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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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Peach Oz: This Sweet And Juicy Cultivar Will Stimulate Your Creativity

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PEACH FUZZ | PHOTO: WONDERBRETT

If you’re looking for a premium cultivar with legendary genetics and a euphoric high, look no further than Peach Oz, the latest addition to Wonderbrett’s stellar strain menu.

A cross of Peach Rings with OZ Kush and a descendent of Zkittlez, the sweet, stimulating citrus taste profile of Peach Oz will get your creative juices flowing.

While the cultivar may be new to the public, according to Wonderbrett Co-Founder and famed Breeder Brett Feldman, it’s five-years-old in the world of genetics.

“There’s only a small handful of heady smokers who follow these things,” says Feldman. “I wanted to bring it to the masses to share the experience with everybody. That’s where my passion comes from with this strain. Similar to an amazing dish at a restaurant, you want to share it with your friends.”

Grown in small-batches at scale from the company’s state-of-the-art Long Beach cultivation facility, the strain was first created by Dying Breed Seeds, then perfected by Cannabis By Corey, before making its way to Feldman.

Wonderbrett’s grow room | PHOTO: Courtesy Wonderbrett

Bursting with flavors and aromas that bring to mind the sweet ocean breeze and fragrant fruit orchards of the California sunshine state, Peach OZ’s four dominant terpenes: Caryophyllene, Linalool, Limonene and Humulene, create a distinct sweet taste of ripe peaches, citrus candy and cream.  

“When any strain has that unique, recognizable consistency in its flavor, whether that be peach, lemon or orange, that’s what myself and other breeders appreciate most and look for when bringing a genetic like this to market. It’s mind-blowing what Peach OZ can do that, translating a fruit flavor to a smoking experience,” explained Feldman.

Peach OZ is available at select dispensary and at Wonderbrett’s flagship dispensary in L.A.

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Pink Lemonade: This Sparkling Strain Is Both Pretty & Potent

The frosted pink buds of Pink Lemonade might dazzle the beholder with glittering layer of golden trichomes, but this gorgeous flower isn’t all looks.

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Pink Lemonade
PHOTO | Anna Wilcox

Dusted with a glittering layer of golden trichomes, the Pink Lemonade strain is endowed with a mystical appearance that embodies everything curious, attractive, and intriguing about cannabis flowers. Tightly bound calyxes dazzle with a bouquet of pink, violet, and sage coloration.

Cracking open one of these flowers emits a comfortable herbal aroma. A burst of crispness teases the nose, somewhat akin to the tart fizz in a carbonated cherry drink. This dessert-like aroma nicely compliments a definite happy hour high. Calm, relaxed, and downright chill, Pink Lemonade is a true afternoon delight.

The Pink Lemonade High

Put on some chill beats and pour yourself a nice drink. This plant is smooth, easy, and well-rounded. If inhaling Pink Lemonade feels like the first meaningful breath you’ve taken all day, you might be pleasantly surprised as a subtle relaxation works its way along the limbs and through the muscles.

There’s no doubt about it–this plant is a go-to strain for mellowing out. While often described as thoughtful and creative, the herb is better suited to leisure activities than it is serious concentration.

While solo consumers may enjoy putting on some Netflix after a little of this plant, it’s peaceful and contented nature is ideal for social gatherings. Spending time with friends may always be fun, but it’s easy to sit back enjoy a pleasant conversation after a few tastes of Pink Lemonade.

It’s worth mentioning, however, that cannabis affects everyone differently. The herb tends to be a mood enhancer rather than an instant remedy for happiness. If you are in an easygoing and relaxed environment, expect even more mellow after enjoying a little bud. If you’ve been having a bad day, strains like Pink Lemonade may provide relief by softening negative emotions and making them more tolerable.

Pink Lemonade Strain Background

Today’s cannabis market is truly a craft one. To say that the lack of federal recognition of the herb is problematic is an understatement. However, one benefit of state-by-state legalization is the development of truly local, expertly crafted products.

Pink Lemonade is a superb example of such a flower. There are many renditions of Pink Lemonade out there, yet the particular version pictured is a cross between two contemporary hybrids, Lemon Cheesecake and Huckleberry Soda.

Each parent strain is exceptional in its own right. Lemon Cheesecake is a sativa-dominant flower with a sour cream aroma and substantial THC production. Huckleberry Soda is a craft hybrid from Annunkanki Genetics, an intriguing cross between two hybrids, Black Cherry Soda and Huckleberry Hound.

Pink Lemonade Strain Benefits

As a craft flower, Pink Lemonade was arguably bred more for enjoyment than serious medical potential. It’s frosted pink buds dazzle the beholder, showcasing the fact that this plant is truly a treat. However, this gorgeous flower isn’t all looks.

The flower produces upwards of 25 percent THC. This means that the plant may be useful to those who benefit from high-THC therapies. Those interested in making a full-extract oil, hash, or other forms of concentrates may also enjoy experimenting with this sugary herb.

This plant is not too energizing nor is it overly sedative. However, those hoping for a little extra help falling asleep at night may find the flower helpful. The relaxed flower may also be beneficial for anxious individuals in search of a social lubricant.

However, the high-THC content in Pink Lemonade can inspire the opposite effect in some people. Bottom line: if you are prone to social anxiety or often respond poorly to THC, this potent flower is likely not the best choice.

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Wizard Stones: The Magic of Making Cannabis Diamonds

Aaron Palmer and Graham Jennings, founders of Oleum Extracts in Washington State, talk about Wizard Stones, their THCA isolate product.

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Wizard Stones
PHOTO | Oleum Extracts

Heat, pressure, and time. The three components required to form a diamond from carbon. But what about diamonds made from cannabis? The founders of Oleum Extracts, Aaron Palmer and Graham Jennings both agree that a good cannabis diamond aka Wizard Stones ultimately comes down to the flavor provided by its terpene fraction.

‘Diamonds’ is a slang term for the crystal formations of the cannabinoid THCA. The molecule’s lattice structure builds upon itself naturally as individual molecules clump together creating the faceted formations that resemble diamond or quartz.

When most people talk about cannabis diamonds, they’re talking about THCA structures that form in their own terpene sauce. So, it’s a little different technique than other isolation methods.

While their chemical composition is the same, the process to make them is slightly different than the traditional diamonds mined from a raw extract. Instead, they use a specially formulated solvent mix to create a solution with a composition that encourages crystallization.

Due to Washington state’s regulations, Oleum is limited in the chemical solvents they can use. So that blend is the crucial variable to isolating THCA into their Wizard Stones product.

Growing cannabis diamonds within their original terpene fraction comes down to creating an environment with the right amounts of pressure and heat to encourage crystal growth.

Within the raw extract, the terpene and cannabinoid compounds are homogenized together, but as they settle and separate the mixture “crashes” — which is the start of crystallization.

Palmer explains that this process “helps to create a seed because if there’s nothing for the THCA molecules to grab onto then they have a harder time starting the diamond formation.”

There are a few ways extractors seed a solution to start diamond growth, but Oleum prefers to use freezing temperatures to solidify and then thaw their extract, helping to create small groupings of THCA for other molecules to stack off.

Another common seeding technique is to drop a previously grown crystal into the extracted mixture of cannabis compounds, giving the THCA something to grow off.

This technique is especially useful when filming a time-lapse of the crystal growth because it gives the camera a focal point knowing where the formation will grow from.

Creating Wizard Stones

The above timelapse video was photographed over a four day period by Dankshire. We can see diamonds begin to form almost immediately. However, the crystallization process can take a month if not longer to complete once a raw extract is jarred and waiting to crash.

Oleum utilizes custom-built isolation vessels for their production diamond runs but admits that the jar tech allows more visibility into the process.

Jennings points out, “You see the jars, we even do the jar stuff a lot. It’s more popular… and people know what it is compared to a large isolation vessel that no one can see into it but you know it’s growing 2,000 grams of crystals.”

Each batch can present a different ratio of diamonds to sauce and it seems like everyone wants a little different combination. “We just give ‘em what it makes,” Jennings said.

That’s the beauty of isolated products like cannabis diamonds and sauce; you can mix your own cocktail of cannabis compounds and really dial in the flavors and feelings that you’re after.

Wizard Stones grown in their own sauce create a potent, refined, and pronounce expression of the strain they are extracted from.

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