Endocannabinoid System Archives · Cornerstone CollectiveCornerstone Collective

Current Challenges in Cannabis-Based Medicine

In the field of cannabis research and cannabinoid science, few researchers have made as large an impact as Dr. Ethan Russo. Russo has written field-defining papers about standardizing cannabis, pain management with cannabinoids, and the proposed synergy of cannabinoids. Russo’s insights range from medical and chemical hurdles of the field to political and government challenges inherent in bringing these medicines to market. Russo also played a key role as research director at GW Pharmaceuticals for over a decade. GW Pharmaceuticals created Sativex, an oral spray consisting of THC and CBD in a 1:1 ratio, that remains one of the only cannabis-based pharmaceutical products available in most countries. As a past president of the International Cannabinoid Research Society and past Chairman of the International Association for Cannabinoid Medicines, he continues to write and travel world-wide to discuss the field. In 2016, Russo released a report titled, “Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues", intended to serve as a collection of recommendations regarding the future of the field. In the report, Russo breaks down many of the issues that have hampered cannabis and cannabinoid-based medicines’ acceptance into Western medicine. Due to the thoughtful writing and easy-to-read nature of the report, we would encourage anyone interested in learning more to take a look at this paper. However, for the sake of convenience, we have summarized the most important topics below: Cannabis Testing Is Largely Inaccurate Russo argues that due to past and current legal constraints, many of the labs that test…

Does the Endocannabinoid System hold the Secret to Ending Migraine Headaches?

The endocannabinoid system, which is the body’s system of natural cannabinoids, receptors that metabolize cannabinoids of any source, and enzymes that control that interaction, is one of the few body-wide systems that has direct interaction with both neurological and physiological disorders. A quick review of the Cornerstone blog yields a wealth of evidence of the endocannabinoid system influencing everything from general pain, to sleep, to neurological malfunction, to immune system regulation, psychological health, and much more. In February 2016, specifically, we wrote about the possibility of cannabinoids/cannabis being used to treat migraine headaches: Soothing Migraine Headaches with Cannabis Anecdotally, this study confirmed that medical cannabis patients experience relief from migraines in a large sample (121 people). However, at the time, little was understood about the potential cause of relief, as well as the ramifications of cannabinoid signaling on other body functions and systems. In July, the International Cannabis Research Symposium Journal published more information shedding light on additional research surrounding cannabinoids and migraines, as well as on the potential interaction with kynurenine, a receptor antagonist (blocker) related to glutamate, one of the main neurotransmitters in the central nervous system, which includes the brain. To review, migraine headaches affect roughly 16% of the population at different stages of life! This has yielded an estimated 18.4 billion euro cost to European healthcare a year, not to mention extreme decrease in quality of life for patients suffering from migraines. While researchers are still trying to pin down what exactly causes migraines, we can…

CBD, Fear And Memory

In previous entries, we’ve covered how cannabis might affect memory and memory consolidation. The basic idea has been that cannabis might prevent the formation of traumatic memory. However, until now, we haven’t seen any research dealing specifically with fear. The connection between memory and fear may not be immediately obvious to readers; however, as it turns out, they’re very much related. A state of fear engages previous memories of threat as well as requires recall of escape/defense strategy. Given cannabidiol’s (CBD’s) success in early studies as an anti-psychotic, researchers might hypothesize a beneficial effect of CBD administration on fear response. However, only recently have Brazilian researchers carried out such an experiment, using rodents and varying doses of CBD. In most animal models of fear, researchers apply a threatening environmental stimulus. Of course, none of these might be more threatening than the mice’ natural predator, a boa constrictor snake! Researchers therefore forced confrontations between mice and snakes using an “arena” or plastic container, where they could record movement information. In one corner of the container, researchers placed a protective burrow. This burrow has two sides and a small opening on either, allowing mice to run in one side to escape the snake, and run out the other side once the snake begins to enter the burrow. Because this is an effective escape, a pro-survival strategy of mice would be to run away from the snake, toward the burrow. This is called “oriented escape”. However, in some cases, the mice become too…

Cannabis and the Elderly

When you picture the average cannabis user, what do you imagine? Chances are you’re not imagining a senior citizen. Due to cannabis’ reputation as a counter-culture recreational drug, many people assume the average cannabis user to be young and liberal. While this seems like a reasonable assumption, the truth is that a large portion of medicinal cannabis patients are elderly. In fact, a recent Israeli study found that “of 279 cancer patients receiving medical cannabis, 50% were aged 60 or older”! In other words, perhaps the largest group of medicinal cannabis users is the senior citizen population. Why? Surely this percentage reflects the basic fact that older individuals are more likely to develop cancer and other diseases that may be treated by cannabinoids. Additionally, elderly populations are more likely to seek cannabis legally, while younger medical cannabis users are more likely to have other avenues of procurement. Moreover, perhaps the specific suite of ailments faced by the elderly fits the target profile of cannabis treatment. Regardless of the reason, however, the population of elderly medicinal users is far from negligible; at Cornerstone it makes up one of our major patient groups! In response to this high concentration of elderly medicinal cannabis use, one research group, led by Itay Katz from the Sheba Medical Center in Israel, has conducted a review of cannabis research relating to elderly populations. This review, published February 2017 in the Israel Medical Association Journal, highlights several common areas of use, as well as Western medicine’s current…

Anti-Viral Activity in CBD?

Chances are every person reading this has some connection to hepatitis, or inflammation of the liver, which can lead to liver failure and death. Unfortunately, there are many potential causes of hepatitis. Excessive alcohol consumption can cause inflammation, as well as autoimmune disease, in which the body mistakenly attacks its own liver cells. Currently five major viruses (which happen to be unrelated) have been identified to cause liver failure, referred to as Hepatitis A through Hepatitis E. Due to the contagious and dangerous nature of these diseases, US schools often require Hepatitis A and B vaccinations. Hepatitis A can spread easily through contaminated food and Hepatitis B (HBV) through blood and other bodily fluids. These vaccinations are simple, cheap, and life saving. Unfortunately, Hepatitis C (HCV) lacks a vaccine. Despite a common prevalence and upwards of 200,000 known cases in the US a year, the disease is difficult to ward off. We use the word “known” specifically because thousands of other people may also be infected but show no symptoms while spreading the disease. There is, fortunately, finally a cure to Hepatitis C. A once-a-day pill taken for several months can eradicate Hepatitis C from a sick patient’s body. Sadly, the cost for that treatment ranges from $55,000 to $150,000! As a result, government health care providers can’t shoulder the burden and only tend to allow coverage for end-stage liver failure. In other words, after all the damage is done, and the patient is dying, they are finally eligible for…

Genetics Modify Response to Cannabis: A Look at the COMT Gene

Last week we talked about the need for genetic testing of both the cannabis plant itself and of patients. Speaking in broad terms, we noted that slight alterations in human DNA can lead to noticeable differences in reactions to cannabis. This is something medical cannabis patients can attest to when comparing strains with other medical users. A strain that makes one person feel tired may have little impact on the energy level of another. Today we can introduce one specific mechanism that seems to influence genetic variation in response to cannabis. Interestingly enough, researchers at Warneford Hospital in the UK actually approached this discovery while searching for causes of psychosis (when thought and emotions are so impaired, patients suffer a disconnect from reality). One of the most debated questions in the scientific community is whether cannabis contributes to the development of psychosis. Believers cite that while many people consume cannabis with no lingering health issue, some develop psychotic symptoms immediately after first exposure. Critics do not necessarily disagree with this observation but believe that many different substances and environmental factors can trigger psychotic illness. Regardless, the data would suggest that if only some patients develop symptoms, the cause might be genetic. What gene is causing this? Researchers have identified catechol-o-methyltransferase (COMT) as a gene that regulates dopamine in the cortex of the brain. Studies show that cognitive function is improved in animals “with reduced COMT activity”. This pattern implies that the gene is some sort of limiter, perhaps designed to…

How Adolescent Social Experiences Affect The Endcocannabinoid System

Lately movies like The Wolf of Wall Street and TV shows like Narcos have managed a difficult task: making villains likable. In some cases, despite all morality, we find ourselves rooting against the clear “good guys” and hoping the “bad guys” will continue to cleverly outfox all authority. How can the writers create such a shift in audience support? Back-story. By taking us along the personal development of the character, we understand what the character dreams for himself/herself and what the character is running from. We see fear and hope in the same troubled character, and this gives us a foothold into understanding his/her decision-making. In absolute contrast, in most Disney movies, villains seem to spontaneously show up bad. We have no mixed feelings, because we have nothing to feel that is good. Likewise until recent advances in neuroscience and psychology, we’ve had little explanation for a variety of illnesses and shifts in behavior. Most scientists of the early 1900’s would not have believed that a poor social interaction during adolescence could physically affect brain development. In fact, to suggest that anything non-physical could have a physical consequence years later would have seemed far-fetched. However, as we now know, the brain is very plastic and responds to environmental challenges. In childhood and adolescence, the brain is creating a structure in response to the environment in an attempt to best prepare itself for future needs. However, as we’ve seen in other illnesses, the brain does not always develop ideally. Harmful socialization…

A Practical Look at Cannabis Extract and Sleep

Estimating the number of individuals suffering from sleep disorder is difficult if only because of the variety of sources. While sleep can be interrupted by chronic pain, as is often the case for arthritis patients, other sources such as gastrointestinal activity, breathing difficulties, epilepsy, Alzheimer’s, etc. can also prevent restful sleep. To date, while multiple over-the-counter sleep medications exist, all have large flaws. Benadryl and other anti-histamines, usually diphenhydramine, are known to have the side effect of sleepiness and are often taken as sleeping pills. However, diphenhydramine can be habit-forming. Melatonin, on the other hand, can help re-enforce natural sleep cycle/rhythm, but can’t overcome serious sleeping barriers. Finally, prescription sleeping medications, such as Ambien, which are much stronger and more resilient, often have semi-psychotic side effects and can produce uncomfortable and sometimes dangerous experiences. While cannabis and cannabinoids may not provide a complete answer, they represent another potential avenue for eliciting sleep, and as a result, the relationship between sleep and the endocannabinoid system should be a priority of researchers. Unfortunately, despite the fact that we all need sleep, we actually understand little about it. We’ve managed to determine that sleep plays an important role in restoring and healing both the body and mind, with the brain passing through several stages of sleep characterized by the pattern of brain waves in each stage. Truly restful sleep seems to be characterized by attainment of the last stage in the sleep cycle, REM. However, much of the specific brain chemistry remains unclear,…

A Lot To “Digest”: Cannabinoids in the Gastrointestinal System

As a society, we are indebted to researchers who’ve dedicated entire lives to investigating less popular subjects. Early on, medical researchers heightened interest in cannabis miffed a lot of the scientific community as a whole, who thought of cannabis as a recreational drug unworthy of study. However, the study of cannabis and its active ingredients lead directly to the discovery of the mammalian endocannabinoid system. While we initially saw this system as an unessential group of cannabinoid receptors, cannabinoids, and enzymes involved in regulating that system, we now understand just how vital it is to the body. Likewise, while we initially thought cannabinoid receptors only played a direct role in bowel inflammation, we now understand that the entire endocannabinoid system plays a major role in the digestive process. Recently, researchers at UC Riverside released an aggregate review of studies involving the endocannabinoid system in relation to the gastrointestinal system. We found this review especially helpful and have summarized important highlights for readers. The full article is free to the public at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940133/ Gut Motility To function, the intestine must absorb nutrients but also send food onward. The ability to move food onward is called “motility” and is driven by timed contraction of the intestinal muscle. The gut interacts with the brain to determine the pace of contraction and therefore, food motility. Unfortunately, sometimes the timing of contractions can go haywire. Cannabinoids, whether naturally occurring endocannabinoids or externally administered cannabinoids, have been shown to reduce motility in a dose-dependent matter.…

Keeping It Together: Cannabinoid Receptors Found In Connective Tissue Regions

Cannabinoid receptors are known to be located all throughout the body. Although most abundant in the central and peripheral nervous system and in immune system cells, cannabinoid receptors are also thought to reside in other types of tissues. However, due to the number of possible locations and the number of experiments necessary to establish localization of those receptors, new areas are still being discovered more than two decades after the discovery of the receptors themselves. Why do we care? If we are interested in the medicinal effects of cannabis and cannabinoids, research focusing on the actual effects of cannabinoids and inhibitors may seem more to the point. Regardless of the localization of the receptors, the bottom line is whether the endocannabinoid system can or cannot be a pharmaceutical target for a given medical condition. This assumes that we already know the conditions we are seeking to cure or treat. Building a functional map of the distribution of receptors throughout the body, while time and labor-intensive, will also likely reveal new conditions that may be associated or even be a direct result of endocannabinoid system operation. This year, a research group from the University of Padua in Italy decided to use samples of myofascial tissue to test for the presence of endocannabinoid receptors. Myofascial tissue is essentially an organic mesh of collagen that has a great strength while at the same time is highly flexible. This type of tissue is employed all throughout the body to keep organs compartmentalized as well…

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