Overview of the Research on Cannabis for Pediatric Oncology

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Cannabis Patient Care October 2022 Digital Edition

Cancer is one of the leading causes of death in children. While leukemia is the most common form of pediatric cancer, tumors of the central nervous system (CNS) are the leading causes of death in children with cancer (1).

Cancer in children is rare (1). Unfortunately, its incidence has increased during the past 40 years, from about 13 cases per 100,000 children in 1975, to about 20 cases per 100,000 children in 2016 (2). Fortunately, however, the survival rate has dramatically improved, from about 10% during the 1970s to now upwards of 90% (2).

Pediatric oncology is different from adult oncology. The most notable difference is the frequencies in which different types of cancer occur in adults versus children. Specifically, forms of cancer more common in adults include cancers of the lung, colon, pancreas, and breast. In contrast, cancer in children is overwhelmingly in the form of either leukemia or CNS tumors (1).

Another important difference between adult and pediatric cancers is their respective causes. Much adult cancer is associated with “cumulative environmental exposures.” In contrast, children haven’t accumulated such exposures, so their cancers tend to result more from genetic mutations or other forms of abnormal development. As a result, tumors from adults and children with similar tissue formations often have very different origins, and thus must be treated differently (1). Finally, children respond differently than adults to cancer treatments, such as chemotherapy (1).

In short, children tend to suffer from different forms of cancer than adults do, the causes of pediatric cancers are different from the causes of adult forms of cancer, and children respond differently to treatments. It follows that research and treatments that apply to adult cancers don’t necessarily apply to pediatric cancers; rather, pediatric cancer must be studied separately. Unfortunately, the small numbers of patients, combined with the ethics associated with conducting research on children, makes it exceedingly difficult to study pediatric oncology.

Studies of Cannabis for Pediatric Oncology

Given the rarity of pediatric oncology, together with the ethics surrounding its study, it’s no surprise that there are few studies in cannabis as a treatment for pediatric oncology, and those that do exist suffer from reliability or validity problems due to their small associated sample sizes. That said, let’s consider what preclinical and clinical studies have discovered about cannabis as a treatment for pediatric oncology patients.

Preclinical research on cannabis for pediatric oncology has established, first, that tumors with more cannabinoid receptors (CB1) at the time of diagnosis tended to shrink either on their own or in response to cannabis treatments. This suggests the endocannabinoid system is involved, and thus, that cannabis may act on tumors. Second, cannabinoids induce death in leukemia cells both 

, and cannabis enhances the efficacy of leukemia chemotherapies. Third, tetrahydrocannabinol (THC) from both natural and synthetic sources has been shown to inhibit tumor growth. And last, THC and cannabidiol (CBD) have been shown to reduce cell viability, both 

Clinical research on cannabis for pediatric oncology has established, first, that cannabis may be more effective than either placebo or conventional therapies in treating nausea and vomiting (1,3). Second, the experience of a pediatric oncology center in Israel using cannabis to treat patients found the majority (80%) of patients treated with cannabis reported “a high level of general satisfaction with the use of cannabis,” specifically, “improved quality of sleep, appetite, and feeling better overall” with only “mild and short-term” side effects (4). Third, studies of dronabinol and nabilone, both synthetic forms of THC approved by the US Food and Drug Administration (FDA) for cancer-induced nausea and vomiting (CINV), have shown cannabis to be an effective treatment for CINV in children (5,6).

Surveys on Cannabis for Pediatric Oncology

Several surveys have been conducted of doctors and of parents with children who have cancer to gauge their attitudes toward medical cannabis, that is, to assess the extent to which doctors and parents would use or actually do use cannabis to treat cases of pediatric cancer.

A small survey (64 respondents) of parents and caretakers of children with cancer on their attitudes toward medical cannabis reported the following (7). The most common form of cancer in patients using cannabis was leukemia. Roughly 20% of respondents reported using cannabis, many of whom reported using it for both treating the cancer itself, as well as managing symptoms of both the cancer and its treatments. All parents and caretakers using cannabis reported improved symptoms, particularly pain. The majority (almost 2/3) obtained their cannabis from friends or dispensaries, rather than from a prescription or agency.

Several surveys of healthcare providers have been conducted on their attitudes toward medical cannabis for pediatric cancer, with the following findings. First, pediatricians are seeing growing demand for medical cannabis for kids (not limited to cancer) (8,9). Second, regarding the use of cannabis to treat cases of children with cancer, healthcare providers are concerned about: the potential for cognitive impairment, the lack of guidance or formulation or dosing, the potential for illicit or toxic use, and the Schedule I status with all its associated baggage. That said, providers are willing to consider cannabis for cases of pediatric oncology (3,8,10). One survey found more favorable attitudes from doctors who were “not eligible to certify” (N-ETC) (that is, prescribe) cannabis for their patients relative to attitudes from doctors who were eligible (ETC). Researchers interpreted the results to mean that N-ETC doctors had attitudes more similar to those of the general public, whereas ETC doctors who risked their license and reputation by recommending medical cannabis were less amenable to its use for their patients (10). Finally, doctors “overwhelmingly identified a role for cannabis in helping treat the symptoms associated with pediatric oncology, but almost none viewed cannabis as an anti-cancer agent” (8).

While the American Academy of Pediatrics generally opposes pediatric cannabis, it does support medical cannabis for use in “children with life-limiting or seriously debilitating conditions,” which arguably includes pediatric cancer and CINV (11).

The biggest risk in using cannabis as a therapeutic to treat cases of pediatric oncology is the potential for cannabis to induce cognitive impairment in children whose brains are still undergoing development. All the studies referenced in this article were quick to cite this concern.

This issue begs some further context. First, the vast majority of providers who have used medical cannabis to treat children with cancer report “a high level of general satisfaction with the use of cannabis” (1,3–6). Second, many children with cancer eventually die from their disease. In the case of the Israeli study previously mentioned, two-thirds of the patients who were treated with medical cannabis died from their disease (4). And third, the children with cancer who survive tend to suffer, some severely, from long-term health problems from their disease. In particular, as of 2020, there are more than 500,000 survivors of childhood cancer currently living in the US (1). More than half (60%) of these survivors suffer from late effects, some of which (about 25%) are severe (1,2). One source lists numerous cognitive and physiological impairments (1), while another source lists psychosocial and mental health disorders (2).

When considered in context, then, the benefits associated with using cannabis to treat pediatric oncology (less nausea and improved appetite, better sleep, increased quality of life) appear to far outweigh the potential costs (long term cognitive impairment), especially given the high incidence either of death or of severe, long-term health problems in survivors of pediatric cancer. Of course, each case is different, and the decision should be left to patients and their doctors, but the option should be there.

Researchers warn that certain enzymes that play large roles in metabolizing cannabinoids (THC and CBD) are also involved in metabolizing several chemotherapeutics. So then taking cannabis while undergoing chemotherapy could alter the bioavailability of chemotherapeutics. “As such, cannabinoid use during conventional cancer therapy should be very carefully considered” (3).

Cannabis provides a conundrum for treating pediatric oncology: while preclinical research provides clear mechanisms of action for cannabis’s potential to treat pediatric oncology, clinical studies are difficult to conduct, due to the associated ethics. At the same time, both preliminary clinical studies, as well as reported use of cannabis administered by parents and caregivers, have established the benefits of cannabis for children with cancer. All this suggests that clinical studies may very well continue to lag case studies, as parents and caregivers forge ahead with cannabis use, while researchers follow behind, documenting results.

https://www.mdpi.com/1424-8247/15/3/359/htm

https://www.lls.org/sites/default/files/National/USA/Pdf/Slides_Transcipts/slides_ped_October2019.pdf

https://www.tandfonline.com/doi/full/10.1080/08880018.2019.1630537?needAccess=true

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708955/pdf/i1551-6776-20-6-462.pdf

https://pubmed.ncbi.nlm.nih.gov/33932156/

https://onlinelibrary.wiley.com/doi/10.1002/cnr2.1551

https://theconversation.com/pediatricians-seeing-a-growing-demand-for-medical-cannabis-for-kids-132426

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744275/pdf/PEDS_20170559.pdf

https://pm.amegroups.com/article/view/5636/html

, is a systems design researcher and analyst. She analyzes markets to determine how environments shape outcomes. She is co-founder of CannDynamics, and author of The Medical Cannabis Primer and Winning the Hardware-Software Game: Using Game Theory to Optimize the Pace of New Technology Adoption. Dr. Fisher has worked in the technology and healthcare sectors on behalf of technology companies, early-stage researchers, physicians, and technology start-ups.

Research Focus

Cannabis provides a conundrum for treating pediatric oncology: While preclinical research provides clear mechanisms of action for cannabis’s potential to treat pediatric oncology, clinical studies are difficult to conduct, due to the associated ethics. Here, we take a closer look at the state of current research.

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.

Is it Safe for Children to Use Cannabis and Do They Get High?

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 Δ

-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.

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 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.

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, 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 

 (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.

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 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.

 R. Pertwee, Ed. (Oxford University Press, 2014) pp. 23–43.

A. Abrahamov, A. Abrahamov, and R. Mechoulam, 

A. Levine, K. Clemenza, M. Rynn, and J. Lieberman, 

Journal of the American Academy of Child & Adolescent Psychiatry 

S.E. Sallan, N.E. Zinberg, and E. Frei III, 

For a listing cannabis clinicians near you visit 

https://www.cannabisclinicians.org/find-a-cannabis-doctor/

D.A. Ladin, E. Soliman, L. Griffin, and R. Van Dross, 

Cannabis for the Treatment of Cancer: The Anticancer Activity of Phytocannabinoids and Endocannabinoids

, 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 

. Healer medical cannabis products are currently available in Maine and Maryland and for more information visit 

. 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 

Doctor Focus

What do we know about the safety and efficacy of THC in children? Here, Dr. Sulak addresses that question and more.

Cannabis for Children with Cancer

A cancer diagnosis creates shockwaves of fear, concern, and worry for any person, as well as for their friends, family, and colleagues. When that diagnosis applies to a child, those emotions are amplified. No one wants to see a childhood interrupted by constant doctor and healthcare appointments, aggressive treatments, and debilitating side effects. Parents and guardians of children impacted by cancer are in a constant search for resources that can lessen the impact of the diagnosis, ease their child’s discomfort, or help hasten a recovery from treatment. It is no surprise that many caregivers wonder if cannabis can help, and with the increasing number of states legalizing medicinal cannabis more parents are asking healthcare professionals for advice.

The growing acceptance and legalization of cannabis has provided access to medical cannabis for children like never before. As a result, more people are inquiring about its potential as a treatment option. In a 2017 

 of cancer care providers conducted by the Yale School of Medicine, 30% of respondents said that patients or their families had asked for medical marijuana at least once in the past month (1). In addition, that same survey found that 92% of clinicians surveyed were willing to help pediatric patients access medical cannabis. Still, the topic of cannabis medicine for pediatric cancer patients remains controversial.

Although stigma surrounding the use of cannabis is diminishing, large portions of the US population still consider it to be potentially dangerous, especially for young people. The “gateway drug” reputation that has persisted for decades continues to create concern. But there are also more realistic and practical concerns surrounding the use of a psychoactive substance by children. Brain maturity continues well past the teenage years, and there is some evidence that full brain development is not complete until well into a person’s 20s. There is concern that any cannabis-based treatment received by children will impact their brain development, according to a 2022 study (2). However, when reduction of pain and suffering for children is a factor, there are those who suggest that limited exposure to potential hazards is worth the risk. A 

 found that many parents of children with severe conditions pursued medical cannabis despite these potential obstacles (3).

Although there is limited data to support the use of cannabis as a first-line treatment in cancer-related symptoms, many adult patients are consuming it to relieve the anxiety, pain, nausea, loss of appetite, and insomnia that often come with a cancer diagnosis and subsequent chemotherapy or radiation treatment. In 2017, the National Academy of Sciences, Engineering, and Medicine released its report on 

The Health Effects of Cannabis and Cannabinoids

 (4). After reviewing more than 10,000 peer-reviewed journals the report concluded:

There is conclusive evidence that cannabis or cannabinoids are effective at treating chronic pain in adults and chemotherapy induced nausea and vomiting.

There is moderate evidence that cannabis or cannabinoids are effective at improving short term sleep disturbances and limited evidence at improving appetite and decreasing weight loss.

Overall, there have been multiple studies suggesting that tetrahydrocannabinol (THC), the psychoactive or intoxicating component of cannabis, can be effective in the treatment of nausea, pain, appetite loss, insomnia, anxiety and inflammation—all of which can be side effects of chemotherapy. And while this research shows that cannabis can help relieve symptoms related to a cancer diagnosis, all the research conducted has been with adult subjects. There is virtually 

no conclusive literature regarding the use of cannabis in pediatric cancer care

This lack of research creates the biggest stumbling block to physicians and clinicians when it comes to recommending cannabis for their pediatric cancer patients. Since pediatric cancers can vary wildly from adult cancers, it is possible that any therapy, including cannabis, may behave differently in children compared to adults. The limited clinical research combined with a widespread lack of knowledge about cannabis among healthcare professionals keeps clinicians hesitant to recommend cannabis to pediatric cancer patients. However, there exist many cases of cannabis use (primarily, cannabidiol [CBD]) in children to treat pediatric epilepsy and chemotherapy-induced nausea and vomiting (CINV) that show both the safety and efficacy of cannabis in pediatric populations (6). The use of cannabis in these cases indicates that it can be used in children in a safe and effective way with minimal side effects and low risk of serious adverse events.

So, even though access to cannabis has greatly increased, stigma is diminishing in most parts of the country, and physicians and clinicians are beginning to recognize the potential of cannabis treatment for children, there is still a long way to go before cannabis becomes a preferred treatment. Physicians and clinicians overwhelmingly prefer to have stronger clinical evidence on therapeutic effects and clear empirical data on any long-term impacts of cannabis use for pediatric cancer patients. So long as the US federal government continues to regulate cannabis as a Schedule I controlled substance, the much-needed research will continue to be mostly stymied.

In order for the promise of cannabis to be realized for pediatric cancer patients, research and clinical trials must be conducted with children. Cancer healthcare providers can lead the charge by advocating for federal legalization and research focused on children. In addition, physicians and clinicians can recognize that while cannabis use is never appropriate for healthy children, these are not the children in need. Sick children undergoing severe treatment with few options to help them feel better are in great need, and if cannabis can help Leaf411 believes every possible option must be considered. Working in tandem with oncologists, physicians, and other providers, an approach that includes cannabis treatment may make the difference between a child merely surviving cancer treatment or thriving in spite of it.

https://medicine.yale.edu/news-article/pediatric-cancer-providers-give-medical-marijuana-a-cautious-thumbs-up/

https://www.ncbi.nlm.nih.gov/pmc/articles/.PMC8954266/#:~:text=Additionally%2C%20promising%20preclinical%20evidence%20showing,other%20populations%20of%20pediatric%20patients

https://nap.nationalacademies.org/resource/24625/Cannabis_committee_conclusions.pdf.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796497/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954266/#:~:text=Additionally%2C%20promising%20preclinical%20evidence%20showing,other%20populations%20of%20pediatric%20patients

 is a registered nurse and CEO, executive director, and founder of Leaf411, a 501(c)(3) nonprofit organization founded in 2019 with a mission to provide education and directional support to the general public about the safe and effective use of cannabis (marijuana and hemp). For more information or to schedule a consultation with a cannabis-certified nurse, call 844-LEAF411 (844-532-3411) or visit 

Nurse Focus

Parents are asking about medical cannabis while seeking relief for their cancer-stricken children, but lack of research and ongoing stigma make things complicated.

Rylie Maedler has led an amazing journey from pediatric patient to teenage advocate. As a child, she was diagnosed with a rare form of cancer with a high recurrence rate and, through treatment with cannabis, is now in remission. She shares her incredible story to change laws and hearts with her powerful message. Rylie has presented around the world, petitioned lawmakers, organized and currently runs a foundation and a nonprofit, and has been featured in documentaries. In this in-depth interview, Rylie shares her motivation for education on alternative pediatric treatments, the challenges she faces in her work, and her ongoing efforts through her organizations to ensure access to medical cannabis.

Life as a Patient and Cannabis as a Treatment

At first glance, 16-year-old Rylie Maedler lives an average life in Delaware, but behind her ever-present smile is an incredible story. Rylie’s childhood was turned upside down with a life threatening diagnosis. “In second grade, I was diagnosed with aggressive giant cell granuloma bone tumors. They ate away my palate, maxilla, left sinus, and the bottom of my eye orbit. I was supposed to be left with no teeth and be deformed for the rest of my life,” Rylie explained. “My doctors told me that I should go on chemo, denosumab, or interferon. Those are the treatment protocols that are standard for this tumor.”

Rylie’s mother, Janie Maedler, was able to negotiate a “watch and wait” period to research alternative options to relieve Rylie’s pain. Cannabis continually popped up, so they decided to try it, though it was not legal in the state of Delaware at the time.

There was not much research on cannabis for this type of tumor, so it was trial and error for a while. “I tried THC and CBD, and I gave her THCA, once I could find it,” Janie recalls. “I separated them so that we could give them at different times. We had to play with the dosing to find the right variety of plant extract that agreed with her. In the beginning, there were a few times where I would start her on a THC and it would make her feel anxious or it might upset her stomach, and then we would change to another,” said Janie.

“Right away, we saw good results in my pain and swelling, and only a few months later, we saw bone regeneration and tumor shrinkage, which we didn’t expect at all,” said Rylie. “From just using cannabis, I didn’t have to use chemo, interferon, or any sort of radiation, and I’ve been in remission for nine years.” Today, Rylie continues to take CBD and THCA in oil form daily as a maintenance regimen and for epilepsy, which started 10 days after one of her procedures as a child. She continues to get scans every two years.

However, with the overwhelming challenges and success with cannabis as a treatment, Rylie also met with the lack of education around cannabis and the stigma assigned to it. “When we first came out to the public about me taking cannabis, a lot of the kids in my elementary school didn’t really know what it was, but a lot of their parents told them to stay away from me because I would be a bad influence, or they were scared of me somehow sharing my medicine,” said Rylie. “You know those drug videos that they show in gym class talking about different drugs? Well, as a patient, I have been forced to watch those videos. Whenever they would talk about cannabis, they would just show it as a drug and they would talk about how it can make you go insane, cause psychosis, and make your IQ drop. It would always make me feel so uncomfortable to watch those videos in class because it’s not true.”

As a result, the beginning of her efforts to change the stigma around cannabis started early in her life. “As I got older, once I was in fifth grade, people definitely started to get more used to it, and as years have gone on, people have been more comfortable,” she said.

The challenges of the stigma may have lessened in some areas, but Rylie still encountered other resistance within the cannabis industry itself. “I’ve had trouble being taken seriously because of my age. Having the positions that I do, a lot of people would see me as just the poster child for something. As if I’m like Wendy from Wendy’s, I’m a face, and I don’t really have anything to do with what’s going on. I have that issue where people just don’t see me as someone working. They just see me as a kid, just putting her face on everything and her name on everything.”

Moving Forward with Advocacy, Education, and Research

Knowing she was entering into an atmosphere of resistance, Rylie was still determined to face it head on. Because of the success she found with medical cannabis, Rylie wanted to spread her story and touch as many lives as possible. While still in elementary school, she began her mission to help other families know about safer treatment options. During her own initial treatment, she became friends with children in the hospital and was familiar with their stories.

“Once I left the hospital, I wasn’t sure why other kids couldn’t have access to cannabis,” she said. “I asked my mom, and she told me that cannabis was illegal. And I said, ‘Why don’t we change that?’” Rylie contacted and petitioned her local legislators and in 2015, Senate Bill 90, also called “Rylie’s Law,” was introduced to allow children in Delaware to use cannabis oil to treat a variety of conditions. The bill was passed unanimously in the Senate and House of Representatives. Soon afterward, Rylie helped introduce Senate Bill 181, which allowed medical cannabis on school grounds (1). Rylie and Janie have shared the draft of the law with advocates in many states, including Maryland and Colorado, to help them apply the same legislation for their schools. Rylie also worked to have autism added to the list of qualifying conditions that could be treated with cannabis, and helped pass the Compassionate Use Law, which gives doctors the ability to prescribe cannabis for any condition they feel would benefit from it, as long as they have research to support it.

There was still work to be done, and Rylie was just getting started. “In third grade, I started the Rylie’s Smile Foundation. That’s a platform I use to advocate for better treatment options, such as cannabis and increased safe access,” she said.

Through her foundation, she began public speaking. “The purpose of my foundation is to educate families about medical cannabis, advocate for safe legal access for pediatrics, and support research of cannabis,” Rylie explained. In sixth grade she began traveling and presenting, first at the Cannabis Science Conference. Afterwards, she presented at conferences across the country and around the world, including countries such as Australia, Israel, South Africa, and Hong Kong. Her biggest learning experience, Rylie recalled, was in Hong Kong. “A lot of people knew nothing about cannabis, and I was called a ‘disruptor’ by the company that invited me to present. Everyone else at their event was talking about business, technology, and innovation, and I was talking about cannabis, how it’s helped me and other people, and my foundation. I got so many people coming up to me and asking strange questions that you would never be asked here. A few people asked me, ‘Do you start to hallucinate when you take cannabis?’ and ‘Do you see circles or spinning things?’ They had absolutely no idea what it was like because they had never really heard about it,” she said.

Janie also recalled reactions from people after a conference in Australia. “The medical doctors were all scared to prescribe it because it had just been legalized there to prescribe to their patients. But they all told me that, after hearing Rylie speak, they were not scared anymore to prescribe it for their patients because they felt like it was not going to harm the children,” said Janie.

In addition to providing education, Rylie and Janie continued to support the plant medicine that helped them so greatly. “In 2017, I founded 

. We grow and process hemp, such as cannabichromene acid (CBCA) and cannabigerolic acid (CBGA) dominant varieties, on our 25 acre farm in Virginia (Eastern Shore of Virginia or ESVA), sustainably and organically, and we make products that are safe for all patients,” said Rylie. “50% of what we grow goes out to families in need, and the other half we sell, and the funds go back to our company. We want to own a patent for the safety of the people who want to use our strain for specific reasons. It keeps people from selling imitations of the strain that we have. If people make imitations, it could be detrimental to the people using it.”

In working closely with Rylie's Lead Advisor, Dr. Reggie Gaudino, from Front Range Biosciences (FRB), Rylie's Sunshine is able to assist FRB in the research of plant performances to make quality medicines. Rylie's Sunshine also recently purchased the breeding rights to the plant that Rylie has used for many years. “Most of the research that we’re doing with Front Range is pretty much how certain phenotypes do in our region with natural soil and irrigation water,” Janie explained. “Everything is organic and natural. We’re trying to figure out which phenotypes do really well in our environment and which do not.”

Some of the plants that they grow have a special connection to them. “The specific strain that we purchased the breeding rights to is the same strain that Rylie has used and a few other children with the same pathology of tumor that she had,” said Janie. “And they’ve all been successful with it, so we’re trying to figure out what makes it different from other strains and other medicines in general.”

Her full recovery from such disfiguring bone tumors and remission has pleased and astounded all of Rylie's doctors. “Currently denosumab is the standard protocol for aggressive giant cell granuloma bone tumors,” said Rylie. “It was chosen after a doctor had used it on two girls and wrote a medical paper on it. So, there wasn’t really much research behind the denosumab.” Rylie has been trying to change the treatment protocol recommendation due to the amount of research on cannabis as treatment. “Cannabis put me into remission and I’ve stayed in remission for nine years, and I didn’t have to go on chemotherapy. From the people we’ve worked with through our foundation, there’s been three other kids with the same type of tumor as me who have been put on the same type of regimen that I was on, and they were all put into remission as well. So, four people in total.” By this measure, cannabis has been unofficially tested as a protocol more times than the current recommended regimen, and with good results.

As Rylie entered more into her advocacy role, the larger picture of how hard it can be to use cannabis to treat pediatric illnesses became clearer. The push for expanding safe access and the chance to use cannabis as a treatment proved to be an uphill and continuous battle.

An example of one obstacle, which is not usually mentioned in Rylie’s presentations, involves the local children’s hospital in Delaware, Nemours Children's Hospital (formerly known as AI duPont), where Rylie initially went to receive treatment for her tumors. The hospital had voiced their support of passing Rylie’s Law, with a few amendments. “Then about the night before Rylie’s Law was signed, they withdrew their support,” Rylie said. “We have learned that the hospital is actually very against medicinal cannabis.” One doctor at the hospital had even tried to revoke Rylie’s medical cannabis card at one point, saying she was addicted to cannabis and that it was not actually helping with her seizures.

Janie explained that this experience was a hard lesson for them regarding advocacy and changing laws. “You can take a group or company’s support, but you also need to look beyond it,” Janie explained. “We learned after the law was signed that by making an amendment to the law, the hospital, in essence, was in control of the law. And then the minute that they withdrew their support, that meant that it was going to be near impossible for any child in Delaware to get a medical card. Thankfully, the 2% of doctors that are not employed by Nemours stepped it up and pretty much came to the rescue of all the children in Delaware.”

“Governor Markell saw that it was important for me and so many other children in the state,” Rylie added. “One of the things that we’ve learned when people are passing legislation is that when a large company like that steps in to give their support, you do not rely on them.” They also learned that while enacting laws are crucial, more support is needed to ensure medical cannabis actually reaches the children who need it.

The Importance of Sharing Other Pediatric Patient Stories

Through their work, stories of others’ experiences with trying to use medical cannabis as a pediatric treatment came forward. Even though medical cannabis is legal in several states, families still encountered resistance to its use in hospital settings and from trying it as a last resort. Families of children undergoing treatment reach out to Rylie and Janie through Rylie’s Smile Foundation to share their stories and ask for help. “There was one family visiting from New Jersey,” Janie recalled. “Their child went into seizures in the emergency room of Nemours. So, the mother immediately used a nose spray and was able to stop the seizure. And the whole staff was like, ‘wow.’ But the doctor called Child Protective Services [CPS] on the family. We got involved and we contacted an attorney that would represent the family.” In addition to having their child in the hospital, the family now had to deal with the fallout of being reported to CPS for cannabis use, though the CPS agent sent to monitor the family in the hospital was understanding. “The family said that CPS even thought it was crazy. They are totally fine with it in our state. It’s just the hospital policy that it could not be on the premises,” Janie added.

Some stories highlight the tragic consequences of withholding treatment opportunities for children with severe conditions. Janie also shared the experience of a friend and parent. “Her child was severely autistic, but he also had epilepsy,” Janie recalls. “I remember he was in the ICU and he had been in status epileptic seizures and was pretty much in a coma. The parents had ordered Charlotte’s Web, and the father was going to bring it into the ICU, he had it in his pocket. The hospital told him that if he stepped foot in there with the Charlotte’s Web, they would call security. And the child died. The parents never got a chance to even try it, and it haunts the mom to this day that they were so close. They were within feet of him with this oil in their hand and they couldn’t even try it. Even though the outcome may have been the same, I wish that the education would get to those advisors and that medical staff to just ease up a little bit. Especially when a child is in such desperate need,” Janie said.

In another story, one that Rylie speaks about in her presentations, an infant was sent home from the hospital with hospice and given two weeks to live due to a severe Mitochondrial Disease. Several people, including a senator who helped with Rylie’s Law, advocated for the infant to be legally recommended medical cannabis as soon as possible, Janie explained. “They asked the hospital, ‘Could you get this baby on medical cannabis because nothing’s going to help her?’ Why not? She’s dying,” Janie stated. “The parents called me crying, saying that they didn’t know what to do because the doctor told them it was no use to try it. He did not want to take that risk. We talked to the state and the state talked to a palliative care doctor who finally bent and approved the medical card for the child. The child's life was extended for about a year and also eased her painful spasms, giving her family more time with her. The family will write to us once in a while still to this day to thank us.” This case happened soon after Rylie’s Law was passed.

With such a large need for education and resources, Rylie continues to help connect parents and their children with the resources they need. “We have a lot of information on my foundation’s website, 

,” Rylie explains. “We have classes and we have doctors and consultants that parents can speak to. A lot of parents will come to the foundation and we’ll give them an introductory course to cannabis as medicine. They take a course that certifies them and helps give them the basics. But if they want specific information about their child’s ailment, that’s when we connect them to a doctor or a nurse or even a researcher to explain more to them in detail as to how they can support their child medically with cannabis. When we were starting out, it was a lot of having to take pieces of a puzzle to put it together.”

In response, Rylie and Janie continue to advocate and connect parents with the resources. “Some kids don’t have that luxury of time like we had,” Janie explains. “So, when parents call us we will do everything we can to connect them to safe access, connect them to who they need to talk to for their medical card and for support in their own state, and then to connect them with some type of medical advisor so that they know the steps that they need to take with their child.”

Equally important is the need to share stories. Rylie’s advice for anyone interested in joining their efforts for advocacy and education is to do your research and share your story. “Speak to as many medical people as you can. Go to conferences and share either your story or what you know about cannabis and do your best to educate as many people as possible, especially medical professionals. Because the more people who are educated on it, the more the stigma of cannabis will go away, and the more widely accepted it will be, and the more people will be willing to learn about it. Help people feel comfortable that you’re not there to go against them, you’re just there to talk and share your story.”

Where does Rylie’s journey go from here, what is she working on now, and what does she hope to accomplish in the future? One thing is for sure: Rylie is still actively advocating for others. “Currently, people living in government housing cannot access a medical card even if they live in a medically legal state, just because they live on government funded property, and they abide by federal laws instead of state laws,” Rylie explains. “I’m speaking to federal legislators to see what we can do about that and see if we can get people living on government property who need cannabis as medicine a way to access it because it’s not fair that they can’t.”

Even after accomplishing so much for so long, Rylie plans to keep pushing forward in the future. “I’m definitely going to keep doing my work because there’s always more work that can be done in medicinal cannabis, especially when it comes to legislation and education,” Rylie explained. “In the future, I hope to see more acceptance, legalization, and rescheduling of cannabis so it can be more widely accepted as any other medicine or any other pharmaceutical.”

“But my dream job, although it may not be realistic, is acting. That would be something that I would love to do. When I go to college, I plan on minoring in acting, and I don’t know what I want to major in yet, but I might get into public policy and international affairs.”

For someone who has already accomplished so much before the age of 18, any future plans are within the realm of realistic, thanks to a little help from medical cannabis.

https://dhss.delaware.gov/dhss/dph/hsp/medmaroclaw.html.

Advocacy Focus

Rylie Maedler shares her amazing journey from pediatric patient to teenage advocate. As a child, she was diagnosed with a rare form of cancer with a high recurrence rate and, through treatment with cannabis, is now in remission. Here, she shares her incredible story to change laws and hearts with her powerful message.


From Pediatric Patient  to Teenage CEO: One Young Woman’s Journey  with Medical Cannabis

Tracy Ryan is the co-founder and CCO for NKore BioTherapeutics. Before that, she was CEO and lead consultant for the parent-friendly California-based cannabis corporation CannaKids, focusing on supplying medical cannabis oil to adults and children looking for holistic relief for serious health conditions, and specializing in pediatric cancer. In June 2013, Ryan’s 8-month old daughter, Sophie, was diagnosed with a brain tumor, which doctors said could end up causing vision loss in both eyes. That set Ryan off on a journey to educate herself on the medicinal powers of medical cannabis in treating her own daughter’s disease, as well as all other pediatric and adult cancers, epilepsy, autism, and beyond. Today, doctors are astounded that Sophie’s tumor has shrunk as a result of two infusions of Natural Killer (NK) cell immunotherapy, cannabis oil, and a probiotic developed by her business partner Dr. Anahid Jewett. This is Ryan's story of overcoming obstacles to discover a better way to improve the health and wellness of her daughter. On a very personal level with other parents facing similar cancer diagnoses, she continues her mission to spread the word about the value of medical cannabis through major media outlets and speaking engagements.

The path to a better understanding of the medical benefits of cannabis can often be difficult to navigate. It usually comes as a surprise, because healthcare workers and providers working within standard mainstream medicine need help for specific hard-to-treat conditions. They will try alternate therapies, which is especially important when it comes to their child just starting out in life.

It has to be something that can really work, and can really help even the very young, even as the medical community keeps pushing back against novel ideas of treatment, trying to conceal the blind spots they have in their own education and training.

Sometimes, someone has to step up and take the risks of trying an unproven treatment that could just save the life of their loved one no matter the pushback they experience. Tracy Ryan, mother of cancer patient Sophie, knows that drill all too well.

Ryan’s journey in cannabis started when her 8-month-old daughter Sophie was diagnosed with a low-grade brain tumor called an optic pathway glioma. Optic pathway gliomas (1) account for 3–5% of all pediatric central nervous system tumors, and represent the most common intrinsic optic nerve tumors. These tumors occur during the first decade of life. Their behavior can be aggressive, and their management is often challenging.

In Sophie’s case, the tumor left her legally blind. The type of tumor that she has wraps around the optic nerves and has stolen a lot of her vision. Various brain surgeries have also caused problems with her eyesight.

“My husband and I discovered very quickly that only 3.8% of all government funding was going to pediatric cancer research,” Ryan said. “There had been little to no advancements in the last 40 years in medicines for children. Our baby only had chemotherapy as an option.”

The chemotherapy they were using “has not been evolved,” Ryan said. “I mean, probably it evolved a little as far as how they administer it. But the treatment itself was the same as it was in the 1980s before we even had cell phones. How is it possible that the world has come this far, in technology, in research, in space travel, all these things that billions and billions of dollars have been spent on, but yet our children have been forgotten? How is that possible?”

It was then when she told her husband, Josh, that she would find out more about helping her daughter. “I’m not going to sit here on my hands and not do anything and just listen to what Western medicine tells us to do for our daughter,” Ryan said. “I would look into Sophie’s eyes and tell her ‘Honey, one day, this is just going to be a story that we tell. I know that in my heart, I’m confident of that. You are going to survive this. You are going to outlive us all. It’s not always going to be this bad.’”

A couple of weeks later, Ryan got a bit of luck from the production partner of TV celebrity Ricki Lake (2). Lake had just begun filming a documentary called 

 (in October 2018), which was released in 2018 and is now on Netflix (3).

Lake’s partner, Abby Epstein, the director of the documentary (4), introduced Ryan to medical cannabis and its potential efficacy just in time to help them find cannabis as an alternative for their daughter.

“So, at nine months old, Sophie took her first dose of cannabis on camera,” Ryan said. “There was THC in it, and she started having these miraculous occurrences in her body.”

Over time, Ryan watched as Sophie’s immune system stayed strong. Sophie stopped needing blood transfusions after previously requiring nine of them, and her body just healed itself, which the doctors couldn’t explain. “Her healing ability after surgeries was unlike anything her neurosurgeons had seen in their careers,” Ryan said. “There was no visible swelling and bruising. Her health as a whole improved. She had failed seven chemotherapies and clinical trials up until a couple of years ago. It was then that I knew that there was something more.”

What she witnessed with her young daughter inspired Ryan to create CannaKids (5), which was essentially a tincture company that serviced patients in California while providing dosing guidance to patients around the world. Ryan served as CEO and Josh was director of outside sales. “When I started seeing the efficacy in so many people for so many different diseases, cancer being one of them, I really wanted to understand more,” Ryan said.

That work with CannaKids led her to Dr. Anahid Jewett (6), the professor and director of Tumor Immunology Laboratory at UCLA Health, who agreed to help with Sophie right after her second brain surgery in 2018. “Dr. Jewett started studying Sophie’s brain tissue. When she looked at Sophie’s blood, she couldn’t understand the immune function that she was seeing in a child that had brain cancer. And it was through that interaction that we became business partners, friends, and colleagues,” Ryan said. “Now we’re trying to change the world together.”

This was a journey for Dr. Jewett as well. She had been saying that she wasn’t the kind of doctor that wanted to face sick children. She wanted to stay in the laboratory, especially when it came to pediatrics because she found it difficult to bear witness to what was happening to these children who weren’t really getting better. They were just being treated and allowed to remain status quo. “Cannabis was never even remotely on her radar,” Ryan said. “She didn’t believe that there was this great therapeutic value to it. But she has since completely changed her mind and now recommends that any patient who comes to us gets on cannabis.”

When Dr. Jewett started working on Sophie, she was amazed. “First of all, this is low-grade glioma and it’s supposed to be low in growing tumors. I found that to be the complete opposite with Sophie. It was growing at a much faster pace in my laboratory,“ said Dr. Jewett. “The second thing was that when I was looking at her immune system, it was very different from what I had seen in cancer patients. So those two things made me not only interested to follow up, but also to understand why Sophie has the cancer with that level of immunity that she has.”

Dr. Jewett thought that the first thing she was going to find was a suppressed immune system in Sophie. “I saw the complete opposite of that. And so that was intriguing to me, and I wanted to follow up.”

Part of why that was happening was the action of certain immune cells—the natural killer (NK) cells—which are lymphocytes in the same family as T and B cells (7). But as cells of the immune system, NK cells are best known for killing virally infected cells, and detecting and controlling early signs of cancer.

The NK cells were “obliterating” the cancer cells in Sophie, explained Dr. Jewett. “NK cells were very important in targeting cancer stem cells, and those are the most aggressive cells,” Dr. Jewett said. “If you can eliminate those cells, you can cure cancer, basically.”

Sophie was six years old at the time of Dr. Jewett’s tests. Her NKs were functioning at five times the level of any healthy patient Dr. Jewett had studied in her 30-plus-year career (8).

Dr. Jewett also found out that synthetic cannabinoids can target the same aggressive tumors. “It’s mind boggling,” Dr. Jewett said. “I would have never guessed that this could be the case, because I’ve looked at big chemo drugs and I’ve given significant levels of chemo drugs, not only in the animal models but also into the cells directly. And I could not see any death in those cells yet. But this synthetic cannabinoid that I’m working on is doing the job.”

Dr. Jewett saw other patients on cannabis also had much better NK activity than even healthy individuals. “So that was intriguing to me also,” she said. “I wanted to know how that is happening, and why that is happening. So I started working on a humanized mouse model system, because I know that is the most relevant model to the human system. And when I injected the same synthetic cannabinoids into a mouse, I saw very high levels of activation of NK cells.”

She said that one of her plans for the future is to actually modify these synthetic cannabinoids in such a way that they could increase the activation of the NKs, and use it as therapeutics.

Ryan said that now they can go forward with more clinical work based on what Dr. Jewett has discovered—such as her findings about cannabinoids, targeting and killing cancer stem cells, and rebooting the immune system.

All of those findings were published in a peer-reviewed cancer journal (9).

“So, we’re working on getting FDA approval,” Ryan said. “We’re going to be submitting our application here in the next few weeks for our human trials. And we’re working on setting up other human trials through medical tourism in countries where it’s much easier to get approved.”

Ryan and Dr. Jewett, along with two other partners, created NKore BioTherapeutics (10), a biotech company that has licensed Dr. Jewett’s core suite of patents for both her supercharged NK cells, her suite of diagnostics that test the NK cell system, and a synthetic cannabinoid that they intend to use as a booster to NKore’s therapy, as well as other chemotherapies available today.

Sophie is much healthier today, especially after getting her father’s activated NK cells. “The NK cell therapy that she got was her dad’s natural killer cells that were activated. And what that means is that they use interleukin 2 (11) that also comes from the body but it’s unfortunately pretty toxic to patients,“ explained Ryan. “It is a short-lived five-day course of this as a booster to the cells. It’s used in activating the cells, simply turning on their killing ability. And then the patient has to get several days of shots of it.

“The NK cells from her father were not supercharged like the ones that Dr. Jewett has invented and that NKore is now working to bring to market,” Ryan said. “However, not only is the therapy working, but it started working basically immediately after the first two-and-a-half months’ scan. We’re seeing the tumor at about an 85% overall reduction in size, and it continues to die off with therapy.”

The reason Sophie got her dad's cells instead of the NKore’s supercharged cell therapy now is because Dr. Jewett created a whole new cell that’s never existed before. The body sees it as a natural component of their immune system, so there’s no possibility of rejection. “But because we are changing the cell structure of our natural killer cells with this new cell, not the DNA, but just the cell itself, we have to get FDA approval,” Ryan said.

She said that they are close to being ready to submit their FDA application to get what’s called investigative new drug (IND) approval, which means they can start to move forward with human trials in the US with their first focus being pancreatic cancer (12). “Once that is approved, under the FDA’s Expanded Access, sometimes called compassionate use (13), which states that if a patient has exhausted everything Western medicine has to give them and are deemed terminal, they can treat individuals with any type of cancer once approved,” Ryan said.

They can get approval for them in 30 days after submitting the application for that patient to the FDA. “So, while we’re going through these very structured human trials here in the United States, we are also planning on opening up the opportunity for these compassionate use single patient IND opportunities for patients,” she said.

The plan is to bring this cell treatment to market through FDA—both the supercharged natural killer cells that her company owns the patents to, and the research Dr. Jewett has been doing over the last 30 years at UCLA, along with the cannabinoid medicine that can be used with the natural killer cells treatment. “My ultimate goal is to have a cancer therapy, which would be a combinational therapy that does not make the patient sick, and fixes the core reason they got cancer in the first place,” said Ryan.

Sophie has had two infusions in recent months: one in September 2021 and the second in December 2021. “She has had 12 days of sickness since September, and that’s it,” Ryan said. “And even after this last infusion, Dr. Jewett continues to study her. Her blood and her immune system continue to function at extremely high levels, even though she hasn’t had a treatment since December.”

Ryan said that she, her husband Josh, and Sophie—working with Dr. Jewett—are optimistic that they will be able to eradicate Sophie’s disease especially after the enormous amount of shrinkage that they’ve seen. “I’m optimistic that we’re going to get rid of the disease,” Ryan said. “After the amount of shrinkage we have continued to see scan after scan, we are confident we have fixed the immune system in her brain. This would be the first time that a low-grade glioma like this has been eradicated with the treatment.”

Ryan has spent the last nine years of her life traveling the world for speaking engagements to try and get the word out about case studies like Sophie’s and other patients that they’ve treated.

“Throughout this journey, not only has it helped Sophie and us believe that cannabis not only protects her body from the chemo and radiation, but it also helps her with side effects and immune stimulation,” Ryan said. “She’s also the happiest child you will ever meet in your entire life. And to watch Sophie be this vibrant, outgoing, spunky child when she’s standing in a row of other cancer patients who are shy and recoiled and traumatized, that makes me hope everyone has an opportunity for their child to have a journey that’s closer in replication to my own daughter’s.”

Sophie still remains on whole plant cannabis as well as a probiotic bacteria called AJ4 that Dr. Jewett has created and that they are in the process of licensing at NKore BioTherapeutics. AJ4 is a probiotic that was developed by Dr. Jewett as a cancer treatment that works to boost NK cell function exponentially. It is not yet available to the public, but there is a probiotic close in relation that is available at 

. “So between the whole plant cannabis and the AJ4, the belief is that it’s continuing to boost her immune system even months and months after her therapy,” Ryan said.

Ryan said that she was literally looking at Sophie’s recent scans as she talked to us. “It is unbelievable how much cell death we are witnessing eight months off treatment after only two infusions of her daddy’s natural killer cells. She’s never been healthier in her entire life,” Ryan said. “Her immune system is so boosted right now with the treatments that we have given her that according to one of the scientists on our team, she has the highest recorded immune function they’ve ever seen documented in pediatric history. So, she just keeps getting healthier, which is what every mother and father wants to see in their child.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169473/

https://www.imdb.com/title/tt7968976/fullcredits?ref_=tt_ov_st_sm

https://www.linkedin.com/in/anahid-jewett-436435103

https://www.immunology.org/public-information/bitesized-immunology/cells/natural-killer-cells

https://www.nkore.com/synthetic-cannabinoid-inhibits-growth-and-induces-cell-death-of-oral-and-pancreatic-stem-like-poorly-differentiated-tumor-cells

https://www.sciencedirect.com/science/article/pii/S266739402200017X

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/interleukin-2

https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application

https://www.fda.gov/news-events/public-health-focus/expanded-access

 has written for many cannabis publications, and organized or moderated sessions at national and international cannabis trade shows. He was voted the 2018 Journalist of the Year by Americans for Safe Access, the world’s largest medical cannabis advocacy organization.

Caregiver Focus

Here, Tracy Ryan discusses the journey her family has taken to find treatment for her daughter Sophie’s brain tumor, the unexpected discovery of natural killer cells with Dr. Anahid Jewett, and the formation of their company NKore BioTherapeutics.