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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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Taking the Temperature of Northern California’s Heritage Cannabis

Long story short, it’s rocky out there for many of the Emerald Triangle’s heritage cannabis businesses — but they want to be doing it legally.

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Heritage Cannabis
PHOTO | Aran

It’s been over two years since Proposition 64 was passed in California. Profit projections, law enforcement, the black market, and climate change have kept the cannabis business in the Golden State everything but predictable. People continue to be imprisoned for crimes connected to cannabis while legal businesses are turning a profit. Legal weed has even backfired on the people who made it legal, as big corporate investors coming in change their business landscape.

Yet it remains a general consensus that legalization is all for the better. No one wants to go to jail anymore for growing or selling weed, there’s absolutely no denying the many medical benefits of the plant and hemp is poised to present itself as the green alternative to the overconsumption of fossil fuel products. Cannabis is a disruptor to big pharma, big alcohol and big tobacco, which in turn has the “bigs” attempting to either sabotage and/or establish themselves in the marketplace.

Long story short, it’s rocky out there for many running legitimate legal cannabis businesses but they want to be doing it.

Northern California took a big hit — and it wasn’t just profit loss. While policymakers tried to model California’s legal market after Colorado, they fell short because the cultivators in California don’t operate the same way. The green rush flooded prime growing communities with people who were so green to cannabis, it doesn’t seem right to even call them that. But many heritage cannabis farmers in these communities wanted to break the cycle of fear instilled over the years and moved forward with legalization regardless, for all the right reasons.

Chiah Rodriques and her husband James Beatty run River Txai Farms and Arcanna Flowers, the brand and sustainable cannabis farm and nursery in Mendocino County. Rodriques and Beatty grew up on a large back-to-land intentional community and are second-generation Mendo cannabis farmers.

Chiah Rodriques and James Beatty. PHOTO | Trina Calderón

Committed to legal growing since the 9.31 ordinance enacted in 2008, they founded Mendocino Generations, a collective of sustainable cannabis farms in Mendocino County who strive to work together as a brand, farm landrace genetics, and promote “better living through cannabis.”

But keeping Mendo’s exceptional cannabis tradition alive throughout legalization has presented challenges. Visiting the area during this season’s harvest, I took the temperature with Rodriques.

“Basically over-regulation is like the ankle-biter,” shared Rodriques. “It’s the Achilles heel of the small farmer because in order to compete in this market you have to cultivate enough cannabis to compete with farms in other counties with larger cultivation allowances. Ultimately, they’re our competition but on a shelf with jars of cannabis, they’re not, because you wouldn’t want to put that cannabis in a pretty jar on a shelf — most of that product is going to oil and biomass. You have different levels of competition. You have competition for pricing because their cannabis is still going into the market, which makes prices fluctuate. Then you have the shelf space for all the brands, and lots of these brands thought that they could do a small brand and survive with that, but I don’t think that that’s really going to play out as we thought. Running a small brand takes a lot of overhead.

PHOTO | Trina Calderón

“Basically it’s hard to know if your brand from one small farm can have enough cannabis if your brand goes big,” she continued. “You may need to start reaching out and getting cannabis for your brand from other cultivators. In Mendocino County, we have a disadvantage because we can only cultivate 10,000 sq. ft., but there is a push for there to be a ballot to change it to one acre. That has mixed reviews from the farmers too, basically half the farmers hate that idea and half the farmers are into it. I think that’s mostly because they don’t have the space or the water or the infrastructure to handle that much.”

Rodriques believes that a contributor to the disconnect in policy is that no one consulted with Mendo’s heritage cannabis farmers when creating regulations.

“Farmers were not invited to the table until much of the ordinance was in place and there was a big rush to push things through as is and make changes later — so the county was ready for Prop 64 to go into effect. It was a race to the finish line. They didn’t think we had valid concerns, or maybe felt like the hippies needed to get organized. Admittedly so, we were all over the place with requests and needs that I’m sure it was overwhelming to lawmakers,” Rodriques said.

There was no real insight into what is actually practical or what is actually happening on farms in the area. Most of the regulations were written around indoor cultivation and don’t play out for sun-grown farms in Mendo.

A more community-oriented step towards action is the Mendocino Appellations Project, a group designed to set up a process for defining cannabis appellations, which are geographic areas in which small farmers can classify their crop with that name. A valiant effort, it plays into marketing and promotion, though the true cannabis aficionado will appreciate the information the same way a wine connoisseur likes to know where exactly a pinot noir grape is grown.

PHOTO | Trina Calderón

Small farming is no easy task in itself and going legal has created hardships for many.

“I think last year sucked so bad most people were struggling pretty hard, and in terms of pricing, it was bad last year,” said Rodriques. “Crops this year were a mixed bag. We definitely had a lot of people who had frost, and we had mold. There’s a lot of powdery mildew this year because the rain didn’t come. It’s like this weird humid that makes no sense because it’s really been dry. There’s been a lot of theft. There have been a lot of fires, so there’s smoke damage material.

“[As for] the market, who knows what it’s actually going to look like in the next couple months. Right now, its sort of a mixture, a lot of people are saying they’re going to back out. A lot of people are scared, but then there’s a lot of people that are moving forward with all these other ideas and plans. They’re doing okay, so it’s hard to tell what’s going to happen with the ultimate heritage cultivators, like my parents’ generation. Most of them aren’t doing it anymore because they were on the brink of retirement anyway so who wants to go through all this bullshit, right?”

Heritage Cannabis

Chiah Rodriques. PHOTO | Trina Calderón

Recently, the county has realized they’re not getting as much tax money as they hoped and the Board of Supervisors are planning to give the small farmers what’s called a Cannabis Cultivation Amnesty Transition Pathway. The plan would give more years for legacy growers to transition into county compliance, which may help attract more applications. The vote was unanimous to create the Amnesty, which Rodriques sees as the county throwing them a bone. Considering 1588 total people applied to participate in legal cannabis in the county, and only 232 were approved and issued permits, and it appears not many more would apply since the regulations are so problematic. Building and planning issues like commercial zoning and ADA rules for bathrooms and parking lots are costing farms money they don’t have. Especially when the reality is it’s usually not probable to have anyone in a wheelchair working on a farm. Workarounds are likely because people are trying to be compliant, but the same rules are putting people in uncomfortable positions.

“Comparatively to Humboldt, I would say that Mendo is struggling a little bit harder and that’s more because the bureaucracy hasn’t allowed people to get into the system,” Rodriques concluded.

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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
PHOTO roxxyphotos

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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Plant Growth Regulators: What They Are & Why You Should Avoid Them

Plant Growth Regulators boost cannabis yields by pumping the nugs full of water at the cellular level which leads to the expansion.

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Plant Growth Regulators
PHOTO | lovelyday12

The dark years of cannabis prohibition in California created an innovative and highly competitive black market for weed that thrives to this day despite the state’s relatively progressive path toward legalization. Risk has always been high for illicit growers and their tactics to avoid the prying eyes of law enforcement have evolved over time. Decades ago, the use of helicopters and spotter planes to target pot farms forced growers to camouflage their cultivation, or in many cases, move it all the way indoors.

This radical change in the way cannabis was grown, particularly in Cali, led to a massive leap in quality control as indoor growers could now “play god” and manipulate all environmental conditions to their liking. However, it also led to a drastic drop in overall yields.

Remember, we are talking about the Nineties, so most of these were not yet warehouse-style grows. They were closets, garages, basements, and spare rooms for the most part and even though you could flip each room a few times per year, the overall weight harvested paled in comparison to the massive trees that could be grown outdoors.

With a limited footprint to grow in, and a limited canopy above (ie. the ceiling and lights), growers began looking for any way they could to boost the number of grams of finished buds that they could pull from each square foot of cultivation space.

For some, like our friend Josh D, that meant revolutionizing hydroponic grow systems and optimizing that method for cannabis production while at the same time introducing and perfecting the ultimate indoor strain — OG Kush. The optimal genetics of this iconic strain naturally produced shorter, bushier plants with massive, dense, and potent buds, making it ideal for indoor cultivation.

Not all growers were blessed with such genetics or know-how, though, and it didn’t take long for some of them to start to seek out some rather unsavory store-bought shortcuts to try to compensate for lackluster harvests.

Plant Growth Regulators (PGRs)

Plant Growth Regulators (PGRs) date back well before the Nineties cannabis boom. First introduced to American agriculture in the 1920s, these chemical compounds were used for nearly half a century to either boost or slow down the natural rate of growth of plants through phytohormonal manipulation.

For example, groves of fruit or nut trees could be filled with shorter trees that yielded more produce thereby reducing the time and risk of harvesting and, in turn, increasing profits.

However, when independent lab studies showed that certain synthetic PGRs could potentially be carcinogenic, the FDA stepped in and banned the use of such products on consumable food crops in the 1970s.

Those products, however, did not vanish. They continued to be used to keep trees at parks from growing too tall, or to make bouquets of grocery store flowers bloom brighter and grow at such uniform sizes and, as we know, to artificially boost cannabis yields. In fact, the global demand for PGRs has more than doubled in the past six years and now stands as a $6.4 billion sector of the agricultural industry.

Some growers are using this particular shortcut knowingly but many others may be pumping their pot full of PGRs without even knowing it as this controversial compound has been found (often unlabeled) in many popular brands of fertilizers and nutrients. If growers use those products and just so happen to see tighter, denser, and heavier nugs as a result… win/win, right? What’s wrong with increased yields and solid buds, anyway?

Guaranteed Mids

It’s no secret that, for the most part, the regulated cannabis market in California is flooded with mid-grade weed that is barely worthy of a blunt wrap for most seasoned smokers. The logistics of the supply chain and the way things have to be packaged in today’s market can mutilate even the best-grown buds by the time they reach the end-user but, sadly, most of the supply these days was pretty shoddy to begin with. We call it California’s “Mids Life Crisis”.

As many state-sanctioned cultivators struggle to stay afloat in the new legal market, too many are feeling the pressure of whatever deal they signed with the devil to fund their startup and are willing to do whatever it takes to make their numbers make sense. PGRs are the perfect tool for such an unscrupulous job.

Simply put, the way that PGRs boost cannabis yields is by pumping those nugs full of water at the cellular level which leads to the expansion. You are not boosting the vigor or potency of the plant, that added weight is literally moisture and cellulose. So while California cannabis testing labs are not required to flag samples for PGR levels, they will show lower overall THC levels — bigger buds do not always equal stronger buds.

So how can you tell if that herb you are inspecting at the dispensary has been treated with Plant Growth Regulators? Here are a few telltale signs to look for:

  • Buds that are extremely hard or dense in structure
  • Buds with an excessive amount of pistils, often matted or intertwined
  • Pistils often have more of a brown hue than the rusty orange seen on healthy buds
  • Distinct lack of visible developed trichomes
  • Lack of strain-appropriate aroma

Still unsure? Ask the budtender direct questions about it. Who grew it? Where was it grown? Research that feedback or pass on those products if that information is unknown. At the end of the day, it is our job as consumers to do the due diligence to ensure that what we put into our bodies is legit. Relying on any company or corporation to do that for you is naïve, particularly when it comes to the Wild West of legal weed.

Safety Meeting

Roughly a decade after the FDA banned the use of synthetic Plant Growth Regulators on crops meant for human consumption, the Environmental Protection Agency followed suit in the 1980s by placing even heavier restrictions on the use of certain PGRs and labeling them as environmental pollutants. The EPA warned that exposure to these synth PGRs could elevate a person’s risk of cancer 240 times higher than the acceptable standard.

That being said, many of those studies involved subjecting rats to astronomical levels of various PGRs in order to trigger negative reactions and there is no hard evidence that smoking weed treated with PGRs is much different than eating In n’ Out instead of a home-cooked burger. But, to us, it does matter and we will avoid synthetic PGR weed at all costs. We don’t want to smoke it, we don’t want to vape it, and we certainly have no interest in extracting it to create full-spectrum cannabis oil. Nothing about Plant Growth Regulators benefits the consumer, period.

Now, that’s not to say that all PGRs are bad news. In fact, there are many natural sources for Plant Growth Regulators that can be useful and healthy supplements for your fertilizer or nutrient base. But as a grower, you should feel obligated to thoroughly understand how they are sourced from nature and exactly how they work with the balanced chemistry of your plants before putting them to use. Failure to do so can take you from “Top Shelf” to “Midzotics” real quick!

Remember, fellow cultivators: If your SOP calls for more PGRs, then your QC is probably BS.

What’s Next?

Look for PGRs to make a major splash in the newly established American hemp marketplace as the importance of higher yields compounds dramatically at the large scale that those farms will be operating at. Combine that with the relative lack of lab testing requirements and Plant Growth Regulators figure to play a large role in helping the U.S. compete in the global market. American hemp is mandated by federal law to produce a ridiculously low 0.3% THC content, so the fact that PGRs murder trichomes only helps growers and manufacturers.

As for what role Plant Growth Regulators will play in the future of cannabis, that will likely come down to regulation since we see that there are too many growers who are willing to cut that corner when it is left up to them. At the very least, plant fertilizer and nutrient companies should be mandated by law to accurately list all ingredients and contents of their products. That way the growers who are trying to do the right thing can make informed decisions about how they treat their gardens, farms, and warehouse grows.

Finally, as consumers, we can speak with our hard-earned dollars. Quit buying PGR tainted buds! Tell your favorite dispensary that you aren’t interested in buying those products. If enough of us do exactly that, the free market will… ahem… weed out the PGR growers and those who push their products.

Beard Bros. Pharms has earned their reputation as a trusted source for cannabis news, content creation, and culture preservation. With decades of experience in cultivation and marketing, their fearless voice for the plant includes advocacy for veterans, inmates, people of color, and anyone else who has been oppressed by generations of cannabis prohibition. See what they’re up to now at BeardBrosPharms.com

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