Previous studies have demonstrated improvements in pain following short-term medical cannabis (MC) use, suggesting long-term MC treatment may alleviate symptoms associated with chronic pain. The goal of this observational and longitudinal study was to examine patients using MC to treat chronic pain pre versus post MC treatment. These interim analyses included 37 patients with chronic pain evaluated prior to initiation of MC treatment and following 3 and 6 months of MC use; pain, clinical state, sleep, quality of life, and conventional medication use were assessed. Correlation analyses examined the relationship between changes in pain and other clinical measures, assessed the impact of cannabinoid exposure on pain and clinical ratings, and assessed whether baseline cannabis expectancies influenced outcome variables. Additionally, a pilot group of treatment-as-usual patients (n = 9) who did not use MC were examined at baseline and 3 months later. Relative to baseline, following 3 and 6 months of treatment, MC patients exhibited improvements in pain which were accompanied by improved sleep, mood, anxiety, and quality of life, and stable conventional medication use. Reduced pain was associated with improvements in aspects of mood and anxiety. The results generally suggest increased THC exposure was related to pain-related improvement, while increased CBD exposure was related to improved mood. Cannabis expectancies were not related to observed improvements. Pilot analyses revealed that treatment-as-usual patients do not demonstrate the same pattern of improvement. Findings highlight the potential efficacy of MC treatment for pain and underscore the unique impact of individual cannabinoids on specific aspects of pain and comorbid symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).