What do we know about the safety and efficacy of THC in children? Here, Dr. Sulak addresses that question and more.
Cannabis is a well-known and broadly accepted treatment for chemotherapy-induced nausea and vomiting, but this is just one fraction of the many potential therapeutic benefits that cannabis can provide to patients with cancer. On the basis of my clinical experience, nearly anyone with cancer can benefit from appropriately-dosed cannabis, regardless of their age. It’s invaluable in treating cancer-related symptoms like pain, mitigating the adverse effects of conventional treatments, supporting emotional and spiritual adjustment to the challenging diagnosis, prognosis, and clinical course, and, when needed, as a tool in end-of-life care.
Among medical specialties, oncologists are some of the most comfortable in recommending cannabis for patients, largely due to the observed benefits and published clinical trial data. Oncology patients are also typically curious about or open-minded to the potential benefits of cannabis. Many clinicians and parents, however, are less likely to consider cannabis for pediatric patients with cancer, often to the child’s detriment.
The thought of a child taking cannabis may, for some, conjure images of teenage illicit cannabis smoking, which clearly has potential risks. More recently, with the approval of a cannabidiol (CBD)-based medication in the United States for two rare seizure disorders, the medical community is beginning to accept the idea that CBD can be helpful for some children, yet tetrahydrocannabinol (THC) is still frequently considered forbidden territory. It’s essential that we set aside these notions and consider the therapeutic and palliative potential of cannabis without bias. What do we know about the safety and efficacy of THC in children? Read on to learn more.
In my clinical experience, and that of several colleagues, we have found that children are less likely than adults to experience adverse psychoactive effects from THC. The late Ester Fride, PhD, who pioneered exploration of the endocannabinoid system (ECS) in early development, reported that the gradual postnatal increase of CB1 receptors and anandamide is accompanied by a gradual maturing response to the psychoactive potential of THC in postnatal mice between birth and weaning (1). This observation in rodent studies is supported by frequent mentions in the 19th-century literature that children often tolerated heroic doses of cannabis medicines that would produce incapacitation in an adult (2). Examples are also found in the modern literature: in a pediatric clinical trial with sublingual Δ8-THC for chemotherapy-induced nausea or vomiting, up to 0.64 mg/kg/dose was virtually totally effective and free of side effects (3). This is a dose that would produce pronounced impairment in most non-cannabis tolerant adults.
In my practice, the most common and often only adverse effects of THC-dominant cannabis in children are giggling, bloodshot eyes, and sleepiness; when these occur, a minor dosage reduction usually resolves them all.
What about the risks in the developing brain? First, it’s important to distinguish the adverse effects of a medically-supervised, judiciously-dosed pediatric trial from the known detrimental effects of adolescent illicit cannabis smoking. The latter has been associated with adverse neuropsychiatric outcomes in adulthood, though the association has not proven to be causal (4). A recent review and meta-analysis of longitudinal studies that evaluated frequent or dependent cannabis use in young people did indeed find a decrease in intelligence quotient (IQ) over time, but that decrease was just under 2 points (5). The authors thought this decrease was not clinically significant and “alone is unlikely to completely explain a range of psychosocial problems linked to cannabis use in this cohort.” In other words, even under the worst circumstances (heavy adolescent use, not medically-supervised), the negative impact on cognition is minimal.
In controlled pediatric trials, THC most commonly led to side effects of drowsiness and dizziness, with severity associated with higher doses; no major side effects were reported after dose reduction. The most common side effects with high-dose CBD are somnolence, diarrhea, and decreased appetite (6). In comparison with the adverse effect profiles of most treatments being considered for pediatric patients with cancer, cannabis is almost always the safest.
Most pediatric patients with cancer will not remain on cannabis indefinitely, but some may require ongoing treatment for cancers that don’t resolve or for symptoms that persist after treatment, such as chemotherapy-induced peripheral neuropathy (CIPN). Unfortunately, there is limited data that sheds light on the potential long-term adverse effects of medical-supervised pediatric cannabis use, highlighting the importance of frequently reevaluating the effects of cannabis on overall function, capacity to participate in school and other activities, sleep, nutrition, and other factors that influence growth and development.
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 chemotherapy-induced nausea who have failed to respond adequately to conventional antinausea treatments. In 2016, an orally administered liquid formulation of dronabinol (Syndros) was approved by the FDA. Two randomized, double blind trials including 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.
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, prognosis, 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 purposes, often starting around 0.05 mg THC per kg body weight per dose and gradually working up from there. Tetrahydrocannabinolic 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 benefits, 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 usually 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 experiencing symptoms 6 months or longer after treatment, sometimes 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 given 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 related to the non-ECS mediated neuroprotective effects of several phytocannabinoids. Recently, a retrospective analysis of 513 patients with cancer, about half who used cannabis, confirmed 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.
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 cancer 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 cannabis make it a good candidate for adjunctive anticancer therapy, but similar to hundreds of anticancer therapies that fail to translate from rodents to humans, we are far from knowing how to apply these preliminary findings to clinical practice. Complex interactions between cannabinoids, the ECS, and the immune system; the presence or absence of cannabinoid receptors and other targets in cancer cells; the diverse phytoconstituent profiles of cannabis preparations; and the wide range of tolerated and potentially effective doses preclude concrete clinical recommendations on how to best use cannabis to treat cancer. This complexity also challenges future clinical trial design. Nevertheless, informed by a recognition of how little we know, clinicians can effectively guide patients’ parents in the use of cannabis for both palliation and potential anticancer effects in children.
For most of my patients with cancer, our shared goal is to mitigate the symptoms of the disease and side effects of treatment, allowing them to complete a full course of conventional therapy while maintaining a high quality of life. With some titrating and fine-tuning of the cannabis regimen, most patients are able to achieve this goal. I believe that, in many cases, the dose of cannabis that supports quality of life, sleep, emotional and spiritual health, and function would be the same dose that conveys any potential anticancer effects. This, however, may not always be the case, and sometimes patients wish to modify their cannabis regimen after learning of cancer progression and lack of response to current therapies. This usually involves a more aggressive, high-dose regimen.
Among the cases claiming spontaneous remission or arrested progression related to cannabis monotherapy, most patients have used very high doses of cannabinoids, in the range 5–20 mg/kg/day. In my opinion, this approach requires a plan for surveillance to determine if the cancer is responding to the more aggressive dosing. By titrating up slowly, patients can often tolerate these high doses, and some also experience progressive improvement in symptoms and quality of life as they reach higher doses. Conversely, I see patients who received excellent symptomatic relief at low and moderate doses subsequently build tolerance and lose these benefits at the higher doses.
Without any certainty that the higher doses are effectively fighting cancer, this trade-off is not, in my opinion, worthwhile, especially when the financial expense of high-dose treatment is considered. Furthermore, I have clearly observed a few cases of an impressive response to low- and moderate-dose cannabis combined with other integrative strategies that typically include diet change and high-dose melatonin.
Children with cancer can safely use cannabis with a low risk of adverse effects and high likelihood of benefit. This medicine can drastically improve resilience to stress, emotional and spiritual well-being, and quality of life, while also improving prognosis by increasing the likelihood of completing a full course of conventional therapy and preventing some of the devastating long-term adverse effects of cancer treatment, such as neuropathy. Furthermore, cannabis may also help directly fight the cancer on its own or in combination with conventional treatments such as chemotherapy and radiation.
While these reasons sound compelling to most clinicians and parents, they are not nearly as compelling as the direct observation of children who are fortunate enough to receive the opportunity to use cannabis for this purpose. The global improvements can be profound to witness. This compassionate treatment can deeply transform the inherently traumatic experience of facing cancer for the child, and for the family. I hope that pediatric oncology care continues to grow in its embrace of cannabis as a solution, and predict that in the future a cannabis plan or referral will become standard of care.
Dustin Sulak, DO, one of the first physicians in Maine to incorporate the legal use of cannabis as a medicine in 2009, is the founder of Integr8 Health, a medical practice that follows more than 8000 patients using medical cannabis. Today he is globally recognized by his peers as a pioneer of clinical applications, formulations, and usage protocols. He is the author of the first foundational text on the clinical use of cannabis and cannabinoid therapies, titled Handbook of Cannabis for Clinicians: Principles and Practice.
Dr. Sulak is co-founder of Healer, a medical cannabis brand founded to address the challenges of helping patients and health providers get the best results with safe, reliably dosable products and education on how to best use them. Healer’s distinctive product formulations and educational material are based on his work. Healer Whole Plant Hemp CBD, CBDA and CBG products are available nationwide at www.healercbd.com/. Healer medical cannabis products are currently available in Maine and Maryland and for more information visit www.healercannabis.com/. For free education on how to use cannabis as medicine and for Healer’s online training and certification program for healthcare providers, industry professionals and consumers, visit www.Healer.com.