There is a wealth of information available in the scientific literature regarding the classes of cannabinoid compounds and the receptors involved in the endocannabinoid system The endocannabinoid (EC) system helps the body manage anxiety, inflammation, and other physiological responses to different forms of stress. CBD is all the rage these days. Everyone seems to be talking about it, but what exactly is CBD and what does it do?
A Chemist’s Perspective: Cannabinoids, Cannabis, and Caryophyllene
It has come to my attention that there has been a lot of confusion recently surrounding the properties of cannabinoid compounds found in certain oils. Individuals with ties to the CBD oil industry would have you believe that beta-caryophyllene, a compound found in Copaiba oil and Black Pepper oil, is not a cannabinoid. The same individuals would also have you believe that cannabidiol (CBD) oil never contains the psychoactive compound tetrahydrocannabinol (THC) or any of its isomers. This is not surprising, because both of these claims promote the CBD oil industry. Unfortunately, this misinformation has been perpetuated to the point that many people are convinced that it is accurate, despite strong evidence to the contrary.
I’ve prepared this article in hopes that I can set the facts straight. Having worked as a medicinal chemist for 15 years, I’ve learned a great deal about the chemical properties of all kinds of essential oils. I’ve even conducted my own chemical analyses of hemp, CBD, and cannabis oil in my lab at doTERRA. In this article, I will discuss the chemical properties of cannabinoid compounds found in the various cannabis oils and compare them with beta-caryophyllene. Beta-caryophyllene is the main compound found in Copaiba, doTERRA’s alternative to cannabis.
Beta-Caryophyllene is a Cannabinoid
There is a wealth of information available in the scientific literature regarding the classes of cannabinoid compounds and the receptors involved in the endocannabinoid system. For several years now, beta-caryophyllene has been known to be a cannabinoid. But don’t just take my word for it. Back in 2008, a study by J. Gertsch et al. rolled off the press with the unambiguous headline, “Beta-caryophyllene is a dietary cannabinoid.” 1 The study was published in Proceedings of the National Academy of Sciences of the United States of America, a prestigious scientific journal. Since then, at least a dozen more papers have been published on the subject, reemphasizing the fact that beta-caryophyllene is a cannabinoid. 2-13
By definition, a cannabinoid is any ligand, molecule, or class of molecules that acts on either or both of the currently identified cannabinoid receptors, CB1 and CB2. Interestingly, these two receptors produce significantly different physiological responses when activated. CB1 activation, caused by THC and other similar cannabinoids, results in a psychoactive drug high. On the other hand, CB2 activation by beta-caryophyllene (BCP) has produced results showing some promising benefits. These include supporting a healthy inflammatory response, soothing discomfort, and positively affecting mood without the psychoactive side effects associated with other cannabinoids. 2-4,10 It is true that the positive benefits associated with BCP have also been observed using other cannabinoids, such as THC, cannabidiol, and cannabinol, but using these compounds can also come with unwanted psychological effects, especially in the case of THC.
Types of Cannabinoids
There are three distinct classes of cannabinoids: endocannabinoids, phytocannabinoids, and synthetic cannabinoids. Synthetic cannabinoids are found in certain pharmaceutical products designed to help with glaucoma, appetite stimulation, antiemetics, and other disease-linked targets. Endocannabinoids, on the other hand, are produced naturally by the body. These molecules are mainly composed of amines and amides. Endocannabinoids are pharmacologically similar to some phytocannabinoids, but vary greatly in their chemical structure. This gives different endocannabinoids the ability to produce different neurological responses, even when administered in similar doses. The primary function of endocannabinoids is to modulate normal physiological functions.
The last class of cannabinoids is known as the phytocannabinoids. These are molecules that are produced by plants such as Cannabis and Copaifera. The Cannabis species produces the commonly known molecules THC and CBD, while the Copaifera plant family produces only BCP. Although BCP differs significantly from other cannabinoids in its structure, it nonetheless reacts selectively with the CB2 receptor, thus defining it as a cannabinoid. 2 However, it is chemically distinct from other cannabinoids, which is why it cannot cause a positive result on a drug test. BCP is classified as a sesquiterpene based on its chemical structure and makeup. Research on BCP is ongoing and will continue to add to our understanding of its potential value.
Cannabidiol (CBD) oil can contain the psychoactive tetrahydrocannabinol (THC)
To be legally marketable, CBD oil is not supposed to contain any discernable amount of THC. 14 However, our own internal investigation involving analytical testing and evaluation has found that various CBD oils on the market do contain significant levels of THC and therefore could very likely trigger a psychoactive response and/or positive drug test. Our evaluation has also shown that commonly purchased brands of CBD oil can vary greatly in their claimed CBD content. In fact, in some samples we were not able to identify the presence of any CBD at all. In contrast, my analyses have shown that doTERRA oils are 100% free of THC, and oil compositions are consistent between batches.
In summary, this article is not intended to be a complete picture of the benefits of beta-caryophyllene nor an outline of the properties of the endocannabinoid system. Rather, it is a statement of scientifically-accepted facts aimed to clear up the misleading information on the molecules in question. My hopes are that reading this article will help individuals in their personal research on cannabinoids and, most importantly, their decisions about which oils to use in their daily life.
Dr. Cody Beaumont, PhD
Director, Analytical Services & Quality Control
In this article, we review the endocannabinoid system and the effects of tetrahydrocannabinol (THC), Cannabidiol (CBD), and Beta-caryophyllene (BCP).
The endocannabinoid system
The endocannabinoid (EC) system helps the body manage anxiety, inflammation, and other physiological responses to different forms of stress. During strenuous exercise, stress, and other related stimuli, the body produces compounds called endocannabinoids. Endocannabinoids (ECs) are signaling molecules that trigger the activation of the EC system when they are detected by cannabinoid receptors.
Cannabinoid receptors (CRs) not only detect the presence of ECs, but they are also affected by molecules from outside sources that chemically resemble endocannabinoids. The term cannabinoid refers to any compound, produced by the body or from an outside source, that triggers the EC system by activating CRs. Anandamide is an EC compound produced in the body. Anandamide activates two types of CRs, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2).
A “runner’s high” is a perfect example of the EC system at work. After a long period of strenuous exercise, the body begins to produce anandamide in order to activate CRs and turn on the EC system. The “runner’s high” has two components: slight euphoria, and soothing of the discomfort in the muscles and joints. These two outcomes are linked with two distinct structures: the CB1 and CB2 receptors. CB1 receptors are mainly found in the brain and central nervous system, and are linked with pleasure and reward pathways. CB1 receptor activation leads to feelings of euphoria. CB2 receptors are found in the rest of the body, like the muscles, skin, and vital organs. They are mainly found on the surface of white blood cells, and their activation affects the regulation of inflammation chemicals called cytokines.
THC & CBD
THC is the main psychoactive compound in marijuana. According to GC/MS analyses conducted by doTERRA’s analytical chemists, it is found in high concentrations in many brands of cannabis oil, and it can also be found in hemp and CBD oil in more than just trace amounts. THC is known to activate both CB1 and CB2 receptors. It is generally accepted as a potent drug with powerful psychoactive properties.
CBD, another compound found in high quantities in marijuana, CBD oil, and hemp oil, does in fact interact directly with CB1 and CB2, but the interaction is so weak as to be negligible. 2 CBD actually exerts its effects on the EC system by a different mechanism than most cannabinoids.
Research shows that CBD acts on the enzyme FAAH, which breaks down anandamide. CBD actually slows down the enzyme’s activity, which leads to increased levels of anandamide in the body. 1 The reason why this is significant is because anandamide interacts with CB1 and CB2 receptors. Higher levels of anandamide would result in increased feelings of euphoria due to increased activation of CB1 receptors, as well as soothing of the tissues due to activation of CB2.
CBD, by increasing levels of anandamide, has similar pharmacological effects as THC in that it affects the same two cannabinoid receptors, however the magnitude of the effect is much smaller compared with THC. CBD is generally considered non-hallucinogenic.
Soothing the tissues without triggering any sort of psychoactive response can be accomplished by using a compound with selective interaction with the CB2 receptor. Beta-caryophyllene (BCP) is a sesquiterpene compound found in hundreds of different plant species, and it has recently been recognized for its unique ability to interact with CB2 but not CB1 receptors. 3 Thus the alleged benefits of CBD or THC can be obtained without the psychoactive effects by using a product containing BCP. doTERRA’s new Copaiba essential oil has the highest BCP content of any oil, around 55% as confirmed by GC/MS analysis of doTERRA’s own Copaiba oil.
There is ample evidence pointing to the benefits of oral supplementation of beta-caryophyllene, but like CBD and hemp oil, further research in the form of human clinical trials is required. More promising are the low doses at which some of these studies have been conducted. These dosages suggest that as little as 1-2 drops of Copaiba oil or 3-4 drops of Black Pepper oil may provide noticeable results in humans. At this time, the systemic soothing properties of beta-caryophyllene have potential benefit as treatment for a wide range of health issues.* Still unexplored are the effects of CB2 receptor activation on human diseases for which there are few experimental models—such as learning disabilities and autism spectrum disorders—that many claim can benefit from using cannabis.
To summarize, there are many ways to modulate the body’s cannabinoid system. Products containing CBD, THC, and BCP all affect the endocannabinoid system. We acknowledge that health care professionals may recommend different products containing different kinds of cannabinoid compounds for different health issues. However, at doTERRA we believe that BCP-containing products are the most effective for healthy individuals seeking a product that they can use for self-care.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
Everything You Need to Know About CBD
CBD is all the rage these days. Everyone seems to be talking about it, but what is CBD and what does it do?
What Is a Cannabinoid?
Perhaps you have heard CBD called a cannabinoid. The term cannabinoid refers to any compound that triggers your endocannabinoid system by activating its receptors. Cannabinoids are produced naturally in your body, but they can also come from other sources.
The cannabinoids that are naturally produced in your body are called endocannabinoids. Cannabinoids that come from plants are called phytocannabinoids. CBD is one example of a phytocannabinoid, though there are many. There are also synthetic cannabinoids.
How Do Cannabinoids Work?
A cannabinoid is anything that triggers your endocannabinoid system (ECS). So what exactly is the endocannabinoid system? The ECS plays an important role in regulating many functions within your body, including the inflammatory system, immune function, sleep, appetite, digestion, pain receptors, hormones, reproductive function, and memory. Your body makes endocannabinoids as needed to help with this regulation. These endocannabinoids activate your cannabinoid receptors—cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) 1 .
CB1 receptors are found mainly in the brain and throughout the central nervous system 2 . They are primarily associated with pleasure and reward pathways.
CB2 receptors are found mainly in the immune system 3 . They are found on the surface of white blood cells throughout the body, including muscles, skin, and vital organs. CB2 receptors are also linked to the regulation of the inflammatory system. CB2 receptors are not as widely distributed throughout the body as CB1 receptors 4 .
Have you ever felt the famed “runner’s high”? You can thank your endocannabinoid system for that. After a period of strenuous exercise, the body begins to produce an endocannabinoid called anandamide. Anandamide activates both CB1 and CB2 receptors. When the anandamide activates the CB1 receptors, it produces an almost euphoric feeling while the activation of the CB2 receptors soothes discomfort in the muscles and joints.
THC & CBD
Delta-9 Tetrahydrocannabinol (THC) is one of “more than eighty biologically active chemical compounds” found in cannabis 5 . THC is a psychoactive cannabinoid and causes psychoactive effects or a “high.” THC activates both CB1 and CB2 receptors.
Cannabidiol (CBD) is another compound found in cannabis. CBD does not have the same psychoactive properties as THC. CBD directly interacts with CB1 and CB2 receptors, but the interaction is so weak it is inconsequential 6 . CBD does still affect your endocannabinoid system, but it actually affects it indirectly and by a different mechanism than most cannabinoids.
CBD acts on an enzyme called fatty acid amide hydrolase (FAAH). FAAH breaks down the before mentioned anandamide. CBD slows down FAAH’s activity, which leads to increased levels of anandamide in the body 7 . Anandamide is an endocannabinoid the body makes which affects both CB1 and CB2 receptors, resulting in increased feelings of euphoria (CB1) and soothing of inflammation in tissues (CB2).
Is CBD Safe and Effective?
It seems that CBD has flooded the marketplace and can be found in every product imaginable, from mascara to doggy treats. Amidst this excitement, however, there are a few reasons you should remain cautious.
The FDA acknowledges, “[S]ome companies are marketing products containing cannabis and cannabis-derived compounds in ways that violate the Federal Food, Drug and Cosmetic Act (FD&C Act) and that may put the health and safety of consumers at risk.” 8
There is relatively little medical and scientific research regarding CBD. This is due in large part to legal and research limitations. Some studies indicate promising benefits, but the research is young, and it is still too early to come to any definitive conclusions about the perceived health benefits of CBD.
Is CBD Legal?
A lot goes into determining whether a substance is legal. It is important to start with some background.
The Food and Drug Administration (FDA) is responsible for reviewing and approving applications to ensure that new drugs meet the standards of the Food, Drug, and Cosmetic Act (FD&C Act).
The Drug Enforcement Administration (DEA) is responsible for enforcing the Controlled Substances Act. They also regulate “the handling of all controlled substances, including those being used by researchers to conduct studies.” 9
“The Controlled Substances Act (CSA) places all substances . . . regulated under existing federal law into one of five schedules. This placement is based upon the substance’s medical use, potential for abuse, and safety or dependence liability.” 10
“[Marijuana] is listed in Schedule I of the CSA due to its high potential for abuse, which is attributable in large part to the psychoactive effects of THC, and the absence of a currently accepted medical use of the plant in the United States.” 11 (Exceptions 12 )
However, the Agriculture Improvement Act of 2018 made some cannabis no longer subject to the Controlled Substances Act by defining hemp as “Cannabis . . . with a delta-9 tetrahydrocannabinol [THC] concentration of not more than 0.3 percent.” 13 This means hemp can be grown in states whose laws allow the industrial production and sale of hemp. This is contributing to the purported presence of CBD in various products, including alleged CBD oil. Any plant containing an excess of 0.3 percent THC is considered marijuana and is therefore a Schedule I controlled substance under the CSA and thus subject to the DEA. Even if something is considered hemp (according to the 2018 Act) by containing less than 0.3 percent THC, it is still subject to all other relevant federal laws. 14
The 2018 Act did not remove the FDA’s “authority to regulate products containing cannabis or cannabis-derived compounds under the FD&C Act and . . . the Public Health Service Act (PHS Act).” 15 This means that any product containing cannabis or cannabis compounds, such as CBD, is still subject to the same laws as any other drug or dietary supplement. This includes CBD oil. Any product containing CBD, regardless of its THC content, cannot currently be sold as a dietary supplement. 16 This is because the FDA has approved neither THC nor CBD under the FD&C Act. 17
Drug Approval Process of Schedule I Substances
- Conducting clinical research for the drug approval process of Schedule I substances requires at least the following:
- Filing a registration application with the DEA
- Initial review of the application and research procedures by the FDA
- Working with the FDA to submit an application to the Center for Drug Evaluation and Research (CDER)
- Obtaining the controlled substance (in this case, cannabis) from the National Institutes of Health (NIH)
- Conducting clinical trials
- Continued review of research procedures and security measures by the FDA
- Compiling scientific data and submitting it to the FDA for approval of controlled substance
Companies that are selling products said to contain CBD are bypassing this process. Their products are not meeting FDA standards because the FDA has not set any. The FDA reviews “applications to market drugs to determine whether proposed drug products are safe and effective for their intended indications.” 19 Without FDA oversight, “the purity and potency of the drug may vary considerably.” 20
According to gas chromatography and mass spectrometry (GC/MS) analyses conducted by doTERRA’s analytical chemists, THC is found in high concentrations in many brands of cannabis oil. THC is found in both hemp and CBD oil in more than just trace amounts.
Without FDA oversight of CBD, it is difficult to be certain of both the amount and purity of CBD a product may contain. Regardless of what a product may claim, it may contain no CBD at all, while others may vary in purity or consistency of formula. “Over the past several years, FDA has issued several warning letters to firms that market unapproved new drugs that allegedly contain cannabidiol (CBD). As part of these actions, FDA has tested the chemical content of cannabinoid compounds in some of the products, and many were found to not contain the levels of CBD they claimed to contain.” 21
In the case of “CBD oils,” the CBD is combined with a carrier oil. This is because CBD is merely an isolate and not an oil by itself. Depending on what CBD is extracted from and depending on its quality, CBD is heavily diluted using varying amounts of a carrier oil.
A doTERRA chemist has stated, “[O]ur own internal investigation involving analytical testing and evaluation has found that various CBD oils on the market do contain significant levels of THC and therefore could very likely trigger a psychoactive response and/or positive drug test. Our evaluation has also shown that commonly purchased brands of CBD oil can vary greatly in their claimed CBD content.” 22
Why Isn’t doTERRA Producing a CBD Oil?
Due to issues of legality, as well as limited research and other concerns, doTERRA is not making any CBD products or oils at this time. We are committed to our standard of CPTG Certified Pure Tested Grade™ oils and nothing less. Right now, it is not possible to deliver a CBD oil that meets our CPTG ® standards.
Are There Alternatives?
While CBD may not be a good option at this point, there are other ways to boost the health of your endocannabinoid system.
Beta-caryophyllene (BCP) is a sesquiterpene found in hundreds of different plant species. It is also known as a cannabinoid because it interacts directly with CB2 receptors around the body, soothing tissues and helping to manage healthy inflammatory responses. 23 Remember that any compound (group of molecules) that acts on either or both of the cannabinoid receptors is a cannabinoid. BCP does not affect CB1 receptors and there is no risk of psychoactive effects. 24
Beta-caryophyllene (BCP) in Copaiba
BCP is the main chemical constituent in Copaiba essential oil, which comes from distilling the oleoresin of the copaiba tree. A GC/MS analysis confirmed that doTERRA Copaiba essential oil has approximately 55 percent BCP content—the highest BCP content of any known oil.
There is substantial evidence supporting the powerful benefits of oral supplementation of beta-caryophyllene. Further human clinical trials are needed, but current studies are already quite promising—as little as 1–2 drops of Copaiba oil produce noticeable results in humans.
All doTERRA essential oils, including Copaiba, are CPTG Certified Pure Tested Grade. This means that the oil is pure: there are no added fillers, synthetic ingredients, or harmful contaminants that would reduce its efficacy. Each batch of oil undergoes rigorous internal and third party testing to confirm that oils are meeting our quality standards. Every bottle of oil has a unique Quality ID that you can use to view the GC/MS test results from an independent, verified third party lab on Source to You.
Because doTERRA Copaiba essential oil has approximately 55 percent BCP content, the amount of oil needed to produce noticeable results is incredibly small—only a couple of drops. doTERRA Copaiba oil is actually a blend of oils that come from four species of the copaifera tree: Copaifera reticulata, Copaifera officinalis, Copaifera coriacea, and Copaifera langsdorffii. This blend of multiple copaifera species contributes to a more potent and effective version of the essential oil.
Because Copaiba is so pure and potent—needing only a drop or two for the BCP to start affecting the human body—its price point as a potential natural solution is affordable. This becomes especially true considering the cost of most CBD products and oils on the market—products and oils that aren’t substantiating the actual amount and purity of CBD you are receiving in their product.
We know that BCP activates CB2 receptors directly. This means that you can have confidence and assurance in BCP’s ability to interact with the endocannabinoid system. Additionally, knowing exactly how BCP triggers the endocannabinoid system (by directly activating CB2 receptors), we are able to collect more reliable information about dosage and effects than we can at this point with CBD.