Abstract Background and Objective This systematic review evaluated the effectiveness, tolerability and safety of cannabis-based medicines (CbMs) for chronic non-cancer pain (CNCP) in long-term observational studies. Databases and Data Treatment CENTRAL, EMBASE and MEDLINE were searched until December 2021. We included prospective observational studies with a study duration ≥26 weeks. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. Results Six studies were included with 2686 participants, with study duration ranging between 26 and 52 weeks. Pain conditions included nociceptive, nociplastic, neuropathic and mixed pain mechanisms. The certainty of evidence for every...