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Everything You Need to Know About the Science Behind Cannabinoids

Get to know the three different classes of cannabinoids: phytocannabinoids, endocannabinoids and synthetic cannabinoids.

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Cannabinoids
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The cannabis plant produces literally hundreds of specialized molecules — cannabinoids, terpenes and flavonoids — that have been shown to deliver medicinal efficacy, lifestyle enhancement and even performance enhancement to human beings. For those afflicted with disease, medical cannabis has been found to offer a wide range of health benefits, from killing cancerous tumors to alleviating the pain of arthritis to reducing the number of seizures experienced by epileptic children.

Of these molecules, cannabinoids are the most cited and understood. The most infamous cannabinoid is tetrahydrocannabinol (THC), the molecule responsible for most of the psychoactive (psychotropic) and euphoric effects of cannabis, but that also has been found to successfully treat serious conditions, such as PTSD and cancer. Another notable cannabinoid is cannabidiol (CBD), a mostly non-psychoactive chemical that has been found to provide a wide range of medicinal benefits, including reductions in pain, anxiety and depression.

Endocannabinoids vs. Phytocannabinoids

First discovered in 1964 by Israeli researcher Raphael Mechoulam, phytocannabinoids from the cannabis plant interact with the human body by mimicking the molecular characteristics of chemicals produced internally. Called endocannabinoids, these internally manufactured molecules include anandamide and 2-AG.

Anandamide has been dubbed the “bliss molecule” because of its ability to decrease depression in humans. It plays a central role in the regulation and modulation of critical bodily functions such as mood, appetite, sleep, immune system efficiency and one’s ability to deal with stress and anxiety.

Synthetic Cannabinoids

Synthetic cannabinoids emerged in the 1970s and are created in a laboratory. An example of it would be dronabinol (Δ9-THC synthetic), which is the active compound of Marinol, a medicine that comes in capsules and has been consumed in the US since 1985 to prevent nausea, vomiting, loss of appetite and loss of weight.

The Endocannabinoid System

All mammals, not merely humans, have evolved with a network of specialized cellular receptors throughout their bodies that are designed to bind with cannabinoids — both endocannabinoids such as anandamide and phytocannabinoids from cannabis — that is called the endocannabinoid system (ECS).

The fact that the ECS is present in all mammals is why companies and product lines dedicated to the health and wellness of household pets are beginning to emerge in legal cannabis markets. Dogs and cats suffering conditions such as arthritis, digestive issues, anxiety and pain can gain significant benefit from the cannabinoids in cannabis and hemp.

Anandamide production has been found to increase and temporarily spike in those who engage in endurance exercise on a regular basis. However, it metabolizes quickly, exhibiting a relatively short duration of effect. Anandamide hints at the chemical underpinnings of the significant health benefits of frequent and intense exercise—and the fact that the mere consumption of cannabinoids is not enough to establish and sustain optimal health of the ECS (a condition called homeostasis that means “balance”).

Both internally produced endocannabinoids and plant-based phytocannabinoids interface with the ECS via specialized cellular receptors that were discovered in the 1990s and called CB1 and CB2. CB1 receptors are found mostly in the brain and central nervous system, whereas CB2 receptors are located primarily in the organs and tissues of the immune system—including the thymus, skin, bone marrow, lymph nodes, spleen, bowel and the mucous membranes of the bladder, genitals, nose and throat.

Major Cannabinoids + Acidic Precursors

More than 113 cannabinoids have been isolated and identified within the cannabis plant — which is, technically, also a vegetable. Beyond the two major cannabis-derived molecules, THC and CBD, are a plethora of healthful cannabinoids that deliver a slew of desirable and beneficial efficacies for lifestyle consumers and patients alike. Among these are cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and tetrahydrocannabivarin (THCV).

Additional healthful cannabinoids include tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). These chemicals represent a class of cannabinoids dubbed acidic precursors. Think of acidic precursors as the larval caterpillar stage of what becomes the butterflies of THC and CBD.

While they provide significant benefits in terms of health and wellness, the exact effects of these molecules differ from their non-acidic versions. For example, while strains of cannabis that are potent in THC can exact a significant toll in terms of psychoactivity and euphoria, THCA delivers no such psychotropic effect. THCA does, however, offer anti-inflammatory and neuroprotective effects, making it helpful for conditions as wide-ranging as Alzheimer’s disease, arthritis, cancer, Crohn’s disease, fibromyalgia, multiple sclerosis and Parkinson’s.

Understanding Decarboxylation

The process by which the transmogrification from the chemical state of acidic precursor (THCA) to its child molecule (THC) occurs is significant (and can be accurately controlled by anyone). A process called decarboxylation, this conversion involves the application of heat (via flame, as in combustion, or from a hot surface or airstream, as in vaporization) to catalyze a chemical reaction in which the THCA molecule drops a carbon and two oxygen atoms (called a carboxyl ring, or COOH) to become THC — and gain its euphoric effects based on its newfound binding affinity with the CB1 receptors of the ECS.

Technically, maximum decarboxylation for a sample of cannabis flowers occurs most effectively when exposed to 220 degrees F (104 degrees C) for a period of 30 to 45 minutes. Decarboxylation is easy and convenient because it can be accomplished using a standard consumer oven.

Thus, one who eats the raw flowers of cannabis will gain significant medicinal benefits, but no euphoria. The simple application of a flame or hot air, however, leads to the nearly instantaneous transformation of these molecules into their chemical cousins, delivering beneficial — but sometimes very different — effects.

The Research

A 2017 research study entitled “Medicinal Cannabis: History, Pharmacology and Implications for the Acute Care Setting” that was published in the journal Pharmacy & Therapeutics found the cannabinoids of cannabis, such as THC and CBD, to be effective in the treatment of a wide range of diseases and conditions.

The study’s researchers stated, the “Beneficial cannabinoids exist, as evidenced by single-entity agents derived from cannabis containing the compounds THC and CBD.” The study concluded that “cannabis is relatively safe; therapy is self-titratable by the patient; and…therapy is relatively inexpensive compared with pharmaceutical agents.”

CBC is a powerful cannabinoid first isolated in 1964 by Israeli researcher Raphael Mechoulam. It is considered one of the “big six” cannabinoids that, according to Steep Hill Labs in Berkeley, California, is ten times more effective than CBD in treating anxiety and stress.

In a 2011 study conducted by cannabis research pioneer Ethan Russo entitled “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-terpenoid Entourage Effects” and published in the British Journal of Pharmacology, Russo found that a CBC-extract displayed “pronounced antidepressant effect,” meaning it may be helpful for humans suffering from anxiety and depression.

Additional evidence of the medical benefits of cannabinoids derived from cannabis — this time for an ocular disease — was revealed in a 2008 study entitled “Possibilities of Applying Cannabinoids in the Treatment of Glaucoma” that was published in the journal Klinika Oczna. The study concluded that cannabinoids like CBG are “able to decrease intraocular pressure. These compounds are characterized by neuroprotection and vasodilatation properties that additionally substantiate their therapeutic utility in conservative treatment of glaucoma.”

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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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