Long-Term Efficacy and Safety of Inhaled Cannabis Therapy for Painful Diabetic Neuropathy: A 5-Year Longitudinal Observational Study

Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evi-dence suggests that cannabis, acting via the endocannabinoid system, may provide anal-gesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. In this prospective, observational study, 52 patients with confirmed painful DN, unre-sponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, < 1% CBD), titrated individually. Assessments oc-curred at baseline and annually for 5 years, including Brief Pain Inventory (BPI) for pain severity and interference, degree of pain relief, Leeds Assessment of Neuropathic Symp-toms and Signs (LEEDS) score, HbA1c, and medication usage. Statistical analyses used repeated measures ANOVA, Kruskal-Wallis tests, Welch's t-tests, and Pearson's correla-tions via Analyze-it for Excel. Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p< 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p< 0.001), LEEDS score (19.4 ± 3.8 to 10.2 ± 6.4, p< 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p< 0.001). An-algesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r=0.74, p< 0.001) and negatively with narcotic use (r=-0.43, p< 0.001) and pain interference (r=-0.43, p< 0.001). No serious adverse events were reported. Inhaled cannabis showed sustained pain relief, improved glycemic control, and opi-oid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings suggest cannabis may serve as an adjunctive therapy, indicating the need for randomized trials to assess efficacy and determine optimal usage.