Cannabinoids and chronic pain medications share many signal transduction systems, creating potential for both therapeutic and adverse effects. We  identified human-based, experimental studies that investigated the co-effects of cannabinoids and non-opioid chronic pain medications, including SSRIs, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, and alpha-2 agonists. Cannabinoids interact with several of these non-opioid analgesics which presents important considerations in clinical practice.