Safety And Preliminary Clinical Outcomes Of A Combined Cannabidiol And Sodium Propionate Enema In Refractory Ulcerative Proctitis: An Open-Label Pilot Study

Introduction: Patients with ulcerative proctitis who fail 5-aminosalicylic acid (5-ASA) therapy often escalate to systemic immunosuppressants or biologics, which carry significant risks. IcBD-01 is a novel enema combining cannabidiol (CBD) and sodium propionate (Na-P), formulated to deliver local anti-inflammatory effects with minimal systemic exposure. This proof-of-concept study assessed the safety, tolerability, and preliminary efficacy of IcBD-01 in patients with mild to moderate ulcerative proctitis. Methods: Fourteen patients unresponsive to ≥3 months of mesalamine were enrolled in a prospective, open-label, single-arm 12-week trial. IcBD-01 was self-administered daily. Disease activity was assessed using the Mayo score, patient-reported outcomes (PROs), endoscopy, histology and inflammatory markers. Results: Of 14 enrolled patients, 9 completed the study and 10 completed ≥10 weeks of treatment. In the intention-to-treat analysis, 50% met the primary endpoint (≥3-point Mayo score reduction); in the per-protocol analysis, 77% achieved this. Full Mayo scores improved from 6.8 ± 1.7 to 3.0 ± 2.5 (p<0.0001), and partial scores from 4.9 ± 1.5 to 1.8 ± 2.0 (p<0.001). Significant improvements were observed in PROs, VAS pain scores, and treatment satisfaction. While histological improvement (Nancy index) was not significant, reductions in ulcerated mucosal length were noted. The treatment was well tolerated, with only mild adverse events and one non-treatment-related SAE. Conclusion: In this open-label, proof-of-concept study, IcBD-01 was well tolerated and associated with clinically meaningful improvements. These hypothesis-generating findings warrant further evaluation in randomized, placebo-controlled trials. ClinicalTrials.gov Identifier: NCT06353828