CARE – A Retrospective, Dual-Cohort, 24-Week Real-World Study from the German Pain e-Registry on the Effectiveness and Safety of CBD-Dominant Oral Cannabis Extracts versus THC/Dronabinol in Older Patients with Chronic Pain

Michael A Überall,1 Philipp Christian Gerhard Müller-Schwefe,2 Michael A Küster,3 Gerhard HH Müller-Schwefe2 1IFNAP – Private Institute of Neurological Sciences; O. Meany-MDPM GmbH, Nürnberg, 90411, Germany; 2Interdisciplinary Center for Pain & Palliative Care Medicine, Göppingen, 76033, Germany; 3Interdisciplinary Center for Pain & Palliative Care Medicine, Bonn, 53177, GermanyCorrespondence: Michael A Überall, Private Institute of Neurological Sciences – IFNAP, Center of Excellence in Health Care Research, Nordostpark 51, Nürnberg, 90411, Germany, Tel +49 911 21773760, Fax +49 911 21773761, Email [email protected]: Pharmacological treatment of chronic pain in older adults presents a therapeutic challenge. The severity of symptoms contrasts with the risk–benefit ratio of available drugs, especially in the presence of comorbidities and polypharmacy. This underlines the need to evaluate alternative therapies such as cannabis-based medicines (CBM).Objective: To assess the safety, tolerability and effectiveness of cannabidiol (CBD)-dominant full-spectrum extracts (CBD > tetrahydrocannabinol [THC]) versus pure THC/dronabinol (THC/DRO) in patients aged ≥ 65 years with chronic or refractory pain.Methods: Retrospective, longitudinal, exploratory analysis of anonymized data from the German Pain e-Registry. Two propensity-score-matched cohorts of 484 patients each were evaluated over ≥ 24 weeks. The primary composite endpoint required no discontinuation due to an adverse drug reaction (ADR) AND a clinically relevant improvement (≥ 20 mm VAS or ≥ 50% from baseline) in average 24-h pain intensity (PIX), pain-related disability (mPDI), or nighttime sleep (mPDI subitem #6). Secondary analyses covered pain intensities, daily-life functioning, quality of life, well-being and affective distress. Safety analyses included ADR frequency, spectrum, and concomitant analgesic use.Results: Both treatments were associated with symptom relief. Greater improvements were observed with CBD > THC across all domains (all p < 0.001). ADRs were less frequent with CBD > THC (104 vs 342 events), with fewer patients affected (15.5% vs 35.7%) and lower discontinuation rates (5.6% vs 19.2%; all p < 0.001). The composite endpoint was achieved by 85.7% (CBD > THC) vs 21.9% (THC/DRO; p < 0.001; OR 21.5; RR 3.9; effect size 0.640; NNT 2).Conclusion: In this real-world cohort of older adults with chronic pain, CBD-dominant extracts were associated with more favorable multidimensional outcomes and better tolerability than THC/DRO. Findings are exploratory and warrant confirmation in randomized controlled trials.Trial Registration: HMA-EMA Catalogues of Real-World Data Sources and Studies. http://www. https://encepp.europa.eu/index_en, EU PAS number EUPAS1000000490.Keywords: chronic pain, elderly, cannabis, CBD, THC, dronabinol, real-world evidence study, German pain e-registry