Cannabidiol (CBD) may be one of the most broadly therapeutic plant extracts of our time. Yes that’s a big bold statement, but one that CBD can justify having said about it. Along with its lengthy list of therapeutic properties, CBD comes with a major added bonus for Aromatherapists: it works in perfect synergy with the compounds found in the essential oils we use every day. Essential oils, in fact, significantly potentiate CBD’s therapeutic benefits.
From a natural therapeutics perspective, there is no question that CBD and essential oils together may very well be part of, if not the treatment for a vast number of ailments and health conditions. But be-fore we get too excited, let’s get a few things straight about Hemp/Marijuana – both are from the same plant (either Cannabis sativa L. and Cannabis indica) – and how CBD relates to these variations of the same plant. The precise binomial nomenclature of Cannabis appears to vary depending on the reference. For the purposes of this paper, Cannabis sativa L. refers to low-THC “industrial” Hemp, and both Cannabis sativa L. and Cannabis indica refer to high-THC species of Cannabis.
CBD is the primary constituent of the CO2 extract of “industrial” Hemp (Russo, 2011). The same plant is also the source of seed, oil and fiber – all 100% legal throughout the USA. Because of its familial ties to Cannabis, however, which is typically grown to max-imize THC (a substance with widely varying degrees of lawfulness from state to state), the legal questions surrounding CBD have confused many at best.
On one hand, all cannabinoids are illegal at the Fed-eral level, leading companies such as PayPal to refuse transactions involving CBD, and Facebook and Google to ban its advertising. On the other hand, the legal grey area surrounding Hemp products in the United States has made it possible for CBD to be freely and thoroughly studied for decades, with astounding results.
There have been over 1,500 research articles pub-lished on CBD (Henein, 2016) that find it a potentially beneficial treatment for a host of common health conditions and ailments. These include all varieties of inflammation, pain, cancers, Alzheimer’s and other neurodegenerative diseases, anxiety, severe acne, epilepsy, and the list goes on. To understand how CBD can have such wide and varied benefits, we need to get a good grasp of the world of cannabinoids.
Phytocannabinoids and endocannabinoids
Cannabinoids were originally defined as a group
of compounds containing 21 carbon atoms (c21) uniquely, and only, produced by the Cannabis species, meaning these were not found anywhere else in the plant kingdom. However, subsequent development of synthetic cannabinoids, and the discovery that the human body can produce its own varieties of these molecules, has blurred this definition.
There are now three classes of these molecules rec- ognized: phytocannabinoids – those made by the plant, endocannabinoids – those made by the body, and synthetic cannabinoids – those made in the laboratory (GW Pharmaceuticals, 2014a).
Cannabis contains more than 500 known compounds (Leaf Science, 2015), of which 113 or more are can- nabinoids. The two cannabinoids found in the highest concentrations in all strains of Cannabis sativa are the widely famous THC (D-9-tetrahydrocannabinol) and CBD (cannabidiol) (Aizpurua-Olaizola et al., 2016). This one plant and these two molecules are at the center of a confusing state of legal affairs.
The legal status of Cannabis, Hemp and CBD
Before December 2016, CBD was legal in the United States. However, in December (during the editorial review of this paper), the United States Drug En- forcement Agency (DEA) made the decision to place CBD on the Schedule 1 list, reserved for chemicals which have a potential for abuse, and no known med- ical benefits. CBD is no longer to be imported or shipped over state lines in the US (however, this may be very difficult to enforce). This is a controversial decision and it is unclear what its implications will be. First of all, this does not mean complete prohibition of cannabinoids will occur. A 2014 Congressional amendment forbids the Justice Department from spending any funds on the enforcement of anti-CBD designations in any state which has legalized medical Cannabis or enacted “CBD-Only” laws. It is currently unclear what effect this will have on CBD’s availability in states where Cannabis itself is illegal. Thus, CBD will still be available, at minimum, in those states which have made medicinal Cannabis legal, as well as those states with “CBD-Only” laws.
Further, in an interview with Leafy.com, Robert Hogan, a Colorado Cannabis attorney and adjunct professor of law at the University of Denver, stated, “This action is beyond the DEA’s authority. The DEA can only carry out the law, they cannot create it. The DEA has devised an entirely new category called ‘marijuana extracts,’ and would like to make all can- nabinoids illegal.” Hoban continues, “But they do not have the authority to do that” (Barcott, 2016).
It is the opinion of many in the industry that CBD will remain available in the 23 states which do not yet have laws legalizing Cannabis for medical use. To this date, CBD is still being imported and shipped across state lines, and there has been no actions tak- en or notifications served to prevent this. In a sense, “the cat is out of the bag” about this truly beneficial substance.
Attempting to take CBD away from the public in states without “CBD-Only” laws, where CBD is actually “technically” legal (because, Federally, all products from Hemp are legal – despite the DEA’s scheduling), and where individuals are already using it with profound health benefits, could create a back- lash government agencies may rather not instigate.
Furthermore, CBD does not actually fit the require- ments of a Schedule 1 drug, which states that “the drug or other substance has no currently accepted medical treatment use in the U.S.” CBD is currently prescribed to treat children with epilepsy.
State laws and CBD
The “official” legal status of CBD varies from state to state in other ways as well. Cannabis grown for both recreational and medicinal purposes is most often cultivated to maximize the amount of THC, reaching upward of 30% of the dried plant material. Twenty-nine states have passed laws legalizing high- THC Cannabis for medicinal or recreational purpos- es. CBD from whatever source (Cannabis or Hemp) is clearly legal in these states.
CBD extracted from Cannabis (not Hemp) is illegal unless legislation within a state has made it clear that its possession, use and sale is exempted from legal prosecution. As knowledge of CBD’s broad therapeutic potential has grown, 16 states have passed “CBD-only” laws, endorsing its medicinal use. Some of these states allow smokeable Cannabis with a high CBD-to-THC ratio, while others allow it only as an extract from the plant.
The legality of CBD in states with no laws addressing this molecule is a little fuzzy, as noted above. Again, all products of government-approved “industrial” Hemp are legal at the Federal level – and thus at the State level by default. It is because all products of the Hemp plant are Federally legal that the CO2 extracts of industrial Hemp are also legal throughout the country.
Hemp can be grown in certain States if one has a permit from the FDA (which they are only just now beginning to issue), and CBD extraction from domestically grown Hemp is in its pilot phase. Thus, at this time, the majority of CBD sold in the United States is imported from European countries where both Hemp growing and extraction are legal (Hemp may be grown in Canada, and an essential oil distilled from it, but CBD extraction is limited only to phar- maceutical interests and available by prescription only).
CBD takes a blow from the FDA and “big pharma”
The FDA has made CBD’s legal matters yet more complicated by outright banning the labeling of CBD as a dietary supplement. While not confirmed out- right, the FDA’s ruling was likely inspired by lobbying from GW Pharmaceuticals of Great Britain. The pharmaceutical giant owns a patent on a synthetic version of CBD (GW Pharmaceuticals, 2014b) for the treatment of severe childhood epilepsy, showing excellent results in phase 2 trials. The molecule will be worth potentially billions of dollars without com- petition from the natural/consumer market.
It is this author’s opinion that the FDA (which de- rives the bulk of its funding from overseeing pharmaceutical drug research) has gone out of its way to prevent the dissemination of CBD’s benefits in order to protect pharmaceutical interests. The recent scheduling of CBD as Schedule 1 by the DEA likely has the same financial impetus, as CBD clearly does not fit the definition of a scheduled drug.
The FDA has issued warning letters to several CBD distributors, stating that no health claim whatsoever may be associated with cannabidiol, references to research cannot be made, and the ingredient cannot appear on the “Supplement Facts” portion of a prod- uct’s label. Because no indication can be made on the product label that a “serving” contains a specific amount, the consumer is left to do some math and measure carefully to determine the precise number of milligrams of CBD.
This leaves the consumer at a dead end with re- spect to finding information about how to actually use CBD. The consumer must try to do their own research – and of all the information available online, specific usage recommendations are the hardest to come by. Finding a holistic health practitioner well- versed in its use is an option, though the added expense and challenge of finding a qualified professional can be daunting.
The consumer may lose motivation altogether due to lack of much-needed information, and/or opt for the FDA-approved, synthetic pharmaceutical version, with a specific dose and regimen prescribed by a medical doctor. Anecdotally consumers tend to take other considerations into account when finding their “dose.” Although one generally cannot take too much CBD, the “cost per milligram” steers consumers to- ward using the least amount for their desired result.
CBD extraction and refining
So how did we isolate this molecule and make it available for our personal use? It first needs to be extracted from the plant, and modern technology has given us the perfect means of doing so.
CBD from the Hemp plant is concentrated via supercritical carbon-dioxide (CO2) extraction. Dried Hemp typically contains CBD concentrations between 1% and 5%, and less than 0.2% THC by weight (Swanson, 2015). The concentrations of CBD in these pasty, waxy, sometimes very “green” smelling CO2 extracts from industrial Hemp general- ly range from 6% in low-grade unfiltered material, to upwards of 30% in refined “gold” extracts.
CBD CO2 extracts from Hemp contain other cannabinoids and essential oil constituents in small amounts. Refinement through improved CO2 ex- traction parameters and filtration does not remove potentially therapeutic constituents (as is sometimes the case when an “active ingredient” is isolated), but removes “inert” plant waxes, making the material easier to work with.
However, extracts of higher and higher concentra- tions are becoming available, with 99%+ pure CBD “crystals” now being sold. These are not simple CO2 extracts, but chemical isolates. As it is often report- ed that whole natural botanical compounds exhibit greater therapeutic activity than isolated “active ingredients,” it is the author’s recommendation to use a whole CBD CO2 extract in therapeutic prepa- rations until the pharmacological difference, if any, between these and CBD isolates can be determined.
Does a CBD extract get one “high”?
Many users do in fact report a noticeably greater sense of well-being even after the first dose, though CBD is not intoxicating in the classic sense. Cannabi- diol lacks the psychotomimetic (psychosis-mimicking) and other psychotropic effects of THC (Campos et al., 2012a). This author has been pleased with the re- sult of ingesting a pea-sized drop of CBD CO2, along with a few drops of Hemp essential oil (more on the reasons for using the oil shortly).
It appears that the presence of CBD in Cannabis can even alleviate some of THC’s potentially unwanted side effects (e.g., paranoia). In fact, while “weed” gained popularity precisely for these psychotropic effects, CBD was actually “bred out” of Cannabis strains (Elder Trees, 2014), as it was these side effects that recreational Cannabis users wanted to induce.
Any effect produced whatsoever is a result of CBD’s interaction with our physiology, which just so hap- pens to appear perfectly designed to receive the benefits of this molecule. Let’s look at the means through which CBD imparts its wealth of health benefits.
How CBD works: the endocannabinoid system
To understand how CBD exerts its many effects, it is first important to understand our body’s endocan- nabinoid system (ECS). The ECS is composed of the cannabinoid molecules made by the body itself, their receptors, and the enzymes which create and break down the endocannabinoids. All these molecules, re- ceptors and enzymes, plus the affected neurons and neural pathways, and the cells in which the endocan- nabinoids are synthesized and broken down, com- prise the total of the ECS (Grotenhermen, 2012).
All cells communicate with one another by releasing messenger molecules that are intercepted by receiv- ers on other cells. Messenger molecules are each unique in size, shape and other properties which encode a “message.” Messenger molecules include the neurotransmitters serotonin, dopamine, acetyl- choline and the like. Also included are hormones such as insulin, testosterone, and estrogen – as well as endocannabinoids.
These messenger molecules bind to receptors in and on each cell. When a messenger molecule connectswith a corresponding receptor, a process (or pro- cesses) is initiated specific to the connection of that particular messenger molecule with that particular receptor.
As with the messenger molecules, there are also many types of receptors, also with their own unique shapes and other properties. Interestingly, there is not a one-to-one correspondence between messen- gers and receptors. One type of messenger molecule may affect a variety of receptors, and any one recep- tor may be affected by several different messenger molecules.
The endocannabinoid system works via these mes- sengers and receptors, with groups of cells, tissues or organs releasing chemical messengers that are then received and acted upon by other groups of cells, tis- sues or organs – typically with benefits to mental and physical wellness. A sense of well-being is one of the most notable effects CBD has on the user regardless of any particular ailment. This comes from a single endogenous molecule, the availability and activity of which is significantly influenced by CBD.
CBD and our own “bliss chemical”: anandamide
There are two known endocannabinoid messenger molecules: anandamide, known as “the bliss chemi- cal” (“Ananda” being the Sanskrit word for “spiritual bliss”) and 2-arachidonoylglycerol (2-AG).
There are also two known cannabinoid receptors: CB1 and CB2, shorthand for Cannabinoid Receptor Type 1 and Cannabinoid Receptor Type 2. CB1 recep- tors are found primarily in cells in the brain, central and peripheral nervous systems, and organs, and CB2 receptors are found throughout the network of cells, tissues and organs of the immune system (Groten- hermen, 2012).
The most well-known cannabinoid, THC, binds to CB1 receptors of the brain and central nervous system. This pairing is primarily responsible for THC’s psychoactive effects. THC binding to CB2 receptors of the immune system is responsible for THC’s anti-inflammatory actions (Leaf Science, 2013).
CBD, however, works completely unlike THC or any other cannabinoid. It does not bind directly to either CB1 or CB2 receptors. Instead its primary action is to significantly increase the availability and activity of our body’s most important and abundant endocanna- binoid, anandamide (Project CBD, 2016).
Anandamide binding to cannabinoid receptors ini- tiates a very wide variety of truly beneficial physio- logical processes. For simplicity’s sake, let’s look at just one phenomenon: the “runner’s high.” Research suggests the feeling of contentment and well-being after a good exercise session is in part from the binding of anandamide to CB1 receptors in the brain – imparting the sense of relaxation and contentment. Anandamide also binds to CB2 receptors throughout the body, initiating processes which reduce inflamma- tory responses (Lavelle, 2015).
But as many of us know, a “runner’s high” does not last very long. One may feel really “blissful” for half an hour after a workout, then that feeling naturally fades away. But why? Does it have to? It appears with CBD in the picture, it just might last longer.
Does taking CBD result in more bliss?
CBD makes the anandamide we do produce available for a longer period of time to bind to CB1 and CB2 receptors, and extends the duration of the cellular processes these couplings initiate. In short: CBD equals more bliss. CBD does this by suppressing the enzyme fatty acid amide hydroxylase (FAAH), which is responsible for breaking down cannabinoids in the body.
Anandamide has a naturally short half-life, typically on the order of a few minutes (Pacher et al., 2005). By suppressing the enzyme which breaks it apart, each messenger molecule of anandamide is free to bind to more receptors for a longer period of time.
Anandamide’s binding to both CB1 and CB2 receptors plays roles in the regulation of appetite, motivation and pleasure, and stimulates immune response (Proj- ect CBD, 2016). Research shows anandamide may also inhibit human breast cancer cell proliferation, lower blood pressure and heart rate, lower ocular blood pressure, and inhibit smooth muscle contrac- tion in the gastrointestinal tract (De Petrocellis et al., 1998), as well as significantly impact how acutely we perceive pain.
Pain perception: CBD plus anandamide is nature’s Tylenol®
Of particular therapeutic importance is anan- damide’s ability to decrease the perception of pain (Clapper et al., 2010). Interestingly, acetaminophen (Tylenol®) is a widely used pain reliever that has no anti-inflammatory activity. Rather, it produces anal- gesic effects by creating AM404, a molecule which inhibits re-uptake and degradation of anandamide (Bertolini et al., 2006). In essence, Tylenol® is a phar- maceutical drug that reduces the perception of pain in the same manner CBD does naturally.
CBD also stimulates the release of the body’s oth- er primary endocannabinoid, 2-AG. This activates both CB1 and CB2 receptors, while at the same time opposing the action of THC at the CB1 receptor (perhaps being the reason less “psychotic effects” are noted when CBD is consumed in conjunction with THC). The overall physiological effects of 2-AG are not well understood and are under investigation, though it is also hypothesized to affect regulation of appetite, immune function and pain perception, as does anandamide (Sensi Seeds, 2013).
In summary, while CBD does not directly activate CB1 or CB2 receptors, it does increase the activity of our own endogenous cannabinoids: anandamide and 2-AG. CBD does however bind to other receptors throughout the body with important therapeutic implications.
CBD and the TRPV1 receptor: reducing pain perception further
CBD binds directly to TRPV1 receptors, with a vari- ety of profound, therapeutic benefits. TRPV1 recep- tors (also known as capsaicin receptors) are primar- ily responsible for detection and regulation of body temperature, as well as the pain perception of heat. The best known activators of TRPV1 receptors are heat (over 109 degrees F), capsaicin (the hot, irritat- ing component of chili peppers) and allyl isothiocyanate, the pungent compound in mustard and wasabi (Everaerts et al., 2011).
TRPV1 receptors are known to lose sensitization upon prolonged activation – it is this desensitization that can allow one to get used to eating spicier and spicier foods over time. In precisely the same way, one may become desensitized to any painful, irritating stimuli over time. This desensitization occurs with any compound or condition that activates these re- ceptors (for example, one can slowly submerge into a bathtub that was at first far too hot to enter).
CBD activates and desensitizes these receptors in a dose-dependent manner – meaning the more CBD one consumes, the more desensitized these recep- tors become (Iannotti et al., 2014). The more desensi- tized these receptors are, the less irritating or painful certain stimuli become. Desensitization of TRPV1 receptors doesn’t just mean less irritation and pain, but has broader health implications as well.
CBD,TRPV1 and epilepsy relief
Epilepsy of one form or another has a 2-3% inci- dence worldwide. Present anti-epileptic drugs of- ten only partially control seizures. Excess calcium ion accumulation in hippocampal brain neurons has long been known to be a major contributor to the etiology of epilepsy;TRPV1 receptors are calcium-permeable channels, and are mediators of seizure frequency (Nazıroglu, 2015).
By binding directly to TRPV1 receptors, CBD releas- es excess calcium ions within hippocampal neurons, reducing or eliminating seizure potential by creating a homeostatic balance of these ions inside and outside of these brain cells.
It is particularly CBD’s anti-epileptic action – most notably for children for whom no other medical treatment has been successful – which drove the movement to legalize CBD-rich Cannabis extracts in several states where recreational or medicinal Can- nabis remained illegal (Bloom, 2015). This is in direct conflict with the financial desires of GW Pharmaceu- ticals and the FDA. It appears the young and adorable “poster children” of these illnesses have created a very consumer- and patient-friendly environment for this issue.
TRPV1 receptors have also been proposed for treat- ment of a wide variety of conditions including anxiety and depression, though research involving CBD and this particular receptor is still in its infancy. CBD does, however, bind to receptors that are well known modulators of our moods.
CBD, 5-HT1A serotonin receptors and PTSD
CBD directly activates the 5-HT1A serotonin re- ceptor, conferring anti-depressant and anti-anxiety effects (Zanelati et al., 2009; Campos et al., 2012b), reducing the perception of pain (Ward et al., 2014), and reducing nausea and vomiting (Rock et al., 2012).
When CBD binds to a 5-HT1A receptor, it slows the signaling downstream. This essentially “turns the vol- ume down” on processes that are activated by other messenger molecules binding to 5-HT1A sites on the same cell. This is in direct contrast to psychedelic drugs – which can create temporary psychosis – that produce an opposite, excitatory, “turning up the vol- ume” response (Project CBD, 2016).
It is through this pathway, by turning the volume down in serotonin-related physiological and psycho- logical processes, that CBD has potential for treat- ment of PTSD (Blessing et al., 2015). Treatment with CBD after a traumatic event – in research, where mice were exposed to a cat – had the mice essentially “forget” about the predatory threat (Campos et al., 2012b).
This model affirms CBD’s use for humans suffering from PTSD, and for anyone recovering from traumatic events in their lives. CBD, A2A, GPR55 and PPAR receptors: support for inflammation, anxiety, blood-sugar control, cancer and dementia
CBD also directly activates adenosine (A2A) recep- tors, found on cells throughout the immune system (De Petrocellis et al., 1998). Up-regulation at these receptors by CBD plays a significant role in reducing inflammation, lowering anxiety (Project CBD, 2016), and stimulating immune response and tissue repair.
CBD acts as an antagonist on GPR55 receptors, blocking their activity or deactivating them. Over-activity of GPR55 receptors is associated with osteoporosis and cancer cell proliferation (Project CBD, 2016). By blocking these receptors, CBD may improve bone density and reduce cancer cell growth. Other research has found an improvement of glu- cose metabolism via lowering of blood sugar and increasing sensitivity to insulin via CBD antagonism of GPR55 receptors (McKillop et al., 2016).
CBD directly activates PPAR receptors on the surface of the nucleus of cells, which regulate tran- scription factors and gene expression. Activation of these receptors has been shown to inhibit cancer growth (Marlow et al., 2009), and indeed CBD has been shown to have a chemopreventive (cancer-pre- venting) effect in mice (Aviello et al., 2012). Whether this is a result of PPARγ receptor activation or other mechanism(s) has yet to be confirmed.
Activation of PPARγ receptors protects brain cells from amyloid plaque deposition, and the resulting cognitive defects associated with dementia and Alz- heimer’s disease (Kummer et al., 2014).
PPARγ receptors also regulate glucose metabolism, and PPARγ agonists are used as treatments for improvement of insulin-sensitivity and blood-sugar control (Li et al., 2008). Through its binding at both GPR55 and PPARγ receptors, diabetics may significant- ly benefit from CBD (Project CBD, 2016).
The complete significance of CBD binding to this multitude of receptors has yet to be uncovered by science, but this web of messengers and receivers holds promise for even more reasons to employ CBD in practice.
CBD’s potentially unique and powerful treat- ment of Acne vulgaris
CBD seems to “go the extra mile” by providing what may be an extremely effective treatment option for acne – addressing each of the disease’s root causes. Acne vulgaris develops as a result of over-production of the skin’s natural oils (sebum), overgrowth of Propionibacterium acnes bacteria in sebum-producing cells (sebocytes), and inflammation resulting from localized infection within these cells (Thiboutot et al., 2009).
Topical CBD effectively reduces skin sebum produc- tion at low concentrations, and at higher concentra- tions causes the death of sebocytes (Russo, 2011). The long-term implications of the loss of sebocytes is unclear; regardless, this effect may be attractive to some Acne vulgaris sufferers, especially those with severe cases.
As CBD displays strong antibacterial action, with powerful activity against methicillin-resistant Staphylococcus aureus (MRSA) at low concentrations (Russo, 2011), it is reasonable to assume it will also show some, possibly significant, suppression of overgrowth of Propionibacterium acnes.
In addition to inflammation reduction via the mul- tiple pathways previously described, CBD also down-regulates inflammatory cytokine production (Nagarkatti, 2009), whereas up-regulation of cyto- kine production is a significant cause of inflammation associated with Acne vulgaris (Jeremy et al., 2003).
While not yet tested as a treatment for Acne vulgaris directly, it appears topical application of CBD has the potential to simultaneously address the multiple factors at the root of this ailment.
An Aromatherapist has a myriad of essential oils at their disposal that can address not only acne, but anxiety, cancer, depression, inflammation and pain, psychological trauma – most, if not all of the ailments CBD may be used to address. So what about using essential oils in concert with CBD? It turns out they work together very, very well!
Cannabinoids and terpenes together create an “entourage effect”
Terpenes are aromatic molecules produced by vir- tually every member of the plant kingdom, and are found in most essential oils. The terpene linalool, for example, is a primary constituent of Lavender (Lavan- dula angustifolia), imparting much of its characteristic scent and therapeutic properties (Koulivand et al., 2013).
Of the 150+ aromatic compounds found in Cannabis sativa, about 140 are terpenes. Hemp essential oil is rich in both myrcene and β-caryophyllene in partic- ular (Zgliczynska, 2016; Novak et al., 2001) which, like CBD itself, have a wealth of scientific research supporting their health benefits. Cannabis essential oil includes the major constituents linalool, humuline, α-pinene and limonene; there is also scientific sup- port for their health-imparting properties (Russo, 2011), and they are widely found throughout the aromatic plant kingdom.
Scientists call the synergy of molecules “the en- tourage effect.” This a well-known term describing the sum total actions on the body by terpenes and cannabinoids in their multitudes of configurations, simultaneously activating and deactivating countless physiological processes and pathways.
Interestingly, all the terpenes and phytocannabinoids of Cannabis sativa’s “entourage effect” share a single molecular precursor. Every terpene and cannabinoid biochemically synthesized by the Hemp plant are:
made from the same molecule, geranyl pyrophosphate (Project CBD, 2016). Nature has found the most conservative means to make a synergistic, diverse array of compounds from the same molecule. Each “tickles” different receptors in and on our cells, and they work together to create an overall greater state of well-being.
A typical GC/MS analysis reveals these terpenes and their relative concentrations (Table 1).
The myrcene and CBD connection
Myrcene is one of the two most abundant constituents in Hemp essential oil (Brenneisen, 2007), composing approximately 30% of its chemical profile (Zgliczynska, 2016). This terpene shares a very special synergy with CBD: myrcene lowers the resistance of the blood-brain barrier allowing CBD and all other cannabinoids to flow more freely and quickly into the central nervous system (Medical Jane, 2016; Steep Hill Labs, 2016).
Moreover, myrcene increases the maximum saturation level of the CB1 receptor (Medical Jane, 2016), meaning these receptors in the brain and central nervous system can utilize a greater amount of cannabinoids in general. Specifically, this enhances CBD’s effect of increasing the amount of circulating anandamide, as these receptors are then able to make use of a greater amount of this endocannabinoid. CBD plus myrcene apparently equals even more bliss!
Myrcene itself is also recognized for a wide variety of therapeutic properties. It is a potent analgesic, anti-inflammatory, muscle-relaxant, and even cancer fighter (Russo, 2011). As CBD also educes
the perception of pain, lessens inflammation, has cancer-fighting properties, and is made more bio-available by myrcene, these two compounds clearly synergize for a greater abundance of health
than use of either alone would provide.
b-caryophyllene, CB2 receptors, pain and inflammation
b-caryophyllene and its isomers vie with myrcene for the most abundant constituent of Hemp essential oil, comprising upwards of 35% of its make up (Zgliczynska, 2016).
b-caryophyllene is the only terpene which directly interacts with any cannabinoid receptor, binding to CB2 receptors throughout the body. CB2 receptors are involved in the modulation of inflammatory and pain responses – how much inflammation occurs and how much pain is perceived from a given physiological or biological “event” (Klauke et al., 2014). By binding to these receptors, b-caryophyllene significantly reduces the perception of pain, as well as lessening states of both acute and chronic inflammation. These actions are also demonstrated by CBD; when used together, b-caryophyllene and CBD address pain and inflammation through complementary mechanisms, with potentially profound results.
The effects of this terpene alone are so profound, researchers in the Journal of European Neuropsychopharmacology concluded a study on this subject by stating, “the natural plant product b-caryophyllene may be highly effective in the treatment of long-lasting, debilitating pain states” (Klauke et al., 2014).
The clear synergy of CBD and essential oils
The two terpenes found most abundantly in Hemp essential oil clearly synergize with CBD through an increase in saturation of the CB1 receptor, while concurrently increasing the amount of cannabinoids the brain and CNS can utilize (Bachmeier et al., 2013; Steep Hill Labs, 2016).
Combining CBD with Hemp essential oil seems to almost be a requirement for the therapist wanting to achieve optimal therapeutic activity of cannabidiol for their clients. This combination of terpenes and cannabinoids alone yields a broad spectrum of therapeutic properties.
We’ve thus far kept to the narrow scope of the single plant synergy – between only Hemp’s cannabinoids and primary essential oil constituents. As CBD will be available for some users from a high-THC/low-CBD Cannabis (rather than Hemp) strain, the next step is to look at the major constituents of Cannabis essential oil and their synergy with cannabinoids.
Cannabis essential oil contains significant fractions of a- and b-pinene, humulene, limonene and linalool, each abundant in the aromatic plant kingdom, and each with its own therapeutic properties.
a- and b-Pinene are known for their anti-inflammatory and anti-bacterial actions, as well as for promoting alertness and exhibiting antidepressant properties (Russo, 2011; Nissen et al., 2010; Guzmán-Gutiérrez et al., 2015). Humulene, an isomer of b-caryophyllene, is noted for its anti-tumorial and anti-inflammatory properties. Limonene has antidepressant and stress-reducing properties, along with antibacterial and anti-fungal actions (Russo, 2011). Linalool reduces anxiety and stress, and has antidepressant properties as well (Guzmán-Gutiérrez et al., 2015).
Of course, a review of these constituents is just the tip of the iceberg. The Aromatherapist has a nearly infinite palate of mono- and sesquiterpenes, monoand sesquiterpenols, esters, phenols, aldehydes and ketones to draw from. While the term “entourage effect” was used to describe the therapeutic actions of cannabinoids and terpenes from Cannabis alone, the Aromatherapist has hundreds of unique compounds to formulate with CBD and create an “entourage effect” for each of their clients’ unique conditions.
Note: This paper purposefully focuses on the essential oil of Hemp, which appears to have a fairly consistent chemistry profile compared to those of illicit Cannabis varieties (that of sativa and indica, as well as numerous hybrid strains). Hemp CO2 and essential oil are available to every Aromatherapy practitioner, whereas essential oils of illicit Cannabis varieties are not. This paper’s primary intention is to elucidate how and why the practitioner may include CBD in their essential oil formulas, and further to examine the synergy between CBD and Hemp essential oil
– two extracts from the same plant. Examining the chemistry profile of illicit Cannabis strains would not have fallen within the scope of this paper, and examining the synergy of “illicit” Cannabis terpenoids and cannabinoids would not have expanded the information already put forth on this subject by the scientific community.
CBD CO2: working with the “raw” paste
CBD CO2 extract, as mentioned earlier, is available from limited sources in “raw” form as a paste, and from many vendors emulsified in an edible carrier oil (Hemp, MCT, etc). The paste is available in varying concentrations of CBD, ranging from approximately 6% to over 25% and climbing.
CO2 extract prices are primarily based on the total number of milligrams of CBD purchased, and secondarily on the percentage concentration of CBD in the material. The cost per milligram of CBD is less in the lower-grade pastes – however, the lowest grade material (~6% CBD) is tar-like, very challenging to work with, and generally not recommended for blending. These extracts can solidify in carrier oils at concentrations in blends with 1mg CBD per drop. The higher grade (>25% CBD) “gold” extracts have an almost creamy consistency, are much more manageable, and the extra cost-per-milligram of CBD in these make them worth the additional expense. These emulsify much more readily, and at higher concentrations of CBD, in carrier oil and carrier/essential
A note about adulteration
Undiluted CBD CO2 extract thus far has not been a candidate for adulteration, yet prepared blends and dilutions are a different matter. It is critical to find a reputable vendor performing batch-testing for accurate, consistent CBD levels when purchasing blends. In 2015 the U.S. Food and Drug Administration tested 18 products from six retailers of CBD formulations. Seven of these products tested negative for any cannabinoids at all (FDA, 2015). Because of the relatively high cost of CBD, adulteration similar to that recognized in the essential oil industry is likely widespread enough that consumers should be wary where prices or claims appear “too good to be true.” For example, while the marketing term “high CBD Hemp oil” is used in advertisements, there is no such product unless the Hemp oil has been purposefully enriched with CBD extract. Without a chemical analysis, “high CBD Hemp oil” is likely to contain no detectable CBD whatsoever.
It does not appear, upon review of the available research, that one can have “too much” CBD (Schubart et al., 2014). It also appears that truly therapeutic doses for many conditions are somewhat higher than the recommendations circulated in the industry currently; average suggested daily doses are between 10 and 20mg per day (CBD Oil Review, 2016).
CBD is well-tolerated at doses up to 1500mg per day (Schubart et al., 2014), equivalent to approximately 6 grams of 25% extract. The only non-symptom-related feedback users have offered
from consuming relatively large amounts (>200mg/day) is that they feel happier than usual. It is important to consider that “everyone is different,” and a client’s weight, gender and age should be considered when developing a therapeutic protocol.
Research available using CBD with human subjects is limited, and so is the dosing information. What data is available is often from smaller studies, though these do at least provide a baseline which then can be adjusted for the specific individual and application. These suggested doses do not take into account the potential for increased bio-availability and other synergies through the combining of CBD with Hemp essential oil and other aromatics and extracts:
Chronic pain: 2.5mg–20mg/day
Chronic inflammation: 20–200mg/day
Sleep disorders: 40–160mg/day
Generalized Anxiety Disorder: 10–40mg/day
(CBD Oil Review, 2016)
Some sources suggest it may be useful to create a “storehouse” of CBD in the body at first, and slowly lower the dose (Project CBD, 2016). This is a reasonable approach, particularly if a client’s condition is severe but perhaps they cannot afford an endless supply of CBD. The half-life of CBD being on the order of one to two days also supports this approach, as a “storehouse” can be created.
This approach may dramatically improve symptoms at the start of therapy such that the condition is tolerable and stabilized. Inflammation, for example, tends to lead to more inflammation. If this is reduced significantly by initial high doses of CBD, the vicious cycle of inflammation and pain can be broken, and lower doses may maintain this new, healthier state.
The bottom line about dosing is that one should use as much CBD as they require for support and healing of their condition; using “too much” does not appear to be a concern, beyond that of cost. At the same time, any negative effect a client expresses should be considered and the treatment adjusted if necessary (though such effects have yet to be reported).
Blending with CBD: formulating precise concentrations
When formulating with CBD CO2 extract, it is first crucial to know the exact number of milligrams of CBD in any amount of the “raw” CO2 paste. The number of milligrams of CBD per amount of CO2 extract is the percent concentration of the extract times the number of milligrams of the extract in total. Thus, in a 6% extract, there are 60 milligrams of CBD per each gram (0.06 x 1,000mg = 60mg), and in a 25% extract, there are 250mg of CBD per gram (0.25 x 1,000mg = 250mg).
The paste can be ingested in capsules or even “neat,” though its flavor is quite pronounced to say the least. As it is a fat-friendly, lipophyllic molecule, absorption begins through the oral mucosa. Holding the raw paste in one’s mouth before swallowing may speed its assimilation and improve bioavailability – only about 6% of ingested CBD is absorbed through the gut, as there is significant “first pass” metabolism by the liver’s CYP3A4 enzymes (Welty et al., 2014).
Blends for ingestion, whether these include essential oils or other CO2 extracts, need to be carefully prepared so that accurate dosing can be achieved – a digital scale accurate to 0.1mg is a must-have. To make a one fluid ounce/30 ml bottle such that each drop contains 1mg of CBD (for example) the exact number of drops of base/carrier in the bottle must first be measured. Assuming typical values such as 20 or 30 drops per milliliter is not advised, as this figure varies widely depending on the viscosity and density of the base, as well as the material and shape of the dropper being used.
Once the number of drops of carrier or carrier-and-essential-oil base is found, a precise amount of CBD CO2 can be weighed for addition to the formula. For example, if there are 30 drops per
milliliter of the base and 30 milliliters in the bottle, the bottle holds 900 drops. In this case, to make a blend delivering 1mg CBD per drop, 900mg of CBD is required.
To find the total amount of CO2 extract needed to create a blend containing 1mg CBD/drop, use the formula (1 / % CBD concentration in the CO2 extract) x number of drops. With a CBD CO2 extract of 25% concentration for example, the equation is (1/0.25) x 900, equaling 3600 milligrams of CBD CO2 (providing 900mg of CBD).
For most accurate dosing, an equivalent volume of base should be removed from the formula/mixing bottle before the CBD CO2 is added – otherwise, the amount of CBD will be reduced below 1mg per drop. Thus, if one is adding 3600mg CBD CO2, this should replace approximately 3.6 milliliters of the base. When mixing the CBD CO2 into the base, gentle heat can be used to more easily emulsify the paste into the base – a hot water bath is the method of choice for many users.
These numbers can be adjusted to deliver higher or lower concentrations of CBD in the formula. It may be convenient, for example, to deliver 2mg of CBD per drop – which is easily done by doubling the amount of CBD resulting from the formula above. Note, however, as the concentration of CBD CO2 extract is increased in the formula much beyond this, a point is soon reached where the blend will no longer remain liquid at room temperature. CO2 extracts with higher concentrations of CBD will allow for greater amounts of CBD per drop, and the currently
available “gold” extracts (>25% CBD) provide the therapist the greatest flexibility in recipe creation.
CBD and essential oil formulas for oral ingestion
The therapist should determine the amount of essential oil and/or other CO2 extract to be included with each dose of CBD on a case by case basis. The blend(s) will likely be consumed daily, often over weeks or months. Frequency and duration of use, along with other factors relating to the individual client’s safe ingestion of these ingredients, must be considered during formulation of recipes and protocols.
As noted earlier, with its high levels of bcaryophyllene and myrcene, Hemp essential oil may be the single most therapeutically synergistic ingredient for use with CBD in a vast majority of applications.
A therapist might decide that one drop of Hemp essential oil per 20mg daily dose of CBD will be safe and effective for their client. A blend delivering one drop of Hemp essential oil per 20 drops (each with 1mg CBD) is easily formulated. Using the previous example of there being 30 drops per milliliter of base oil, and 900 drops total in the fluid ounce, one could first add 45 drops of Hemp essential oil to the bottle, 855 drops of carrier oil, and 3600mg of 25% CBD CO2.
There are many, many essential oils and CO2 extracts which complement the actions of CBD. Frankincense (Boswellia spp.), Sandalwood (Santalum spp.) or Myrrh
(Commiphora myrrha) may be used for anti-cancer formulas. Turmeric (Curcuma longa), Ginger (Zingiber officinale), Black Pepper (Piper nigrum) and/or German
Chamomile (Matricaria chamomilla) CO2 extracts are perfect complements for their anti-inflammatory properties. Lavender is an excellent choice for anti-anxiety preparations.
The experienced therapist will easily see the vast number of oils and extracts that may be effectively combined with CBD for the client’s therapeutic benefit.
CBD in topical formulas
CBD has great many properties that can be successfully employed in topical formulas. Pain relief has been the focus of most vendors offering topical formulations, with inflammatory skin conditions being a close second.
Research has only just begun to touch on the efficacy of CBD applied topically, and has thus far only focused on pain management. CBD topically applied in a gel base has been shown in research to effectively alleviate arthritis inflammation and pain in animal models (Hammell et al., 2016). Anecdotally, CBD-containing salves are reported to significantly reduce pain from arthritis, fibromyalgia, and physical injuries (Sisters of the Valley, 2017).
Anecdotal reports have also noted CBD alleviated irritated or inflamed skin conditions such as psoriasis and diaper rash (Lland, 2016). This frontier is truly new, and worthy of the creative Aromatherapist’s inspired blend development.
Skin sensitivity to CBD has yet to be formally evaluated, although concentrations of up to 10% have been used in research without side effects (Hammell et al., 2016). No irritation of the mucosal lining of the mouth and throat was reported by users ingesting CBD CO2 extract in 25% concentration. While the Aromatherapist should be aware of CBD extracts’ potential to cause skin irritation, it appears not likely to do so unless an individual is otherwise overly sensitive to topical formulations.
CBD: is it nature’s most profound medicine yet?
Before addressing whether CBD is “nature’s most profound medicine yet,” the first question that must be asked is, “is it safe and effective?” For cannabidiol, it is a definite yes on both counts. As to CBD’s safety: it doesn’t appear one can have too much CBD, and it is well tolerated at doses which far exceed the therapeutic norms. There have been no reports of adverse reactions recorded as of this date, and concentrated forms of CBD have been on the market for several years.
On CBD’s efficacy: The sum total of research thus performed clearly indicates CBD’s efficacy in the treatment of a significant number of common, even life-threatening, health conditions and ailments. More human studies are warranted that optimize condition-specific dosing protocols, most certainly – yet successful outcomes have resulted from dosing ranges discussed earlier.
Researchers often state that CBD exerted its beneficial effect in a dose-dependent manner (meaning, the more that was used the greater the effect), thus it appears the only possible detriment to using CBD is using too little to cause the desired result.
Discretion is advised for particular clients and conditions, and careful thought must be put to the development of formulas for ingestion, including essential oils used. There is certainly no need to use more CBD than necessary for a desired outcome, though the therapist should feel absolutely confident in its safety and efficacy.
Is CBD “nature’s most profound medicine yet”? The answer is an opinion of course, but CBD is worthy of the question. It is almost beyond comparison with other natural therapeutics in the range of health conditions it addresses, again, with no side effects. In this regard, it may certainly be called a “truly effective natural medicine.” When used in concert with synergistic essential oils, its efficacy multiplies significantly – so much so that CBD and essential oils together just may well be deserving of the label: “nature’s most profound medicine yet.”
Aizpurua-Olaizola O, Soydaner U, Öztürk E, Schibano D, Simsir Y, Navarro P, Etxebarria N, Usobiaga A. (2016). Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis Sativa Plants from Different Chemotypes. Journal of Natural Products. 79 (2), p324-331.
Aviello G, Romano B, Borrelli F, Capasso R, Gallo L, Piscitelli F, Di Marzo V, Izzo A A. (2012). Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. J Mol Med (Berl). 90 (8), p925-934.
Bachmeier C, Beaulieu-Abdelehad D, Mullen M, Paris D. (2013). Role of the cannabinoid system in the transit of beta-amyloid across the blood–brain barrier. Molecular and Cellular Neuroscience. 56, p255-262.
Barcott B. (2016). New DEA Rule Says CBD Oil Is Really, Truly, No-Joke Illegal. Leafy.com (14 December 2016). Available: https://www.leafly.com/news/politics/new-dea-rule-says-cbd-oil-really-truly-no-joke-illegal. Last accessed 21 Feb. 2017.
Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. (2006). Paracetamol: New Vistas of an Old Drug. CNS Drug Reviews. 12.3-pro4, p250-275.
Blessing E M, Steenkamp M M, Manzanares J, Marmar C R. (2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 12 (4), p825-836.
Bloom S. (2015). CBD Oil Now Legal in 16 States. CelebStoner.com. N.p., (1 July 2015). Available: http://www.celebstoner.com/news/marijuana-news/2014/03/13/four-states-on-verge-of-passing-cbd-only-laws/. Last accessed 26 Oct. 2016.
Brenneisen R. (2007). Chemistry and Analysis of Phytocannabinoids and Other Cannabis Constituents. In Mahmoud A. El Sohly, Marijuana and the Cannabinoids. Humana Press. p17-49.
Campos A C, Moreira F A, Gomes F V, Del Bel E A, Guimaraes F S. (2012a). Multiple Mechanisms Involved in the Large-spectrum Therapeutic Potential of Cannabidiol in Psychiatric Disorders. Philosophical Transactions of the Royal Society B: Biological Sciences 367.1607, p3364-3378.
Campos A C, Ferreira F R, Guimarães F S. (2012b). Cannabidiol Blocks Long-lasting Behavioral Consequences of Predator Threat Stress: Possible Involvement of 5HT1A Receptors. Journal of Psychiatric Research. 46 (11), p1501-1510.
CBD Oil Review. CBD Oil Dosage: General Advice to Assess How Much CBD to Take. Available https://cbdoilreview.org/cbd-cannabidiol/cbd-dosage/. Last accessed 16 Dec. 2016.
Clapper J R, Moreno-Sanz G, Russo R, Guijarro A, Vacondio F, Duranti A, Tontini A, Sanchini S, Sciolino N R, Spradley J M, Hohmann A G, Calignano A, Mor M, Tarzia G, Piomelli D. (2010). Anandamide Supresses Pain Initiation through a Peripheral Endocannabinoid Mechanism. Nature Neuroscience. 13 (10), p1265-1270.
Colbert M. (2016). Cannabinoid Profile: Cannabidiol (CBD). The Leaf Online. Available: http://theleafonline.com/c/science/2014/06/cannabinoid-profiles-crash-course-cbd/. Last accessed 19 Nov. 2016.
Davis M P. (2016). Cannabinoids for Symptom Management and Cancer Therapy: The Evidence. Journal of the National Comprehensive Cancer Network. 14 (7), p915-922.
De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M, Di Marzo V. (1998). The Endogenous Cannabinoid Anandamide Inhibits Human Breast Cancer Cell Proliferation. Proceedings of the National Academy of Sciences. 95 (14), p8375-8380.
Elder Trees. (2014). How Did Growers Breed out CBD from Marijuana Strains and How Do They Breed CBD Back in Them Again? Available:
https://www.reddit.com/r/eldertrees/comments/1vqmtt/how_did_growers_breed_out_cbd_from_marijuana/?st=iuq7f3p6&sh=2cbc83a. Last accessed 25 Oct. 2016.
Everaerts W et al. (2011). The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil. Current Biology. 21 (4), p316-321.
Grotenhermen F. (2012). The Therapeutic Potential of Cannabis and Cannabinoids. Dtsch Arztebl Int. 109(PMC3442177), p495-501. doi:10.3238/arztebl.2012.0495.
Guzmán-Gutiérrez S L, Bonilla-Jaime H, Gómez-Cansino R, Reyes-Chilpa R. (2015). Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sciences. 128, p24-29. GW Pharmaceuticals. (2014a). Cannabinoid Compounds. Available: https://www.gwpharm.com/products-pipeline/research-trials/cannabinoid-compounds. Last accessed 25 Oct. 2016.
GW Pharmaceuticals. (2014b). Epidolex. Available: http://www.gwpharm.com. Last accessed 25 Oct. 2016.
GW Pharmaceuticals. (2016). Epilepsy. Available: http://www.gwpharm.com. Last accessed 26 Oct. 2016.
Hammell D C, Zhang L P, Ma F, Abshire S M, McIlwrath S L, Stinchcomb A L, Westlund K N. (2016). Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European Journal of Pain. 20 (6), p936-948.
Hasko G and Pacher P. (2007). A2A Receptors in Inflammation and Injury: Lessons Learned from Transgenic Animals. Journal of Leukocyte Biology. 83 (3), p447-455.
Henein M. (2016). The Battle for Cannabidiol (CBD): Big Pharma VS The People. Honey Colony. Available: https://www.honeycolony.com/article/the-battle-for-cannabidiol-cbd/. Last accessed 27 Nov. 2016.
Hill Labs Inc. Steep Hill Labs Inc. (2016). Cannabinoid and Terpenoid Reference Guide. Available: http://steephilllab.com/resources/cannabinoid-and-terpenoid-reference-guide/. Last accessed 25 Oct. 2016.
Iannotti F A, Hill C L, Leo A, Alhusaini A, et al. (2014). Nonpsychotropic Plant Cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), Activate and Desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) Channels in Vitro: Potential for the Treatment of Neuronal Hyperexcitability. ACS Chemical Neuroscience. 5 (11), p1131-1141.
Jeremy A H, Holland D B, Roberts S G, Thomson K F, Cunliffe W J. (2003). Inflammatory events are involved in acne legion initiation. Journal of Investigative Dermatology. 121 (1), p20-27.
Kasper S. (2013). An orally administered lavandula oil preparation (Silexan) for anxiety disorder and related conditions: an evidence based review. Int’l J of Psychiatry in Clinical Practice. 17 (Suppl 1), p15-22.
Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. (2006). Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn-Schmiedebergs’s Archives of Pharmacology. 372 (5), p354-361.
Khetrapal A. (2016). What Is Neuromodulation? News-Medical.net. AZoM.com Limited (23 Nov. 2015). Available: http://www.news-medical.net/health/What-is-Neuromodulation.aspx. Last accessed 25 Oct. 2016.
Klauke A L, Pradier B, Markert A, Zimmer A M, Gertsch J. (2014). The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Journal of European Neuropsychopharmacology. 24 (4), p608-620.
Koulivand P, Ghadiri M, Gorji A. (2013). Lavender and the Nervous System. Evidence Based Complementary and Alternative Med. Available: http://dx.doi.org/10.1155/2013/681304. Last accessed: 4 Jan. 2017.
Kummer M P, Schwarzenberger R, Sayah-Jeanne S, Dubernet M, Walczak R, Hum D W, Schwartz S, Axt D, Heneka M T. (2014). Pan-PPAR Modulation Effectively Protects APP/PS1 Mice from Amyloid Deposition and Cognitive Deficits. Molecular Neurobiology. 51 (2), p661-671.
Lavelle J. (2015). Exploring The Molecular Basis of “Runner’s High.” Chemical and Engineering News. Available: http://cen.acs.org/articles/93/web/2015/10/Exploring-Molecular-Basis-Runners-High.html. Last accessed 12 Sept. 2016.
Leaf Science. N.p. (2013). News and Facts On Cannabinoid Receptors. Available: http://www.leafscience.com/endocannabinoid-system/works/cb1-cb2-receptors/. Last accessed 25 Oct. 2016.
Leaf Science. (2015). What Are Cannabinoids? Available: http://www.leafscience.com. Last accessed 25 Oct. 2016.
Leaf Science. (2016). Cannabis Oils: A Look at What’s Available in Canada. Available: http://www.leafscience.com/2016/02/21/Cannabis-oils-look-whats-available-canada/. Last accessed 27 Nov. 2016.
Lland R. (2016). Can Cannabis and CBD be part of your skin care regimen? Leafy. Available: https://www.leafly.com/news/health/Cannabiscbd-skin-care. Last accessed 1 Jan. 2016.
Li Y, Qi Y, Huang T H, Yamahara J, Roufogalis B D. (2008). Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties. Diabetes Obes Metab. 10 (1), p10-17.
Marlow L A, Reynolds L A, Cleland A S, Cooper S J, Gumz M L, Kurakata S, Fujiwara K, Zhang Y, Sebo T, Grant C, McIver B, Wadsworth J T, Radisky D C, Smallridge R C, Copland J A. (2009). Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth. Cancer Research. 69 (4), p1536-1544.
McKillop A M, Moran B M, Abdel-Wahab Y H A, Gormley N M, Flatt P R. (2016). Metabolic Effects of Orally Administered Small-molecule Agonists of GPR55 and GPR119 in Multiple Low-dose Streptozotocin-induced Diabetic and Incretin-receptor-knockout Mice. Diabetologia. 59 (12), p2674-2685.
Mecha M, Feliú A, Iñigo P M, Mestre L, Carrillo-Salinas F J, Guaza C.(2013). Cannabidiol Provides Long-lasting Protection against the Deleterious Effects of Inflammation in a Viral Model of Multiple Sclerosis: A Role for A2A Receptors. Neurobiology of Disease. 59, p141-150.
Medical Jane. (2016). Terpenes – Learn how terpenes work synergistically with cannabinoids. Available: https://www.medicaljane.com/category/Cannabis-classroom/terpenes/. Last accessed 15 Nov. 2016.
Nagarkatti P. (2009). Cannabinoids as novel anti-inflammatory drugs. Future Medicinal Chemistry. 1 (7), p1333-1349.
Nazırog lu M. (2015). TRPV1 Channel: A Potential Drug Target for Treating Epilepsy. Current Neuropharmacology. 13 (2), p239-247.
National Conference of State Legislatures (NCSL). (2016). State Industrial Hemp Statutes. Available: http://www.ncsl.org/research/agriculture-and-rural-development/state-industrial-Hemp-statutes.aspx. Last accessed 27 Nov. 2016.
Nissen L, Zatta A, Stefanini I, Grandi S, Sgorbati B, Biavati B, et al. (2010). Characterization and antimicrobial activity of essential oils of industrial Hemp varieties (Cannabis sativa L.). Fitoterapia. 81, p413-419.
Novak J, Zitterl-Eglseer K, Deans S G, Franz C M. (2001). Essential oils of different cultivars of Cannabis sativa L. and their antimicrobial activity. Flavour and Fragrance Journal. 16 (4), p259-262.
Orav A, Kailas T, Jegorova A. (2003). Composition of the essential oil of dill, celery, and parsley from Estonia. Proceedings of the Estonian Academy of Sciences: Chemistry. 52, p147-154.
Pacher P, Bátkai S, Osei-Hyiaman D, Offertáler L, Liu J, Harvey-White J, Brassai A, Járai Z, Cravatt B F, Kunos G. (2005). Hemodynamic Profile, Responsiveness to Anandamide, and Baroreflex Sensitivity of Mice Lacking Fatty Acid Amide Hydrolase. AJP Heart and Circulatory Physiology. 289 (2), H533-41.
Project CBD. (2016). Cannabis Dosing. Available: https://www.projectcbd.org/Cannabis-dosing. Last accessed 16 Dec. 2016.
Project CBD. (2016). How CBD Works. Available: https://www.projectcbd.org/how-cbd-works. Last accessed 26 Oct. 2016.
Rock E, Bolognini D, Limebeer C I, Cascio M G, Anavi-Goffer S, Fletcher P J, Mechoulam R, Pertwee R G, Parker L A. (2012). Cannabidiol, a Non-psychotropic Component of Cannabis, Attenuates Vomiting and Nausea-like Behaviour via Indirect Agonism of 5-HT1A Somatodendritic Autoreceptors in the Dorsal Raphe Nucleus. British Journal of Pharmacology. 165 (8), p2620-2634.
Russo E. (2011). Taming THC: potential Cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 163 (7), p1344-1364.
Russo E and McPartland J. (2001). Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? Journal of Cannabis Therapy. (3/4), p103-132.
Schubart C D, Sommera I E C, Fusar-Polib P, de Wittea L, Kahnc R S, Boksa M P M. (2014). Cannabidiol as a potential treatment for psychosis. European Neuropsychopharmacology. 24, p51-64.
Sensi Seeds Blog. N.p. (2013). Cannabinoid Science 101: What Is 2-AG? Available: https://sensiseeds.com/en/blog/cannabinoid-science-101-what-is-2-ag/. Last accessed 26 Oct. 2016.
Shang X, Wang Y, Zhou X, Guo X, Dong S, Wang D, Zhang J, Pan H, Zhang Y, Miao X. (2016). Acaricidal activity of oregano oil and its major component, carvacrol, thymol and p-cymene against Psoroptes cuniculiin vitro and in vivo. Vetrinary Parasitology. 15 (226), p93-96.
Sisters of the Valley. (2017). Testimonials. Available: https://www.sistersofcbd.com/testimonials/. Last accessed 1 Jan. 2017.
Steep Hill Labs. (2016). Terpenes. Available: http://steephill.com/science/terpenes. Last accessed 13 Feb. 2017.
Swanson T E. (2015). Controlled Substances Chaos: The Department of Justice’s New Policy Position on Marijuana and What It Means forIndustrial Hemp Farming in North Dakota. North Dakota Law Review. 90 (3), p613.
Thiboutot D, et al. (2009). New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group. Journal of American Academy of Dermatology. 60 (5 Suppl), S1-50.
Tinseth G. (1994). Hop Aroma and Flavor. Brewing Techniques. 2 (1). Available: https://www.morebeer.com/brewingtechniques/library/backissues/issue2.1/tinseth.html. Last accessed 4 Jan. 2017.
U.S. Food and Drug Administration (FDA). (2015). Warning Letters and Test Results cannabidiol-related products. Available: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm435591.htm. Last accessed 19 Nov.2016.
Ward S J, Mcallister S D, Kawamura R, Murase R, Neelakantan H, WalkerE A. (2014). Cannabidiol Inhibits Paclitaxel-induced Neuropathic Pain through 5-HT1A receptors without Diminishing Nervous System Function or Chemotherapy Efficacy. British Journal of Pharmacology. 171 (3), p636-645.
Welty T, Luebke A, Gidal B. (2014). Cannabidiol: Promise and Pitfalls. Epilepsy Currents. 14 (5), p250-252.
Zanelati T V, Biojone C, Moreira F A, Guimarães F S, Joca S R L. (2009). Antidepressant-like Effects of Cannabidiol in Mice: Possible Involvement of 5-HT1A Receptors. British Journal of Pharmacology. 159 (1), p122-128.
Zgliczynska M. (2016). Hemp Essential Oil Analysis. Available: http://www.anandaapothecary.com/Hemp-essential-oil-analysis.pdf. Last accessed 4 Jan. 2017.
Eric Cech is the owner of The Ananda Apothecary, founded in 2004. He received a B.S. in Environmental Science from the University of California at Santa Barbara, and became interested in natural therapeutics of all kinds after moving to Boulder, Colorado, in 1998. He was soon intrigued by the medicine essential oils had to offer, and after many years of research and sourcing, The Ananda Apothecary was born. His part of work is getting to help individual clients choose and use oils for themselves, and he wishes he had more opportunity to do so. www.anandaessentialoils.com