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The Endocannabinoid System and Clinical Endocannabinoid Deficiency

We spoke exclusively to Ethan Russo who believes that many common diseases stem from clinical endocannabinoid deficiency.

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Clinical Endocannabinoid Deficiency
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The discovery of the endocannabinoid system in the mid-1980s was a major breakthrough in modern medicine. Yet, if you looked at the curriculum for most medical schools, you might not know it. The finding would not have been possible without the help of the cannabis plant, which remains illicit in most countries around the world. After wide-spread legalization of medical cannabis and over three decades of research, knowledge about the endocannabinoid system and its associated pathologies, like clinical endocannabinoid deficiency, remain sorely overlooked.

The Endocannabinoid System: The Find of the Century?

Two decades before the discovery of the endocannabinoid system, a team of scientists led by Dr. Raphael Mechoulam, a professor of medical chemistry a the Hebrew University of Jerusalem, had finally isolated the primary psychoactive constituent of the cannabis plant—tetrahydrocannabinol (THC). After the discovery, researchers around the globe began the quest to figure out exactly how the compound worked.  A group led by Dr. Allyn Howlett, a neuroscientist then with St. Louis University, finally cracked the mystery: THC produced its psychoactive effects through engagement with specialized cell receptors.

A cell receptor can be thought of as a lock that is embedded on the surface of a cell membrane. These locks only respond to specific chemical keys. In this case, THC was the key that engaged a cannabinoid receptor. As research would soon reveal, cannabinoid receptors are part of a larger endocannabinoid system (ECS), a neurotransmitter and cell signaling network like none other.  Made up of receptor sites, their respective chemical activators, and the enzymes that deactivate these compounds, scientists quickly unveiled that the ECS was ubiquitous throughout the human body. Cannabinoid receptors are nearly everywhere — connective tissue, the brain, the spinal cord, internal organs, the digestive tract, the skin, and immune cells.

After what surely was many long hours in the lab, Howlett and her team landed on something big. Why on earth would these receptors be found in so many places? Nearly three decades down the line, scientists are still exploring the wide-reaching ramifications of the endocannabinoid system, Howlett included. In the time since its first discovery, the ECS has been found to be a potent regulator of brain activity, hormonal function, and immune response, linking the three main regulatory systems together. It’s this pervasive modulatory network that responds to THC and other cannabis constituents. When a person consumes intoxicating forms of cannabis, THC hijacks the cannabinoid receptor sites that are normally inhabited by compounds that the body produces naturally.

These compounds are called endocannabinoids. The prefix endo- refers to endogenous or internal cannabinoids. In contrast, the cannabinoids found on the cannabis plant are phytocannabinoids with the prefix phyto referring to plants. As it turns out, endocannabinoids are molecules that help maintain a state of equilibrium, or homeostasis, throughout the nervous, endocrine, and immune systems. Endocannabinoids play the part of harmonizers or middlemen, managing how each of these systems responds to stressful stimuli and communicates with the others.

Endocannabinoids are at least in part responsible for regulating the biological clock, managing things like hunger and sleep over the course of the day. Cannabinoid receptors are also highly concentrated in areas of the brain responsible for memory, emotion, and metabolism, giving them regulatory effects over a remarkable number of physiological functions. One endocannabinoid, called anandamide, even takes its name from the Sanskrit word for bliss Ananda thanks to its calming and relaxing effects.

With such a profound influence over so many basic bodily commands, it is now theorized that problems in the ECS may contribute to a wide variety of difficult-to-treat pathologies. These potential pathologies include ailments as diverse as migraines and autism.

Clinical Endocannabinoid Deficiency May Contribute to Disease

Howlett and Mechulam may have kicked off the first forays into the endocannabinoid system, but they are far from the only scientists who made serious contributions to this emerging arena of health and medicine. Back in 2001, Ethan Russo, a neurologist and medical researcher, first made the case for clinical endocannabinoid deficiency (CECD). Russo is currently the Director of Research and Development with the International Cannabis and Cannabinoids Institute (ICCI). His theory? That many common diseases stem from deficiencies of the endocannabinoid system.

“Many human disorders relate to deficiencies of neurotransmitter function,” Russo told Cannabis Aficionado. “We know that a lack of acetylcholine, the memory neurotransmitter, is key to dementia in Alzheimer disease and related disorders. Parkinson disease is associated with a lack of dopamine function. Depression is related to problems with serotonin.”

Now, Russo suggests that something similar could occur in the endocannabinoid system. “In 2001,” he explains, “I hypothesized that various human disorders could be related to a lack of endocannabinoids, the natural chemicals within our brain and bodies that are similar in activity to THC, the main psychoactive compound in cannabis.”

Since endocannabinoids have wide-spread functions in the body, a lack or deficiency of these signaling molecules could cause a whole host of trouble. Symptoms like seizures, mood troubles, and generalized pain, nausea, and inflammation are all possible side effects of an endocannabinoid imbalance. Further, the universal nature of the ECS means that ailments which are seemingly unrelated to each other may now be classified together under the endocannabinoid umbrella.

“The prime candidates for clinical endocannabinoid deficiency are migraine, fibromyalgia and irritable bowel syndrome,” says Russo, describing conditions that are currently thought of as distinct and separate pathologies. “All [three] have compelling evidence in the interim that there are deficiencies in endocannabinoid function. Additional evidence has accumulated to include post-traumatic stress, autism, and other disorders.”

It is the ECS that perhaps describes why conditions like migraine and irritable bowel syndrome may share so many overlapping symptoms, including changes in mood, digestive distress, pain, and fatigue. These problems may be genetic in nature or acquired over time. At least one scientist has even gone as far as to describe the endocannabinoid system as a “bridge between body and mind”, connecting the physical reality with an emotional and intellectual one.

Toward Recognition of the ECS

Researchers have been investigating the influence of the endocannabinoid system in disease pathology for the past 30 years. Despite advancements in our understanding about the ECS, however, therapies targeting the endocannabinoid system are still few and far between. While some cannabinoid-based therapies are available to select patients, medical cannabis still remains one of the primary therapies that targets the ECS.

Yet, while the herb has been immensely helpful to patients around the world, both cannabis and endocannabinoid research still suffers from underutilization and harsh political barriers to research. In fact, a 2018 study from the Washington School of Medicine found that only a meager nine percent of medical schools teach their students about medical cannabis. This is despite the fact that the medicinal use of the herb is legal in 33 U.S. states and all of Canada.

“In my opinion, the media attention [on the endocannabinoid system] is not yet sufficient,” says Russo, “as the scientific evidence behind the theory is now quite solid based on serum and cerebrospinal fluid tests and other data.” He is referring to tests conducted in patients with schizophrenia,  migraine, and epilepsy. In each of these conditions, patients exhibited a dysregulation of endocannabinoid molecules in their cerebrospinal fluid. In post-traumatic stress, scientists at the New York University Langone Medical Center made a similar finding back in 2013. Compared with controls, PTSD patients demonstrated reduced endocannabinoid circulation.

“Considering the extreme amount of suffering and economic costs associated with clinical endocannabinoid deficiency disorders, it is necessary to have better research support and clinical investigations,” he presses. Better research and support would enable medical researchers and other scientists to more efficiently establish key therapies and interventions for endocannabinoid disorders. “While it is clear that cannabis in one form or another can be very effective in treating such disorders, certain lifestyle approaches, such as low impact aerobic activity, and dietary manipulations with prebiotics and probiotics may also be effective.”

Unfortunately, nearly 75 percent of medical schools also fail to provide students with the required amount of nutrition education. In a world of quasi-legal remedies and underacknowledged illnesses, its past time that formal institutions look seriously into endocannabinoid health.

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Cannabis

Everything You Need to Know If You’re New to Dabbing

Dabbing is an ideal ingestion method best for those that have a high tolerance to cannabis or patients that need a quick, controlled dose of cannabis.

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Dabbing
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Dabbing is an ideal ingestion method best for those that have a high tolerance to cannabis or for medical users that need a quick, concentrated and controlled dose of cannabis. However, it can be confusing, even for long-time pot smokers. In fact, unless you’ve done it, seen it, or read up on it, dabbing can be a total mystery.

Dabbing is a relatively new way to consume cannabis and it is has become very popular in recent years despite rumors that it is dangerous.  It is a highly concentrated experience, with THC at levels much more elevated than most regular flower you would encounter in a joint.  For patients, dabbing can be a very effective way to dose because the effects hit the user very quickly and can typically be measured more easily. For those with a high tolerance for cannabis, dabbing can be a way of feeling the effects of pot with more potency.

Before you can get into dabbing, you need to know a little about cannabis concentrates and extracts. Shatter, budder, wax, crumble, pull and snap, and hash oil are a few of the most popular types of cannabis concentrates and extracts. Extracts and concentrates are named so because they are products of a process where THC and other cannabinoids are extracted from the flower. Sometimes, during the extraction process, a solvent (like alcohol or butane) can be used and other times a solvent is not used. Either way, the final product is a smaller, stickier package that packs a powerful punch.

The Dabbing Process

Keep in mind that nails and domes can get incredibly hot. Like, RED hot, literally. Do not underestimate the heat that can occur — be cautious to prevent any burns.

First, you will need something to dab. We have heard the recommendation more than once to keep away from alcohol-based extracts when dabbing. Consult your budtender about this one, or just skip alcohol based-extracts — your call. There are a lot of concentrates and extracts to choose from, enjoy the hunt for your perfect pick.

Next you need something to dab out of. You can purchase a dab rig or just convert an existing glass water pipe with glass dab attachments. You are also going to need a titanium, ceramic, quartz or electronic nail that fits the glass dab attachment you are using. A typical nail is going to require the use of a dome in order to trap the vapor before it dissipates into the air. A dome can be as simple as a glass piece that fits over the reservoir where the extract or concentrate is vaporizing.

Get your dabber ready. A dabber is a tool that is ceramic, metal, glass, that is used to place the dab, or concentrate/extract, on the super-hot nail.

Lastly, unless you are using an electronic nail or e-mail, you will need a mini torch. Some less patient dabbers will use a full-on, propane-fueled torch in order to more quickly heat their nails — experiment at your own risk. In case the dab is a little overwhelming for you and your body, the safest place for you to be is sitting down to avoid any falls.

Turn on your e-nail OR use your torch to heat your nail until it is red-hot. Allow it cool for at least 10 seconds (for titanium) and up to 45 seconds if you are using ceramic or quartz nail.

Once cooled, use your dabber to place your concentrated dab on the nail. Place the dome over the nail as you inhale. Then, exhale. Victory!

If you weren’t already sitting down, you probably will be now!

Take these words of advice to heart — start small. If you haven’t tried dabbing at all before, don’t make your very first dab a large one. You won’t regret taking a small dab, but you might regret taking one that is too big. Always ask your budtender any questions you have about your purchase and if the product you are buying is the best thing you can buy for dabbing, vaporizing, smoking, etc.

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10 Couch-Lock Cannabis Strains to Help You Stay Home

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PHOTO | Sunset Sherbert

COVID-19 has changed the world as we knew it. For the foreseeable future, we all have to do our bit and stay home to try and flatten the curve and prevent the virus from spreading further. But it’s not all bad news. Try to think of this time to stay home and reset. Why not start that project you’ve been putting of, or earn a new language? Maybe rearrange all the furniture in your house and alphabetize your record collection. Then, once that’s finished, sink into your couch and enjoy one of these iconic couch-lock cannabis strains while you binge on Tiger King.

Afghani

Named after its geographic origin, Afghani grows in the Hindu mountains, where cannabis was first discovered over 1000 years ago. Afghani delivers a deeply relaxing,mood-boosting high, perfect if you have issues with insomnia, chronic pain and stress disorders.

Buy seeds from sensiseeds.com

Girl Scout Cookies (GSC)

A potent mix of an OG Kush x Durban Poison x Cherry Kush mother backcrossed with a prime-looking OG Kush father created Girl Scout Cookies. The winner of multiple Cannabis Cups and packing a powerful 28% THC, GSC is possibly one of the best Northern California strains of all time.

Buy seeds from homegrowncannabisco.com

Granddaddy Purple

Delivering a THC level between 17-27%, Granddaddy Purple is not a strain to take lightly. If you’re looking for a mental and body high that will feel like you are floating euphorically, as well as being great for easing pain and relaxing muscles, this distinctively fruity tasting strain is for you.

Buy seeds from seedking.com

G-13

Perhaps one of the most notorious cultivars out there, the legend of G-13 is that it is an escapee from a breeding experiment funded by the U.S. government. With 22-24% THC level potential, G-13 provides a couch-locking feeling of euphoria.

Buy seeds from pacificseedbank.com

Northern Lights

Multiple award wins have solidified Northern Lights as another classic indica strain.  THC levels range from 16-26% and promise a mellow and pacifying high.

Buy seeds from seedsman.com

OG Kush

World-renown for its potency and distinct flavour, the legendary OG Kush needs to introduction. Tokers will enjoy equally intense body and head highs from around 20% THC levels.

Buy seeds from royalqueenseeds.com

Superglue

Superglue brings calming relaxation to the mind and body while leaving you functional and energetic enough for social activities or a productive afternoon.

Buy seeds from cannaconnection.com

Sunset Sherbert

Mario Guzman aka Mr. Sherbinski grows some of the finest cannabis you’ll ever smoke. Stress and tension will melt away as a full-body high creeps, delivering a deep physical relaxation.

Buy seeds from homegrowncannabisco.com

Super Skunk

Super Skunk delivers a notoriously powerful body high thanks to a THC content of 20% or higher. Consumers can expect a whole-body relaxation that kicks stress to the curb and will have you in full couch-lock mode.

Buy seeds from homegrowncannabisco.com

Triple Cheese

Known to consistently reach 22% THC or higher, Triple Cheese by world-renowned breeder Barney’s Farm offers Cheese lovers a very enjoyable high and a unique terpene profile.

Buy seeds from barneysfarm.com

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Cannabis

Borneol: The Terpene That Can Improve Your Heart & Gut Health

This terpene Borneol offers many health benefits, including improved digestion (via the stimulation of gastric juices) and better blood circulation.

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Borneol
PHOTO | Jesse Barney

Of the 20,000 aromatic molecules called terpenes found throughout nature, roughly 200 have been discovered in the cannabis herb. As an aggregate, the most common health efficacies offered by cannabis-derived terpenes are reduced systemic inflammation, anti-cancer properties, and analgesic (pain-killing) benefits. The terpene Borneol emits an odor involving scents of camphor, earth, and menthol; its scent is sometimes described as “herbal minty.” It is found in many plants other than cannabis, including camphor, mint, and rosemary. It is a natural insect repellent and is utilized industrially in the manufacture of perfumes and colognes.

Borneol is not extremely common in cannabis. Strains of cannabis offering more significant amounts of this terpene include Hazes and K-13.

The Details of Borneol

This terpene offers many health benefits, including improved digestion (via the stimulation of gastric juices) and better blood circulation. It also effectively treats bronchial symptoms to improve lung function and ease breathing (helpful for sufferers of bronchitis and asthma). Like many of its sibling terpenes, it has been found to reduce anxiety.

Borneol also assists in the healing of wounds. Historically, it has been incorporated into topical treatments for such applications, including the treatment of hemorrhoids. Combined with other terpenes that convey sedative qualities — such as myrcene and linalool — the terpene can effectively combat insomnia. It is also antibacterial and antiseptic.

Borneol exemplifies the dynamics of the entourage effect, a theory that cannabinoids and terpenes work together, synergistically, to offer particular therapeutic and medicinal benefits to humans via supplementation of the mammalian endocannabinoid system (ECS). Borneol amplifies the permeability of the blood/brain barrier, allowing other molecules and compounds to more efficiently bind with specialized receptors in the brain and central nervous system.

When isolated, it can act as an irritant to eyes, skin, and the respiratory system. As a good demonstration of the impact of accurate and strategic titration (dosing), at large doses, it is extremely toxic and harmful if swallowed. A “probable lethal dose” is 50-500 mg/kg of body weight, which equates to between only a teaspoon and an ounce for a 150-pound human.

The Research

Multiple studies have demonstrated the wide-ranging medicinal efficacy of the terpene, including its pronounced role as an anti-inflammatory, bronchodilator, and cancer killer.

A 2017 study entitled “Terpenes from Forests and Human Health” and published in the journal Toxicological Research investigated how borneol reduced inflammation of the lungs. Concluded the researchers, “Borneol alleviated acute lung inflammation by reducing inflammatory infiltration, histopathological changes, and cytokine production.”

A 2013 study published in the journal PLOS ONE and entitled “Natural Borneol, a Monoterpenoid Compound, Potentiates Selenocystine-induced Apoptosis in Human Hepatocellular Carcinoma Cells” revealed the anti-cancer properties of this terpene.

The study’s researchers concluded, “Borneol effectively synergized with SeC to reduce cancer cell growth through the triggering apoptotic cell death. These results reveal that borneol strongly potentiates SeC-induced apoptosis in cancer cells by enhancement of cellular uptake. Borneol could be further developed as a chemosensitizer of SeC in treatment of human cancers.”

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