INTRODUCTION: Adhering to treatment plans can be challenging for medical cannabis patients. According to the constrained-disorder principle (CDP), biological systems are defined by their degree of variability. CDP-based second-generation artificial intelligence (AI) systems use personalized variability signatures to improve chronic medication response. AIM: We retrospectively analyzed real-world data regarding chronic pain patients using the second generation of artificial intelligence systems to improve adherence to medical cannabis and increase its effectiveness. DESIGN AND METHODS: A retrospective analysis of real-world data of 27 patients using prescribed medical cannabis for chronic pain was conducted. Patients received treatment according to a regimen provided by the CDP-based second-generation AI Altus Care™ app that managed the product's dosage and administration times. The app offers a therapeutic regimen by varying dosages and administration times within predefined ranges. We included 16 patients who participated for more than a week. We assessed adherence to therapy and clinical response in real life based on pain scale measurements. RESULTS: The patients were followed up for 64 days (30-189). Second-generation, AI-based, personalized regimens had a high engagement rate and adherence. 50% of patients showed a high compliance rate. Chronic pain improved in patients who reported their pain score. SUMMARY: This preliminary real-world data analysis suggests that an algorithm-based approach using a second-generation AI system may enhance the adherence to and clinical effectiveness of medical cannabis. These findings require confirmation through prospective controlled studies.