What are Cannabinoids?
Chapters
- Introduction: What is Cannabis Oil Extraction?
- A Short History of Cannabis and Hemp Extraction
- What are Cannabinoids? (THC, CBD, CBN, CBG, THCV, etc.)
- Biomass: Starting with the Right Stuff
- Extraction Process Overview (Derivatives and their Processes)
- Strategic End Product Market Opportunities
- Common Extraction Methods and Technology
- Extraction Equipment and Systems
- The Practical Science Behind Extraction
- Types of Viable Business Models
- Top 10 Questions (and Answers) from the Experts
- Cannabis Extraction Glossary of Terms
- Industry Resources and Links
What are Cannabinoids?
Definition of Cannabinoids
Why do we feel high when we smoke weed? Why does consuming cannabis and hemp seem to have such a broad range of beneficial effects? It all comes down to tiny lipid-loving compounds that the flower produces: cannabinoids.
Cannabinoids are compounds mostly found in cannabis as well as a few other plants such as Echinacea (US), Radula marginata (New Zealand), and Helichrysum umbraculigerum (Hawaii). But for the purposes of cannabinoid extraction, we’ll refer to the cannabis and hemp plant because there are such high concentrations of cannabinoids to be produced by this wonderfully complex plant.
There are three categories of cannabinoids:
- Phytocannabinoids produced in plants like cannabis,
- Endocannabinoids produced naturally by our bodies, and,
- Synthetic cannabinoids that are made artificially in a lab.
Unless you’re a scientist, most people mean phytocannabinoids when they use the term cannabinoids. Scientists have identified over 127 phytocannabinoids, and more are discovered every year. These can be broken up into two categories:
- Primary cannabinoids: Generally considered to be the two most commonly expressed phytocannabinoids in mature cannabis flowers – THC and CBD.
- Secondary cannabinoids: All of the phytocannabinoids excluding THC and CBD.
How were cannabinoids discovered?
Researchers in the mid-19th century were very interested in discovering active compounds in natural products. During this period, drugs like cocaine and morphine were first purified from the plants that produced them. Because of the colonial expansion of the British empire into India, British researchers were well aware of the medicinal benefits of cannabis. And they were eager to discover why. Unfortunately, because cannabinoids are terpenophenolic and not alkaloid, it took longer to isolate them than other plant-derived medicines.
In 1898, researchers at Cambridge extracted a resin from cannabis plant material using alcohol. They found it contained high amounts of the compound they named cannabinol (CBN), though it’s full structure was not fully identified until 1940.
Upon testing the effects of CBN, researchers realized they had not found the active compound in cannabis, and the search continued. THC was finally isolated by Israeli researcher Raphael Mechoulem in 1964. It’s been less than 60 years since we discovered the molecule that makes us feel high. Is it any wonder we’re still discovering the effects cannabis can have?
What part of the cannabis plant do cannabinoids come from?
The highest concentration of cannabinoids is found in the mature flowers of the female cannabis plant. The flowers the plant produces are inflorescences, which means what we call “buds” are actually tight groupings of many, many flowers. Biologists call each individual flower “bracts” though they are more often informally (and incorrectly) called calyxes. They are specialized leaves that grow to protect the reproductive organ, or pistil, of the female plant. They protect the seed while it grows.
The pistil is the entire reproductive organ of the cannabis flower and contains two stigmas and an ovule. When fertilized, the ovule will turn into a seed. The stigmas at the hairs that come out of each bract and are designed to catch pollen. Stigmas get longer, darker, and stickier the later it gets in the season—all in an attempt to catch any pollen on the wind.
The real reason we’re talking so much about bracts is because that’s where the magic happens. Bracts are covered in trichomes, and trichomes make cannabinoids.
What are trichomes?
Trichomes are hairlike outgrowths found on many plants, and of particular interest for cannabis connoisseurs. Trichomes are found in many places on cannabis plants, but are most densely populated on bracts themselves. They’re where cannabinoids, terpenes, and flavonoids are produced—most of the active compounds of the cannabis plant. In many ways, extraction is simply the process of separating the trichomes from the plant material and refining the oils therein.
There are three types of glandular trichomes found on cannabis: bulbous, capitate sessile, and capitate stalked.The most common, and of most interest, are the capitate-stalked trichomes. They look like tiny mushrooms, with a gland-head cap and a stalk that supports it.
Most of the active chemistry found in cannabis is produced in the gland head. There are secretory cells and secretory vesicles (or storage cells) in the gland head. These are where terpenes and cannabinoids are produced and stored.
Gland heads easily fall off during handling, and their presence, or lack thereof, can be an indicator of quality. Overhandled cannabis won’t be as potent as cannabis that has been treated gently.
Why did trichomes evolve?
Researchers think cannabis developed trichomes around 27 million years ago. As mystical as it might seem, they did not evolve to get humans high. There are two prevailing theories as to why they evolved:
- Cannabis evolved on the steppes of Central Asia, a place where most plants cannot grow because of the dry, sunny weather. To survive in such harsh conditions, a plant would need to develop a way to prevent evaporation and protect itself from UV damage. Enter trichomes. The oily substances they produce—cannabinoids and terpenes—can protect sensitive plant material from burning.
- Cannabinoids and terpenes can be very bitter. Which is an important protection against the hungry herbivores and insects that were evolving like crazy in the same time period. Some terpenes can even be toxic to some insects.
Cannabinoid Development
Phytocannabinoids go through several chemical stages as they develop and age. Those changes can result in compounds that have radically different effects in the body—and important consideration for any extractor interested in targeting a specific therapeutic benefit.
- Acidic cannabinoids (aka “raw” cannabinoids): Most cannabinoids found in the raw flower are in their acidic forms, although sunlight and time can change some of them into their neutral forms. All cannabinoids start out in their acidic forms—that’s why eating a raw flower won’t get you high, but smoking it will. The THC (tetrahydrocannabinol) you inhale once heated starts out as THCA (tetrahydrocannabinolic acid).
- Neutral cannabinoids (aka “active” cannabinoids): Arriving at this stage means that a tiny piece of the acidic cannabinoid has broken off due to heat, leaving the remaining compound chemically ‘neutral’. This is the stage most people aim for if they’re interested in the intoxicating effects of THC, or the therapeutic effects of CBD.
- Oxidized cannabinoids (aka “aged” cannabinoids): ‘Oxidized’, or aged, cannabinoids are degraded forms of cannabinoids that develop as the compound changes shape over time. You’ll find higher levels of these cannabinoids, like CBN, in older plant material.
The different stages of cannabinoids have different therapeutic values.
For example, THCA is thought to have some anti-inflammatory effects though it’s mechanism of action is unknown. The neutral form, Δ9-THC, is the most widely studied cannabinoid and has therapeutic potential across the board. Its slightly smaller size means it interacts with some targets in the body more easily.
The degraded form, CBN, is ⅙ the potency of THC and thought to share some, but not all, of the therapeutic properties of Δ9-THC.
CBG: The Mother Cannabinoid
Most cannabinoids start out as CBGA (cannabigerolic acid). Genetic markers determine what cannabinoid family they develop into. Until recently, it was difficult to produce large amounts of CBG (cannabigerol). The only way to produce it was harvesting plants really early, before the cannabinoids developed into anything else. In the last few years, breeders cracked the code on cannabis plants that retained CBG as they matured and now it is fast becoming a highly-sought after cannabinoid because of possible therapeutic effects without the user feeling high.
How Cannabinoids Interact with the Endocannabinoid System
So we know cannabinoids are produced by plants to protect them. But what about what they do for people? People have been cultivating cannabis for a long, long time. There’s evidence of hemp cultivation in Japan from about 8,000 BCE. The first reference of its medicinal properties were recorded in the Pen Ts’ao Ching—a near-mythical Chinese medical text reported to have been written around 2,800 BCE. Humans have loved this plant for a long, long time.
The discovery of cannabinoids in the mid-20th century led to another landmark discovery: that of the endocannabinoid system. For decades, researchers had heated debates about how cannabis actually got people high. The answer started to become clearer in 1988. Researchers discovered a receptor that THC directly interacted with, and it was everywhere in our bodies. In 1993, another receptor was found. Suddenly, there was a whole new system in our bodies, and it was named the endogenous cannabinoid (or endocannabinoid) system or ECS for short.
The endocannabinoid system (ECS) is widely distributed throughout the central and peripheral nervous systems, and involved in many other systems as well. It’s components are found in the reproductive, immune, and digestive systems, as well as in bones and skin, just to name a few. In 1998, Italian researcher Vincent Di Marzo summed up the effects of the ECS by saying it was responsible for regulating “relaxing, eating, sleeping, forgetting, and protecting.” And that just scratches the surface.
Changes in endocannabinoid receptor levels have been reported in almost all diseases affecting humans. These changes are why there is so much interest in developing a wide range of pharmaceutical drugs from cannabinoids.
The ECS is currently understood as being composed of two receptor types, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), the compounds our bodies produce that naturally bind to those receptors, and the metabolic pathways responsible for those compounds’ creation and destruction.
There is a catch. Cannabinoids are incredibly promiscuous molecules, and only a few of them bind to CB1 or CB2. A more recent development in the understanding of the endocannabinoid system takes into consideration the wider system that the ECS might be a part of. The larger system—which could include TRP receptors, serotonin receptors, orphan receptors, and more—is sometimes called the endocannabinoidome.
The Cannabinoid Receptors
- Cannabinoid Receptor Type 1 (CB1): The CB1 receptor is primarily found on neurons in the central nervous system. They’re the receptors responsible for making us feel high when we consume THC. If you’ve ever experienced the runner’s high, you’ve experienced the direct benefit of CB1.
- Cannabinoid Receptor Type 2 (CB2): This receptor is primarily found in peripheral tissues—most notably on cells in the immune system. Activating this receptor does not have the same intoxicating effects as CB1 activation, but instead plays an important role in regulating our immune responses. It also plays a role in regulating pain and inflammation, the anxiety response, and appetite stimulation.
The Cannabinoids our Bodies Produce
After researchers discovered why THC made us high, they were determined to discover what our bodies produced naturally that stimulated those same receptors. Bodies don’t create systems that are only stimulated by external compounds, there had to be naturally occurring ones too. Enter endocannabinoids. They were discovered a few short years after CB1 and CB2.
Endocannbinoids’ endorphin-like effects last a few brief minutes—their metabolites are released at the same time they are. The reason that THC’s high lasts longer than a runner’s high is that THC is not broken down by the same metabolites as endocannabinoids. Interestingly, endocannabinoids are found in relatively high levels in breast milk. Turns out maybe babies are high all of the time!
Over a dozen other compounds have been suggested to play a role in regulating and engaging with the endocannabinoid system. The two most common endocannabinoids—and the best studied—are:
- 2-Arachidonoylglycerol (2-AG), discovered in 1995
- N-arachidonoylethanolamine (AEA, aka anandamide), discovered in 1992
We are still learning about what roles endocannabinoids play. They could be the key to important therapeutic breakthroughs related to cannabis.
The Major Cannabinoids: THC and CBD
Cannabis produces an incredible spectrum of chemistry in every flower, and THC and CBD are the most commonly produced of the cannabinoids. They are responsible for many of the therapeutic benefits enjoyed by consumers. Other cannabinoids, terpenes, and flavonoids can have a significant impact on their effects, but they’re the rockstars. Consequently, they’re the best studied of the cannabinoids. All of this has led to their distinction as “major” cannabinoids.
Tetrahydrocannabinol (THC)
THC is the most well-known of the phytocannabinoids. Specifically the neutral form, Δ9-THC. This is the compound that causes the classic feelings of intoxication associated with consuming cannabis. It’s also where many of the therapeutic benefits—from pain-killing to cancer-fighting—come from. Most of those benefits appear to stem from its ability to activate both CB1 and CB2 receptors.
It is also the most common phytocannabinoids produced by drug varieties of cannabis. The concentration of THC in the flowering tops of the plant can reach 30% or higher.
Cannabidiol (CBD)
CBD is the most common phytocannabinoid produced by non-drug varieties of cannabis (aka hemp), and is increasingly being bred to express high levels in plants that have had THC bred out of them.
CBD does not bind to the two receptors most commonly studied in relationship to cannabis, the CB1 and CB2 receptors. Instead it interacts with over 65 different targets in the body, from opioid receptors to the receptor that causes capsaicin to burn. We have a long way to go before we fully understand CBD’s impact on our bodies.
CBD is often described as being non-psychoactive. This is not quite true. CBD is non-intoxicating—it doesn’t bind to the receptor that is associated with the feeling of being high. It does, however, bind to the serotonin receptor 5-HT1A. Its activation of that receptor is thought to be responsible for its anti-anxiety. Any compound that affects the mind, like quelling anxiety, is technically psychoactive.
The Minor Cannabinoids
The minor cannabinoids are every other cannabinoid that is found in cannabis besides THC and CBD. Well over 100 cannabinoids have been identified to date, and a handful of new ones are identified every year. Although we know next to nothing about most of them, there is enormous interest in discovering which one could be the next CBD.
The minor cannabinoids are every other cannabinoid that is found in cannabis besides THC and CBD. Well over 100 cannabinoids have been identified to date, and a handful of new ones are identified every year. Although we know next to nothing about most of them, there is enormous interest in discovering which one could be the next CBD.
Some minor cannabinoids are limited to medical applications. Cannabimovone (CBM), for example, is a vanishingly rare cannabinoid that shows promise in sensitizing diabetes patients to insulin. And that’s just about all we know about it. If you do find a rare cannabinoid in one of your extracts, let folks know! Researchers could just be your perfect market.
If you’re interested in extracting minor cannabinoids from plant material, be prepared to go through an enormous amount of biomass, and an enormous amount of research, to make it worth it.
What is the next cannabinoid trend?
Out of the hundreds of minor cannabinoids, which ones are worth investing in? Before discussing any of them, it’s important to note that research is extremely sparse on almost all minor cannabinoids. Despite that dearth, the market has already jumped at a few, like CBG and CBN. It’s worth it to keep a pulse on the newest research developments in cannabinoid pharmacology to predict what could be coming next.
- Cannabigerol (CBG): In 2019 breeders began releasing plants capable of producing high levels of CBG at maturity. It was a game-changer, and now we can already see CBG products popping up everywhere. It’s of particular interest for helping to control nausea, combat MRSA, and fight inflammation. Learn more about CBG extraction.
- Delta 8-Tetrahydrocannabinol (Δ8-THC): Δ8-THC is thought to have anti-anxiety properties, as well as appetite-stimulating and pain-killing ones. Like its analogue Δ9-THC, Δ8-THC activates the CB1 receptor, although more weakly. This affinity could lead to similar benefits as Δ9 without the intoxication.
- Cannabinol (CBN): Cannabinol products have been on the market for several years. There is a great deal of interest in its supposed sedative qualities, although there is little scientific evidence to support the notion. That said, in many ways CBN could be like a weaker form of Δ9-THC—a benefit to those too sensitive to otherwise partake. Learn more about CBN extraction.
- Tetrahydrocannabivarin (THCV): There is a huge amount of interest in THCV’s potential to suppress appetite. Thus far there haven’t been any human studies, but it actually has the opposite effect on CB1 than Δ9-THC. It’s currently being studied as a treatment for obesity and diabetes.
- Cannabichromene (CBC): There are no studies examining CBC’s impact in humans, but it shows early promise as a pain-fighting and anti-depressant compound. It could also have cosmetic effects, and has shown promise as an acne inhibitor.
Which ‘new’ cannabinoid should you be extracting now?
CBN and CBG have already entered the market, and are poised for success with consumers. It could be worth investing in these cannabinoids to diversify your end-product offerings. These two, in particular, are appealing because they can be found in much higher amounts than other minor cannabinoids.
Breeders have successfully bred cannabis varieties that produce up to 20% CBG at maturity. And all you need to extract CBN is old plant material—the THC starts degrading into CBN at about a year, and much faster if it’s exposed to light and heat. This is the most wonderful thing about CBN, you never need to waste any part of this wonderful plant, even old, aged, and ‘stale’ cannabis has gifts to share!
Most of the other minor cannabinoids have struggled to gain traction in the marketplace. This is largely due to lack of consumer education, or plant material rich enough in the cannabinoids to make extraction worth it.
Even so, it could pay to keep an eye on cannabis research and your lab results. If you find a spike of one of these promising minor cannabinoids, and you have the marketing budget to educate consumers on what that compound might do, it could just be the next big thing.
In Summary
We are just at the tip of the iceberg in terms of learning about all the wonderful things that this complex plant can do for the human body and for the planet. We have touched on the most popular cannabinoids but there are almost another 120+ to explore, with new ones being discovered all the time!
To learn more about how to extract these cannabinoids and all the myriad of derivatives and end-products that can be gleaned from this amazing plant read Chapter 7: Cannabis and Hemp Extraction Methods.