Use of Cannabinoids in Cancer Patients: A Society of Gynecologic Oncology (SGO) Clinical Practice Statement

A comprehensive report published by the National Academies of Science, Engineering and Medicine in 2017 concluded that there exists conclusive or substantial evidence that cannabis or cannabinoids are effective in treatment of chronic pain in adults and as an antiemetic agent in patients undergoing chemotherapy. Despite this recommendation, barriers remain to determining the significant short- and long-term health effects of cannabis. This report aims to synthesize the pharmacology and clinical applications of cannabis-based therapy in the management of gynecologic cancers. Clinical practice recommendations were developed by the Society of Gynecologic Oncology Clinical Practice Committee and Palliative Care Task Force, and levels of evidence were assigned for referenced studies. The endocannabinoid system is linked to pain modulation,memory, appetite, and the immune systemand carries out effects by binding cannabinoids and their metabolites to G protein-coupled receptors in the brain and periphery. Cannabinoid absorption occurs through many routes of administration and is metabolized through the cytochrome P450 hepatic pathway. Level II evidence exists showing cannabinoid efficacy in treating chemotherapy-induced nausea and vomiting compared to placebo or other antiemetics. American Society of Clinical Oncology guidelines and the Cochrane Database review recommend US Food and Drug Administration-approved cannabinoids including dronabinol only for treatment of chemotherapy-induced nausea and vomiting that is unresponsive to other agents. Level II evidence also exists for the treatment of taxane-induced neuropathy. Administration of tetrahydrocannabinol (THC) and cannabidiol (CBD) appears to alleviate neuropathic pain in rodents, and in clinical trials, inhaled THC has been shown to have a greater analgesic effect than placebo. Monotherapy trials involving CBD show less efficacy, and a recent meta-analysis suggests only a modest effect of a combination regimen of CBD and THC on chronic pain. Randomized trials have shown that when used in combination with opioids, cannabinoids may cause improvement in pain scores. Further investigation into cannabinoids as an agent to reduce opioid use is warranted. Level III evidence exists for special considerations, including anti-inflammatory effects, interference with immunosuppressive medications, antitumor properties, and use in a high-risk population. Immunomodulatory effects of cannabinoids (mainly CBD) through the CB2 receptor have shown antagonistic effects on tissues with CB2 receptors, blocking shuttling of immune cells and suppressing inflammation. Studies have demonstrated CBD immunosuppression to noxious stimuli including reduction of proinflammatory cytokines and activation of immune processes through stimulation of natural killer-T-cell production and interleukin 12. Because of complex interplay with immune processes, more research is needed on cannabinoid use in immunotherapy. The use of cannabinoids in adolescent patients carries a risk of mental illness including anxiety, depression, and schizophrenia and use of cannabinoids, especially THC, should be carefully considered in patients with mental health disorders. Cannabinoids may also be linked to an increased risk of female infertility and increased risk of cardiovascular events and falls in elderly patients. Health care providers should seek additional training on medical cannabinoid use because of the breadth of commercial products and potential interplay with cancer treatments. Discussions with patients should center on indications, risks, alternatives, and benefits in the context of legal and local resources.