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Background: The use of medical cannabis (MC) for palliation of symptoms is on the rise in cancer and rheumatological patients. Whether there is a potential for opioid dose reduction (ODR) and or quality of life improvements (QOL) is unclear. Methods: A retrospective cohort was evaluated to understand the pattern of care and QOL outcomes with MC use across rural multidisciplinary practices in New Mexico. MC use (> 1 mo.), EMR interrogation, urine toxicology screening were used to identify patients. QOL questionnaire included a graded pain scale. Morphine equivalent (ME) dose was used to estimate changes in opioid dose. ODR was defined as any reduction of baseline opioid dose. A chi-square was performed to evaluate associations. Results: A total of 133 patients were identified between Jan 2017- May 2017. (M/F) 65/68; median age of 53 (range 20 - 84). Nineteen percent (25/133) had a cancer diagnosis. Pain score improved in 80 % of patients with cancer and in 75% (64/89) of non-cancer patients (x2 0.24 p = 0.62). ODR was achieved in 41% (54/133) of all patients on MC. Of these, 63% (34/54) had a 25% ODR and 37% (20/54) had 26% or more ODR (x2 12.8 p = 0.002). In cancer patients, a 25% ODR was achieved in 73% (x2 0.51 p = 0.771). All patients (15/15) using MC and high dose opioid (morphine equivalent ≥ 50 mg/day) had some ODR. Co-adjuvant NSAIDs with MC improved pain score in 67% of all cases vs 33% among non-NSAID cohort (x2 10.7 p = 0.001). ODR was achieved in 32% of patients with active depression vs 68% of patients without (x2 0.044 p = 0.83). Conclusions: In this rural cohort, MC use led to ODR in 41% of all patients. Depression was a negative predictor of ODR. NSAID use facilitated ODR. It will be important to assess MC toxicity before considering this intervention. This study did not include toxicity data due to the retrospective nature of this study and its inherent limitations. Prospective data are needed to confirm these findings.