Endocannabinoids and CBD Explained Simply

Endocannabinoids are naturally occurring compounds found within the human body. They've been there for 600,000 years or more, but we've only just noticed it! One of the remarkable things about endocannabinoids is their striking similarity to the active ingredients of cannabis called phyto-cannabinoids. In fact, it was the effort by scientists to understand the exact mechanism by which cannabis works in the body that led to the discovery of the Endocannabinoid System little more than a decade ago.

The science of endocannabinoid medicine has progressed to a dizzying degree in the past few years. There is wider awareness that the 'endocannabinoid system' is the largest neurotransmitter system in the human body, regulating relaxation, eating, sleeping, memory, and, as noted by the Italian scientist Vincenzo Di Marzo, even our immune system.

Cannabinoids promote homeostasis, the maintenance of a stable internal environment despite external fluctuations, at every level of biological life, from the sub-cellular, to the organism. For example, endocannabinoids are now understood as the source of the runner's high. The endocannabinoids naturally found in human breast milk, which are vital for proper human development, have virtually identical effects as cannabinoids found in the cannabis plant. Amazingly, the mechanism at work after smoking or eating cannabis, when adults get the "munchies, is essentially the same as what causes breastfeeding babies to seek protein-rich milk.

Universally accepted following its discovery in 1995, the endocannabinoid system asserts it power to heal and balance the other systems of the body by turning on or off the expression of genes. Cannabinoids hold the key that unlocks receptor sites throughout the brain and immune system triggering potent healing and pain-killing effects.

The endocannabinoid anandamide, (Ananda = bliss in Sanskrit + amide = chemical type) a naturally neurotransmitting lipid compound made by all mammals, is basically a self-manufactured "natural THC" circulating within. Anandamide and THC act through the cannabinoid receptors and have similar effects on pain, appetite, and memory, etc.

There are two types of cannabinoid receptors in the body --the CB1 receptors found primarily in the brain and the central nervous system, and the CB2 receptors that are distributed but primarily found in the immune system. These receptors respond to cannabinoids, whether they be from breast milk, or from a cannabis plant.

Aside from the cannabinoids produced by the body and those found in cannabis, there are numerous substances that interact with the endocannabinoid system, such as cacao, black pepper, echinacea, tumeric and even carrots. But it is the Cannabis plant that produces the most powerful cannabinoids mimicing most closely those produced by the body. No downsides, no side-effects, no drug interaction issues, and so far, no giving up your hard earned funds to big pharma.

Make no mistake, I'm not referring to THC, of which Americans smoke more of per person than any other people on Earth, but rather the "other," non-psychoactive cannabinoid called Cannabidiol (CBD), a prominent molecular component of the cannabis plant. While CBD does not bind to either the CB1 or CB2 cannabinoid receptors directly, it does stimulate endogenous cannabinoid activity by suppressing an enzyme that breaks down anandamide. CBD is also a counterbalance to the action of THC at the CB1 receptor, mitigating or muting the psychoactive effects of THC. Weed enthusiasts would be wise to keep some CBD on hand for when things get... out of hand.

If just 10% of what research doctors are now saying about CBD is true, then this is a discovery with significance similar in medical impact to the discovery of antibiotics. Myriad serious scientific peer-reviewed studies in Europe have pointed to CBD as having almost unprecedented healing power over an extraordinary variety of pathologies. Even the stodgy National Cancer Institute has referenced this on their website.

Surprisingly, there is still little awareness of this outside of the medical research community. Surely an unknown plant newly found in a remote rainforest with the same medical profile would be heralded as a miraculous cure. But in the last half-century, this particular plant has been better known as an intoxicant than a medicine.

The stigma that obscures wider awareness of its beneficial nature has been carefully cultivated. For decades, Hearst newspapers bombarded Americans with images of Mexicans and African Americans led into vice and violence by the evil weed. In the public mind, cannabis was transformed from an obscure ingredient in patented medicines with pharmacy sales rivaling aspirin, to an intoxicant the use of which would lead inevitably to decline and debauchery.

In a spectacular confluence of politics, racism, corporate greed, and political corruption, the federal government managed to outlaw cannabis for all purposes in 1937, with medical research becoming virtually impossible in the U.S.

Now, in California and around the country, research doctors are peer-reviewing the recent explosion of clinical studies from abroad, as well as conducting their own pre-clinical research without humans. Persuasive evidence abounds that CBD is effective in easing symptoms as well as reversing of a wide range of difficult-to-control conditions, including: rheumatoid arthritis, diabetes, alcoholism, PTSD, epilepsy, antibiotic-resistant infections, neurological disorders, and muscular dystrophy.

CBD has no side effects and becomes very effective as an anti-psychotic when given in larger doses. With more antioxidant potency than either vitamin C or E, CBD has consistently demonstrated neuroprotective effects, and its anti-cancer potential is, by all accounts, enormous. Sean McAllister, PhD at California Pacific Medical Center said "CBD could spell the end of breast cancer," and claims it could render chemotherapy and radiation a distant 2nd and 3rd options for cancer patients.

Don Abrams M.D. at UCSF says the studies point to "a remarkable ability of CBD to arrest cancer cell division, cell migration, metastasis, and invasiveness." The vast impact of the endocannabinoid system on human health explains and validates anecdotal reports of cannabis used effectively for a wide range of health conditions. Studies on the efficacy of CBD treatment are already driving the design and development of precision targeted single-molecule medicines. Indeed, we are hard-wired for cannabinoids.

The US government may not admit the medical efficacy of cannabis, but the global pharmaceutical industry has been researching it for many years. Some 350 scientists from drug-company labs including Merck, Pfizer, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, and Allergan (maker of Botox and silicone breast implants) regularly attend meetings of the International Cannabinoid Research Society. They are all trying to develop synthetic drugs that confer some of the health benefits of cannabis without the psychoactivity. "It's a foregone conclusion," says Julie Holland, M.D.,"that the next decade will see a new generation of Big Pharma medications based on cannabis."

According to Martin A. Lee, author of Smoke Signals, vitamin D combined with CBD could become "the killer public health app of the post-prohibition era." A new CBD/THC medicine for cancer pain called Sativex from the British company, GW Pharmaceuticals, is finishing the final FDA-approval process. While there is no time limit on enduring prejudice, as science reveals more about how the cannabinoid system works, the stigma associated with cannabis use is expected to fade.

CBD-enriched health foods, tinctures and oils are the next revolution in food and medicine. There is currently an explosion of entrepreneurial activity and creativity around making up for lost time with CBD. LA-based cannabis physician Allan Frankel explains that, "up until this past year, it has been impossible to help patients using CBD. Cannabis growers were focused on the stoniest weed," hence, CBD which is non-psychoactive, was nearly lost. Now, more CBD rich strains are turning up, in part because there are laboratories that can accurately assess how much of which cannabinoid is present and check for mold and pesticides.

We are still in the early stages of understanding the synergistic effects of all the cannabinoids, not to mention the terpenoids--the sticky aromatic terpenes that give cannabis its characteristic smell. Research, as well as results in the field, shows that the presence of some THC and other cannabinoids in smaller amounts potentiate the healing effects of CBD. The combined effects of the cannabinoids, terpenes and perhaps another 200 other molecules all working together and carefully balanced in nature is what Dr. Ethan Russo calls an "Entourage Effect".

The burgeoning edible cannabis industry until recently was focused on making food items so radically THC dominant that you could easily become catatonic 3 hours after ingestion. Anecdotal evidence suggests while most people enjoy these powerful treats, many people have had challenging experiences, replete with anxiety, panic, and functional psychosis.

Fortunately, for seekers of good health or for those targeting disease, there are now CBD-rich edibles that don't make you high, such as raw organic cacao from the Green Cacao Company, multi-flavored CBD dominant lozenges CBD-OOS, and other similar products delightful to the palate as well as therapeutically effective.

As the health benefits are better understood, the huge market potential of non-psychoactive CBD-foods will likely be recognized. CBD-rich tinctures, such as Dew Drops Hemp Oil from Denver based Dixie Botanicals sells their industrial hemp oil over the internet with no medical marijuana permit required. Before long, there will be a plethora of food products rich in CBD, essentially creating a new food sector more legitimately called "health food," than what is currently found in natural foods stores.

CBD-rich foods need not make any health claims thus avoiding issues with the FDA. Imagine creamy CBD enhanced peanut butter, cooking oils, cereals, and beverages. Don't be surprised that in a few short years, you will be hearing doctors (not just cannabis physicians) advise their patients to "exercise, and get your CBD." Obtaining enough CBD to make a medically significant difference requires edible, vapor, or sublingual delivery thus avoiding the health risks associated with smoking.

In this fast and fanciful look forward, one should not leave out the inevitable resurgence of large-scale cultivation and production of fiber hemp, a versatile, ecologically sustainable plant with more than 25,000 known industrial applications--everything from hemp clothing, cosmetics, and foods (hemp seeds are a powerful source of protein), to oil-free plastics, hemp surfboards, insulation, and car panels.

Practically speaking, CBD, or what Robert Louis Stevenson called the "golden oil," is but a by-product of the non-psychoactive hemp plant. As you read this, thousands of industrial hemp farms are stripping the CBD-rich leaves and stems from the desired fiber and composting them. It's reasonable to suppose that the tragedy of losing all that medical value for victims of cancer and other maladies will not be lost on those that follow us.

If the cannabis plant hasn't done enough for us--providing wellness for the body and change for the mind, it can also help us pull the petroleum out of our economic jugular, possibly giving rise to a healthier vegetable-based organic life-support system for our children.

Image by M. Martin, courtesy of Creative Commons license.

Autism and The Endocannabinoid System

Two autism-related mutations in a synapse-adhesion protein lead to deficits in prolonged endocannabinoid signaling in mice. It’s a surprising connection that suggests such signaling problems could be implicated in autism spectrum disorders, according to a paper published today (April 11) in Neuron.

Tonic endocannabinoid signaling is long-lasting and contrasts with the brief pulses characteristic of phasic signaling. Endocannabinoid signaling in general affects memory formation, learning, pain, and other important processes, but the distinctions between tonic and phasic signaling have been poorly understood.

“It’s a very stimulating finding which could be a real turning point in understanding tonic endocannabinoids and how this otherwise mysterious lipid signaling really works,” said Bradley Alger, a neuroscientist at the University of Maryland School of Medicine who was not involved in the study. But he warned that the paper, while tantalizing, did not even definitively show that endocannabinoid signaling deficits could lead to autistic behaviors in mice, let alone in humans.

The researchers studied two mutations in neuroligin-3 (NL3), a gene encoding a protein involved in building and maintaining synapses. One mutation is a deletion of the entire gene, while the other, called R451, involves a single amino acid substitution. “These two mutations both have been associated with autism in humans,” said coauthor Thomas Südhof, a cellular physiologist at Stanford University.

Südhof and colleagues sought to understand what physiological effects the mutations had in common, assuming that if they could find a shared effect it might explain how they both led to autism. Using mice with each of the mutations, they made electrophysiological recordings of the interactions between pairs of cells in the hippocampal areas of the mouse brains. They compared recordings in the two types of mutant mouse brain cells to recordings done in normal mouse brains.

While synaptic changes often differed depending on the mutation, one type of cell containing cannabinoid type-1 (CB1) receptors showed similar alterations in its patterns of excitation for both types of mutant mice. Further investigation showed that tonic endocannabinoid signaling had been disrupted in these cells. “By this comparative physiology we were able to point out differences that pointed to this endocannabinoid signaling,” said Csaba Földy, also a cell physiologist at Stanford and an author of the paper.

The mechanism for how mutations in NL3 lead to endocannabinoid signaling deficits remains unclear. Could lacking properly functioning NL3 be interfering with endocannabinoid secretory machinery? Could it be somehow causing degradation of endocannabinoid signaling ligands? “We’re left without a really good idea of what it’s doing in single synapses or whether it’s effective behaviorally,” Alger said. Moreover, it is not yet clear how endocannabinoid signaling deficits would be involved in autistic symptoms, the authors said.

Alger added that, if the endocannabinoid system does turn out to be connected to autism in humans, medical marijuana could turn out to hold possibility for treating autism. But Südhof said that he did not know at this point whether marijuana would intensify or ameliorate autistic symptoms.

More immediately, said Alger, the findings will spur research into NL3 and other neuroligins, molecules he had never dreamed might have an effect on endocannabinoid signaling. “We’re really just starting to understand how this works,” he said. “In terms of autism, we’ll have to refer to future research.”

Földy et al., “Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling,” Neuron, doi:10.1016/j.neuron.2013.02.036, 2013