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Overview This is the third quarterly progress report for an ongoing living systematic review on cannabis and other plant-based treatments for chronic pain. The first progress report was published in January 2021 and the second in March 2021. The draft systematic review was available for public comment from May 19 through June 15, 2021, on the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care website. The systematic review synthesizes evidence on the benefits and harms of plant-based compounds (PBCs), such as cannabinoids and kratom, used to treat chronic pain, addressing concerns about severe adverse effects, abuse, misuse, dependence, and addiction.  The purpose of this progress report is to describe the cumulative literature identified thus far. This report will be periodically updated with new studies as they are published and identified, culminating in an annual systematic review that provides a synthesis of the accumulated evidence. Main Points In patients with chronic (mainly neuropathic) pain with short-term treatment (4 weeks to &lt;6 months): •	Studies of cannabis-related products were grouped based on their tetrahydrocannabinol (THC) to cannabidiol (CBD) ratio using the following categories: high THC to CBD, comparable THC to CBD, and low THC to CBD.  •	Comparable THC to CBD ratio oral spray is probably associated with small improvements in pain severity and may be associated with small improvements in function. There was no effect in pain interference or serious adverse events. There may be a large increased risk of dizziness and sedation, and a moderate increased risk of nausea.  •	Synthetic THC (high THC to CBD) may be associated with moderate improvement in pain severity and increased risk of sedation, and large increased risk of nausea. Synthetic THC is probably associated with a large increased risk of dizziness.  •	Extracted whole-plant high THC to CBD ratio products may be associated with large increases in risk of withdrawal due to adverse events and dizziness.  •	Evidence on whole-plant cannabis, low THC to CBD ratio products (topical CBD), other cannabinoids (cannabidivarin), and comparisons with other active interventions was insufficient to draw conclusions.  •	Other key adverse event outcomes (psychosis, cannabis use disorder, cognitive deficits) and outcomes on the impact on opioid use were not reported.  •	No evidence on other plant-based compounds, such as kratom, met criteria for this review.

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: May 2021 Update