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Endo-Canna What?!?!?


What the heck is an Endocannabinoid system?


How can one plant help so many different conditions? How can it provide both palliative and curative actions? How can it be so safe while offering such powerful effects? The search to answer these questions has led scientists to the discovery of a previously unknown physiologic system, a central component of the health and healing of every human and almost every animal: the endocannabinoid system.


The endogenous cannabinoid system, named after the plant that led to its discovery, is perhaps the most important physiologic system involved in establishing and maintaining human health. Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. In each tissue, the cannabinoid system performs different tasks, but the goal is always the same: homeostasis, the maintenance of a stable internal environment despite fluctuations in the external environment.

Cannabinoids promote homeostasis at every level of biological life, from the sub-cellular, to the organism, and perhaps to the community and beyond. Here’s one example: autophagy, a process in which a cell sequesters part of its contents to be self-digested and recycled, is mediated by the cannabinoid system. While this process keeps normal cells alive, allowing them to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products, it has a deadly effect on malignant tumor cells, causing them to consume themselves in a programmed cellular suicide. The death of cancer cells, of course, promotes homeostasis and survival at the level of the entire organism.

Endocannabinoids and cannabinoids are also found at the intersection of the body’s various systems, allowing communication and coordination between different cell types. At the site of an injury, for example, cannabinoids can be found decreasing the release of activators and sensitizers from the injured tissue, stabilizing the nerve cell to prevent excessive firing, and calming nearby immune cells to prevent release of pro-inflammatory substances. Three different mechanisms of action on three different cell types for a single purpose: minimize the pain and damage caused by the injury.

The endocannabinoid system, with its complex actions in our immune system, nervous system, and all of the body’s organs, is literally a bridge between body and mind. By understanding this system we begin to see a mechanism that explains how states of consciousness can promote health or disease.

In addition to regulating our internal and cellular homeostasis, cannabinoids influence a person’s relationship with the external environment. Socially, the administration of cannabinoids clearly alters human behavior, often promoting sharing, humor, and creativity. By mediating neurogenesis, neuronal plasticity, and learning, cannabinoids may directly influence a person’s open-mindedness and ability to move beyond limiting patterns of thought and behavior from past situations. Reformatting these old patterns is an essential part of health in our quickly changing environment.

What Are Cannabinoid Receptors?

Sea squirts, tiny nematodes, and all vertebrate species share the endocannabinoid system as an essential part of life and adaptation to environmental changes. By comparing the genetics of cannabinoid receptors in different species, scientists estimate that the endocannabinoid system evolved in primitive animals over 600 million years ago.

While it may seem we know a lot about cannabinoids, the estimated twenty thousand scientific articles have just begun to shed light on the subject. Large gaps likely exist in our current understanding, and the complexity of interactions between various cannabinoids, cell types, systems and individual organisms challenges scientists to think about physiology and health in new ways. The following brief overview summarizes what we do know.

Cannabinoid receptors are present throughout the body, embedded in cell membranes, and are believed to be more numerous than any other receptor system. When cannabinoid receptors are stimulated, a variety of physiologic processes ensue. Researchers have identified two cannabinoid receptors: CB1, predominantly present in the nervous system, connective tissues, gonads, glands, and organs; and CB2, predominantly found in the immune system and its associated structures. Many tissues contain both CB1 and CB2 receptors, each linked to a different action. Researchers speculate there may be a third cannabinoid receptor waiting to be discovered.

Endocannabinoids are the substances our bodies naturally make to stimulate these receptors. The two most well understood of these molecules are called anandamide and 2-arachidonoylglycerol (2-AG). They are synthesized on-demand from cell membrane arachidonic acid derivatives, have a local effect and short half-life before being degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

Phytocannabinoids are plant substances that stimulate cannabinoid receptors. Delta-9-tetrahydrocannabinol, or THC, is the most psychoactive and certainly the most famous of these substances, but other cannabinoids such as cannabidiol (CBD) and cannabinol (CBN) are gaining the interest of researchers due to a variety of healing properties. Most phytocannabinoids have been isolated from cannabis sativa, but other medical herbs, such as echinacea purpura, have been found to contain non-psychoactive cannabinoids as well.

Interestingly, the cannabis plant also uses THC and other cannabinoids to promote its own health and prevent disease. Cannabinoids have antioxidant properties that protect the leaves and flowering structures from ultraviolet radiation – cannabinoids neutralize the harmful free radicals generated by UV rays, protecting the cells. In humans, free radicals cause aging, cancer, and impaired healing. Antioxidants found in plants have long been promoted as natural supplements to prevent free radical harm.

Laboratories can also produce cannabinoids. Synthetic THC, marketed as dronabinol (Marinol), and nabilone (Cesamet), a THC analog, are both FDA approved drugs for the treatment of severe nausea and wasting syndrome. Some clinicians have found them helpful in the off-label treatment of chronic pain, migraine, and other serious conditions. Many other synthetic cannabinoids are used in animal research, and some have potency up to 600 times that of THC.


Cannabis, The Endocannabinoid System, And Good Health


As we continue to sort through the emerging science of cannabis and cannabinoids, one thing remains clear: a functional cannabinoid system is essential for health. From embryonic implantation on the wall of our mother’s uterus, to nursing and growth, to responding to injuries, endocannabinoids help us survive in a quickly changing and increasingly hostile environment. As I realized this, I began to wonder: can an individual enhance his/her cannabinoid system by taking supplemental cannabis? Beyond treating symptoms, beyond even curing disease, can cannabis help us prevent disease and promote health by stimulating an ancient system that is hard-wired into all of us?

I now believe the answer is yes. Research has shown that small doses of cannabinoids from cannabis can signal the body to make more endocannabinoids and build more cannabinoid receptors. This is why many first-time cannabis users don’t feel an effect, but by their second or third time using the herb they have built more cannabinoid receptors and are ready to respond. More receptors increase a person’s sensitivity to cannabinoids; smaller doses have larger effects, and the individual has an enhanced baseline of endocannabinoid activity. I believe that small, regular doses of cannabis might act as a tonic to our most central physiologic healing system.

Many physicians cringe at the thought of recommending a botanical substance, and are outright mortified by the idea of smoking a medicine. Our medical system is more comfortable with single, isolated substances that can be swallowed or injected. Unfortunately, this model significantly limits the therapeutic potential of cannabinoids.

Unlike synthetic derivatives, herbal cannabis may contain over one hundred different cannabinoids, including THC, which all work synergistically to produce better medical effects and less side effects than THC alone. While cannabis is safe and works well when smoked, many patients prefer to avoid respiratory irritation and instead use a vaporizer, cannabis tincture, or topical salve. Scientific inquiry and patient testimonials both indicate that herbal cannabis has superior medical qualities to synthetic cannabinoids.

In 1902 Thomas Edison said, “There were never so many able, active minds at work on the problems of disease as now, and all their discoveries are tending toward the simple truth that you can’t improve on nature.” Cannabinoid research has proven this statement is still valid.

So, is it possible that medical cannabis could be the most useful remedy to treat the widest variety of human diseases and conditions, a component of preventative healthcare, and an adaptive support in our increasingly toxic, carcinogenic environment? Yes. This was well known to the indigenous medical systems of ancient India, China, and Tibet, and as you will find in this report, is becoming increasingly well known by Western science. Of course, we need more human-based research studying the effectiveness of cannabis, but the evidence base is already large and growing constantly, despite the DEA’s best efforts to discourage cannabis-related research.



Does your doctor understand the benefit of medical cannabis? Can he or she advise you in the proper indications, dosage, and route of administration? Likely not. Despite the two largest U.S. physician associations (American Medical Association and American College of Physicians) calling for more research, the U.S. Congress prohibiting federal interference in states’ medical cannabis programs, a 5,000 year history of safe therapeutic use, and a huge amount of published research, most doctors know little or nothing about medical cannabis.

This is changing, in part because the public is demanding it. People want safe, natural and inexpensive treatments that stimulate our bodies’ ability to self-heal and help our population improve its quality of life. Medical cannabis is one such solution. This summary is an excellent tool for spreading the knowledge and helping to educate patients and healthcare providers on the scientific evidence behind the medical use of cannabis and cannabinoids.

Many of us have heard of some of the transmitter systems within our bodies, such as the sympathetic nervous system, which gives us our fight-or-flight response. Fewer have heard of the more recently discovered endocannabinoid system (ECS), which is amazing when you consider that the ECS is critical for almost every aspect of our moment-to-moment functioning. The ECS regulates and controls many of our most critical bodily functions such as learning and memory, emotional processing, sleep, temperature control, pain control, inflammatory and immune responses, and eating. The ECS is currently at the center of renewed international research and drug development.


What is the ECS?

The ECS comprises a vast network of chemical signals and cellular receptors that are densely packed throughout our brains and bodies. The "cannabinoid" receptors in the brain — the CB1 receptors — outnumber many of the other receptor types on the brain. They act like traffic cops to control the levels and activity of most of the other neurotransmitters. This is how they regulate things: by immediate feedback, turning up or down the activity of whichever system needs to be adjusted, whether that is hunger, temperature, or alertness.

To stimulate these receptors, our bodies produce molecules called endocannabinoids, which have a structural similarity to molecules in the cannabis plant. The first endocannabinoid that was discovered was named anandamide after the Sanskrit word ananda for bliss. All of us have tiny cannabis-like molecules floating around in our brains. The cannabis plant, which humans have been using for about 5,000 years, essentially works its effect by hijacking this ancient cellular machinery.

A second type of cannabinoid receptor, the CB2 receptor, exists mostly in our immune tissues and is critical to helping control our immune functioning, and it plays a role in modulating intestinal inflammation, contraction, and pain in inflammatory bowel conditions. CB2 receptors are particularly exciting targets of drug development because they don’t cause the high associated with cannabis that stimulating the CB1 receptors does (which is often an unwanted side effect).

The ECS's role in learning and memory

It is known that the ECS plays a critical role in learning and memory due to several lines of research. The most obvious observation is that one of the main side effects of high dosages of recreational cannabis use is the temporary disruption of short-term memory. Memory returns to normal with abstinence. There have also been some sophisticated studies of how humans acutely respond to the administration of THC (the active ingredient in cannabis) and the ways in which this alters both their ability to memorize things in the short term and the patterns observed on their functional brain imaging.

According to the popular writer Michael Pollan in his bestselling book The Botany of Desire, cannabis is one of the plants that humans have cultivated, or co-evolved with, for thousands of years. This is in part, Pollan writes, because the act of forgetting plays a valuable role in the ability of our brains to function without being overloaded with data from our senses that we are continually bombarded with. Pollan hypothesizes that if we didn’t forget, we wouldn’t function, and cannabis helps us do this. The role that the ECS plays in forgetting also opens up opportunities for the treatment of PTSD, a condition in which there are unpleasant, intrusive memories that people can’t help but remember, and that cause a whole syndrome of troublesome and dangerous symptoms related to the pathological remembering.

The ECS's role in hunger and fine-tuning weight-loss medications

The cautionary tale of the drug rimonabant, a drug that blocks the CB1 receptor, is an interesting example of the central role the ECS plays in so many crucial functions. It was developed as an anti-obesity drug. The thinking was that the ECS controls hunger. This because, among other lines of evidence, cannabis gives you "the munchies," so if you block the CB1 receptor it should cause weight loss. Rimonabant did cause weight loss, quite successfully. But, because the ECS also regulates mood, it had to be withdrawn from the market on an emergency basis because people who were taking it were becoming suicidal. However, we can imagine a case, as we better understand the complexities of the ECS, where we may be able to create a weight-loss medication that acts on those cannabinoid receptors that affect weight loss, but that doesn’t act on those receptors that control mood.

Exploration of the ECS may lead to new drug discoveries

Study of the ECS was initially focused on attempts to understand (and demonize) an illegal drug, but new research has since flourished into a far more broad-based exploration into what is an astoundingly intricate and far-reaching system by which our bodies learn, feel, motivate, and keep themselves in balance. We are truly at the dawn of an age of discovery of the ECS and the development of new medicines that may help alleviate some of the cruelest diseases that people (and animals) suffer from. I am incredibly excited to see what discoveries await us as we continue to untangle the mysteries of the ECS.



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