As consumers continue to look for alternatives to conventional pharmaceuticals for health and wellness, CBD-based therapies are rapidly making their way into the spa and wellness industry.
By: Adam Abodeely MD, MBA, FACS, FASCRS

In 2018 the value of the topical cannabis industry was roughly $350 million with a predicted compound added growth rate of 37% by 2024. CBD-based therapies have taken the health and wellness industries by storm. Individuals with skin problems, chronic pain, and autoimmune conditions represent a sizeable market due the growing interest and research into the applications of topical creams, lotions, and oils.

As a Double-Board Certified surgeon specializing in surgical oncology and gastrointestinal surgery, I have witnessed the health benefits that cannabis can provide in treating a variety of medical ailments. As humans, we have an innate desire to heal with natural remedies. I observe patients desperately searching for alternatives to conventional pharmaceutical drugs which are often associated with numerous undesirable side-effects. The cannabis plant continues to show a great deal of promise for those aspirations.

The cannabis plant is a complex organism consisting of thousands of different chemicals. The 3 largest categories of chemically active and medically relevant compounds found within the plant include 1. Cannabinoids (over 100 identified including THC, CBD, CBC, CBG, CBN, etc.), 2. Terpenes (aromatic compounds found within plants), and 3. Flavonoids which are powerful antioxidants.

The increased understanding and accessibility to cannabis has been welcomed and embraced by the millions of Americans who can attest to the beneficial effects of cannabidiol (CBD) and several other cannabinoids. As we continue to pursue ways to improve our health and cure medical ailments in a natural way, it should come as no surprise why CBD is rapidly being utilized in traditional spas, medical spas, and various other healthcare practices.

Although we still have a great deal to learn about the healing applications of cannabis, the science supporting its use continues to grow and overall early outcomes have been enormously encouraging. Much of the research on the health benefits of cannabis are criticized because they are not considered high quality by traditional medical and pharmaceutical standards. The main reason this dilemma exits is because it is difficult to conduct studies on the plant due to the uncertainty of the legal system, and the difficulty in standardization of the “drug”. As physicians, we are accustomed to working with single molecule drugs and the FDA prefers to approve single molecule drugs since the study-designs are much easier. Every cannabis plant can vary with respect to their relative ratios of cannabinoids, terpenes, flavonoids, and other chemically active compounds. This coupled with the numerous routes of administrations (inhalation, tinctures, edibles), which all have varying absorptions and effects, make treating the cannabis plant as a traditional pharmaceutical drug nearly impossible.

Although we still need more clinical studies in humans, preclinical studies (animal and bench research) have recognized cannabinoids for their ability to act as anti-inflammatories, modulate pain, act as an antibiotic and antifungal, and potentially protect against cancer cell growth. After studying the science and treating thousands of patients with cannabinoid therapy, there is no doubt that the cannabis plant possesses healing properties and can help support general wellness by supporting the human endocannabinoid system.

The human endocannabinoid system plays a crucial role in maintaining homeostasis. It is a source of balance, in other words, and helps to stabilize the various physiological processes that keep us alive, including when we are enduring stress, injury, or illness. The endocannabinoid system is alive and well in the skin as well as every other organ in the human body.

The use of CBD in traditional and medical spas which offer such services as massages, facials, body treatments, manicures, and several other body and skin services, is rapidly growing. The one thing that the majority of these treatments have in common is that they involve the application of a variety of topical salves, balms, and oils. The skin is the largest human organ and is rich in cannabinoid receptors making it an ideal target for CBD therapy. Activation of the endocannabinoid receptors in the skin can help regulate pain and inflammation, enhance the skin immune system, protect the skin from cellular damage and aid in the repair of damaged skin cells.

One of the most challenging aspects of the topical applications of cannabinoids revolves around the poor skin absorption of cannabis oils. Cannabinoids including CBD are hydrophobic meaning they don’t mix well with water. The skin is an aqueous barrier leading to difficulty in deep tissue penetration of the oils produced from cannabis. Despite this, numerous studies have reported benefits of the cannabinoids to the more superficial layers of the skin and have the potential to block ultraviolet radiation, decrease inflammation, enhance skin cell proliferation, provide anti-bacterial and anti-fungal activities. Additionally CBD-based oils are an excellent source of antioxidants. There are several ways to formulate products in ways which allow for better tissue absorption. One of these ways is through the use of terpenes. Terpenes are compounds commonly found within flowering plants that are responsible for the aroma of plants and provide several protective effects and are often touted for their own therapeutic value. The combination of all the compounds in the plant work together to provide a combined therapeutic effect commonly referred to as the “Entourage Effect”.

In order for a spa to successfully utilize CBD-based treatments there are several keys to success. First, success begins by offering the highest quality products with varying routes of administration. Choosing a high quality product is based on several factors including identifying formulations designed to have optimal absorption, and synergy with the human endocannabinoid system. This also involves the use of broad or full-spectrum products as opposed to isolates which only contain a single cannabinoid and is void of the full “entourage effect”. The products should also be transparent with regards to sourcing, ingredients, extraction techniques, and be able to provide access to 3rd party testing results.

The combination of the rapidly evolving science and growing number of product offerings will make salesforce training challenging and imperative at the same time in order to ensure the best consumer experience. If quality products are combined with educational support and adequate training, spas will likely continue to see considerable growth and consumer satisfaction.

New research on the endocannabinoid system may help us overcome the obesity epidemic
By: Dr. Adam Abodeely MD, MBA, FACS, FASCRS

It’s hard to know what to make of the relationship between cannabis and metabolism. On one hand, it’s been well-established that plant-based cannabinoids can make us hungry or put us to sleep, and popular culture has done a great deal to preserve their link to stereotypes of slackers who gorge on junk food, while remaining locked to the couch. On the other hand, I’ve found cannabis users are often highly active, and have a low body mass index (BMI), and there’s little empirical evidence that cannabis leads directly to obesity. In fact, there is ample reason to believe the opposite is true: one study from 2010 compared incidents of diabetes and cannabis use in the United Kingdom, and found that reported diagnoses of diabetes had increased between 2003 and 2006, at the same time that cannabis use in England had declined. In the United States, in states where medical cannabis is still restricted, diabetes remains a growing health problem. Nationwide, the disease affected 30.3 million Americans—nearly a tenth of the population—in 2015.

As an advocate of medical cannabis, I feel a special responsibility to explain this paradox. But frankly, it should be important to anyone who cares about the prevalence of metabolic disorders in the United States. According to the Centers for Disease Control (CDC), obesity affects approximately 93.3 million adults each year, and is directly linked with cardiovascular disease, type 2 diabetes, and certain types of cancer. In my experience as a double board certified surgeon, specializing in gastrointestinal ailments, I’ve seen how much metabolic problems can affect people’s quality of life, reduce their resistance to disease, and lead to premature death. Obese patients take longer to operate on, are more difficult to anesthetize, and are more exposed to postoperative complications–such as wound infections, pulmonary complications, blood clots, pulmonary embolisms, and death. All of this carries over into a greater burden to the country’s health care system: one study, published in 2009, linked obesity to $147 billion in annual healthcare spending.

So long as metabolic disorders pose a significant national crisis, it’s worth asking if or how cannabis might offer us a way out. But not all of the contemporary theories on cannabis and metabolism are compelling: some researchers, for example, have proposed that overeating might compete with cannabis in the brain’s reward pathways, or that sedative effects of cannabis can make people more likely to sleep than eat.[1] Others have noted a correlation between cannabis use and higher levels of physical activity, as well as decreased consumption of alcohol–both of which are key vectors in obesity. This is a somewhat more persuasive theory, but it doesn’t seem to account for the clear link between increased appetite and increased caloric intake associated with cannabis consumption.[2] If we’re going to explain how cannabinoids can make us eat more–without necessarily making us fat—we’ll probably have to look at the role the human endocannabinoid system plays in regulating the way we process food and convert food into energy.

Luckily, a lot of research has already been done in this area. One study from 2006 found that stimulating the cannabinoid receptor CB1 stimulated a greater accumulation of lipid droplets in fat cells called adipocytes, and decreased the expression of adiponectin, a protein involved in fat breakdown.[3] Two studies, from 2005 and 2009, found that the endocannabinoid modulator anandamide (AEA) accelerated the process by which adipocytes develop and expand.[4][5] Another study, from 2003, found that the CB1 receptor agonist WIN-55,212 could increase the rate at which mice synthesized fat cells, while yet another study, from 2008, found that activating CB1 receptors increased the rate at which adipocytes were secreted and proliferated.[6][7] These storage-oriented processes are helped along by AEA’s ability to increase glucose uptake into the cells, a process that is mediated by CB1 receptors, according to a study from 2013.[8] Another study, from 2008, indicated that deactivated CB1 receptors expressed by white adipocytes slowed the activity of mitochondria, the cell organelles responsible for converting glucose into energy.[9]

None of this is to suggest that there is a direct correlation between endocannabinoid activity and energy storage in the form of fat. To begin with, while there’s some evidence THC reduces the rate of fat breakdown within the visceral organs and under the skin of mice, there has been some variation observed in the parts of the body where fat metabolism was affected, in mice whose CB1 receptor gene was artificially deleted.[10][11] Moreover, a study from 2013, found that AEA can actually attenuate the synthesis of fat when converted into a compound called prostaglandin F2a ethanolamide (PGF2aEA).[12] Furthermore, there are some signs that CB1 receptor expression is directly regulated by the endocannabinoid receptor peroxisome proliferator-activated receptor d (PPARd), resulting in a “braking” mechanism on the build-up of adipocytes.[13]

You can see more of these contradictions in the way the endocannabinoid system participates in digestion and hunger. For example: studies from 2011 and 2013 have indicated that the taste of long chain unsaturated fatty acids stimulates appetite partly by increasing the abundance of endocannabinoid modulators in the gut.[14][15] At the same time, by activating endocannabinoid messengers in the small intestine, fat-containing chyme seems to cause the formation of lipid mediators that promote satiety, according to studies from 2003 and 2008.[16]

The developed world’s appetite for cheap, convenient foods have thrown an additional wrench into these mechanisms. We can see this in the way cannabinoids can accelerate the process by which sugar–an abundant ingredient in the Western diet—is converted into fat. But another troublemaker is these foods’ high levels of omega-6 fatty acids—which, in addition to increasing the risk of stroke, heart disease, and other inflammatory or circulatory dysfunctions, have been shown to break down into anandamide and 2-arachidonoylglycerol (2-AG). These endocannabinoid modulators, in turn, bind to CB1 receptors in the brain, further mediating energy uptake and storage into fat tissue, while also stimulating appetite.

For a brief period of time, doctors believed they’d found a simple solution to this complicated problem: all they needed to do was to find—or develop—a compound that had a high affinity for CB1 receptors, and could thereby block it from being activated by AEA or 2-AG.

On the surface of things, this strategy made a lot of sense. Weight loss was linked to a blockage of CB1 receptors in obese mice, for example, while the outright loss of CB1 receptors in mice adipocytes improved the metabolic profile and mitochondrial density of their fat cells. Clearly, there was some direct relationship between the loss of those CB1 receptors and fat metabolism, and rimonabant, a CB1 receptor antagonist, showed some promise as a weight-loss aid. In one study, human subjects treated with rimonabant lost weight by a rate of four to six kilograms, over a period of six to twelve months, compared to subjects who received a placebo. These results were seen alongside improvements in diabetic symptoms–including insulin sensitivity–and reductions in fat cell proliferation.[17] As a result, rimonabant was briefly applied in Europe as a treatment for obesity. The downsides were considerable, however: over time, the drug was also associated with severe psychiatric effects, including anxiety and depression, and due to these concerns, it was only available commercially for a few years before being taken off the market.

Meanwhile, there is still some interest in CB1 receptor antagonists that cannot overstep the blood-brain barrier, and therefore only function peripherally. The results have been mixed: in 2010, researchers developed a CB1 antagonist called AM6545, which had none of the emotional or behavioral effects mediated by rimonabant, and which reduced body fat levels in obese mice. The compound also seemed to improve glucose tolerance, reduced insulin levels in the blood, and increased the proliferation of adiponectin, but it remains unclear where its impact on metabolism really took place. At present, the strongest candidate for these reactions is within the liver–which is responsible for the breakdown of glucose and fats—in part because a specific genetic removal of the CB1 receptors from mice seemed to protect them from glucose intolerance, and from fat accumulation within the liver.[18] Further research into what these compounds can do has been limited, and so the search for an approach to obesity through the help of cannabis continues.

This is motivated by the abundance of clear evidence for plant-based cannabinoids’ ability to lower BMI. One 2018 review article looked at all the available investigations into cannabis use and adiposity; after removing studies that only took place over a few days (making it would be difficult to distinguish fluctuations in water weight from genuine changes in body composition), and taking out studies in which the subjects had been diagnosed with AIDS, cancer, or other serious illnesses (for which cannabis was meant to stimulate appetite and increase caloric intake), the authors took a closer look at a pool of nine studies. All of these correlated reductions in BMI with cannabis use, and in all but one of these was the correlation statistically significant.

There are some reasonable explanations for why the evidence should be so compelling. To begin with, the high level of omega-6 fatty acids in the Western diet—especially in processed foods made with refined grains and hydrogenated vegetable oils—almost certainly results in elevated levels of AEA and 2-AG. This is because omega-6 fatty acids are the precursors for the production of AEA and 2-AG.

Therefore more omega-6 fatty acids results in the increased production of our natural endocannabinoids. Levels of AEA and 2-AG which are too elevated may cause over-activation of CB1 receptors, setting off appetite signals in the brain, enhancing the tastes and smells of foods, rapidly increasing the rate at which glucose is transferred into the cells, and accelerating the degree to which fat cells develop and proliferate around the body. It’s worth keeping in mind that all of these changes are linked to metabolic dysfunction associated with obesity and type-2 diabetes, while these symptoms are typically reversed when CB1 receptors are activated less.

The underlying logic is that plant-based cannabinoids–such as THC–have the potential to correct the imbalance in AEA and 2-AG levels that are the consequence of a diet high in omega-6 fatty acids. Some of this could be seen among frequent cannabis users, for whom the CB1 receptor is down-regulated during chronic use and for several weeks after abstaining from cannabis use, according to a study from 2016.[19] This downregulation of the CB1 receptor will help offset the increased activation of the receptor despite the elevated levels of circulating AEA and 2-AG. Another, strongly supported theory is that moderate cannabis use reduces symptoms related to metabolism—including diabetes, chronic insulin resistance, and Alzheimer’s.[20] All of these conditions are marked by an abundance of inflammatory markers, which plant-based cannabinoids such as THC and CBD have been shown to slow down and attenuate.

The most interesting theory, however, has to do with what happens when people adjust their diet to include higher levels of omega-3 fatty acids. These can be found in green vegetables, certain varieties of eggs, oceanic fish, and seaweed, and have been correlated with some improvements in inflammatory or cardiovascular dysfunctions. More importantly, omega-3 fatty acids and omega-6 fatty acids are broken down by the same enzymes—including elognase and Δ-6-desaturase, both of which are produced in finite quantities. By “competing” with omega-6 fatty acids for these enzymes, omega-3 fatty acids effectively slow down the synthesis of compounds that activate CB1 receptors, including AEA and 2-AG.[21] With this in mind, it’s possible that people who take daily omega-3 fatty acid supplements–while also consuming moderate amounts of cannabis–can reduce the activation and proliferation of CB1 receptors in their fat tissue, leading to far greater improvements in BMI and other cardiometabolic risk factors than diet alone.

All of this warrants a great deal more investigation and research which is continuing to emerge and hopefully cannabis will provide another weapon against the obesity epidemic. Though the overall potential for cannabis in addressing metabolic disorders is not quite clear, there are some very encouraging signs, and I am convinced that cannabis treatments hold a great deal of promise in helping patients better manage problems related to irregular blood sugar, pancreatic cell dysfunction, insulin sensitivity, and obesity. In the future, there is ample reason to believe that cannabis can have a positive role in treating these ailments.

References

1.
Warren M, Frost-Pineda K, Gold M. Body mass index and marijuana use. J Addict Dis. 2005; 24:95–100.

2.
Sabia JJ, Swigert J, Young T. The effect of medical marijuana laws on body weight. Health Econ. 2017;26:6–34.

3.
Matias I, Gonthier MP, Orlando P, et al. Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab. 2006; 91:3171–3180.

4.
Bouaboula M, Hilairet S, Marchand J, et al. Anandamide induced PPAR-gamma transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur J Pharmacol. 2005;517:174–181.

5.
Karaliota S, Siafaka-Kapadai A, Gontinou C, et al. Anandamide increases the differentiation of rat adipocytes and causes PPARgamma and CB1 receptor upregulation. Obesity (Silver Spring). 2009;17:1830–1838.

6.
Bellocchio L, Cervino C, Vicennati V, et al. Cannabinoid type 1 receptor: another arrow in the adipocytes’ bow. J Neuroendocrinol. 2008;20 Suppl 1:130–138

7.
Cota D, Marsicano G, Tschop M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest. 2003;112:423–431

8.
Silvestri C, Martella A, Poloso NJ, et al. Anandamide-derived prostamide F2alpha negatively regulates adipogenesis. J Biol Chem. 2013;288:23307–23321.

9.
Tedesco L, Valerio A, Cervino C, et al. Cannabinoid type 1 receptor blockade promotes mitochondrial biogenesis through endothelial nitric oxide synthase expression in white adipocytes. Diabetes. 2008;57:2028–2036.

10.
Kola B, Hubina E, Tucci SA, et al. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem. 2005;280:25196–25201.

11.
You T, Disanzo BL, Wang X, et al. Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise. Lipids Health Dis. 2011;10:194.

12.
Matsusue K, Peters JM, Gonzalez FJ. PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation. FASEB J. 2004;18:1477–1479.

13.
Furuya DT, Poletto AC, Freitas HS, et al. Inhibition of cannabinoid CB1 receptor upregulates Slc2a4 expression via nuclear factor-kappaB and sterol regulatory element-binding protein-1 in adipocytes. J Mol Endocrinol. 2012;49:97–106.

14.
DiPatrizio NV, Joslin A, Jung KM, Piomelli D. Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats. FASEB J. 2013;27(6):2513–2520.

15.
Schwartz GJ, et al. The lipid messenger OEA links dietary fat intake to satiety. Cell Metab. 2008;8(4):281–288.

16.
Gaetani S, Oveisi F, Piomelli D. Modulation of meal pattern in the rat by the anorexic lipid mediator oleoylethanolamide. Neuropsychopharmacology. 2003;28(7):1311–1316.

17.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370(9600):1706–1713

18.
Tam J, et al. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest. 2010;120(8):2953–2966.

19.
D’Souza DC, Cortes-Briones JA, Ranganathan M, et al. Rapid changes in cannabinoid 1 receptor availability in cannabis-dependent male subjects after abstinence from cannabis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;1:60–67

20.
Eubanks LM, Rogers CJ, Beuscher AE, et al. A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol Pharm. 2006;3:773–777

21.
Kim J, Li Y, Watkins BA. Fat to treat fat: emerging relationship between dietary PUFA, endocannabinoids, and obesity. Prostaglandins Other Lipid Mediat. 2013;104–105:32–41.

22.
Clark, Thomas M.; Jones, Jessica M.; Hall, Alexis G.; Tabner, Sara A.; Kmiec, Rebecca L.; Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis Users. Cannabis and Cannabinoid Research. 2018;259-271:3.1

 

Evidence continues to grow for the potential power of cannabinoids to improve the relationship between gut bacteria and digestive health
Written by- Dr. Adam Abodeely MD, MBA, FACS, FASCRS

Ten years ago, few patients were asking their doctors about what bacteria could improve their gastrointestinal health. These are eventful times for anyone who is interested in how microorganisms in our gut can affect our resistance to disease, and as a double board certified surgeon, specializing in gastrointestinal ailments, I’ve paid attention to the wealth of new research into the relationship between the human microbiome and the digestive system. Since entering private practice in 2010, I’ve treated tens of thousands of patients for conditions affecting the gastrointestinal system, and I’ve embraced every opportunity to learn what I can about how gut microbiota can help people overcome the dysfunctions that bring them to my office.

This research also matters to me as someone involved in medical cannabis. Since 2015, I’ve been a member of the Society of Cannabis Clinicians and the American Academy of Cannabinoid Medicine, and I currently serve as chairman of the Dispensary Review Committee for the Association of Cannabis Specialists, applying efforts to ensure that dispensaries operate safely and responsibly, and uphold best practices when educating their customers. I’ve tried my best to stay informed—not only because cannabis therapy can be a powerful tool in the treatment of irritable bowel syndrome, nausea, colorectal cancer, ulcerative colitis, or Crohn’s disease, but also because patient outcomes and feedback have been essential to creating the line of cannabis products that I’ve developed on my own.

An exciting new frontier in the field of gastroenterology lies in finding out how cannabinoids interact with natural bacteria in the gut, building on some already-substantial knowledge of the role that the human endocannabinoid system plays in digestion.

As many people know, this role is significant. CB1 receptors, for example, are prolifically expressed by enteric nerves in the intestines, which are responsible for motility and enzyme production. Immune cells in the digestive tract, which form our first defenses against unwanted microbes entering the body, express an abundance of CB2 receptors. Cells in the stomach and intestinal tissue also express GPR 55 receptors, transient receptor potential cation channel subfamily V (TRPV), and peroxisome proliferator-activated receptors (PPARs). Together, these help the colon to maintain a healthy barrier against pathogens, altering gastric acid and intestinal secretions, regulating appetite, and surveilling the growth of potential cancers.

There is a wealth of evidence that plant-based cannabinoids can restore the epithelial membrane, and help it recover from stress or inflammation. Mice with colitis, for example, showed improved signs of colon injury—including reduced edema in mucosal tissue, and regeneration of digestive glands—after being treated with CBD [1]. CBD has also been shown to increase zona occludens-1 mRNA expression in leaky intestinal tissue, down-regulating enzymes like nitric oxide synthase (iNOS), and inhibiting the release of cytokines and reactive oxygen species associated with inflammation [2].

Given the richness of these interactions, cannabis holds tremendous potential for treating irritable bowel syndrome (IBS), a disorder that affects approximately 9-23% of adults worldwide [3]. Symptoms such as abdominal pain, diarrhea, bloating, and altered bathroom habits can be brought on by stress or a meal, but even if they appear without a visible trigger, the endocannabinoid system can have a role in managing them: CB1 receptors, for example, have been shown to inhibit muscle contractions in the intestine, while CB2 receptors expressed by immune cells can help to reduce the amount of inflammation within the intestinal lining. In addition to numerous patient surveys, preclinical data, and anecdotal data, one randomized study looked at 52 patients with IBS, and found that subjects who received cannabinoid therapy had substantially fewer colonic contractions during fasting states—and reported a significant reduction in bowel contractions and motility—compared to those who received a placebo [4].

Cannabis can also offer a great deal of hope for people with inflammatory bowel disease (IBD), a condition brought on by an abnormal immune response within our gastrointestinal tract. In advanced stages, it can develop into Crohn’s disease, which is characterized by high levels of inflammation in the intestinal lining. By activating CB2 receptors, which can slow the release of inflammatory cytokines, cannabinoids can help to bring inflammation down to a more appropriate (“homeostatic”) level, and in my clinical practice, the majority of my IBD patients who enter cannabis into their treatment plans report significant relief from abdominal pain and diarrhea, and show improvements in overall quality of life. This is in correlation with the other published surveys, anecdotal data, and some smaller preclinical studies: animal models, for example, have shown decreased IBD symptoms with the introduction of plant-based cannabinoids like THC, CBD, and CBG, or with synthetic cannabinoid analogs such as O-1602 and WIN-55,212-2 [5].

Most dramatic of all has been the impact of cannabis on the lives of patients with colorectal cancer (CRC), which is the cause of 50,000 deaths every year [6]. Part of this is in the treatment of cancer- or chemotherapy-induced pain: by binding to receptors on a nerve cell transmitting a pain signal, endocannabinoid neuromodulators, such as anandamide (AEA) or 2-arachidonoyl-glycerol (2-AG) have the power to muffle that signal by inhibiting the release of neurotransmitters such as histamine, bradykinin, GABA, or serotonin. In support of this pathway, the phytocannabinoid CBD has been shown to reduce the expression of fatty acid amide hydrolase (FAAH), an enzyme that typically breaks down the endocannabinoid AEA, thus activating a negative feedback mechanism to slow a pain signal down [7].

Cannabis also has a well-established role in reducing the nausea and vomiting induced by chemotherapy, which is cited by 40%-90% of patients undergoing this type of treatment, including those who already use anti-nausea or antiemetic drugs. Numerous clinical studies have highlighted the efficacy of cannabis treatments in this area, particularly among patients who cannot tolerate oral medications due to nausea, and who seek out cannabis in its inhalational form. This offers a potential solution to a major problem: one study from 2015 found that a third of cancer patients—who received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist and corticosteroid medications—were not able to overcome nausea and vomiting, despite the use of a prophylaxis [8]. In 2017, in recognition of the help cannabis could bring, the National Academy of Medicine, Science and Engineering made the conclusion that, “there is conclusive evidence that oral cannabinoids are effective antiemetics in the treatment against chemotherapy-induced nausea and vomiting [9]”.

Furthermore, the endocannabinoid system has indicated some ability to identify and destroy gastrointestinal tumor cells, reduce blood flow to tumors, and inhibit the ability of these tumors to migrate and spread. On one hand, it’s worth remembering that cannabinoid therapy for CRC is extremely complex, and that caution must be used when recommending cannabis to treat it, since certain cannabinoid receptors, when activated, may in fact promote tumor growth and progression. On the other hand, activation of the CB2 receptor has been directly connected to tumor suppression, and there is a wealth of evidence that activation of CB2 is involved in assisting our immune system to detect certain tumor cells before they develop into malignancies [10]. It’s also worth mentioning that many of the conventional pharmaceutical agents used to treat IBD are often associated with significant side effects and toxicity; they have the power to make patients more susceptible to other opportunistic infections and even cancer. Moreover, by using cannabis in the place of opioid medications for the treatment of pain, patients can avoid unpleasant side-effects, including constipation, fatigue, somnolence, and sedation, as well as serious addiction and dependency risks—all of which, in turn, can affect the loved ones who are caring for a person with CRC.

Again and again, researchers have found that there is a direct link between the endocannabinoid system and our immune system’s response to gastrointestinal disease, and the work done by bacteria is crucial to this relationship. Of course, the microbiome is also crucial to the proper function of so many other organ groups. Patients with hepatic encephalopathy, for example, showed significant improvement after being treated with oral antibiotics, in a study during the 1990s that opened up discussion about the existence of a gut-brain axis (GBA). More recent investigations have found that certain gut bacteria can help people resist symptoms of anxiety and depression; there is also some evidence connecting imbalances in gut bacteria with some of the more severe consequences of autism [11].

At the same time, the disruption of the GBA has been closely associated with changes in intestinal motility and strength. In some cases, this can begin with the use of antibiotics, leading to bacterial overgrowth, and the occurrence of post-infectious IBS. I’ve seen this many times in my practice: someone with an infection will be prescribed antibiotics, leading to a severe adjustment of their intestinal flora. Ultimately, antibiotics can make inflammation even worse, so that soon, steroids like prednisone are thrown into the mix, leading to even further immune dysfunction. Another consequence of a mistreated microbiome is “leaky gut syndrome,” a term used to describe changes in the ratio of gut bacteria that leads to inflammation, affecting the permeability of the intestinal walls. When that ratio is wrong, some otherwise helpful microorganisms can form a colony that penetrates the mucosal lining of the colon.

This process can furthermore lead to CRC. It’s worth noting that about 80% of CRC cases are sporadic—meaning the patient had no family history of the disease. Factors like diet or alcohol consumption can affect our risk, but what we’re starting to learn is that inflammation associated with the disease is often a direct response to imbalances in gut bacteria. In response to other changes in the genetic and immunological microenvironment of the gut, tumor cells in an otherwise normal epithelium can begin to spread and proliferate, forming a polyp that protrudes from the inside of the colon, and sometimes becomes malignant [12]. Microbes such as E. coli can increase the frequency of mutation, for example, while Enterococcus faecalis can stimulate the release of high levels of reactive oxygen species, a mediator of inflammation, which can also do damage to DNA [13] [14] [15]. In earlier stages, it’s not at all unusual for this process to manifest itself in IBD, which is why the American Cancer Society guidelines recommend screening colonoscopies every 1-2 years for patients with these conditions.

It is also why cannabis therapy can be appropriate. There is a wealth of evidence that the endocannabinoid system can help to manage inflammation, keep endothelial membranes healthy, improve cellular regeneration, and block reactive oxygen species, which promote the growth of certain tumors. By activating CB1 receptors in the intestine, CBD has been shown exert anti-proliferative effects on colorectal carcinoma cells, and several studies have indicated that cannabinoids can prevent the growth and migration of epithelial malignancies in both CB1 and CB2 receptors [16].

Cannabis may furthermore have a role in altering gut microbiota to stimulate weight loss, which can help obese patients reduce their risk of CRC. This was borne out in a study from 2015, in which lean and obese adult male mice were treated daily with small doses of THC for a period of four weeks. The authors found that THC reduced weight gain, fat mass gain, and energy intake in the obese mice, in addition to an increased ratio of the bacteria Firmicutes to Bacteroidetes, which has been correlated with the progression of colorectal cancer [17]. Though it is unclear whether these changes in gut microbiota caused the weight-loss associated with THC, or vice versa, these are extremely interesting findings.

Over three thousand years ago, cannabis was mentioned in the Atharva Veda, a collection of religious and ethical texts, written in Sanskrit, which remain a primary source for information about the customs, beliefs, and scientific advances of ancient India [18]. The plant was recommended as a sedative and spasmolytic, and, in moderate use, was said to support healthy digestion, and in the modern era, moderate cannabis use continues to have a place in Ayurvedic therapy, based on its ability to stimulate the nervous system, and resolve intestinal dysfunction. In a sense, Western medicine is simply catching up with these insights, as evidence continues to accumulate for the potential power of cannabinoids to improve the signaling that exists between gut bacteria and the human endocrine, lymphatic, and nervous systems. Witnessing these advancements, and seeing how they can help my patients, has made it deeply rewarding to be a gastrointestinal surgeon and specialist in cannabinoid therapy in the present day.

References

1. Romano, B.; Borrelli, F.; Fasolino I.; Capasso, R.; Piscitelli, F.; Cascio M.G.; Pertwee R.G.; Coppola, D.; Vassallo, L.; Orlando, P.; Di Marzo, V.; Izzo1, A.A. The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis. Br J Pharmacol. [Online] 2013, 169(1), 213–229. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632250 (accessed Feb 3, 2019).

2. Alhamoruni, A.; Lee, A.C.; Wright, K.L.; Larvin, M.; O’Sullivan, S.E. Pharmacological effects of cannabinoids on the Caco-2 cell culture model of intestinal permeability. J Pharmacol Exp Ther. [Online] 2010, 335(1), 92-102. https://www.ncbi.nlm.nih.gov/ pubmed/20592049 (accessed Feb 3, 2019).

3. Saha, Lekha; Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine. World J Gastroenterol. [Online] 2014, 20(22), 6759–6773. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051916 (accessed Feb 3, 2019).

4. Esfandyari, T.; Camilleri, M.; Busciglio, I. Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study. Am J Physiol Gastrointest Liver Physiol. [Online] 2007, 293, G137–G145 . https://www.ncbi.nlm.nih.gov/pubmed/17395895 (accessed Feb 3, 2019).

5. Ahmed, W.; Katz, S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (N Y). [Online] 2016, 12(11), 668–679. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193087 (accessed Feb 3, 2019).

6. American Association for Cancer Research: Colorectal Cancer Screening in the United States. https://www.aacrfoundation.org/Science/Pages/colorectal-cancer-screening-united-states.aspx (accessed Feb 2, 2019).

7. Bisogno, T.; Hanuš, L.; De Petrocellis, L.; Tchilibon, S.; Ponde, D. E.; Brandi, I.; Moriello, A.S.; Davis, J.B.; Mechoulam, R.; Di Marzo, V. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. [Online] 2001, 134(4), 845–852. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017 (accessed Feb 3, 2019).

8. Warr, D.G. Chemotherapy- and cancer-related nausea and vomiting. Curr Oncol. [Online] 2008, 15(Suppl 1), S4–S9. https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC2216421 (accessed Feb 3, 2019).

9. Parker, L. A.; Rock, E. M.; Limebeer, and C. L. Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol. [Online] 2011, 163(7), 1411–1422. https://www.ncbi.nlm.nih.gov/pmc/articles (accessed Feb 3, 2019).

10. Śledziński, P; Zeyland J; Słomski R.; Nowak A. The current state and future perspectives of cannabinoids in cancer biology. Cancer Med. [Online] 2018, 7(3), 765-775. https://www.ncbi.nlm.nih.gov/pubmed/29473338 (accessed Feb 3, 2019).

11. Carabotti, M.; Scirocco, A.; Maselli, M. A.; Severia C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. [Online] 2015, 28(2), 203–209. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4367209 (accessed Feb 3, 2019)

12. Brennan C. A.; Garrett W.S. Gut Microbiota, Inflammation, and Colorectal Cancer. Annu Rev Microbiol. [Online] 2016, 70, 395-411. https://www.ncbi.nlm.nih.gov/pubmed/ 27607555 (accessed Feb 3, 2019)

13. Wang, X.; Allen, T.D.; May, R.J.; Lightfoot, S.; Houchen, C.W.; Huycke, M.M.; Enterococcus faecalis induces aneuploidy and tetraploidy in colonic epithelial cells through a bystander effect. Cancer Res. [Online] 2008, 68(23), 9909–17. https://www.ncbi.nlm.nih.gov/pubmed/19047172 (accessed Feb 3, 2019).

14. Cuevas-Ramos, G.; Petit, C.R.; Marcq, I.; Boury, M.; Oswald, E; Nougayrède, J-P. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc. Natl. Acad. Sci. USA. [Online] 2010, 107(25), 11537–42. https://www.ncbi.nlm.nih.gov/pubmed/20534522 (accessed Feb 3, 2019).

15. Nougayrède, J-P.; Homburg, S.; Taieb, F.; Boury, M.; Brzuszkiewicz, E. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. [Online] 2006, 313(5788), 848–51. https://www.ncbi.nlm.nih.gov/pubmed/16902142 (accessed Feb 3, 2019).

16. Alhamoruni, A.; Lee, A.C.; Wright, K.L.; Larvin, M.; Sullivan, S.E. Pharmacological Effects of Cannabinoids on the Caco-2 Cell Culture Model of Intestinal Permeability. Journal of Pharmacology and Experimental Therapeutics. [Online] 2010, 335(1), 92.

https://www.ncbi.nlm.nih.gov/pubmed/20592049 (accessed Feb 3, 2019).

17. Cluny, N.L.; Keenan, C.M.; Reimer, R.A.; Le Foll, B.; Sharkey, K.A. Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol. PLoS One. [Online] 2015, 10(12), https://www.ncbi.nlm.nih.gov/pubmed/26633823 (accessed Feb 3, 2019).

18. Thomas R.; Griffith, H. The Hymns of the Atharvaveda, Volume 1; E. J. Lazarus & Co.: Benares, 1895; p 46.

Written by- Mary Clifton, MD

Chronic or acute pain, stress, fatigue, CBD works in the body in all of these situations, because
of the existing endocannabinoid system. Your body already has CB1 receptors located
throughout the peripheral, central nervous system, and CB2 receptors located throughout the
immune system, and also in the muscles, and skeleton. Your body, when there are episodes of
pain, stress, or fatigue develops a stress response. A system that’s primarily mediated by the
hypothalamic-pituitary-adrenal axis, cortisol, norepinephrine, epinephrine, serotonin, and
dopamine all work in this fight or flight phenomenon that it needs to be restored to equilibrium
after the episode of stress, or pain.

And, that’s where the endocannabinoid system comes in. It plays a significant role by increasing
the levels of endocannabinoids, and receptors in areas of pain and stress, and that helps to
restore equilibrium, and control the amount of inflammation, or stress that the body experiences
in these settings. This system is already in place in your body. There are CB1 and CB2 receptors,
and the endocannabinoid, endo meaning coming from within, and cannabinoids being the
molecules, the cannabinoids, anandamide, and 2-AG being the predominant ones contribute to
this termination of a stress response that is also reasonable, and valuable in the setting of
treating issues of pain, or stress, and fatigue that leads to problems with appetite, sleep
disorders, or chronic pain, or inflammation.

The CB1 receptors are expressed throughout the peripheral, and central nervous system in the
GABA and glutaminergic nerve terminals, but there are also effects of CB receptors in serotonin,
norepinephrine, and dopamine terminals in the central nervous system, the brain, and the spinal
cord, but also in the peripheral nervous system. These nerves are found throughout the body
and help us to feel our hands, feet, as well as to move our bodies, and be aware of the sensation.
The brain area where motor control lies is also where situations such as tremors or muscle
spasms originate. These areas are also the source of memory and cognition impairment which is
impacted by anxiety, lack of sleep, stress or PTSD. This area is rich in CB1 receptors.

CB2 receptors are located primarily in the immune system, the spleen, lymph nodes, and the bone marrow, but also in the musculoskeletal cells. These cells also respond to stimulation with CBD, so our endocannabinoids that the body naturally produces, the anandamide, and 2-AG are found all over the body, but studies have shown that in areas of chronic inflammation such as arthritic joints, there is a higher concentration of endocannabinoids suggesting the up-regulation of those molecules, and an up-regulation of the CB receptors similar to other body systems. When you need control of inflammation, the body brings additional receptors and additional endocannabinoids to the sites. It makes sense that CBD would be effective for the treatment of chronic non-cancer pain, insomnia, stress and anxiety because it’s going to activate the same CB1, and CB2 receptors that already exist over your entire body system. This restores equilibrium and plays a significant role in terminating a stress response either due to chronic stress, inflammation, or pain.

Despite solid clinical data, CBD is showing a great deal of promise for combating the immediate as well as long-term consequences associated with menopause.
By Dr. Adam Abodeely MD, MBA, FACS, FASCRS

Natural menopause is defined by the permanent cessation of a women’s natural menstrual cycle for 12 consecutive months. Following menopause, women enter post-menopause. 95% of women develop menopause between the ages of 45-55 years of age and the experience for women is extremely individualized. Although some women may breeze through menopause with very few problems, approximately 80% of women experience significant symptoms which can affect a women’s health and well-being. However, only 20-30% of women seek medical attention for their symptoms. Some women simply accept this as a natural part of aging while others struggle to deal with the physical and emotional changes which occur during menopause.

Menopause occurs as a result of ovarian follicular depletion which results in decreased levels of estrogen. These decreased levels of estrogen can have significant immediate, as well as the long-term, consequences [1-2].

Immediate signs & symptoms of menopause:

Hot Flashes are the most common symptoms of menopause occurring in 80% of menopausal women. Hot flashes typically begin as flushing of the face and chest and can last for several minutes and can be associated with excessive perspiration and anxiety.

Sleep disturbances and insomnia during menopause are multifactorial and can occur as a result of hot flashes, depression and anxiety. This condition occurs in approximately 30-40% of women during menopause but can increase and affect as many as 50% of women towards the end of menopause [3].

New onset depression and anxiety is significantly increased during menopause and is believed to be a result of both decreased estrogen coupled with the emotional experience that can occur during this transitional time in life [4].

Cognitive changes including memory loss and difficulty concentrating are frequently reported symptoms occurring during menopause. These changes may occur as a result of a decline in estrogen in conjunction with the increased rates of depression and anxiety which may occur during menopause.

Pain syndromes including ligament and joint pain, breast pain, or menstrual migraines are well-documented and frequent problems for menopausal women [5-6].

Genitourinary changes including urinary incontinence, vaginal dryness, and vaginal atrophy occur as a result of diminished estrogen. At the same time, the decreased estrogen levels also result in decreased vaginal lubrication, diminished sexual drive/function, as well as painful intercourse.

Long-term consequences of estrogen deficiency (post-menopause):

The risk of cardiovascular disease increases after menopause as a result of decreased estrogen as well as changes in cholesterol and lipid profiles.

Bone loss for women begins during menopause and the rate of bone density loss has been correlated with estrogen deficiency. This can also lead to increased rates of osteoarthritis [7].

Skin changes occur during and after menopause as a result of decreased production of collagen which is essential for skin integrity and is heavily influenced by estrogen.

Towards the end of menopause and during the postmenopausal period, women frequently experience weight gain and an increase in central fat distribution. This also is a result of diminished estrogen which tends to shunt excessive energy into fat storage as opposed to the creation of lean muscle mass [8].

Traditional pharmacologic treatments for combating menopausal and postmenopausal symptoms have included hormone replacement therapy utilizing either unopposed estrogen therapy versus combined estrogen–progestin therapy. Although there appears to be some benefit from utilizing hormone replacement therapy, as women age the risks associated with hormone replacement therapy have been shown to outweigh the benefits associated with their use particularly in women over the age of 50-60. Studies from the Women’s Health Initiative (WHI) have shown that there are increased risks associated with hormone replacement therapy. These risks include blood clots, pulmonary embolism, stroke, coronary heart disease, and particular cancers including breast cancer and endometrial cancer. As a result of these risks, women continue to look for alternatives to conventional pharmaceuticals and hormone replacement therapy.

There is a tremendous opportunity to utilize CBD and cannabinoid-based products for women, particularly those who are menopausal or postmenopausal. Although there is very little data specifically looking at CBD and cannabinoid therapy for menopausal and postmenopausal woman, evidence continues to grow for the use of CBD products for several of the conditions associated with menopause and postmenopausal women. For example, CBD and cannabinoid therapy has shown promise for both depression and anxiety [9]. Treating menopausal women for depression anxiety can have significant positive effects including an improvement in overall quality of life. Additionally, treating depression anxiety with cannabinoid-based therapies may also improve cognitive function as well as sleep disturbances which are often linked to depression and anxiety during menopause.

CBD as well as other cannabinoids have been shown to have significant effects on pain and inflammation. The joint pain, breast pain, and menstrual migraines experienced during menopause are frequently treated with several medications including anti-inflammatories, opioids, and hormone replacement therapy. Given the anti-inflammatory, antioxidant and pain relieving properties of CBD, this plant-based compound offers an excellent alternative to conventional pharmaceutical agents and treating some of the pain syndromes associated with menopause [10-11].

Cannabinoid-based products with CBD are showing a great deal of promise not only to treat the symptoms of menopause but may also potentially protect women against future health problems including cardiovascular disease, stroke, declining cognition, cancer, and osteoporosis. Several of these ailments are associated with increased inflammation, unhealthy lipid profiles, and oxidative damage to healthy cells. For example, osteoporosis continues to be a challenging condition to treat and can lead to decreased strength, fractures, and imposes a significant burden on our health care system. Activation of particular cannabinoid receptors have been shown to increase the activity of bone cells called osteoblasts. These cells are responsible for bone formation and cannabinoids have been shown to increase the activity of osteoblasts thereby increasing bone production to combat osteoporosis [12]. Additionally the anti-inflammatory and antioxidant effects of the cannabinoids may help prevent several age-related illnesses and improve quality of life.

The skin is the largest organ of the human body and is dense with endocannabinoid receptors making the skin an excellent target for cannabinoid therapy and some of our best data we have is on the use of cannabinoids for particular skin conditions. Several cannabinoids have been shown to have skin healing properties due to their anti-inflammatory, antioxidant effects as well as their interaction with the endocannabinoids system [13]. There is also evidence that certain cannabinoids are effective at protecting her skin from ultraviolet radiation exposure and may decrease rates of some associated skin conditions including skin cancers and aging skin. Healthy skin is not only a sign of wellness but also can be an important part of a women’s self-esteem and quality of life.

Combining cannabinoid-based therapies with other plant-based and natural compounds offer a unique opportunity to provide a safe and natural alternative to conventional hormone replacement therapy, antidepressants, and other pharmaceutical agents for the treatment of menopause. There are several ways to formulate and optimize a CBD based product not only through the cannabis plant but also by utilizing several other potential and natural alternatives. Women over the age of 50 who are menopausal require increased consumption of particular vitamins and nutrients including calcium, vitamin D, and vitamin E. Additionally there are several other natural alternatives which show promise to combat menopausal symptoms and aging including resveratrol, flaxseed, rhubarb extract, and black cohosh (just to name a few). Formulating products utilizing cannabinoid therapy, terpene therapy, and several other alternative and natural nutrients will continue to provide women with an excellent alternative to conventional pharmaceutical agents and hormone replacement therapy.

1. Taffe JR, Dennerstein L. Menstrual patterns leading to the final menstrual period. Menopause 2002; 9:32.

2. Harlow SD, Gass M, Hall JE, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 2012; 97:1159.

3. Hollander LE, Freeman EW, Sammel MD, et al. Sleep quality, estradiol levels, and behavioral factors in late reproductive age women. Obstet Gynecol 2001; 98:391.

4. Maki PM, Freeman EW, Greendale GA, et al. Summary of the National Institute on Aging-sponsored conference on depressive symptoms and cognitive complaints in the menopausal transition. Menopause 2010; 17:815.

5. Szoeke CE, Cicuttini FM, Guthrie JR, Dennerstein L. The relationship of reports of aches and joint pains to the menopausal transition: a longitudinal study. Climacteric 2008; 11:55.

6. Dugan SA, Powell LH, Kravitz HM, et al. Musculoskeletal pain and menopausal status. Clin J Pain 2006; 22:325.

7. Neer RM, SWAN Investigators. Bone loss across the menopausal transition. Ann N Y Acad Sci 2010; 1192:66.

8. Lee CG, Carr MC, Murdoch SJ, et al. Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. J Clin Endocrinol Metab 2009; 94:1104.

9. De Mello Schier AR, de Oliveira Ribeiro NP, Coutinho DS. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS Neurol Disord Drug Targets. 2014;13(6):953-60

10. Costa B, Trovato AE, Comelli F The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007 Feb 5;556(1-3):75-83.

11. Booz GW Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011 Sep 1;51(5):1054-61

12. Idris AI, Sophocleous A, Landao-Bassonga E. Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells. Cell Metab. 2009 Aug;10(2):139-47.

13. Bíró T, Tóth BI, Haskó G,The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009 Aug;30(8):411-20

Benjamin-Alexandre Jeanroy, of Paris-based cannabis consultancy Augur Associates, outlines his vision for the emerging European adult-use markets

This article was first published in English on Business Cann and in French on Newsweed

CANNABIS prohibition in Europe has been a failure.

It has not only failed to protect citizens, especially young people, but it has also placed a heavy burden on public finances whilst allowing criminal groups to thrive. 

Inspired by early 20th Century conservative policy movements in South Africa, Egypt and the US, cannabis prohibition is now being reversed in a growing number of these jurisdictions. 

Europe has stood still until now. Following Uruguay in 2013, Canada in 2018, and Mexico in 2021, Switzerland and the Netherlands began their own legalisation moves in 2021. 

Luxembourg and Malta are exploring novel decriminalization schemes, so as we move past the binary choice in favour or not of legalisation, where should the rest of the continent – and in particular Germany – head next?

Countering Black Market – A Priority

Cannabis legalisation remains highly complex. Its success relies on operational implementation and strategic choices made in line with the chosen – explicit and implicit – goals of the reform. 

In a European context, this should focus on several specific objectives. They could serve as the basis for realistic, sustainable and evolving regulatory models that will finally enable states to regain control of a situation that previous public authorities have allowed to fester for far too long. 

These objectives are concerned primarily with:

-fighting back the criminal market;

-giving meaning anew to the rule of law, to properly protect the youth, and refocus on use disorders;

-developing a sustainable and vibrant European cannabis industry.

They could be financed by direct and sensible tax revenues and controlled by a regulatory authority. Several dimensions must be taken into account for the success of this strategy: 

Cost – the price must initially be below the black market price

Supply – avoid limits on the type of product and the concentration of active ingredients;

Accessibility – overly restrictive limits on the maximum purchase quantity, or prohibition on delivery and online sales,

And finally inclusiveness – social justice factors should be central.

The latter is perhaps structurally the most important challenge. In that regard, the UK charity Release has published a report highlighting 14 guiding social equity principles to be integrated into a future legally-regulated cannabis market. 

In a complementary fashion, the transnational NGO the International Drug Policy Consortium, has published its principles for the responsible legal regulation of cannabis. 

Another exceptionally robust work is to be found with the Transform Drug Policy Foundation, whether with their Blueprint for Cannabis Regulation or their comprehensive overview of cannabis regulation in Canada; as-well as with the Cannabis Sustainable Development Toolkit from FAAAT.

Making Cannabis Accessible

Today, European users have almost instant access to cannabis, via an increasingly sophisticated illegal supply, accessible throughout the continent, with a large number of physical and online distribution entry points. 

Therefore, a successful legal transition must incorporate similar levels of accessibility and convenience for distribution. 

For example; specialised shops, social clubs, online purchase and home delivery. Distribution licences may also be made conditional to staff training in basic knowledge of cannabis and harm reduction.

Legalisation policy makers must learn from current foreign mistakes and not strangle economic actors with costly and abusive regulations that would form a strong barrier to entry for small producers, and by ripple effect, allow the black market to thrive.

Uruguay found creative ways to tackle the issue. Retail in pharmacies was one of these. Initially co-opting the publicly-legitimate and economic pharmacy sector, it quickly became one of the major hurdles of the regulation, severely impacting the capacity to compete against the black market.

State monopolies have shown their limitations. Without a competitive market, pricing strategies, appropriate taxation and non-discriminatory access, no efficient legalisation can be achieved. 

As a consequence, crime remains and states continue to mobilise resources without meaningful results, while fuelling prohibitive discourses. Quebec is also a good example of such regulations still embedded in prohibitionist biases.

Not Another Quebec, Please!

By over-regulating – THC limits, and production quotas – public authorities perpetuated a system that is not fit-for-purpose, leading to major stock-outs, long queues at sales outlets, and a generally disappointing access scheme.

Elsewhere in Canada, while price and availability remain a strong component of the competitiveness of the legal market, the issue lies more with product quality. 

Luckily, things are improving with newly-arrived micro-producers, whose craft, quality crops challenge larger established medical cannabis producers.

An exciting development is that of the Dutch cultivation scheme, an experimentation to legally supply coffee shops in select voluntary cities. 

Albeit laboriously, 10 growers were approved with a range of cannabis varieties able to satisfy the diversity, sophistication, and intensity of the demand. Effects on crime reduction, public health, and the environment, will be measured. Producers will not be required to be pharmaceutical grade.

Germany – Europe’s heavyweight – can set some of the continent’s cannabis regulatory standards. However, being the biggest market for medical use doesn’t guarantee success.  

Standardisation Analysis Is Key

Medical cannabis companies, in regard to so-called ‘recreational’ users, may not be the most appropriate to influence future adult-use regulations. 

Indeed, the difference between these two markets not only lies in their distinct production and  distribution processes, but in their very raison d’être. 

The former exists to respond to therapeutic needs of patients; the latter, to overcome the illicit market. While the former needs, to a certain extent, to be regulated by pharmaceutical rules, dubbing the latter in a similar fashion shows a deep misunderstanding of the adult-use market and what its consumers are looking for and ready to pay for.

Most of today’s medical companies cannot produce cannabis that will compete in quality with what is available in the street, even if it can be looked upon as ‘cleaner’. By definition, pharmaceutical quality production will tend towards stabilisation and reproducibility, as-well-as a limited pool of seed varieties. 

This is the exact opposite of what an adult-use market needs. 

Under the guise of quality and safety its more-or-less a front for corporate greed, and a limitation on the right to grow is essentially a relic of prohibition – inhibiting reform from the word go. 

It’s drug policy 101 – if you do not properly regulate to answer the demand, illicit markets will.

By contrast, allowing production and distribution of cannabis through a flexible and financially-accessible licensing system, and appropriate regulation, can ensure compliance with health standards for human consumption without falling into the pharmaceutical realm.

Cannabis production could be controlled by the implementation of a seed-to-consumer tracing system following sanitary and phytosanitary standards of other agricultural products. 

A system of public subsidies for analyses should also be contemplated in order to make product control accessible to all at the various links in the production chain.

In the short term, the regulatory authority could also set up its own analysis units in order to ensure optimal price reduction and quality control throughout the production and processing chain. 

In the long term, a proper analysis framework and standardisation are what is solely required for quality control in the adult use market: one that ensures the product is fit for consumption with no pesticides, heavy metals, and mould, and can determine the exact composition of the product.  

Right To Grow – A Civil Right

To complement these market dimensions, it remains essential to allow personal cultivation, which represents only a fraction of users and will continue to exist regardless. 

This right must be granted, as it is fundamentally based on individual freedom. In addition to being a structural part of the history of the modern cannabis reform movement, it also echoes many European examples of legal private production of alcohol and tobacco. 

Cannabis Social Clubs (CSC) should also be allowed in order to create virtuous, non-commercial, short-circuit eco-systems. They are great tools to foster a fine-tuned policy of harm reduction for users and producers alike, while pooling resources to produce and share harvest. 

When properly regulated, such as the proposal of the Catalan parliament in 2015, it gives sufficient control on the production by the CSC, to assure quality standards for the consumers. Research has shown peer-supervised consumption within CSC to be less risky. 

With no profit incentive to increase sales CSC’s offer a more prudent and public health-oriented alternative allowing to counterbalance larger-scale retail markets dominated by commercial interests. 

In that spirit, the whole regulation process around the private sector should rely upon Ecological, Social, and Governance (ESG) guidelines, encompassed within the UN 2030 Sustainable Development Goals. This last framework allows for cannabis to make an impactful difference in our world.

In this spirit, the Social and Solidarity Economy sector is probably the best suited to respond competitively to the needs of millions of consumers. It also provides a structure that avoids falling into a pure mercantilism, detrimental to public health. If producers are to be free to experiment with different models, adherence to the rules of organic or living soil production should therefore be encouraged.

Wine Drinkers Don’t Need EU-GACP Grapes

In addition to the passive protection offered by the Nagoya UN Protocol on Access to Genetic Resources, it is essential to deploy proactive sustainable development and conservation strategies. 

To use the Capsicum analogy, Appellations of Origin (AOs) and Geographical Indications can be relevant tools to enhance the market value of quality, specificities, and organic properties linked to the origin and traditional practises of cultivation and/or processing.

When drinking, consumers are not looking for EU-GACP grapes turned into wine within EU-GMP facilities. 

Consumers will look at the cepage, the land, the AOs and other quality indicators; an organic label perhaps, and the year of production. 

For a similarly sophisticated cannabis market, consumers will pay attention to genetic information and cultivar lineage, cannabinoids and terpenes quantified presence; how and where it was produced; but also increasingly if it was grown sustainably and organically, hence progressively, it’s terroir. 

Continental Europe (Albania, Greece, Southern Spain), but also overseas territories of France, the Netherlands, or the Canary islands, could establish standards for designating areas of origin for cannabis products and facilitate establishing AOs for each of the practises, standards, and varieties applicable to cannabis within specific geographical areas. 

Like the wine market, there will be shares for cheap and lower-quality products, as well as for highly qualitative  – yet accessible – products. And similarly, once a consumer tastes good wine or cannabis, it is very hard to go back. 

Subjecting cannabis to both logics – market and non-profit – will significantly shrink illicit markets: by allowing for the combination of free choice of products and prices, making the aspiration of adequate-competitive accessibility and a sufficiently-high quality of service. 

Such supply and quality allow for prevention, education and harm reduction decent policies, focusing in particular on vulnerable groups and people at risk.

By becoming mainstream in that fashion, cannabis can forge its own path. Global experiences give valuable insights for Germany and the greater EU to follow: success is based on contextually based, agile, goal-driven, realistic and sustainable regulations. 

This article was written & published by East Fork Cultivars.

There are compelling and urgent reasons for informed consumers to choose sungrown cannabis. These include:

  • experiencing the full natural expression of the plant

  • a 99% lighter carbon footprint (or even carbon-negative impact) toward climate change

  • the enrichment of soil and ecosystems through regenerative farming

Read on for exactly why and how these factors matter so much.

Nature’s Full Expression

At East Fork, our cannabis is grown outdoors, under the sun, in living soil.

“Growing with the sun is incredibly efficient, and the most sustainable way to cultivate – and it produces superior cannabis!” declared East Fork CEO Mason Walker. 

Cannabis connoisseurs – as well as scientists – have long noted that cannabis grown outdoors in an organic environment offers a more robust expression of the plant’s character than if it were grown indoors under controlled conditions.

“The sun has a magnificent spectrum of light that technology hasn’t quite been able to mimic yet,” Mason explained. “That full-spectrum energy contributes immensely to the development of the many compounds, including terpenes, that make cannabis such a dynamic plant.” 

The concept of terroir – from the wine world – extends to the nuances of sungrown cannabis. Terroir is the unique flavor and character imparted to a consumable farmed good by the specific characteristics of the environment in which it is produced, including local climate, soil, and topography. 

Cannabis terroir means that savoring a plant product grown in a certain place during a certain year is a special and distinct experience.

“The stress of growing outside can also be beneficial,” Mason notes, “as stressed plants produce interesting compounds as defense mechanisms against pests and adverse environmental conditions.” 

The bottom line: “We’re looking for stressed yet healthy plants, which we can accomplish in our native soil, under the sun, in the elements.”

The Climate Change and Environmental Impact of Indoor Growing

To produce high-quality cannabis, indoor cultivation is unnecessary – and it creates an astounding carbon footprint.

Indoor production is “a luxury we can no longer afford,” declared the September 2021 issue of The Cannabis Scientist, calling the industry “The Cannabis Carbon Bomb”.

Growing in a warehouse consumes a huge amount of electricity, requiring high-powered intensive lights to mimic the sun, industrial HVAC and climate control systems, fans, water pumps, and other heavy equipment. 

Indoor growing practices are a historical byproduct of prohibition laws and the current state-restricted markets that have followed, as Rolling Stone detailed in an extensive 2021 feature “How Federal Prohibition Is Turning Cannabis Into a Climate Villain.” However, even with illogical laws, there are much better ways of growing available.

As Rolling Stone summarizes, “This indoor cultivation comes at an alarming climate cost, turning what could be a green enterprise into yet another dirty business — with a carbon output that rivals major extractive industries.” 

Keep in mind, too, that many states’ energy grids still rely heavily on coal-burning power plants or oil combustion to create electricity. Climate change scientist Evan Mills calculated that average annual cannabis production in the US emitted around 15 million metric tons of CO2 into the atmosphere. 

For perspective, that means that a single joint made from indoor-grown cannabis equates to 3 pounds of CO2 emissions – equal to driving a hybrid car 22 miles or running a 100-watt light bulb for 25 hours. 

In Hawai’i, to produce a single ounce of indoor cannabis emits as much carbon as burning a full 16-gallon tank of gasoline.

A 2021 study in the journal Nature Sustainability found that indoor cannabis cultivators in Colorado now account for a greater percentage of the state’s total CO2 emissions than the state’s active coal mining industry. 

Some indoor growers also pump large amounts of extra carbon dioxide (CO2) into the spaces to boost plant growth, eventually releasing it into the atmosphere. This is not insignificant – it can account for 11% to 25% of facilities’ greenhouse gas emissions.

Indoor grows are generally wasteful of soil as well, trucking in new growing media every few months and discarding the used soil to landfills. This soil is often contaminated from the intensive use of synthetic fertilizers and pesticides, adding heavy levels of pollutants to our water and soil systems.

Environmental Impacts and The Regenerative Future

Outdoor-grown cannabis has a vastly lower carbon footprint than that grown in warehouses: the energy use of cannabis greenhouses is only about 1% of indoor cannabis production, a study estimated. 

But carbon emissions and energy use are only one important piece of the equation in considering environmental impact. The deliberate use of regenerative agricultural practices benefits local ecosystems, improving soil health and even sequestering carbon. However, this depends substantially upon the specific cultivation methods used. 

Cannabis is a “feeder” plant that can strip the soil of nutrients if not carefully managed. Many outdoor growers add harmful synthetic fertilizers (aka “salts” or “nutes”) and toxic synthetic pesticides to their plants. Whether used in indoor or outdoor grows, the use of these chemical inputs harms our human and natural ecosystems, with lasting downstream effects in our water and soil systems. 

Outdated practices like trucking in new soil also create additional emissions, and careless watering systems waste copious amounts of this precious resource. These destructive practices are unneeded. 

At East Fork, we’ve demonstrated that farmers can produce vibrant, potent cannabis by growing in native soil using organic fertilizers and inputs such as compost teas and Korean Natural Farming (KNF) techniques. 

We use organic integrated pest management (IPM) programs to manage our plant health through natural pest deterrents, including beneficial insects and bacteria. And we preserve water by using an efficient drip irrigation system and biochar that we make on site.

We grow top-quality CBD-rich cannabis in a way that is sustainable to not only the 34-acres that are part of the farm, but also the larger environment and community. 

Vote with Your Dollar

Climate activism is urgently needed for regulatory reforms to minimize the carbon impact of creating cannabis products. But we as consumers can also push the industry to do better through demand for cannabis products from farms that care for planetary health.

It’s imperative for consumers and retailers to support sungrown farmers who use regenerative agricultural practices. Your dollar “vote” matters crucially to the survival of farms like ours, and has very real impacts upon the environment and climate. 

A shortcut to finding environmentally responsible farms is to look for certifications issued by a nonprofit independent organization (not an industry trade group or a “pay to play” model). 

Sun + Earth Certified offers the current absolute highest standard for cannabis products, verifying not just sungrown regenerative cultivation practices, but also ethical treatment of employees and community involvement. Hemp farms are also eligible for USDA Organic certification, which is a basic must for consumers sourcing hemp-based products. 

East Fork is proud to be Sun + Earth Certified for our cannabis and hemp farms, and USDA Organic on the hemp side. 

Learn more about our cultivation philosophy, our sustainable agricultural practices, and the new projects we’re piloting this year.