay of colonic transit in CNR1 rs806378 CT/TT carriers was observed.

RCT, n=36 IBS-D patients, dronabinol 2,5 mg (n=10) or 5 mg (n=13) vs. placebo (n=13) for 2 days. No significant overall treatment effects on gastric, small bowel, or colonic transit demonstrable. Genotype-dependent trend: CNR1 rs806378 CT/TT associated with moderately delayed colonic transit at 24 h (p=0,13 for differential treatment effects).

No statistically significant differences in pain scores between CBD and placebo at group level; high intra- and inter-individual variability.

n=32 female IBS patients, randomised double-blind crossover RCT with CBD chewing gum (50 mg) vs. placebo; symptom-driven dosing (max. 6 gums/day). Primary outcome: abdominal pain intensity (VAS 0–10) and quality of life (IBS-36 questionnaire). Result: no statistically significant difference in pain scores between CBD and placebo at group level (p not significant); high intra- and inter-individual variability; average gum use lower than expected.

Delta-9-THC did not alter rectal perception upon distension in either healthy volunteers or IBS patients compared with placebo.

n=22 (10 IBS patients + 12 healthy volunteers), double-blind randomised crossover with Δ9-THC (dronabinol 5/10 mg) vs. placebo; barostat measurement of rectal sensitivity before and after sigmoid stimulation. Δ9-THC did NOT alter baseline rectal perception thresholds or discomfort thresholds after stimulation (no significant differences from placebo in either group). Central nervous system side effects (dizziness, drowsiness) and increased heart rate at the highest dose; no effect on visceral hypersensitivity in IBS.