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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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THC: This Cannabinoid Is the Reason You Get High From Weed

THC may be best known as a euphoriant that delivers a psychoactive effect, it also offers a multitude of medicinal benefits.

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THC
Mortgage Lifter PHOTO | Courtesy Humboldt Seed Company

Of the 113 cannabinoids that have been discovered in the cannabis herb, none is more infamous than tetrahydrocannabinol, or THC. Responsible for most of the psychoactivity and euphoria of cannabis, this cannabinoid does more than merely give suburban soccer moms a modicum of stress relief and college students ravenous munchies.

With all due respect to the molecules caffeine and ethanol, probably no other molecule in the history of humanity has been as misunderstood, stigmatized, or politicized as THC. From the reefer madness era of the late 1930s to the stereotype-laden films of Cheech and Chong in the 1970s to more recent movies like Pineapple Express (based on the name of a popular strain of cannabis), the truth about THC and its efficacy for humans often evades laypeople who consume content from only national media outlets.

The medicinal benefits of the molecule are numerous, ranging from relaxation and pain relief to appetite stimulation and sedation (great for insomniacs). Negative effects of this molecule include intense appetite stimulation (with predictable gastrointestinal consequences the following day), dry mouth, potential short-term memory impairment, paranoia and panic attacks (especially with sativa strains), and lethargy (typically in indica varieties).

The Details of THC

While THC may be best known as a euphoriant that delivers a psychoactive effect, it offers a multitude of medicinal benefits that far exceed the fabled “stoner” mannerisms of lethargy and forgetfulness. Despite its delivery of what is sometimes a potent euphoric effect (especially for new consumers), it is impossible to overdose on THC.

Assuming moderate and reasonable consumption levels, cannabis can serve as a positive lifestyle enhancement that delivers stress relief, mental wellness, improved energy levels, and even performance enhancement. Strains featuring relatively potent levels of THC include Blueberry, Ghost Train Haze, Master Kush, Trainwreck, and White Rhino.

Predicting the exact potency and efficacy of a particular strain of cannabis is difficult for a variety of reasons. For example, a theory called the Entourage Effect identifies how other cannabinoids and their aromatic cousins called terpenes can modify the effects of other cannabinoids and terpenes, including buffering or amplifying the effect or potency of THC.

One distinct characteristic of the molecule is tolerance building. While a subjective area of cannabis efficacy, tolerance building for daily consumers can be significant. To combat this problem, some indulge in a decades-long practice dubbed a tolerance break, during which they significantly decrease or cease consumption for between a few days and a week.

The Research on THC

A 2011 study conducted by cannabis research pioneer Dr. Ethan Russo entitled “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-terpenoid Entourage Effects” and published in the British Journal of Pharmacology provides a critical overview of THC’s medical benefits.

Concluded Russo and his team, “THC is the most common phytocannabinoid in cannabis and…is a partial agonist at CB1 and cannabinoid receptor 2 (CB2),” pointing out the herb’s myriad medical applications, including “activities as a psychoactive agent, analgesic, muscle relaxant, and antispasmodic.”

Russo’s team concluded that THC also functions as a bronchodilator and neuroprotective antioxidant while featuring 20 times the anti-inflammatory power of aspirin and twice that of hydrocortisone.

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Everything You Need to Know About Microdosing Weed

There are great reasons for microdosing weed including medical conditions that benefit from it, and a few different ways to achieving the perfect dose.

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Microdosing Weed
PHOTO | Gracie Malley

Microdosing is the latest craze in cannabis. It has been utilized for some time, both with cannabis and LSD, but only now is the mainstream getting hip to the low dose strategy. There are great reasons for microdosing weed including medical conditions that benefit from and improve because of it, and a few different ways to achieving that perfectly sensible dose.

Wait, First… What Is It?

Microdosing weed is when a person consumes very small amounts of cannabis in order to receive the benefits of whole plant medicine (THC, CBD, terpenes, etc) while experiencing very little to none of the “high.” It isn’t for those times when you want to get ripped and watch an entire season of Westworld and chow down, it is not going to produce that kind of experience. It is more or less a medical use technique that can be utilized day to day without affecting one’s overall state of mind. It is basically the opposite of a dab or trying to find the biggest pre-roll with the highest THC strain you can.

So Why Microdose?

As cannabis becomes more popular, and more people want to harness its power, the demand for less psychoactive pot rises. Not everyone likes to get the giggles, or the munchies, or the long trains of thought that tend to present themselves when a person gets stoned. Others do enjoy the laughing, eating and philosophizing but need something more manageable during their work day and family time.

Microdosing to the rescue. Now you can get just a little high, without any of the headiness or outward signs that you have been consuming anything at all.

Family reunion? Microdose.

Big meeting at work? Microdose.

Irritatingly long wait at the DMV? You guessed it – microdose.

More seriously, if you work a 9-5 and suffer from back pain from sitting at your desk all day long – you could be microdosing to alleviate those aches and pains without making it obvious that you are medicating with cannabis throughout the day.

Potential Medical Benefits

Unfortunately, because cannabis is a Schedule I drug, the federal government claims that it has no medical value and therefore has not been studied as much as it should be. Most scientific studies on that have been completed on cannabis consumption are animal based. While many of those animal studies can absolutely translate to apply to human beings, it is certainly not the same as results garnered from actual human studies.

There have been studies on the benefits of administering low doses of synthetic cannabis pharmaceuticals in humans. Those results are typically positive in regards to microdosing. However, like the animal studies, results from synthetic cannabis studies do not fully represent the results that could be gathered from studying real, naturally sourced marijuana.

With that said, there are incredible amounts data supplied by cannabis users, and a bevy of recorded favorable results, that go toward proving that marijuana is an effective way to treat a variety of medical conditions. Microdosing can help almost anything that using cannabis will – just in a much smaller and more controlled way. Post Traumatic Stress Disorder (PTSD), insomnia, glaucoma, nausea, wasting syndrome, and moderate pain are just a few of the conditions that can benefit from microdosing weed. However, medical issues like cancer and epilepsy, that are treated with large amounts or very concentrated forms of cannabis, are not necessarily best suited for treatment with microdosing.

Think of it like this… if you have achy muscles you can take an over the counter pain reliever twice a day for relief but if you have severe pain in your joints and muscles that requires a prescription painkiller, the over the counter medicine isn’t really going to make a dent. The same can apply for microdosing. If your condition can be treated throughout the day in small doses, microdosing could be a beneficial, natural way to treat the problem. If you only experience relief from consuming an entire joint or 100 mg edible, microdosing is likely not going to be the best way to alleviate the issue.

Start low and find your sweet spot.

Consumption Options for Microdosing Weed

Microdosing weed can be achieved a few ways.

An oil cartridge and vape pen is one of the easiest ways to consume small, controlled doses of cannabis. A vape pen is discreet, clean, and odorless. Many vape pens have an auto-shutoff after a few seconds, so doses can be regulated with ease.

Edibles are another great way to microdose. Infused food or candy manufacturers have caught on and started producing products in smaller doses in order to service the microdosing market. Edibles of yesteryear could only be found in 50 mg, 100 mg or higher dosages. Now, you can purchase a bag of candies infused with 2.5 mg, 5 mg or 10 mg.

You can also microdose with smoked cannabis, but it is more difficult to do so covertly. If keeping your use under wraps is important, smoking cannabis should be your last choice due to the lingering smell alone. However, a loaded one-hitter or chillum is an adequate way to limit the dose you consume while still benefiting from the plant’s medical properties.

Whether you vape, eat, or smoke cannabis to microdose is up to you. In many circumstances and for many medical conditions, microdosing can be a better option than an all-out cannabis consumption free for all — less fun, sure, but not everyone is after the same experience with weed. As cannabis becomes more widely accepted, so does the trend of microdosing. Give it a shot, see if the shoe fits!

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Why Independent Third-Party Cannabis Testing Is Important

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Cannabis Testing
PHOTO | HQUALITY

During cultivation, the cannabis plant acts like a sponge. It absorbs everything it is exposed to, from pesticides, nutrients, and heavy metals present in the soil. For these reasons, it is essential that reputable and reliable third-party labs carry out cannabis testing to assure safety and efficacy of the product.

Lab testing of cannabis products is an essential part of the regulated market’s supply chain. It detects offensive chemicals or contaminants that can lead to adverse health effects when consumed, while additionally providing cultivators and retailers with efficacious cannabinoid and terpene profiles of legal cannabis products. 

In Canada’s regulated market, batch release quality control testing is required for potency and product safety, so it is necessary to measure substances like pesticides, mycotoxins, bacteria, and molds. Unfortunately, reports on potency and contaminants can vary from lab to lab, while recalls of contaminated products threaten consumer trust of legal products. 

Sigma Analytical Services is a full-service pesticide, elemental, molecular, genetic, and pathogen analysis laboratory for cannabis, hemp, and cannabis-derived products. It delivers reliable science for cannabis products to the cannabis industry and cannabis consumers.

Cannabis Aficionado spoke with Ashton Abrahams, co-founder and COO of Sigma Analytical Services, to learn more about the importance of cannabis testing and Sigma’s strict processes.

Cannabis Aficionado: Tell me about your entrepreneurial journey to cannabis.

I’m a serial entrepreneur with over 20 years of experience in starting and growing several successful ventures. In 2017, when Canada was in the process of legalizing cannabis, my partner and I saw an opportunity to focus on a different side of the new cannabis industry — ancillary testing and quality reassurance requirements. We knew there would be new products in the market, and they would all require testing. So, we started a testing lab that focused on cannabis and cannabis products, and this is how Sigma started.

What sets Sigma apart from other testing labs?

We want to ensure products available in this new market are efficacious and safe, and ensure the levels of both remain consistent. Sigma is the only GMP (Good Manufacturing Practice) certified, cannabis-focused lab in Canada and the only cannabis-focused lab with cross-continental operations. We developed and validated our methods back in 2018 and 2019, so we are the frontrunner in Cannabis 2.0 product testing and are set up to test a comprehensive list of cannabis products — including flower, edibles, beverages, and topicals. 

Sigma also has validated methods for quantifying and testing 16 cannabinoids and 43 terpenes — one of the highest in the market — and our analytical and microbiology tests are compliant with Health Canada, EU, and US Pharmacopeia.

Additionally, Sigma was awarded the Best Cannabis Lab/Testing Facility in Canada at the Grow Up 2019 awards.

Inside Sigma Analytical Services’ state-of-the-art lab.

What need does Sigma fill in the global cannabis industry?

Sigma brings reliable science that is already available in food and pharma to the cannabis industry, its products, and consumers.

Cannabis, food, and pharma share certain quality requirements. However, there is a big difference: in terms of quality assurance, food and pharma have decades of testing experience, while cannabis is a new industry, and the science is still being developed. 

What kind of samples do you test?

We have developed and validated testing methods for many different types of cannabis products, from traditional dried flower and oils to Cannabis 2.0 products , such as concentrates, beverages, edibles, and topicals. From a testing standpoint, each and every one of these products is different and can have a different matrix. In turn, we develop a testing  method for each one.

What should customers be looking for to see reassurance that a product’s been tested? 

Make sure their products are purchased through legal channels. It’s the regulatory bodies’ responsibility to make sure the products launched in the market are not just tested, but tested specifically by qualified labs.

Moldy cannabis is a problem in legal markets and there are numerous reports of Health Canada product recalls after customers discovered moldy flower. Can you talk to us about how you test for these pathogens?

From day one, instead of using the traditional culture-based method, Sigma has tested for mould and all microbial contamination using a newer technology called qPCR (quantitative Polymerase Chain Reaction). When we first started it in late 2018, nobody was familiar with it in the cannabis industry, so we had to take time to explain to our clients that it was a better, more reliable, and faster process. In the last six months, however, we have seen a huge shift in attitude. Not only have the cannabis producers accepted qPCR, but more cannabis labs are starting to use the technology to test for microbial contaminations.

Cannabis Testing
Moldy cannabis. PHOTO | LabRoots

What are some of the most exciting developments in cannabis testing?

Using qPCR for microbial contamination is very new for the cannabis industry. We’re happy and excited about it because we see the benefits and we hope the whole cannabis industry embraces it. 

Secondly, the challenges of formulating, developing, and testing new products. The developments in the past six months have been really promising.

Thirdly, discovering more about the cannabis plant and what ends up in cannabis products is really an exciting development. As we progress, we are sure to learn more about the effects of cannabinoids and terpenes.

What’s your pinnacle vision of cannabis testing?

There are two sides to it. There is a regulatory side, and there is the testing side. On the regulatory side, it’s about what needs to be tested, and how it needs to be tested. 

A very important part of the quality assurance initiative for cannabis is ensuring the testing sample is representative of that batch. There are different factors in place. Is that batch homogeneous or not? Are the characteristics consistent or not? Cannabis is a plant. It’s an agricultural product. It’s not something that’s coming out of a machine, so we cannot expect all of the plants to have exactly the same characteristics. I believe one key is to limit the size of the batch. Other jurisdictions have clearly defined regulations. For example, in California, it clearly states that each batch cannot be larger than fifty pounds. In the Canadian regulations, there is no definition at all.

Secondly, labs need to get more serious. Some labs are testing cannabis products with outdated instruments or unvalidated methods, meaning their results cannot be truly accurate or reliable. Cannabis labs cannot use a 15-year-old second-hand instrument and expect to get the same results as pharmaceutical labs that use the best, most advanced instruments. Some people might think that testing cannabis products is not as important as pharmaceutical products, but it is just as important.

Cannabis has a very complex matrix which requires complex testing methods. Not all labs have good enough or validated methods. However, I’m optimistic that it’s a matter of years, maybe between five to ten, for cannabis testing to get there.

How is Sigma helping to foster the growth of a responsible and safe legal cannabis industry?

I think everyone active in the cannabis industry has a responsibility to make sure they are doing a good job and providing safe and efficacious products to the consumer. That’s because, if the consumer is not happy with what they’re getting from us, it will translate into unhappiness with the whole legalized framework.

Finally, what’s next for Sigma?

We are going through some expansion at our headquarters in Toronto and we’re about to acquire a lab in British Columbia, which will be our second lab in Canada. Additionally, we have a joint venture in Colombia and are setting up the first GMP certified cannabis lab in South America.

We are also becoming more involved with helping develop formulations for new products, and testing them, especially for the producers that follow GMP requirements either in pursuit of higher quality or for international cannabis markets.

We also recently received our GMP clearance from the Australian Therapeutic Goods Administration (“TGA”). The approval designates Sigma as an approved testing laboratory for Canadian companies to introduce their products into the Australian cannabis market.

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