Greater Risk or Therapeutic Benefit? The Ongoing Debate Around Cannabis and Schizophrenia

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For decades, the misunderstood relationship between cannabis and schizophrenia has sowed fear among regulators, healthcare providers, and law enforcement. Opposition to legalization has often come wrapped in alarm that rising cannabis consumption will trigger rising rates of psychosis and schizophrenia. 


Yet, more than 80 years after the film “Reefer Madness” incited this panic about cannabis, we still know frustratingly little about whether the madness theory is true. In a confusing turn of events, newer research suggests that cannabinoid therapy may actually reduce the symptoms of psychosis and schizophrenia. 


Why Does the Relationship Remain Elusive?


Although there has been substantial scientific attention given to this relationship over the last half-century, the current body of work faces issues related to the nature of epidemiological study and the inherent biases in cannabis research. By their very nature, population-wide studies simply cannot control for all the variables, which is especially true within the long-term studies needed to explore how cannabis relates to schizophrenia.


When it comes to cannabis, there is also the established inherent bias against the plant’s medicinal properties. As a recent analysis uncovered, research into the potential harms of cannabis received 20 times more funding over the last two decades than the plant’s therapeutic value. While new studies suggest cannabis and cannabinoids could help reduce the symptoms of schizophrenia, historic biases mean this is still an extremely challenging topic to fund and receive approval. Therefore, most research to date has focused on the negatives.


Thankfully, several publications and research centers have taken a more objective approach to this topic over the last few years. This new impartial assessment has not led to any breakthroughs—yet—but it has helped redefine and rebalance the current scientific landscape.


The 3 Theories Connecting Cannabis with Schizophrenia


In 2019, Current Psychiatry Reports published “Cannabis and Psychosis: Are We any Closer to Understanding the Relationship?” by Ian Hamilton and Mark Monaghan. The authors succinctly summarize the three contemporary theories about the relationship between cannabis and schizophrenia. 


  1. Direct Relationship: Cannabis consumption can trigger psychosis and schizophrenia, even in people who would never have developed the mental health condition without cannabis use.

  2. Reverse Causation: People with a predisposition to schizophrenia use cannabis to reduce symptoms, which in turn increases the risk of this condition developing.

  3. Common Cause: Genetic predisposition, childhood trauma, and other factors increase the risk for both schizophrenia and cannabis use. 


The direct relationship theory has “proved to be difficult to investigate with confidence,” as Hamilton and Monaghan detail. So far, it seems as if dose size and frequency may come into play, but the THC metabolite lingers in the human body much longer than the actual intoxication, which complicates the conclusions. 


Depending on a variety of factors, patients may test positive for THC more than a month after consumption. It’s also challenging to study because dose size and frequency of use are generally self-reported by the patient, not clinically controlled. Whether or not a historical use of cannabis can be connected to a recent schizophrenia diagnosis remains suspect. 


The second hypothesis, reverse causation, has gained more traction in recent years. Instead of cannabis directly triggering the onset of schizophrenia, the theory suggests it activates a predisposition toward the condition (genetic or environmental). Some literature suggests that cannabis appeals to schizophrenia patients for the purpose of reducing the early symptoms of the disease, although this remains unproven. 


The final idea explores a shared genetic vulnerability, which would increase the likelihood of both cannabis use and schizophrenia. In a 2018 analysis published in Drug and Alcohol Dependence, researchers determined that “high schizophrenia vulnerability was associated with a stronger increase in cannabis use at age 16-20.” These findings support “a relation between genetic risk to schizophrenia and prospective cannabis use patterns during adolescence. In contrast, no relation between alcohol and smoking was established.” 


Unfortunately, despite interesting research into these genetic connections, it is exponentially more challenging to assess any added environmental influences.


A Revolutionary Idea: Cannabinoid Therapy to Treat Psychosis and Schizophrenia


As Hamilton and Monaghan highlighted in their paper, “cannabidiols have been shown to provide therapeutic value in the treatment of schizophrenia with a relatively low risk of adverse effects.” Researchers now have a much better understanding of cannabis outside of the single intoxicating compound, tetrahydrocannabinol (Δ9-THC). Other compounds, like cannabidiol (CBD), are a novel target for research projects exploring potential new treatment options. 


Cannabidiol is already an effective and proven antipsychotic when it comes to countering the psychoactive properties of THC. Now, this idea has expanded to explore CBD for the treatment of mental health disorders like schizophrenia. In one such study, researchers gave 88 patients with schizophrenia a dose of CBD or a placebo for six weeks. The CBD was over and above their regular antipsychotic prescriptions.


The results of this short study showed statistically significant reductions in what are called positive psychotic symptoms. It also demonstrated that CBD provided a greater improvement in cognitive performance. Better yet, rates of adverse effects were equal between the two groups. 


This study strongly suggests that CBD could help treat schizophrenia and related disorders in a conjunctive role with traditional pharmaceuticals. It may also help explain why people with a predisposition to schizophrenia may already turn to cannabis to reduce systems. Since January 2018, more than 2,000 patients have reported using cannabis for schizophrenia within the RYAH Data ecosystem.


What Does This Mean for Healthcare Providers and Patients?


Despite more than 80 years of research, it is still incredibly challenging for patients and healthcare providers to navigate the relationship between cannabis consumption and schizophrenia. It is difficult to conclude whether cannabis helps, hinders, or directly triggers schizophrenic episodes, either in those with a predisposition or those without.


From Hamilton and Monaghan’s perspective on the direction of research: “As cannabis use and the development of psychosis are both influenced by social as well as biological factors, it is important that we keep pursuing a balanced blend of enquiry.” 


From a patient perspective, caution is needed. Several factors, including genetic vulnerability, environmental factors, and cannabis potency, may increase the risk of consuming cannabis for some people. And while new research indicates cannabinoid therapy improves symptoms, this is a relatively new idea that requires much more research before it’s rolled out in practice. 










What's the Hype? Cannabinoid Therapy for COVID-19

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The world is in the midst of an unprecedented global pandemic. Governments, research centers, and international health organizations are throwing everything they have at finding a solution to the newly discovered coronavirus disease (COVID-19). With 30 million total cases and counting, there is a pressing need for a vaccine and an effective treatment. Two such treatment proposals are cannabis and cannabinoid-based therapies.


Several sensationalized headlines have crudely characterized new cannabis strains and terpene formulations as treatment options. These headlines have triggered both excitement and skepticism. But while the attention-grabbing headlines may have inaccurately depicted the early research, the results are indeed worth true evaluation.


For the public, and perhaps even some industry insiders, cannabis for COVID-19 seems an almost ludicrous idea. How could cannabis treat chronic respiratory disease? Yet long before COVID-19 shut down the world, researchers had already identified two fundamental properties in cannabis that are now immensely more valuable — its antiviral and antiinflammatory characteristics.


The Hype Around Cannabis for COVID-19


In Canada, broadcasters published the headline, “Are new cannabis strains key to fighting COVID-19? These Alta. researchers think so.” South of the border, in the US, there have been similar trending stories, like “Researchers look into cannabis as a potential COVID-19 treatment” from CBS and “Cannabis May Reduce Deadly COVID-19 Lung Inflammation: Researchers Explain Why” from Forbes.


But like much reporting on scientific research, the headlines fail to explain the essential details. Cannabis is far from a cure for COVID-19. The research is still in vitro and hypotheticals. As of August 2020, there were several ongoing projects investigating cannabinoid and terpene therapy for COVID-19, but all are in the preclinical stages. Many research projects are also solely educated assumptions based on previous studies on similar pathogens or lung conditions. 


According to an analysis by Prohibition Partners, published in August 2020, 16 different teams are working with cannabis and cannabinoid-based therapies for the novel coronavirus. Half of these projects were still in the planning stages, and the remainder may have demonstrated positive in vitro results, but none had gone on to clinical trials. Prohibition Partners reported on several research targets: cannabidiol (CBD), tetrahydrocannabinol (THC), cannabis flower, and unidentified cannabinoid extracts. In addition to this, it’s worth mentioning an Israel project working with a patented terpene formulation for a condition related to COVID-19. 


The Promise of Cannabinoid Therapy for COVID-19


But what’s triggered this hype around cannabis for COVID-19? The predominant cannabinoids in cannabis, THC, and CBD, have properties with real potential to treat the symptoms of COVID-19. Cannabis’ antiviral and antiinflammatory properties could reduce the severity and duration of some comorbidities related to COVID-19, given the preliminary study results.


For example, there has been substantial work done on CBD’s antiviral capabilities. There are three studies of particular importance. The first examined CBD against both the hepatitis C virus and hepatitis B virus. At least in the Petri dish, CBD reduced cell proliferation of hepatitis C by 86.4 percent (but had no measurable impact on hepatitis B). 


A second study pitted CBD against Kaposi’s sarcoma-associated herpesvirus (KSHV), a type of herpes commonly associated with HIV. Once again, the in vitro results indicated CBD could reduce the proliferation of infected cells. 


The third study of CBD’s antiviral potential looked at a mouse model for viral-induced paralysis and multiple sclerosis called Theiler’s murine encephalomyelitis virus. During the later stages of this condition, CBD improved motor symptomatology and neuroinflammation.


These three studies outline CBD’s potential to target virus-related inflammatory conditions, which has immediate implications for COVID-19. In June 2020, researcher Kevin P. Hill affirmed this therapeutic trajectory to Cannabis and Cannabinoid Research: “THC or CBD may be beneficial in viral infections where the host inflammatory response is pathogenic.” Although Hill confirms there has not yet been a study about cannabis for any virus within the coronavirus family, this seems the next logical step.


Cannabinoids for A Cytokine Storm


Early on in the COVID-19 outbreak, medical centers began reporting a serious and potentially fatal complication: acute respiratory distress syndrome (ARDS). This condition developed following a COVID-19-triggered cytokine storm. Lung damage caused during this chronic inflammatory response seems to develop into ARDS. 


In the words of Jennifer R. Tisoncik Marcus J. Korth, et al., “The term ‘cytokine storm’ calls up vivid images of an immune system gone awry and an inflammatory response flaring out of control.” Cytokines are small proteins produced by the human body for intercellular communication. Part of this role is to regulate the inflammatory response. When they “storm,” these tiny proteins spill over from the localized infection site to create system-wide problems. With no off switch, these proteins run amuck, triggering a cycle of inflammatory damage. This damage lays the groundwork for ARDS and other acute lung injuries. 


According to the National Heart, Lung, and Blood Institute, ARDS is “a serious lung condition that causes low blood oxygen” where “fluid builds up inside the tiny air sacs of the lungs, and surfactant breaks down.” With no surfactant, it becomes difficult to fill the lungs and keep oxygen moving throughout the body. 


Although recent comparisons have found subtle differences between ARDS related to COVID-19 and the condition related to other diseases, ARDS remains a fatality risk for patients hit hardest by the infection.


So how does cannabinoid therapy come into play for COVID-19-related cytokine storms and the risk of ARDS? As Hill outlined in his review, cannabis is a potent anti inflammatory, and it “could possibly be a part of a treatment regimen, with nonsteroidal antiinflammatory drugs (NSAIDs) and other medications that target immune pathways, that could downregulate the cytokine storm.” Cannabinoids could be the off switch to an aggressive inflammatory response, thereby reducing the risk of ARDS.


A research partnership out of Israel provides recent (if preliminary) proof of cannabis’ ability to target cytokine storms. Eybna (a manufacturer of terpene-based medicines) and CannaSoul Analytics found positive results from a unique CBD-terpene formula for treating in vitro cytokine storms. This team assessed several options including CBD, their proprietary terpene blend, and a conventional pharmaceutical, Dexamethasone. 


The most effective formula for inhibiting cytokine activity was a combination of CBD with the proprietary terpene blend. These results strongly suggest that CBD could play a role in COVID-19-related cytokine storms. The project discussed initial findings with Forbes in July, although the final results were unavailable at the time of writing.


Another study coming out of the University of Lethbridge supports the results of the Israeli study. The research team tested seven strain-specific extracts and found that three cannabis-derived extracts profoundly downregulated the expression of the specific proteins responsible for the cytokine storm. However, this research is still in preprint The authors propose, “The extracts of our novel C. sativa lines may be used to modulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis.” 


Real Potential Beyond the Hype, But a Long Way to Go


The media tends to ignore the most important caveats buried within exciting new scientific developments. The publicity around cannabis for COVID-19 is no different. But, for those interested in the details, the hype of cannabinoids as antiviral and antiinflammatory therapies does hold up under closer inspection.


Currently, all research into THC, CBD, or terpenes for COVID-19 sits in Petri dishes. The evolution of this study into animal models and humans will take a long time, especially considering the legal status in many countries. But, should cannabinoids continue to reduce cytokine storms and the risk of ARDS in future research, medical cannabis could finally break into conventional medicine at a global scale.











Curiosity About Medical Cannabis: Special Considerations for Older patients

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First it won over millennials. Then came the Baby Boomers. Now medical cannabis is piquing the interest of patients over the age of 65. Despite initial hesitations during the first wave of legalization, seniors are slowly coming around to the value of medical cannabis. 


This rapid shift is thanks to the unique combination of legalization, changing social norms, and the potential that cannabinoid therapy holds for age-related conditions. Cannabis is already approved as medicine (at the state level) for several age-related diseases like arthritis, chronic pain, Parkinson’s, and oncologic co-treatment. With this in mind, the increased (and for some renewed) interest in cannabis’s power is perhaps not so surprising.  


The sudden uptick in cannabis consumers over the age of 65 has also caught the attention of marketers. Seniors represent a large and mostly untapped demographic. As per some assessments, seniors, on average, have between five to seven ongoing prescriptions. If seniors choose to replace one or more of these prescriptions with medical cannabis, it could lead to exponential market growth. 


It’s worth taking a closer look at these changing perspectives among people over the age of 65 and the age-related illnesses medical cannabis may treat.


Increased Curiosity Among Patients 65 Years and Up


In 2019, the Journal of International Medicine published a research letter entitled “Trends in Cannabis Use Among Older Adults in the United States, 2015-2018.” The authors sought to determine if cannabis use among people over the age of 65 continues to rise based on national trends. As they detail, between 2004 and 2016, rates of cannabis use among this demographic “increased sharply” from 0.4 percent to 2.9 percent. Would the pro-cannabis trend continue?


Based on more than 14,000 respondents, the researchers determined, yet again, much more interest in cannabis among an older demographic. Between 2016 and the end of 2018, “the prevalence of past-year cannabis use among adults 65 years and older increased significantly from 2.4% to 4.2%.” This increase equals a more than 75 percent relative increase.


Many physicians are reporting similar trends in their discussions with older patients. In one poignant example, Peter Grinspoon, MD, a contributor to Harvard Health, detailed his experience seeing many more older patients asking questions about cannabis use. When his older patients bring the topic up, “some of them — typically ‘children of the 60s’ — are quite comfortable with the idea of using medical marijuana; others bring it up quietly, as if they are asking permission to break the law.” 


National trends and physicians are all reporting that the stigma about medical cannabis is crumbling—which is perhaps surprising for the generation who lived through the War on Drugs, and one which is often assumed to have more conservative views on the subject. It’s time for a more thoughtful approach to medical cannabis for seniors.


Age-Related Conditions Already a Target for Cannabinoid Therapies


In “Medical Cannabis for Older Patients—Treatment Protocol and Initial Results” published in 2019 in the Journal of Clinical Medicine, the authors explored medical cannabis use among seniors and its efficacy. They included participants over the age of 65 with the following cannabis treatment indications in descending order of prevalence: chronic pain, Parkinson’s disease, orthopedic pain, oncologic treatment, dementia, arthritis, restlessness, fibromyalgia, and palliative care. After six months, nearly 60 percent of respondents were still using medical cannabis, and at the one-year follow-up, more than 84 percent reported some benefit to their condition. 


For each of the conditions included in the above study, there is growing preliminary evidence about the effectiveness of cannabis. Rheumatic diseases (fibromyalgia, chronic pain, osteoarthritis, and rheumatoid arthritis) are perhaps among the most prominent examples of relevant medical cannabis research. Several preclinical studies within this realm have already been completed, including a survey of Israeli patients prescribed medical cannabis for the treatment of fibromyalgia. The results published in the Journal of Clinical Rheumatology concluded, “All the patients reported a significant improvement in every parameter,” with some patients reducing or eliminating other medications in favor of cannabis.


In a much earlier phase, another study reported positive results of cannabidiol (CBD) for the treatment of a rat model of rheumatoid arthritis. This study, combined with benefits reported by patients themselves, is leading to cautious optimism about the future of cannabis for age-related illness, especially rheumatic disease.


Special Considerations for an Aging Demographic


Yet, despite this excitement, caution is required. The researchers behind the study in the 2019 Journal of Clinical Medicine clarified, “The potential risks of cannabis should not be disregarded.” An older demographic poses a set of unique challenges. Physicians and regulations need to take special care when working with patients over the age of 65.


One of the primary issues when working with seniors is the risk of adverse effects. Medical cannabis continues to defy the traditional understanding of pharmaceuticals. There are significant, and often confounding, differences among patients in terms of efficacy, dose size, and THC sensitivity. With guidelines on the proper dose a long way off, keeping patients safe is a difficult task.


Most evidence suggests that adults generally become more sensitive to THC the older they get, which often leads to an increase in adverse events during treatment. An intense adverse event can lead to problems with adherence. In the 2019 study above, at the six-month follow-up, more than 30 percent of elderly participants reported an adverse event. The adverse events included sleepiness, dizziness, and fatigue. 


How does this stack up against the side effects of other common pharmaceuticals? In contrast with one of the most prevalent prescriptions among seniors, opiates for chronic pain, cannabis-related issues are frustrating, but mild in comparison. 


As only one example of this stark contrast, the study “Opiates and elderly: Use and Side Effects” explores several of the most common opiate-related side effects. As per the review, “constipation is the most common side effect of morphine in hospice patients with a prevalence of 48% and it impacted negatively on quality of life significant side effects.” Other serious side effects include respiratory depression, sedation, cognitive impairment, and nausea. These are all much more serious than fatigue, sleepiness, and dizziness. 


The high rate of cannabis-related adverse events among the 2019 study participants likely comes down to a lack of supervision on dose protocols. Dose is everything with THC-rich medical cannabis, and without adequate guidelines on size and frequency, patients are at higher risk for adverse events. This is especially true for THC-naive patients. Should patients receive personalized instruction and a careful self-titration schedule, theoretically, the risk of side effects could be substantially reduced.


Finally, the risk for cannabis-related side effects must also consider potential interactions between cannabis and additional prescription —and, the increased rates of heart disease, respiratory disease, nervous system impairment, and other pharmacokinetic risks that increase with age. Medical cannabis use amongst this demographic is naturally more challenging than other age groups.


Have We Reached the Last Frontier of Medical Cannabis?


Are people over the age of 65 the last frontier of medical cannabis? A lot is riding on the rollout of medical cannabis amongst an older demographic, and not just a new profitable market. Physicians, researchers, and regulators must take a cautious approach that balances the potential medicinal value with the risk of side effects. 


With that in mind, an 84 percent success rate for symptom improvement among the 2019 study participants is remarkable. Furthermore, it’s worth comparing the relatively mild side effects of cannabis-related treatment with those of other commonly prescribed pharmaceuticals, like opiates. 


Medical cannabis has colossal potential for helping seniors relieve the symptoms of age-related disease. Now it’s time for more research to help create improved and senior-septic dosing options. 









UK Public Awareness of Medical Cannabis is Positive, But the System is Broken

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The UK may have legalized medical cannabis in 2018, but that doesn’t mean patients can access it. According to a recent report in The Guardian, just two patients are receiving medical cannabis through the National Healthcare Service (NHS). Both received special emergency interim licenses from the Home Office. Outside the public system, there are perhaps 313 private prescriptions for unlicensed cannabis-based medicines. But these numbers come from a country of 66 million.


With only 315 prescriptions and the vast majority private, something seems amiss in the UK. Is a lack of public awareness to blame, or a system incompatible to the complexities of plant-based medicines? It turns out the UK public is well aware of the therapeutic value, but the fear-mongering policies of the past linger throughout the system.

Public Perception of Medical Cannabis in the UK Not the Issue


In 2018, YouGov commissioned a poll exploring attitudes towards cannabis, for both recreational and medicinal purposes. The organization released the results several months before legalization. 


The final report found an astounding 75 percent also supported the ability of physicians to prescribe medical cannabis. However, as the publication noted, black-and-white questions like “To what extent would you support or oppose the legalization of cannabis in the UK?” tended to cover up these subtler opinions. For example, 43 percent supported legalization, with 41 percent opposed to it. 


Other pre-legalization polls discovered that roughly 13 percent of people in the UK were already planning to ask their physician about medical cannabis once it was legalized. Combined with the 76 percent of people who reportedly were open to a cannabis prescription from their doctor, it seems that public opinion about the medicinal applications is positive.


Public perceptions and use of cannabidiol (CBD), the non-psychoactive hemp-derived cannabinoid, have also shifted. According to a report by the Center for Medicinal Cannabis (CMC), “CBD has now gone mainstream in the UK.” The CMC estimates that between four to six million people in the country have tried this cannabinoid for therapeutic purposes. Much like CBD paved the way for positive public perceptions of cannabis in the US, it is likely to do the same in the UK.

Despite Lack of Prescriptions, Patients Still Seeking Access 


Following legalization, a few rough estimates have circled about the use of illicit, black market cannabis for medicinal applications. As the CMC explained, most early reports estimated between 50,000 to 1.1 million UK residents were currently using cannabis for therapeutic relief. However, the data behind these reports were somewhat unreliable.


In 2019, the CMC launched a new nationwide survey, which collected more than 10,000 responses. This revised poll was finally “representative of the general population in Britain.” This online poll asked pertinent questions about the current use of medical cannabis, frequency of use, and comfort level seeking cannabis through illicit channels. 


The results suggest that as many as 1.4 million people in the UK use medical cannabis, purchased through the black market, to treat various conditions. Furthermore, patients come from all cohorts of society and spend approximately £100 per month on treatment. As the CMC explained, “We found that respondents were concerned over such illegal activity, quality and supply chains, and would prefer more transparency and regulation when obtaining their medicine.”

Problems Lie With Those in Power and an Incompatible System


With perceptions about medical cannabis at an all-time high, and a significant portion of patients desperate enough to seek medical cannabis on the black market, it seems the discrepancy between legislation and ease of accessibility must lie within the system. 


At the time of writing, there were three licensed cannabis-based medicines, all pharmaceuticals: Epidiolex, nabilone, and Sativex. The only approved applications are multiple sclerosis and intractable epilepsy. Physicians may still legally prescribe unlicensed medical cannabis (such as medical cannabis oil), but this must be the last resort. There is no coverage of these expenses through the NHS. 


Cannabis, which is hundreds of natural compounds including terpenes and cannabinoids, is often considered too complex to fit within the traditional single-molecule clinical trial format. Therefore, regulators and the NHS continue to deny access to non-pharmaceutically produced cannabis because they claim limited evidence, limited medical education, and unreliable supply. 


As the polling numbers show, people in the UK are increasingly aware of the potential of medical cannabis and are open to its idea within the traditional medical system. But while public pressure may have passed the initial legislation, those in power seem wary of actually making cannabis accessible. They demand results from traditional clinical trial models or, worse, still live in fear about the risks of a formerly illicit substance.


A telling example of this misunderstanding about medical cannabis comes from a recent report in The Guardian. Hannah Deacon, one of the country’s most vocal cannabis advocates, wrote to every member of parliament about the “abject despondency” parents feel about the current state of the medical cannabis program. Thus far, she has received a single reply from a politician who told her that “cannabis use was detrimental to the mental and physical health of communities.” 


Deacon, the mother to one of the two children prescribed cannabis oil through the NHS, now watches her son bike to school, instead of suffering up to 500 life-threatening seizures a month. Needless to say, the politician’s complete lack of awareness about the medical properties of cannabis did little to satisfy her complaints.


Clearly, the fear-mongering about cannabis continues to affect the mindset and awareness of the politicians, regulators, and others in power. This fear limits physicians’ ability to prescribe, the system to improve accessibility, and politicians’ will to get involved. The UK may have legalized medical cannabis, but have failed to understand it under a modern lens.


With medical cannabis programs successfully rolling out in other countries, the UK struggles to get off the ground almost two years later. If the public is desperate enough to turn to the black market to get the medicine they need, the current system fails to a remarkable degree.


As Steve Rolles, senior policy analyst for the Transform Drug Policy Foundation, told the Guardian, “Unless some kind of bespoke regulatory framework can be found that reduces barriers to access, the more risky scenario of unregulated self-medication with illegally sourced supplies will continue.” Medical cannabis may be theoretically legal in the UK, but the ramifications of decades of cannabis alarmism continue to haunt the rollout.








The Endocannabinoid Theory: Applications for Cannabinoid Therapy

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The endocannabinoid theory of disease began with the discovery of the endocannabinoid system. Unlike the central nervous system, the respiratory system, and other essential systems which have been investigated for centuries, researchers only stumbled onto the existence of the endocannabinoid system less than 30 years ago.


As one of the newest physiological revelations, it’s also the least understood. But a growing chorus of voices has hypothesized how clinical endocannabinoid deficiency could help understand chronic subjective pain syndromes such as irritable bowel syndrome, fibromyalgia, and migraine.


What do these conditions have in common? Many of these conditions are difficult to diagnose and even more difficult to treat, yet they often respond well to medical cannabis therapy. It’s not uncommon to read reports of patients who have exhausted all other pharmaceutical and therapeutic solutions, who eventually settle on cannabis. These patients detail how cannabinoids help alleviate the physical and mental symptoms when nothing else has worked.


Cannabis’ ability to relieve the symptoms of treatment-resistant conditions like those mentioned above is perhaps why patients tout it as the next miracle “cure-all” capable of treating any and all diseases. More likely, it’s not so much a miracle but rather evidence of the existence of clinical endocannabinoid deficiency. 


The Recent Discovery of the Endocannabinoid System


Cannabis earned the attention of modern medicine at the turn of the 20th century. Over the proceeding century, researchers carefully identified and synthesized the primary compounds, called cannabinoids. At last count, the literature identifies more than 150 cannabinoids, with more uncovered every year.


Studies began hinting at the existence of a cannabinoid receptor by the 1970s. But it wasn’t until more than a decade later that Allyn Howlett and his laboratory demonstrated proof of these mysterious receptors. In 1990, researchers successfully cloned (and therefore confirmed) the existence of the CB1 receptor. By 1993 came the discovery of the CB2 receptor. Within only a few years, researchers added two endogenous cannabinoids (internally produced, as opposed to ‘phyto’ or plant-produced cannabinoids) into the equation. 


Thus, by the mid-1990s, researchers had uncovered the structure of the endocannabinoid system —a network of receptors and endogenous chemical messengers spread throughout the body. Since then, scientists have pieced together enough information to grasp how this system manages mood, memory, pain, inflammation, reproduction, and much more.


In Detail: The Components of the Endocannabinoid System 


Remarkably, researchers only stumbled onto this system because of investigations into cannabis and cannabinoids. But, how do the CB1 and CB2 receptors and chemical messengers work together to promote balanced physiological function?


As per a summary by Bradley E. Alger, Ph.D., published in Cerebrum, “CB1 is densely located in the neocortex, hippocampus, basal ganglia, amygdala, striatum, cerebellum, and hypothalamus. These major brain regions mediate a wide variety of high-order behavioral functions, including learning and memory, executive function decision making, sensory and motor responsiveness, and emotional reactions, as well as feeding and other homeostatic processes.”


The CB2 receptors are mainly outside the central nervous system, concentrated on immune cells. Although not as clearly understood as CB1 receptors, the “likely roles of these [CB2] receptors, including modulation of cytokine release and of immune cell migration,” and occur mainly in the immune cells.


The two main endocannabinoids are anandamide, which regulates brain reward circuitry, and 2-arachidonoyl glycerol (2AG), a CB1 agonist with neuromodulatory effects. Anandamide and 2AG may be the primary endocannabinoids, but we now know about other less direct neurotransmitters, which work within the endocannabinoid system as well.


Phytocannabinoids, just like endocannabinoids, can be full or partial receptor agonists and receptor antagonists, engaged in a well-choreographed dance to maintain homeostasis. As the study of cannabinoid therapy has unfolded, it has become clear how these compounds can help regulate an imbalanced endocannabinoid system.


The Endocannabinoid Deficiency of Disease, a New Theory

Endocannabinoids, such as anandamide and 2-AG, are responsible for regulating mood, memory, pain, appetite, and many other critical functions. However, what happens when the endocannabinoid system is in a state of dysfunction, throwing it off rather than returning it into balance?


Ethan B. Russo, a leading cannabis researcher, first hypothesized about clinical endocannabinoid deficiency in 2008 and revisited it in 2016. The clinical endocannabinoid theory of disease holds that “numerous common subjective pain syndromes that lack objective signs and remain treatment resistant” are caused by a deficiency in cannabinoid production and abundance. Importantly, Russo notes, these very same conditions are also responsive to cannabinoid treatment. 


As Russo summarizes, the endocannabinoid deficiency theory developed after researchers identified several neurological conditions that come from a deficiency in neurotransmitters. A few examples include acetylcholine (Alzheimer’s disease), dopamine (Parkinson’s’ disease), and serotonin and norepinephrine (depression). The endocannabinoid theory postulates that an endocannabinoid deficiency could trigger conditions related to endocannabinoid function like pain, fatigue, mood disorders, and more. 


Both Russo’s 2008 and 2016 papers highlight irritable bowel syndrome, fibromyalgia, and migraines as chronic, psychosomatic conditions, with evidence of differences in endocannabinoid tone. According to Russo, these conditions have the most clinical backing.


As a telling example, scientific analysis has demonstrated a genetic polymorphism of the CB1 receptor among patients with IBS. Not only does the polymorphism affect endocannabinoid tone, it also creates more severe cases. The authors of “Irritable bowel syndrome: a dysfunction of the endocannabinoid system?” confirm that “the endocannabinoid system, including their receptors and metabolic pathways, may be involved in the pathophysiology of IBS and it is now multifold evidence from genetic studies, clinical trials, and basic science that supports this notion.”


Beyond these three conditions, could endocannabinoid deficiency cause other common psychosomatic conditions? Preliminary research suggests that motion sickness, multiple sclerosis, Huntington’s disease, Parkinson’s disease, and post-traumatic stress disorder may also be attributed to endocannabinoid malfunction.


The Potential of Cannabinoid Therapy for Clinical Endocannabinoid Deficiency


Interestingly, all of these conditions have several common overlapping symptoms, like depression, pain, and fatigue. In Russo’s analysis of IBS, migraine, and fibromyalgia, many patients qualify for several comorbidities. Under the modern pharmacological approach, treatment plans include single active ingredients targeting a single symptom. But cannabinoids seem to provide a more holistic treatment option. 


Russo’s 2016 review states that patients with these challenging conditions often turn to cannabis as a last resort. When it comes to IBS, conventional treatment includes anticholinergics, opioids, and antidepressants, but their effectiveness is “suboptimal.” Although there has thus far been only limited clinical study of cannabinoids for inflammatory bowel conditions, consistently surveys find patients are already relying on it. Patients report pain relief, diarrhea relief, and improvements to appetite.


Small studies of cannabis for migraines have demonstrated marvelous results. As Russo details, one study in 2016 reported 85.1 percent of participants had decreased migraine frequency, 39.7 percent felt positive effects, and 19.8 percent said it prevented the onset. 


Finally, fibromyalgia patients have long reported benefits from the use of cannabis. As an example, a study of 28 patients with fibromyalgia showed a statistically significant reduction in pain and stiffness two hours after cannabis consumption. They also reported an “enhancement of relaxation, and an increase in somnolence and feeling of well being,” on top of other mental health effects. 


Cannabis: The Key to the Endocannabinoid System


Medical cannabis advocates often describe it as a miracle because it seems capable (at least according to patients) of treating a wide variety of conditions. How can one plant treat so many people with such powerful reported results? 


Cannabis isn’t a cure-all, but its effectiveness for many seemingly unrelated conditions is telling. According to Russo and others, effective cannabinoid treatment could instead highlight a clinical endocannabinoid deficiency, connecting all these conditions together. Not only did cannabis help lead to the discovery of the endocannabinoid system, but it may also now hold the key to unlocking the treatment of common painful conditions, from migraines to IBS to fibromyalgia and more.








An Update on the German Model: A Study Case for the Rest of the EU

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 The European cannabis market is a much different beast than what has evolved across the pond in North America. If North America is about wild market predictions, high-risk investments, and murky regulation, Europe is the exact opposite. 


The European markets are slow to launch, measured in their approach, and highly regulated. Germany, which RYAH reported on in 2019, remains the largest market on the continent but has continued its incredibly cautious approach since its inception in 2017.


Because Germany is the continent’s biggest and most promising market, it’s worth closer inspection. There have been small but significant changes to the medical cannabis space in the country over the last year. With several wholesalers and importers operating in the space, the many layers of regulation are better understood than before.


From the patient perspective to the import requirements, each level of medical cannabis distribution in the country is key to grasping the needs of the market. Once other European countries come online to launch their own national programs, the German medical cannabis model is likely to become the European standard. What works for Germany is expected to work elsewhere. Breaking into the German market could be a predictor of greater European success.


From the Perspective of the Patient


On the patient end of the equation, Germany treats cannabis as it treats other prescriptions. For the German patient, there are only slight differences between pharmaceuticals and cannabis when it comes to point of prescription and purchase.Unlike in the United States and Canada, the system funnels all patients through a prescribing physician and then a pharmacy. There is no secondary ‘cannabis doctor,’ no dispensary, and no budtender.


In another stark contrast to the US system, statutory health insurers in Germany must cover the cost of medical cannabis prescriptions so long as they meet specific criteria. Coverage kicks in as long as the patient is seriously ill and has exhausted all other treatments, and if cannabis is likely to treat the condition (or alleviate the symptoms) effectively.


Should the patient’s condition fall outside these parameters, or they are working through a private insurance company, the patient may also pay out of pocket under a private prescription. Patients still require a prescription and will still access the product through a pharmacy. 


A medical cannabis prescription in Germany is for an exact product, down to the strain. In 2020, the range of cannabis products has grown substantially since the launch of the program in 2017. According to “Medical Cannabis in Europe: the Markets & Opportunities” an updated report by Marijuana Business Daily, there are now more than 30 strains available, plus THC- and CBD-isolated cannabinoid extracts, several full-spectrum extracts, plus a handful of finished pharmaceuticals (Sativex, as an example). Pharmacists are not allowed to adjust the prescription to new strains or products without a reissue of the original order.


Under this system, cannabis is treated, essentially, like any other medication. Access is restricted and all funneled through official channels. Physicians prescribe only when deemed absolutely necessary. But, as we argued in the 2019 analysis, this system is naturally safer for the patient treating a chronic condition. Patients receive accurate information from well-trained healthcare professionals, and the product is clean, regulated, and consistent.

Layers of Regulation Transform Cannabis into a Prescription


The German market still relies entirely on cannabis imports to supply its program. With the first harvest of german products predicted for later in 2020, today the majority of medical cannabis comes from the Netherlands and Canada. 


Cracking into the German market has proven challenging for many international sellers. Only a few, like Aurora in Canada and Demecan in the Netherlands, have thus far successfully entered into Germany. 


Wholesalers seeking to export into Germany must first come from countries that abide by the 1961 Single Convention on Narcotic Drugs. Second, the wholesalers must observe both the Good Agricultural and Collection Practices (GACP) and Good Manufacturing Practice (GMP) quality standards. Third, international cannabis producers must meet the protocols of the German Pharmacopoeia (DAB) Monograph and the European Pharmacopoeia, both of which cover potency and contaminates. 


One of the biggest changes to the German market last year was the new requirement that all imports be irradiated, a  common practice for other consumable crops, which uses ionizing radiation to kill microbial or other living contaminates. This new requirement temporarily halted imports from some producers as they scrambled to receive their AMRadV license. To date, all wholesalers have now received this license and have resumed imports to Germany. 


On top of the requirements for producers, cultivators must also work with an approved importer. Reports indicate that the number of importers has skyrocketed over the last year. Licensed cannabis importers in Germany must seek the standard scope of licenses as a traditional importer but also obtain a pharmaceutical wholesaler license (regional level) and a license for detailing with the narcotics (federal level). With the increasing number of approved wholesalers, at least this regulatory hurdle seems to have gotten easier.

Germany as a Model for the Rest of Europe


Germany is the largest market in Europe, making up more than 75 percent of the continent’s sector. Many other countries in Europe remain stalled or non-existent, so Germany continues to serve as a crucial entry point. 


With the multi-layered and lengthy licensing process, the German market naturally restricts the playing field to those adhering to strict GMP protocols. In North American, even legal producers are well behind the eightball on achieving GMP certification. If brands, products, and technologies can successfully make it in Germany, likely they will find success elsewhere as the other markets evolve.


With this in mind, RYAH announced a multi-country strategic distribution arrangement with Northern Green Canada in April 2020. Northern Green is the first private, licensed producer of cannabis in Canada to achieve EU GMP certification. This is a highly complementary partnership combining plant-based medicine and RYAH Dry-Herb Inhaler and data analytics platform in German-speaking countries. Sofiya Kleshchuk, Client Relations at Ryah Medtech, confirms, “Germany is a major market that has a lot of impact in the region, and we think RYAH is a great fit for its model and priorities.” 


The RYAH clinical grade dry-herb Inhaler is ideal for a pharmaceutical approach to medical cannabis. Kleshchuk explains, that “Distributing sealed disposable cartridges through pharmacies looks like a perfect solution for the concept of treating cannabis like any other medication, while dose and temperature control that RYAH provides is essential for the patient’s safety and comfort.” Importantly, she details how “Germany favors medicating with dry herb, and that’s exactly where our strengths are. Entering German market is a huge milestone for RYAH.”


As many analysts expect other countries in the EU to adopt the German model in the years to come, lessons learned in Germany will become exponentially more valuable as the EU medical cannabis market grows


The German model is a markedly different approach to the American or even the Canadian medical cannabis programs. Importantly, it is the first successful national program to treat cannabis on the same level as other pharmaceuticals. For medical cannabis-focused companies, seeking to set themselves apart from the murky recreational-medicinal markets, Germany is a critical first step. Their approach has always put patients’ safety first and market concerns second.








The Incredible Anxiolytic Properties of CBD: Research today & tomorrow

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Nearly a decade ago, a team of researchers hailing from the University of São Paulo, Brazil, worked with a group of 24 participants diagnosed with social anxiety disorder. Divided into groups, the participants received a dose of cannabidiol (CBD), and the researchers asked them to perform a simulated public speaking test. Through both psychological and physiological assessments, the groups receiving pretreatment with CBD had “significantly reduced anxiety, cognitive impairment and discomfort in their speech performance.” 


In the world of CBD for anxiety, this single experimental study has garnered the most global attention and spawned a decade of deeper research into the anti-anxiety powers of this cannabinoid. Since the publication of this study in Neuropsychopharmacology in 2011, CBD has become a household name with all types of CBD-infused products tucked neatly away into many people’s medicine cabinets. 


Legalization has made this non-intoxicating cannabinoid more accessible around the world. Its usage has quickly spread, and perhaps for good reason: In the US, anxiety disorders are the most common mental illness. The Anxiety and Depression Association of America estimates that over 18 percent of the American population experiences a period of anxiety in any given year. 


With COVID-19 heightening these rates of anxiety and putting everyone’s mental health to the test, more people may be reaching for CBD to find relief. Over the preceding years of research into CBD for anxiety disorders, has there been any progress?


Nearly a Decade On, Does the Research Confirm CBD is Anxiolytic?


A 2015 research review in Neurotherapeutics outlined the case for the treatment of anxiety with CBD. Unlike many areas of cannabis research, there is surprisingly a substantial body of work on CBD for stress and anxiety. In part, this may be thanks to the non-intoxicating properties of CBD (compared with its cousin cannabinoid, THC) and the ability to source CBD from hemp instead of medical or recreational varieties of cannabis. 


Animal models of anxiety have helped researchers determine that the anxiolytic effects of CBD are dose-dependent and fall on a bell-shaped curve. There is a happy medium between too much and too little for the most anxiolytic impact. Animal models have also helped identify specific biological mechanisms, including CBD’s effects within the midbrain dorsal periaqueductal gray area of the brain (responsible for the production of “intense distress and dread”). Early studies have also pinpointed its work within the bed nucleus of the stria termialis area, which is responsible for our sustained fear response. 


At this point, researchers have determined CBD activates the 5-HT1A receptor (a serotonin receptor). Previous research has confirmed the 5-HT1A receptor governs mood and certain psychological effects, specifically anxiety and depression. If CBD activates the 5-HT1A receptor, logically it may have anti-anxiety effects.


Human Experimentation and Clinical Trials Looking at CBD for Anxiety


The authors of “Cannabidiol as a Potential Treatment for Anxiety Disorders” also summarized human research into CBD and anxiety disorders. There has also been substantial clinical work completed within this area of cannabis research.


Beyond the Brasilian study on CBD’s anxiolytic effects during a simulated public speech, several newer studies also prove the cannabinoid’s anti-anxiety potential. For starters, scientific investigations have determined CBD mitigates the anxiety triggered by acute doses of THC. Higher doses of CBD have also reduced anxiety at baseline levels. 


CBD is fascinating because it seemingly reduces anxiety in both people with an anxiety disorder and in healthy control subjects. One study looked at pretreatment with CBD before a nerve-wracking medical procedure (single-photon emission computed tomography imaging). Both cohorts, those with and those without anxiety, reaped the benefits of pretreatment.


What is notable about the current body of evidence is that most of it focuses on acute experiences of anxiety. As the authors explain, “Thus, overall, no outcome data are currently available regarding the chronic effects of CBD in the treatment of anxiety symptoms.” This is an area of study needing much more attention.


In conclusion, based on this summary of findings, “Preclinical evidence conclusively demonstrates CBD’s efficacy in reducing anxiety behaviors relevant to multiple disorders.” Thus far, the evidence supports CBD for specific disorders, including social anxiety, generalized anxiety, obsessive-compulsive, and post-traumatic stress disorders. 


What the Future Holds for Treatment with CBD


Despite the wealth of evidence supportive of the anxiolytic properties of this little cannabinoid, it hasn’t yet reached any final phase clinical trials. At the time of this writing, four clinical trials are working on CBD for anxiety, but they are in the recruitment or pre-recruitment stages. There are also a handful of other CBD trials in the pre-recruitment stages, touching on symptoms of anxiety but targeting other medical conditions including cancer, Alzheimer’s, and Parkinson’s disease.


Unlike earlier research, many of these new trials will explore a much longer course of treatment from four to eight weeks. Their results will help paint a picture of CBD for the treatment of chronic anxiety disorders, well beyond the acute treatments explored thus far.


It will be a few more years before the Food and Drug Administration or any other governing body approves the use of CBD-derived pharmaceuticals for anxiety. But, thanks to the non-psychotropic and non-intoxicating nature of CBD, it’ll likely face much fewers bureaucratic hurdles and regulatory restrictions than other popular cannabinoids. Plus, with hemp now legal to grow, sell, and process across the country, and new and improved THC remediation technologies, it’s increasingly a widely available medicinal ingredient.  






The Great French National Medical Cannabis Experiment

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The French are standing on the precipice of significant policy change. In the last year, France has made progressively confident legislative steps towards a medical cannabis program. In January 2020, the great French medical cannabis experiment kicked off and should pave the way to cautious but essential changes within the country.


True, compared with many progressive American states, the French are remaining quite careful about their initial foray into medical cannabis — but their approach remains in line with other European countries. The sentiment of the new experimental program is both curious and conservative. It may also be a stalling tactic until the European Union has a chance to clarify its official position on medical cannabis.


The Need for Medical Cannabis in France


According to some assessments, in France there may be as many as 1.5 million patients who could benefit from access to medical cannabis. These patients suffer from a variety of medical conditions, but many which are well-established within cannabis research, including epilepsy, cancer, HIV/AIDS, multiple sclerosis, and chronic pain. These are some of the most commonly accepted qualifying conditions in the US.


As French patient advocacy groups have argued, it’s unethical to prevent these patients from accessing any effective treatment, especially when conventional options may be failing them. Cannabis, as proven elsewhere, is a useful tool for combating some of the most challenging issues related to these diseases.


There are notably very few statistics available about the use or acceptance of medical cannabis among French citizens. Yet, despite strict punishment under French law for possession, the French are quite familiar with the plant, at least from numbers reported by the  French Observatory for Drugs and Addiction (OFDT). 


As per their assessment, 700,000 people in the country use cannabis daily, and double that number confirm they use the plant regularly. Additionally, the OFDT reports that roughly 17 million citizens have tried cannabis at some point in their lives. These numbers don’t differentiate between medical use and recreational, but we can, at the very least, assume a general societal acceptance and familiarity with the plant.


The Great French Experiment with Medical Cannabis


In the fall of 2019, France passed the Social Security budget for 2020, which included a few key approvals for a small experiment. The French Agency on the Security of Medicine and Health Products (ANSM) received permission to conduct a trial on medical cannabis for pain among 3,000 patients who were already undergoing treatment for the chronic condition.


Physicians will administer cannabis-based drugs to the selected pain patients through official medical channels in the country. Starting in January 2020, the two-year experiment will intake patients for six months, provide treatment for six months, then assess outcomes for another six months. Upon completion, a report will be submitted back to the ANSM for a final decision on the efficacy of cannabis as a therapeutic option.


All aspects of this government-run trial are under the strict control of the ANSM. They control which conditions qualify for participation within the study, which physicians are allowed to issue cannabis prescriptions, and which routes of administration are allowable. Although physician participation within this project is entirely voluntary, the ASNM requires stringent training and adherence protocols. 


In 2018, the now-disbanded Specialized Committee on Cannabis (CSST) recommended the study of cannabis for “epilepsy, to relieve symptoms of nausea and anorexia among cancer patients, for patients with multiple sclerosis, or palliative care.” This new experiment only covers illness-related pain. Broadly speaking, that still includes a number of possible chronic conditions including chronic pain, epilepsy, spasticity in multiple sclerosis, and neuropathic disorders.


In contrast to other countries or regions with medical cannabis legislation, the French are allowing for only five types of prescriptions for medical cannabis based on different cannabinoid profiles. The official recommendation is for vaporizing dry leaves or edible oil preparations, including oil pills or drinks. Policymakers are strongly advising doctors to direct their patients to avoid smoking.


The Expectation in France and Abroad


What is the purpose of this extensive and exhaustive study of medical cannabis in France? As is the case in the UK and Germany, France is curious but extremely cautious about the potential of medical cannabis. Markets in all of these European countries haven’t launched in the same way as they have in the US. If the US market is the wild west of medical cannabis, the new French experiment is a markedly reserved comparison study. 


The primary objective of the pilot medical cannabis project is to evaluate the efficacy of cannabis for therapeutic applications among real-world patients. It’s specifically quite restrictive in terms of participants, physicians, and dosing guidelines in the initial phases as a way to deliver quality data in 2021 when the pilot completes. Too many variables and it’s very challenging to analyze the results.


The secondary objective, even if program administrators haven’t publicly stated it, may be to see how global policy shifts regarding medical cannabis play out. While the Canadian and US markets have been picking up momentum over the last few years, EU countries are still taking it easy. There have been only tentative entries into the world of medical cannabis among EU member states. 


Back in 2019, the Director General of the World Health Organization (WHO) wrote to the Secretary General of the United Nations requesting a rescheduling of cannabis under the international drug control framework. The recommendation to reschedule was to allow for easy international trade of cannabis for both therapeutic and scientific applications. Unfortunately, while the UN was poised to review the scheduling in March 2020, it seems as if the governing body has postponed the decision until further notice.


As James Walsh, the US representative and principal deputy assistant secretary for the Bureau of International Narcotics and Law Enforcement Affair, stated, “We do regret that the [UN Commission on Narcotic Drugs] was unable to take action on the WHO cannabis recommendations this week, given that Member States have been working hard since February 2019 to engage in an in-depth consultative process on the legal, administrative, social and economic impacts of the recommendations.” Members have proposed to revisit this topic in December.


Among the EU member states, there are significant disagreements about the legitimacy of medical cannabis. Even if there are medical cannabis programs in place within the most prominent economic players on the continent (Germany, France, and UK), there is still no consistency, supply channels, nor trade agreements facilitating these programs. France may be implementing this pilot project as a stalling tactic to await official changes to EU and international policy.


The EU Approach: Slow and Steady


The great French experiment is adopting a very European approach to medical cannabis, mimicking the program recently launched in Germany. 


Unlike in the US, where medical cannabis programs operate outside of federal law, the French government is managing the program down to the most minute details like dosing and type of cannabis prescribed. Furthermore, the government is ensuring it’s physicians, not budtenders, who are working with patients to titrate to the proper dose. 


Although this approach may seem overly cautious when compared to markets in the US, it’s necessary to ensure proper rollout within a government-run medical system. It also allows France space to await international policy changes, which in the end will make their national program easier to supply. 






Cannabinoids in Pediatric Care

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Cannabis for pediatric care? What initially may sound like a shocking and perhaps controversial subject is already a reality. In 2020, cannabis and the plant’s derivatives are well into preclinical and clinical trials for the treatment of several pediatric conditions, including intractable forms of childhood epilepsy. In fact, a pharmaceutical preparation of cannabidiol (CBD) made history in 2018 as the first Food and Drug Administration (FDA)-approved cannabis-derived medicine, and it’s approved for children.


The new wave of support for medical cannabis, and especially for cannabidiol (CBD), is thanks to the efficacy of cannabis in pediatric care. Parents of children fighting catastrophic diseases were some of the original advocates for medical cannabis. The social acceptance and reenvisioning of cannabis for pediatric care came in 2013 when the remarkable story of Charlotte Figi made national headlines. 


Charlotte’s family (now of Charlotte’s Web fame) were some of the first to publicly break the taboo around medical cannabis for chronic pediatric conditions. Her parent’s fight to get her the life-saving plant-based medicine she needed is what convinced many policymakers about the power of this plant.   


So while it may sound controversial to talk about cannabis-based medicines in pediatrics, it’s one of the most established areas of medical cannabis today. 


The State of Cannabinoids in Pediatrics 


Federally, cannabis remains classified as Schedule I under the Controlled Substances Act (CSA). Yet, a single pharmaceutical preparation of the plant is now available for the treatment of Lennox-Gastaut syndrome and Dravet syndrome. Epidiolex, by GW Pharmaceuticals, consists of CBD and now falls under a Schedule V regulation. It is approved for use among children as young as two. Of course, the state-level situation varies significantly from the federal approach.


In a 2019 publication for Contemporary Pediatrics, author Mary Beth Nierengarten discusses the state of cannabinoid-based therapies in US pediatrics today. Colorado, Florida, and California are only a few examples of states with medical cannabis programs allowing for recommendations for children under the age of 18. In many of these states, the list of approved qualifying conditions for medical cannabis includes pediatric ailments like cancer, epilepsy, nausea, muscle spasms, and end of life care. 


Still, state-based programs may require special protocols before a child receives a recommendation, including the requirement to try other federally regulated pharmaceutical options first. More than one doctor may also have to sign off before a child can receive a legal recommendation.


For parents, medical cannabis is often a medicine of last resort. When all other conventional pharmaceuticals have failed, parents turn to alternative options in a desperate attempt to fix their child’s life-threatening or life-debilitating condition. 


The desperation to cure a child has uprooted entire families from their homes to move into cannabis-friendly states. It has also created advocacy groups fighting to allow children to take medical cannabis in school. In some cases, parents begin seeking medical cannabis for their child without approved recommendations, sourcing suspect products and treating their child outside the system entirely. A lack of consistency, regulation, and information has been challenging for parents, pediatricians, and school boards.


The American Academy of Pediatrics (AAP) released an updated policy for cannabis in pediatrics in 2015. Their updated policy is conservative, stating, “The AAP opposes ‘medical marijuana’ outside the regulatory process of the US Food and Drug Administration.” However, they also tentatively acknowledge a place for cannabis in pediatric care: “Notwithstanding this opposition to use, the AAP recognizes that marijuana may currently be an option for cannabinoid administration for children with life-limiting or severely debilitating conditions and for whom current therapies are inadequate.”


Notably, since the release of this policy, there have been several developments about the potential of cannabis use for the treatment of medical conditions in children, including the approval of Epidiolex and new preclinical and clinical trials.


The Growing Potential Behind Cannabinoid Therapy in Pediatric Care


In only a few short years, medical cannabis has gone from an alternative fringe therapy for the treatment of intractable childhood epilepsy to making history as the first cannabis-derived FDA-approved drug of its kind in the US. Seizure disorders are often the first qualifying conditions approved under state medical cannabis programs. As in the case of Charlotte Figi, families often report near-miraculous improvement to intractable epilepsy following treatment with cannabis and cannabis derivatives.


Beyond straight CBD therapies for seizure disorders, there is growing scientific support for mixtures of THC and CBD, including a recent Canadian study. Yet, seizures and epilepsy are not the only areas of pediatric care getting a cannabinoid treatment.


In 2017, the Journal of Pediatrics published “Medical Cannabinoids in Children and Adolescents: A Systematic Review.” The researchers repeated the necessary but common refrain that “additional research is needed to evaluate the potential role of medical cannabinoids in children and adolescents,” but they also found evidence supporting its use for nausea and vomiting associated with chemotherapy among children. 


Numerous studies have demonstrated that THC (or synthetic preparations of THC) effectively decreased chemotherapy-induced nausea and vomiting, with a high degree of tolerability. The systematic review above detailed several case reports identifying pediatric applications of dronabinol (a synthetic cannabinoid) for chronic pain, neuropathic pain, depression, and muscle spasticity as well as anxiety and sleep. Many of these case reports have opened the door for current preclinical studies.


An Introduction to Transdermal Cannabinoids in Pediatrics


Among adults, smoking is consistently the most popular route of administration, but it is an unacceptable delivery method within pediatrics. Not only does it go against all social conventions, but it is also poorly suited for physician-directed delivery or consistency between treatments. 


Transdermal routes of administration are uniquely suited to pediatric care. There are already many approved patch-based medicines used in pediatrics today, including fentanyl, buprenorphine, clonidine, scopolamine, methylphenidate, oestrogens, nicotine, and tulobuterol. 


Transdermal cannabinoids make sense because they are non-invasive, convenient, consistent, and, most importantly, remove the need for inhaled routes of administration. With the advances made in RYAH’s Smart Patch, which allows for slow-release and precise dose control, the future of a transdermal cannabinoid application in pediatrics is apparent. 


Considerations for Future Applications


As with all types of medicine, special conditions apply for pediatric therapy—and cannabis is no different. As the AAP made clear in their 2015 policy update, there are still serious concerns about the long-term impact of chronic cannabis exposure among adolescents. 


Smart transdermal applications naturally lower the risk of over-ingestion and potential for abuse. But, finding the balance between therapeutic benefit and long-term outcomes is the next frontier of research into cannabinoids in pediatric medicine. 






Transdermal Medicine in Sports, A New Approach with Cannabinoids

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Whether national sports leagues are ready for the transition or not, cannabis is a growing component of sports medicine and athletic wellness. Players from across the sports spectrum are advocating for changing the current rules around cannabis consumption. From celebrity NFL quarterback Joe Montana, who is now a cannabis investor, to longtime MMA fighter Nick Diaz’ advocacy work, to Scott McCarron’s reported use of CBD oil for sleep, athletes are standing behind the benefits of cannabinoids.

While not all sports organizations are on board, some official opinions are changing. A primary example is the World Anti-Doping Agency (WADA), which may not allow for substances containing natural or synthetic cannabinoids, yet they have made an exception for cannabidiol (CBD). Major League Baseball has gone one step further. As of December 2019, it will treat cannabis-related offenses under protocols similar to those for alcohol.

What makes cannabis so attractive for both professional and amateur athletes? It’s a plant with the potential to soothe pain from lingering injuries, reduce inflammation, calm nerves, and improve sleep. The science is increasingly supportive of the plant’s many compounds in sports recovery. 

Additionally, topical and transdermal treatments are already well-established in sports. Muscle rubs and therapeutic transdermal patches are widely used and accepted within the sports community. Cannabinoids translate well into these methods, with research supporting their effectiveness when applied to the skin. Logically, cannabis makes sense in sports medicine.

Is Cannabis in Sports Ethical?

In study after study, the evidence-based consensus is clear: Cannabis is not a performance-enhancing substance. Although the United States Anti Doping Agency (USADA) and WADA may state otherwise, recent reviews of the literature strongly suggest cannabis may actually make athletic performance worse, not better.

In 2018, a team of researchers based in Quebec, Canada, released a nonsystematic literature review in the Clinical Journal of Sports Medicine. Their analysis explored themes within relevant publications related to cannabis (or marijuana) and sports (or athletic) performance. Following their assessment, they came to several conclusions:

  1. Athletes use cannabis for both medical and non-medical reasons.

  2. There is promising evidence supporting cannabis for pain management.

  3. Beyond the potential for abuse and mental health concerns, there is limited evidence that cannabis use is harmful to athletes.

  4. Finally, “there is no evidence for cannabis use as a performance-enhancing drug.”

When it comes to the question of sports ethics, the fourth and final point is the most important. Several studies contributed to this conclusion, starting with some of the first research completed in the 1970s. Since then, numerous scientific investigations have indicated cannabis use reduced physical work capacity and reduced maximal work capacity. There is no evidence suggesting cannabis is an ergogenic substance, which means there have been no measurable improvements to performance or stamina. 

Although many sports organizations ban cannabinoids based on a stated fear of enhanced performance, the authors of this literature review conclude otherwise. These international governing bodies may only ban cannabis out of fear of harmful side effects and the view that using “an illicit substance is contrary to the spirit of sport.” It remains to be seen how these organizers will evolve with the legalization of cannabis.

Topical and Transdermal Approach to Medicine

Topical and transdermal approaches to care and recovery are familiar to most athletes. There is already an entire industry built around sports medicine compounding, where pharmacies compound custom pharmaceuticals into topicals, creams, gels, and patches. It’s a method of application well-established in sports medicine.

Some of the most common transdermal formulas cover pain related to tissue damage (Ketoprofen). Both Cyclobenzaprine and Ketoprofen also help with muscle relaxation and even Ibuprofen is effective for pain relief. With cannabis and cannabinoids already well-established pain relievers, it makes sense there would be increasing interest in them for transdermal applications.

Cannabinoids work within the endocannabinoid system. This system manages several key operations like pain, inflammation, mood, memory, and more. Relatively recent research has uncovered endocannabinoid components inside the skin of humans and laboratory animals. Researchers are now exploring the role of the endocannabinoid system at the skin level for the management of disease, inflammation, and pain. There seems to be natural inherent scientific reasoning for exploring the therapeutic value of cannabinoids through both topical and transdermal applications.

According to “Cannabinoid Delivery Systems for Pain and Inflammation Treatment” published in Molecules in 2018, there are already several preliminary studies looking at topical or transdermal applications of cannabinoids as anti-inflammatories. The handful of studies with transdermal methods of application have almost exclusively examined preparations with CBD. Furthermore, the authors note that CBD seems particularly useful as it ”inhibits the proliferation of hyperproliferative keratinocytes” and possesses “remarkable antibacterial activity.”

An Argument for Transdermal Cannabinoids in Sports

Generally speaking, transdermal delivery comes with several immediate benefits, including improvements to bioavailability and avoidance of first-pass metabolism effect common from oral deliveries. As the RYAH Smart Patch demonstrates, there are also intelligent techniques, like the addition of a gentle heating element, to increase bioavailability even further. 

Medicines derived from cannabis, which are commonly smoked or consumed orally, lose much of their medicinal value through digestion. Cannabinoid-based medicines benefit from topical and transdermal approaches because they can increase bioavailability, which translates into smaller doses and fewer wasted products.

The transdermal format is also already well-established and familiar in sports medicine. Athletes and their doctors likely already use transdermal patches and gels for relief and recovery. Introducing cannabinoids into the mix won’t mean a steep learning curve or a new application method. A cannabis-based transdermal patch is simply a new compound presented within a familiar format. 

Most importantly, cannabinoids may be strikingly useful in sports because of the conditions they target. Pain and inflammation are ongoing issues for athletes, and these are both issues cannabinoids are proven to treat—at least according to the current research. 

As political and social opinions change, eventually there will also have to be a change among all sports leagues to reflect the world around them. With new research suggesting powerful benefits for pain, inflammation, performance anxiety, and more, the potential for cannabinoid medicine to enter into the big leagues is why so many professional athletes are risking their careers to use it already.