Long-Term Pain Response to Cannabis Therapy in Chronic Low Back Pain: A Four-Year Prospective Observational Study Evaluating Patient-Reported Outcomes and BioWell Parameters

Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population. While cannabis-based therapies have shown short-term analgesic potential, long-term evidence remains scarce. This study assessed the four-year efficacy of inhaled cannabis therapy on pain and disability outcomes, while exploring BioWell gas discharge visualization (GDV) parameters as non-invasive biomarkers. Methods: In this prospective observational study (IRB 0634-25-RMC and 807-21-RMC), 241 adults with CLBP (mean age 49.3 ± 14.9 years; 62.2% male) who had failed ≥1 year of conventional therapy initiated inhaled cannabis (predominantly smoking, 91%). Cannabis contained THC (4–22%) and CBD (2–22%), with dosing titrated from 21.5 g/month (Year 1) to 56.7 g/month (Year 4). Primary outcomes—NRS, ODI, BPI severity and interference—and secondary BioWell stress and vitality were assessed annually. Analyses included repeated-measures ANOVA, mixed-effects models, ROC analysis, network analysis, K-means clustering, and survival analysis. Results: Of 241 enrolled patients, 229 (95.0%) completed Year 4 follow-up. NRS decreased from 8.08 ± 1.61 to 2.71 ± 1.46 (p < 0.001), ODI from 55.05 ± 15.90 to 36.82 ± 8.47 (p < 0.001), BPI severity from 7.94 ± 1.71 to 1.11 ± 0.53 (p < 0.001), and BPI interference from 5.84 ± 2.02 to 2.20 ± 1.69 (p < 0.001). BioWell stress discriminated moderate-to-severe pain (NRS > 4) with AUC 0.71 (95% CI 0.65–0.77). Fibromyalgia at baseline predicted discontinuation (HR 1.59, 95% CI 1.18–2.14, p = 0.003). Conclusions: Inhaled cannabis therapy was associated with sustained reductions in pain and disability over four years. BioWell stress showed modest discriminative ability as a biomarker. These findings are associative and require confirmation in controlled trials.