Predicting Therapy Dropout in Chronic Pain Management: A Machine Learning Approach to Cannabis Treatment

Annalisa Santucci ^1* Anna Visibelli ¹ Rebecca Finetti ¹ Bianca Roncaglia ¹ Paolo Poli ² Ottavia Spiga ¹

• ¹ University of Siena, Siena, Italy
• ² PoliPainClinic, Pisa, Italy

Introduction: Chronic pain affects approximately 30% of the global population, posing a significant public health challenge. Despite their widespread use, traditional pharmacological treatments, such as opioids and NSAIDs, often fail to deliver adequate, long-term relief while exposing patients to risks of addiction and adverse side effects. Given these limitations, medical cannabis has emerged as a promising therapeutic alternative with both analgesic and anti-inflammatory properties. However, its clinical efficacy is hindered by high interindividual variability in treatment response and elevated dropout rates. Methods: A comprehensive dataset integrating genetic, clinical, and pharmacological information was compiled from 542 Caucasian patients undergoing cannabis-based treatment for chronic pain. A Machine Learning (ML) model was developed and validated to predict therapy dropout. To identify the most influential factors driving dropout, SHapley Additive exPlanations (SHAP) analysis was performed.The Random Forest classifier demonstrated robust performance, achieving a mean accuracy of 80% and a maximum of 86%, with an AUC of 0.86. SHAP analysis revealed that high final VAS scores and elevated THC dosages were the most significant predictors of dropout, both strongly correlated with an increased likelihood of discontinuation. In contrast, baseline therapeutic benefits, CBD dosages, and the CC genotype of the rs1049353 polymorphism in the CNR1 gene were associated with improved adherence. Discussion: Our findings highlight the potential of ML and pharmacogenetics to personalize cannabisbased therapies, improving adherence and enabling more precise management of chronic pain. This research paves the way for the development of tailored therapeutic strategies that maximize the benefits of medical cannabis while minimizing its side effects.