Osteoarthritis (OA), the most common form of arthritis, is a leading cause of disability, affecting the quality of life, pain, and physical functioning of 4.6 million Canadians. About half of OA patients have limited response to primary therapy. The number of OA patients continues to rise, affecting the quality of life of those with OA. There is a dire need to develop future effective treatment options. Cannabis is a potential therapy for those with OA and may provide analgesic, anti-inflammatory, and disease modifying effects. The common barriers to use are a lack of knowledge regarding efficacy, access, and commonly used products, doses and routes of administration. No high-quality clinical trials of cannabis for OA have been conducted, leaving physicians struggling to guide and inform patients regarding symptom relief. Findings from clinical trials of cannabis for other painful conditions have been variable, perhaps due to suboptimal cannabis products and failure to consider important patient characteristics. The goal of the current study is to characterize patient- and cannabis-level factors that are associated with OA pain and address other knowledge gaps.

Given the heterogeneity of OA, it is likely that any therapeutic (or harmful) effect of cannabis will vary based on patient characteristics and levels of cannabinoids in the cannabis product used. In this study, the investigators will measure the association between patient- and cannabis-level characteristics and patient outcomes among OA patients who use cannabis to manage their MSK symptoms and those who do not. 1) A number of patient-level factors are capable of modulating the symptoms and pathology of OA. These include microRNAs (miRNAs), metabolites, and cytokines/growth factors. Alterations in these molecules have been detected in the blood of patients with OA and thus are potential biomarker candidates of disease, prognosis or even therapeutic efficacy. Biomarkers will be measured in a cohort of patients with OA to investigate whether they predict the perceived effectiveness of cannabis and whether they differ among cannabis users and non-users. In addition, the investigators will look at the correlation between biomarker(s) levels and patients' reported outcomes among cannabis users vs non-users. 2) Chondrocytes from OA joints express a wide range of cannabinoid receptors, so there is the promise that these cells could respond to cannabinoid-based medicines. In a subset of cannabis users, tissue samples from the knee will be collected to determine if the products being consumed penetrate the tissues. 3) Due to the varied chemical constituents in cannabis products, and the lack of clear understanding of the pharmacological effects of hundreds of varieties of medical cannabis, there is a need for in-depth investigations into cannabis strains produced in Canada and those consumed by patients. Research led by our group found that industry products vary from batch to batch and labeling can be inaccurate, highlighting the need for further investigation into the relationship between cannabis' chemical constituents and its clinical effect.

A total of 1200 adults with knee osteoarthritis, 600 participants who use medical cannabis to manage their symptoms and 600 who do not use it will be included. All participants will complete a set of questionnaires that will collect information about demographics, medical condition(s), current pharmaceutical pain management, and cannabis use (if any). In addition, these questionnaires will evaluate pain severity and the impact of pain on day-to-day life, anxiety, depression, and quality of life. Participants will also be required to provide a blood sample to identify biomarkers. An additional blood sample will be collected from participants who use cannabis to measure level of cannabinoids in the blood. In a subset of 105 participants (100 cannabis users and 5 cannabis non-users) undergoing total knee replacement surgery, samples of tissue discarded during surgery will be collected.

Inclusion Criteria:

1. Age ≥25
2. Able to understand and read English
3. Diagnosed with knee OA or seeking treatment for knee related OA
4. Experienced pain in the knee on most days for at least 3 months

Exclusion Criteria:

1. Used cannabis recreationally, but not medically in the past 3 months.
2. Total joint arthroplasty (TJA) within a year of informed consent.

Adults with knee osteoarthritis (n=600 cannabis users and n=600 cannabis non-users); a subset of the cannabis users (n=100) and cannabis non-users (n=5) will be undergoing total knee replacement surgery.