Complete Guide to CBD, Terpenes and Cannabinoids
This is our complete guide to CBD, terpenes and cannabinoids in 2020 based on the latest research and scientific studies on cannabis.
In this guide you’ll learn:
How to find the right CBD product for your needs
How your body’s Endocannabinoid System interacts with cannabis compounds
Common misconceptions about CBD
Understanding terpenes and how they interact with cannabinoids
If you are looking for a rock solid base knowledge of what you should know as a cannabis consumer in 2020, this guide is for you.
Let’s dive right in.
CBD (Cannabidiol) is a therapeutic compound found in the Cannabis Sativa plant. In this case the compound is known as a cannabinoid, a family of active compounds found in cannabis. There are over 100 cannabinoids that have been identified in cannabis, such as THC and CBG, yet CBD has caught the most attention of all cannabinoids recently due to its consumer reports of reducing pain and anxiety without providing an intoxicating effect. While most reading this article probably came to learn more about CBD, it’s impossible to understand CBD without taking into account how other compounds that might be present along with CBD will impact the end user/patient experience. Understanding the differences between cannabinoids will help provide a more complete knowledge of the potential applications of cannabis profiles and products. This article is intended to provide a complete base understanding of the key factors that determine medicinal potential and effects of cannabis products. Our goal is to help you as a consumer to find the best product for your individual needs.
2. Plants before humans
While it may seem like Cannabis Sativa was put on earth for human consumption/medicinal needs, since cannabinoids naturally connect to receptors located in the human brain and body (known as CB1 and CB2 receptors, which we’ll cover later), that is not the case. The cannabis plant has been around much longer than human civilization. Think of it more as a “chance” accident of nature that Cannabis Sativa produces compounds that happen to be beneficial to humans.
3. Used as medicine for centuries
Medicine has gone through a lot of changes over the past 50-100 years. Medicine previously was mostly natural plant derived extracts or substances that provided benefits for certain symptoms and conditions. Cannabis extracts used to be sold in pharmacies and doctor’s offices during the 19th and early 20th centuries. In the 1830s, Sir William Brooke O’Shaughnessy, an Irish doctor studying in India, found that cannabis extracts could help lessen stomach pain and vomiting in people suffering from cholera. In the 1600’s, certain states like Connecticut and Massachusetts required all property owners to grow at least a ¼ acre of hemp to be used for medicine, building, clothing and other materials. Only recently has pharmacology started reversing the traditional medicine creation thought process from “found in nature, let’s see what it could be useful for” to “We found this new receptor in the human body, let’s create a synthetic compound that will interact with the new receptor perfectly, and see what the side effects are”. While creating synthetic compounds to perfectly bind with cell receptors may seem like a good idea, the side effects of medications made in laboratories are typically much greater than medicine derived from nature.
4. The Endocannabinoid system
While cannabinoids were discovered in the late 1800’s and into the 1900’s, it wasn’t until 1992 that the Endocannabinoid System (ECS), a complex cell-signaling system in the human brain and body, was discovered by Raphael Mechoulam when researching the effects of THC. Scientists are still working to fully understand and explore the ECS, but it is believed to play a key role in regulating a range of functions including sleep, mood, appetite, memory and reproduction. Endocannabinoids are molecules similar to cannabis-derived cannabinoids, but they are produced by your body. Endocannabinoids bind to and interact with receptors in the ECS to send signals and notify the brain and body to take action. Mechoulam realized that the cannabinoid THC achieves its impact on the human brain and body by replicating the effects of endocannabinoids naturally made in our bodies. Around the same time, Mechoulam simultaneously discovered the first naturally occurring endogenous cannabinoid, or endocannabinoid, called Anandamide. Anandamide, also known as N-arachidonoylethanolamine or AEA, is believed to impact a host of physiological functions including appetite stimulation, mood and pain management. Both THC and Anandamide seem to interact and bind with receptors in the Endocannabinoid System in a similar fashion.Since Mechoulam’s study, additional information has been gathered on the endocannabinoid system, although there is still much scientists do not yet understand. What we do know is that two primary receptor types make up the endocannabinoid system (although there are additional receptor types): CB1 and CB2 receptors. These receptors are the most common found throughout the human body and the mechanism that maintains homeostasis. They are found in every organ and also in the human brain. These receptors essentially sit on the outside of cells and “listen” to the conditions outside of the cell. They transmit information about changing conditions to the inside of the cell, kick-starting the appropriate cellular response. From there, endocannabinoids interact with the receptors to mediate and direct the changing conditions outside the cell.
CB1 receptors are found in the central nervous system and are particularly rich in certain brain areas such as the basal ganglia, cerebellum, and hippocampus. CB1 receptors are also found in the human testis, retina, sperm cells, colonic tissues, peripheral neurons, adipocytes and other organs including the human adrenal gland, heart, lung, prostate, uterus, and ovary. Since they’re most concentrated in our brain, stimulation of the CB1 receptors can result in a heady euphoria and intoxicated effects commonly associated with being “high”.
CB2 receptors are located mostly in the peripheral nervous system, and are primarily associated with the immune system and inflammation response. Because they’re most concentrated in our body’s periphery, their stimulation doesn’t result in any heady euphoria or intoxication. Activating the CB2 can relax the body, help it repair itself and reduce the sensation of pain without impairing cognition.
Endocannabinoids: Anandamide and 2AG
There are two major endocannabinoids that have been identified by scientists: anandamide and 2-AG. These endocannabinoids are made from fat-like molecules within cell membranes, and are synthesized on-demand. This means that they get made and used exactly when they’re needed, rather than packaged and stored for later use like many other biological molecules.
Anandamide is a highly potent endogenous agonist of the cannabinoid CB1 and CB2 receptors made naturally in the human body, which essentially means that it “causes an action” to be taken at a receptor site (as opposed to antagonist, which blocks an action from occurring). The name originates from the sanskrit “ananda,” which roughly translates to “bliss” or “joy,” an indication of Anandamide’s properties as a mood enhancer. Also called N-arachidonoylethanolamine (AEA), anandamide interacts with the body’s CB receptors similarly to cannabinoids like THC. It’s a neurotransmitter and cannabinoid-receptor binding agent that functions as a signal messenger for CB receptors located in the body. It was discovered that Anandamide is the chemical responsible for the “high” experienced during cardio exercise, commonly referred to as the “runner's high”.
2-AG is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB1 receptors. It is involved in a wide array of (patho)physiological functions, such as emotion, cognition, energy balance, pain sensation and neuroinflammation. It is the most prevalent endogenous cannabinoid ligand in the brain, and the key endocannabinoid involved in retrograde signaling in the brain.
While endocannabinoid receptors and endocannabinoids play essential roles in regulating our ECS, metabolic enzymes play a large role in the creation and breakdown of endocannabinoids. Metabolic enzymes quickly destroy endocannabinoids once they are used. The two major enzymes are FAAH, which breaks down a=Anandamide, and MAGL, which breaks down 2-AG. These enzymes ensure that endocannabinoids get used when they’re needed, but not for longer than necessary. As previously mentioned, this distinguishes endocannabinoids from many other molecular signals in the body, such as hormones or classical neurotransmitters, which can persist for many seconds or minutes, or get packaged and stored for later use.
5. The traditional classifications of Cannabis Sativa as Indica, Sativa, or hybrid are nonsense
Now that we understand the main players involved in the Endocannabinoid System and their key functions, it’s time to better understand the effects of cannabis compounds. If you’ve been a cannabis consumer for more than a few years, you’re likely familiar with the sativa, indica, and hybrid classifications that the cannabis industry has used to summarize the potential effects of a particular genetic strain. Sativa strains and effects were generalized as uplifting without the couch lock effect of indica strains, which typically produce a more creative, less intoxicated, but more sedated feeling. While these terms may have served the black market effectively, they are very inaccurate and too generalized to have merit moving forward. What it really comes down to is, what compounds are present in the cannabis end product and at what concentrations? Ultimately, the cannabinoid, terpene and even flavonoid profile will determine the expected effects of a cannabis product. This is why it's important to understand the medicinal potential and mood effects of cannabinoids and terpenes in order to determine if the product would be a good match for you wellness needs. Certain cannabis companies have begun to categorize products by effect, to make it easier for consumers to quickly determine what would be the best match for their needs.
Consumers should pay close attention to the terpenoid profile within cannabis products. Terpenes are compounds naturally found in cannabis as well as a range of other plants such as fruits, spices and herbs. They are the main contributor and influence of how a cannabis product will smell and taste and what kind of effects it will provide. Typically plants are high in a single, or sometimes a few different terpenes, however cannabis can contain over 200 different terpenes. This is the main component that gives different cannabis genetics, and thus end profiles, their difference in consumer experience. It’s why one strain can lock you into your couch, and another can promote energy and focus. Since so many different terpenes are present in cannabis, it can make it challenging to summarize the data in a way for consumers to understand the end user experience.
The most common terpenes found in cannabis are Myrcene, Limonene and Beta Caryophyllene. While these terpenes are common in cannabis, they are also found in additional plant types. Limonene is found in lemon rinds, Myrcene is found in mangoes, and Beta Caryophyllene is found in black pepper. Terpenes have been studied at a much greater rate than cannabinoids largely due to their availability from other plants not under schedule 1 FDA status. Limonene provides mood boost and antidepressant like effects, Beta Caryophyllene interacts with the CB2 receptor similar to certain cannabinoids and can reduce inflammation and pain, and Myrcene provides a sedating couch lock effect. These effects are quite different, and thus it can be helpful to have a basic understanding of terpenes and their properties so you don’t get a couch lock effect when you were looking for a mood boost or inflammation relief.
While it may seem that this advice would only apply to high THC flower products, which have been traditionally classified this way, the same advice rings true for CBD products. Consumers should be checking lab reports to ensure accurate CBD content and lack of contaminants, and also to review the terpene profile. If you are using your CBD product to promote sleep, you will probably want a product high in Myrcene and Linalool. These additional terpenes will promote sedation and relaxation. However, if you are looking to stay productive, you won’t want a product high in Myrcene. The same logic that discredits sativa, indica, and hybrid classifications applies to CBD products. From a consumer perspective it doesn’t matter how tall the plant is or the shape of its leaves - what matters is the end profile of cannabinoids and terpenoids in understanding the potential benefits of a product.
We’ve spoken briefly about endocannabinoids naturally produced in our bodies, and terpenes which are essential oils found in cannabis, but what about phytocannabinoids like CBD and THC? Phytocannabinoids are similar in structure to the endocannabinoids produced within our bodies such as Anandamide, but they come from plants like cannabis. While they haven’t been studied at the same rate as terpenes due to their schedule 1 status, according to Dr. Ethan Russo of GW Pharmaceuticals, we have studied phytocannabinoids stufficiently enough to generally understand their function and effects. Russo was instrumental in describing the interaction between phytocannabinoids and terpenoids to create an outcome greater than the sum of its parts, a phenomenon he coined the entourage effect. Essentially, terpenes interact with cannabinoids to alter their effects, make them more powerful or even reduce their potency. This can make it even more challenging to predict what kind of effect these compounds will produce and what the end user experience will be like.
THC is the most well known cannabinoid due to its psychoactive and intoxicating effects in humans. It is also the most common cannabinoid found in marijuana, however this is largely due to selective breeding practices of the black market prior to marijuana legalization in states in the US and some countries abroad like Canada and Israel. THC mostly affects the CB1 receptor and breaks through the blood brain barrier, which are the main contributors to it’s intoxicating attributes. Despite it’s intoxicating effects, there are many medicinal properties of THC that can provide patient benefits. The main medicinal application of THC is for pain relief. Research studies have shown that THC contains about 20 times the pain relieving properties of Advil, and twice that of cortisol. This property alone makes THC an interesting cannabinoid, especially with the rise of opioid addiction in the US. THC also has bronchodilator effects and was previously used to treat asthma. Much of the challenge with THC comes from it's potential side effects of anxiety and paranoia for certain patients. Nonetheless, as we’ll discuss in the next section, pairing THC with CBD and terpenes that produce anti-anxiety effects can help solve this challenge and unlock the medicinal potential of THC while reducing it’s intoxicating side effects.
Cannabidiol, or CBD, has more recently caught the attention of consumers largely due to its non-intoxicating nature and high concentration in hemp genetics of cannabis. Most articles on the internet, or even CBD specific hemp companies, will tell you that CBD is non-psychoactive, however that is a misconception. Just because something is non-intoxicating, this doesn’t mean it isn’t a psychoactive substance. In this case, CBD has shown the ability to impact mood and anxiety levels, which is why it is considered a psychoactive substance. Nevertheless, CBD is a cannabinoid with loads of medicinal potential that doesn’t create intoxicating effects like THC.
While more clinical trials need to occur in order to be certain of the effects of CBD, researchers like Ethan Russo at GW Pharmaceuticals have taught us much about CBD’s potential through preclinical animal studies and by observing the type of interactions CBD has primarily on CB2 receptors (although it does stimulate the CB1 receptors as well). CBD has the potential to be anti-anxiety and antipsychotic with less side effects than current alternatives. A recent research study showed that a daily dose of 300mg of CBD was able to reduce anxiety significantly in patients with social anxiety disorder during a public speaking exercise. Other anxiety drugs and antipsychotics can cause significant side effects, whereas CBD side effects thus far have proven to be relatively tame. CBD is able to reduce anxiety through serotonin production. Some known side effects of CBD include mood changes, diarrhea, and changes in appetite, which are much less severe than most pharmaceutical alternatives on the market today. Another benefit of CBD is its ability to counteract some of the less desirable characteristics of THC. Besides proper terpene counterparts like Linalool, Limonene, and Beta Caryophyllene which can also provide anti-anxiety benefits and counteract THC, ensuring an equal or greater ratio of CBD to THC can prevent paranoia and anxiety generally associated with high THC use.
Due to CBD’s interaction with the CB2 receptor, it has also shown the ability to reduce pain and provide anti-inflammatory properties. It may not be quite as powerful as THC for pain, but CBD comes in as a close second and without the intoxicating properties. For this reason, CBD has lots of potential to help patients battling chronic pain and opioid addiction. Another interesting yet unproven observation of CBD from researchers like Ethan Russo is its potential to help the body heal broken bones faster than traditional timelines. It could become a useful tool for sports injuries in the future as the science is proven through double-blind placebo clinical trials.
The first pharmaceutical CBD product to be approved by the FDA was Epidiolex, as it was shown to reduce seizures in two rare forms of epilepsy. The approval was a major win for the cannabis industry in that it validated that CBD does have medicinal potential and applicability to modern medicine. However, in other ways it showed how the FDA pharmaceutical process is extremely costly and inefficient, adding significant cost to medicine that costs way less to produce. The $36,000 a year bill that families have to fork over to use Epidiolex is simply ridiculous. Luckily, these patients have the ability to use other CBD products available on the market to greatly reduce their medical costs. High quality CBD products may seem expensive when 1000mg tincture products come close to $100 a bottle. However, compared to the cost of Epidiolex, it's a small price to pay.
The primary effects of CBD over time are the modulation of the endocannabinoid system. CBD accomplishes this by reducing the breakdown of endocannabinoids and keeping metabolic enzymes like FAAH at bay when they are overactive and bringing the system out of homeostasis. The ability to modulate our ECS system, the largest system of receptors in the human body, is quite exciting and an impactful discovery to optimize human health. This can be very helpful for patients with clinical endocannabinoid deficiency, thought to be the cause of many auto-immune diseases by researchers like Ethan Russo. While much research needs to occur to fully prove out the medicinal qualities of CBD, the preliminary science and understanding of its interactions with CB2 receptors suggests that the sky’s the limit for how CBD can impact modern medicine and provide relief for some of the most debilitating, poorly addressed diseases.
9. Government Patent on CBD
If you need additional proof that CBD has great medicinal potential, look no further than our own US government’s patent on CBD. Below is an excerpt from the patent held by the US Government:
“The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as Cannabidiol, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention.”
You may be thinking to yourself - If the US Government holds a patent on CBD and sees its potential as neuroprotective, why is the FDA recommending consumers proceed with caution? In some ways the FDA may be right in advising consumers to avoid CBD, as a number of companies have emerged and there are questions about the integrity of testing procedures. However, it does seem a bit hypocritical to hold a patent that claims significant medicinal applicability of CBD but advise patients not to use it. Additionally, one must wonder how much revenue both the US Government and companies following the traditional FDA approval process like GW pharmaceuticals stand to lose if hemp companies could freely produce and sell products high in CBD.
10. Misconceptions of CBD
There are a few misconceptions regarding CBD that are worth noting so you are best equipped as a consumer. The first misconception is dosage. Many people have reported “miracle” like effects from only taking a single drop or a few drops of a CBD tincture, the equivalent of 1-5mg of CBD per dose. CBD is not a potent compound, largely due to its lack of bioavailability, which is its ability to enter the bloodstream - an essential component for CBD to become therapeutic. As stated earlier, studies on anxiety have shown CBD to be effective at ~300mg per day. Patients with less chronic issues probably won’t need to approach 300mg per day, however to think that you only need 1-5mg per serving is simply a placebo effect. Finally, certain people believe that CBD can have a sedative like effect, which is simply not true. CBD at low doses creates an alertness effect and most likely terpenes like Myrcene are responsible for some patients feeling drowsy after consuming CBD products. This is why it is important to pair cannabinoids with the proper terpenes that will create the intended user experience.
11. Additional Cannabinoids
Additional cannabinoids like CBG, CBC, CBN, CBDV, THCV, etc. are not going to be covered in detail in this particular article, although I would urge you to read additional early studies and findings. While cannabinoids tend to produce similar effects, small changes in chemical structure create subtle differences. For example CBG, although similar in structure to CBD, produces similar anti-inflammatory properties but may also decrease GI motility at a greater rate than CBD. CBN has long been thought to produce a sedative effect, although the studies suggesting this are not yet very strong.
See Table 1 in Ethan Russo’s research study, “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects” for a summary of studies conducted on various cannabinoids prior to 2011. It should be noted that additional research has occurred since 2011 and that the below list is not exhaustive.
Cannabinoids have significant medicinal potential, however when paired with the proper terpenes they can become an even stronger medicinal tool. We’ve talked briefly about terpenes, some of their effects, their synergistic nature with cannabinoids and importance in ensuring the proper terpene profile is present in a given cannabis product to create the intended effect. Fortunately, terpenoids have been studied at a greater rate than cannabinoids due to their availability in other common plants or trees. Generally speaking, almost all terpenes have shown broad antibiotic, anti-inflammatory, and emotion and mood effects. It’s important to know the basic emotion and mood effects of common cannabis terpenes to ensure a cannabis product is optimized for your needs.
Alpha Pinene is a common terpene found in cannabis as well as in pine needles and pine cones. The most noteworthy effects of Alpha Pinene are its ability to promote alertness and counteract short term memory loss. Due to these properties, Alpha Pinene can help counteract certain undesirable side effects of THC such as sedation and short term memory loss, and is a helpful terpene if you need to stay alert and focused while medicating.
Myrcene is the most common terpene found in cannabis and is one of the largest reasons that cannabis high in THC can make one feel “stoned” and create a couch lock type effect. High concentrations of myrcene should be avoided if you need to stay productive and alert as it can also cause sedation. Myrcene can have strong analgesic effects, so if you experience chronic pain it may be a helpful compound.
Limonene, a very prevalent cannabis terpene which can also be found in orange rinds, has shown the ability to boost mood and is a very powerful antidepressant. A Japanese study of patients suffering from depression showed Limonene could produce antidepressant effects similar to SSRIs. SSRIs are typically a psychiatrists first form of defense against depression. 50% of the patients in the study suffering from depression were able to stop taking SSRIs, showing how powerful a terpene like Limonene can be. The study also showed Limonene to boost immune function.
Linalool, a cannabis terpene also found in lavender, has shown strong anti-anxiety and antidepressant applications. Linalool is the main reason why you may have experienced calming or stress relieving properties from a lavender infused bath bomb or essential oil product.
While the above terpenes are known as monoterpenes, another class exists for terpenes that act as both terpenes and cannabinoids, called sequesterpenoids. Sequesterpenoids are more complex than monoterpenes. They can impact mood but also interact with the CB2 receptor similarly to CBD. This makes sequesterpenoids such as Beta Caryophyllene a powerful anti-inflammatory and gastroprotective agent that can also provide some anti-anxiety effects by selectively antagonizing the CB2 receptor.
For more information on terpenes and their effects, check out our previous article, “What Are Terpenes and Why Are They Important for CBD, Hemp and Cannabis Products?”
13. Fix your gut, fix your endocannabinoid system
Our last topic is on gut health, which also trickles over into other poorly understood health conditions. For decades, doctors have struggled to explain the cause of Irritable Bowel Syndrome (IBS). They typically recommend changes in diet, probiotics, and to increase fiber intake. While these changes typically do provide some relief for patients with IBS, they can reduce quality of life. If you’ve ever tried to adhere to the highly restrictive “low-fodmap diet”, commonly recommended for IBS symptoms, you’d understand some of these quality of life issues. New research suggests there is a condition called clinical endocannabinoid deficiency which can lead to a whole host of health problems. This happens when your body chronically produces endocannabinoids at too low of a rate to properly deal with internal and external environmental factors like stress, injuries, diet, bacteria, etc. IBS is caused by inflammation of the intestine, which can create a host of different side effects. While eliminating foods that cause inflammation, exercising, and eating more fibrous foods can certainly help, don’t underestimate the need to bring the endocannabinoid system back to homeostasis. We talked earlier about Anandamide, an endocannabinoid that is produced during exercise and creates the feeling of the “runners high”. Diet and exercise can improve your endocannabinoid system function just like phytocannabinoids such as CBD, and improper functioning may be the cause of certain conditions like IBS. If you suffer from IBS, you may want to consider adding inflammation fighting compounds like CBD, CBG, and Beta Caryophyllene to your daily wellness regimen.
What benefits have cannabis products provided you in your life? What compounds do you most look for to ensure an optimized experience that will benefit your wellness needs?
About the author:
Nate Spock is the Founder and Chief Strategy Officer for Potter, a hemp wellness company that produces CBD, CBG, and terpene optimized products in Massachusetts. He has been researching cannabis for more than a decade largely due to health conditions such as IBS, IBD, SIBO, and resulting anxiety. Nate’s been able to utilize cannabis products to improve his quality of life and wants to educate the public on the helpful information he has uncovered during his research. His goals are to bring the cannabis industry forward by creating optimized natural medicines, educate consumers about the truth of cannabis research, remove the potential of a “poor experience” with cannabis, and reduce the intimidation factor for the “canna curious” so that all consumers can experience the benefits that cannabis has to offer.