Introduction Evidence suggests that cannabidiol (CBD) has anti-inflammatory properties that may provide symptomatic relief of IBD. This proof-of-concept double blind, randomised, placebo controlled trial assessed efficacy, safety and tolerability of CBD botanical drug substance (BDS) in patients with mild to moderate UC.

Method Patients with left-sided or extensive UC aged ≥18 years, with a Mayo score 4–10 (endoscopy score ≥1) and on a stable dose of 5-ASA (or previous 5-ASA use), were randomised 1:1 to CBD BDS (n = 29) or placebo (n = 31). IMP was presented as hard gelatin capsules containing 50 mg CBD BDS (purified from a proprietary Cannabis sativa L. chemotype containing CBD and ∼4% Δ⁹tetrahydrocannabinol [THC]); or excipients alone for placebo. Patients titrated to their maximal tolerated dose over 2 weeks, aiming to achieve 250 mg b.d., and then maintained this dose for 8 weeks. The primary endpoint was the number of patients in remission (Mayo total score ≤2; no sub-score >1) at week 10. Statistical tests were two-sided at the 10% significance level.

Results Patients on active IMP found it harder to tolerate than placebo patients, taking on average 1/3 fewer capsules during the maintenance period, and having a higher number of compliance-related major protocol deviations (12 vs. 4); principally insufficient exposure. 59% protocol compliance in the CBD BDS group meant the more relevant per-protocol (PP) analysis set was used to assess many efficacy measures. End of treatment remission rates were similar between treatment groups (CBD BDS, 28% vs. placebo, 26%). PP analysis of Mayo total and partial scores were significantly in favour of CBD BDS (p = 0.068 and p = 0.038, respectively). PP analysis of Physician’s Global Assessment of Illness Severity, Subject Global Impression of Change and patient-reported quality of life outcomes also significantly favoured CBD BDS (p = 0.069, p = 0.003 and p = 0.065, respectively). All 60 patients were included in the safety analysis; the majority of AEs were mild to moderate in severity and many in the CBD BDS group were likely attributed to its THC content. A higher proportion of GI-related AEs, indicative of a worsening in underlying UC, were seen in placebo patients.

Conclusion This exploratory trial did not reach its primary endpoint, but several signals suggest CBD BDS may be beneficial for symptomatic treatment of UC; larger trials are warranted.

ClinicalTrials.gov ID: NCT01562314. Funding: GW Research Ltd.

Disclosure of interest P. Irving Consultant for: Abbvie, MSD, Shire, Takeda, Tillott’s Pharma, Genentech, Vifor Pharma, Pharmacosmos, Warner Chilcott, Conflict with: Lecture Fee (s): Abbvie, MSD, Shire, Takeda, Tillott’s Pharma, Ferring, Warner Chilcott, T. Iqbal: None Declared, C. Nwokolo: None Declared, S. Subramanian Consultant for: Has been an advisory board member for Dr Falk, Abbvie, Vifor pharma, Conflict with: Lecture fee (s): MSD, Abbvie, Warner Chillcott, Dr Falk, S. Bloom: None Declared, N. Prasad: None Declared, A. Hart Conflict with: Served as consultant, advisory board member or speaker for Abbvie, Atlantic, Bristol Meyers Squibb, Celltrion, Falk, Ferring, MSD, Napp Pharmaceuticals, Pharmacosmos, Shire, Takeda., C. Murray Consultant for: Advisory Boards for MSD and Abbvie, Conflict with: Speaker fees for Abbvie and MSD, J. Lindsay Grant/ Research Support from: Takeda, Shire, MSD, Consultant for: Abbvie, Atlantic Healthcare, MSD, Ferring, Takeda, Warner Chilcott, Knap Pharma, Celtrion, Shire, Speaker Bureau of: Abbvie, MSD, Ferring, Takeda, Warner Chilcott, A. Taylor Employee of: Employed by GW Pharmaceuticals (study sponsor), R. Barron Shareholder of: Has Shares with GW Pharmaceuticals (study sponsor), Employee of: Employed by GW Pharmaceuticals (study sponsor), S. Wright Shareholder of: Has Shares with GW Pharmaceuticals (study sponsor), Employee of: Employed by GW Pharmaceuticals (study sponsor), Conflict with: Directorship (s): Research and Development Director at GW Pharmaceuticals (study sponsor).