This systematic review and meta-analysis evaluates the benefits and adverse events of cannabinoids for medical use. The study included 79 randomized clinical trials (RCTs) involving 6462 participants, focusing on conditions such as nausea and vomiting due to chemotherapy, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette syndrome. The review found moderate-quality evidence supporting the use of cannabinoids for chronic pain and spasticity, low-quality evidence suggesting improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome, and very low-quality evidence for anxiety disorders. Cannabinoids were associated with an increased risk of short-term adverse events, including serious ones. The review highlights the need for further large, robust RCTs to confirm the effects of cannabinoids and to study cannabis itself due to limited evidence.This systematic review and meta-analysis evaluates the benefits and adverse events of cannabinoids for medical use. The study included 79 randomized clinical trials (RCTs) involving 6462 participants, focusing on conditions such as nausea and vomiting due to chemotherapy, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette syndrome. The review found moderate-quality evidence supporting the use of cannabinoids for chronic pain and spasticity, low-quality evidence suggesting improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome, and very low-quality evidence for anxiety disorders. Cannabinoids were associated with an increased risk of short-term adverse events, including serious ones. The review highlights the need for further large, robust RCTs to confirm the effects of cannabinoids and to study cannabis itself due to limited evidence.