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12 doctor focus cannabis patient care | vol. 3 no. 3 cannapatientcare.com light on the potential long-term adverse effects of medi- cal-supervised pediatric cannabis use, highlighting the im- portance of frequently reevaluating the effects of cannabis on overall function, capacity to participate in school and oth- er activities, sleep, nutrition, and other factors that influence growth and development. FDA-Approved THC for Children with Cancer? You may be surprised to learn that the US Food and Drug Administration (FDA) has approved the use of a synthetic preparation of THC, called dronabinol, in children with chemo- therapy-induced nausea who have failed to respond adequate- ly to conventional antinausea treatments. In 2016, an orally administered liquid formulation of dronabinol (Syndros) was approved by the FDA. Two randomized, double blind trials in- cluding pediatric oncology patients in the United States found THC to be a superior anti-nausea or vomiting agent to placebo (7,8). While these medications can be helpful, herbal cannabis preparations are usually more effective, likely because of the synergistic and additive effects among the numerous plant constituents. Dronabinol and Syndros are sometimes but not frequently prescribed by oncologists, usually as a second- or third-line anti-nausea agent, and even less frequently offered to pediatric patients than adults. How to Safely Recommend Cannabis for Pediatric Patients with Cancer? Ideally, parents of children with cancer should work with a cannabis specialist (9) like myself to improve the safety and potential efficacy of the treatment. Parents in this situation usually have so much on their plate and often have a hard time remaining objective, so it's important to have expert help. A specialist would review the current symptoms, diagnosis, prog- nosis, plans for conventional therapy, goals of the family, and other factors before recommending a therapeutic trial. If the first cannabis approach isn't fully effective, there are usually many other cannabis strategies that can be trialed. In my pediatric patients with cancer, I typically observe pain relief, appetite increase, nausea reduction, improvements in sleep, and excellent palliative effects at the end of life. Low oral doses of THC are often the most effective for these pur- poses, often starting around 0.05 mg THC per kg body weight per dose and gradually working up from there. Tetrahydrocan- nabinolic acid (THCA) and cannabidiolic acid (CBDA) can both be effective for nausea that doesn't respond to THC, and CBD can be helpful for mitigating psychoactive adverse effects of THC. My patients usually use the lowest effective dose of THC, to prevent building tolerance and losing the therapeutic bene- fits, and liberal doses of the other cannabinoids. I'm especially liberal with CBD and other non-psychoactive cannabinoids on the days of and surrounding treatment with neurotoxic chemotherapy agents (that is, platinum, taxane, and vinca alkaloid classes of chemotherapeutics). CIPN is an adverse effect experienced by 40–80% of patients with cancer 3–6 months into their chemotherapeutic treatment. It usu- ally presents as a loss of sensation, increased sensitivity to pain, or allodynia (pain that's caused by a stimulus that does not normally elicit pain). Symptoms of CIPN may not stop after discontinuing chemotherapy, with 30–40% of patients experi- encing symptoms 6 months or longer after treatment, some- times leading to debilitating chronic pain. In all patients with cancer, but especially in children, I want to do anything I can to prevent the survivors from having to live with debilitating nerve pain. Several animal studies have shown that targeting the ECS can do just that—prevent CIPN (10). This is not surprising giv- en the neuroprotective role of the ECS; treatment with herbal cannabis can enhance the activity of these ECS mechanisms to prevent CIPN, and convey additional protective benefits re- lated to the non-ECS mediated neuroprotective effects of sev- eral phytocannabinoids. Recently, a retrospective analysis of 513 patients with cancer, about half who used cannabis, con- firmed this hypothesis. The data showed that the cannabis users were half as likely to develop CIPN than the non-users (15.3% versus 27.9%), and the best outcomes occurred in those who started cannabis before the neurotoxic chemotherapy (11). Because very high doses of CBD, CBDA, and cannabigerol (CBG) are well tolerated by most, I usually increase the dose of these agents by 2-5x during neurotoxic chemotherapy. Can Cannabis be Used to Treat Cancer in Children? It is well established that the endocannabinoid system plays a fundamental role in our innate resistance against cancer. Given our knowledge of cannabinoid (CB) receptor activity, as well as several non-CB-receptor-dependent mechanisms of action, it is not a surprise that substantial preclinical in vitro and in vivo evidence shows that exogenous cannabinoids can inhibit can- cer growth, trigger apoptosis, prevent metastasis, and reduce tumor angiogenesis (12). Some studies demonstrate synergistic and protective effects with conventional chemotherapy and radiation. A large body of human anecdotal evidence suggests that many patients experience improved anticancer efficacy when they add cannabis to conventional treatment, and several cases of clear anticancer effects of cannabis monotherapy have also been reported (13). The low toxicity, palliative, and protective effects of canna- bis make it a good candidate for adjunctive anticancer therapy, but similar to hundreds of anticancer therapies that fail to trans- late from rodents to humans, we are far from knowing how to apply these preliminary findings to clinical practice. Complex in- teractions between cannabinoids, the ECS, and the immune sys- tem; the presence or absence of cannabinoid receptors and oth- er targets in cancer cells; the diverse phytoconstituent profiles