Phytocannabinoids: 25 Things to Know Now

In WholeFoods Magazine’s 5th annual in-depth look at the cannabis/hemp/phytocannabinoid/CBD market, we explore the latest research, regulatory issues, legal concerns and more

In January 2015, WholeFoods took a deep dive into the legal cannabis market, hemp-based products and cannabidiol (CBD), alerting readers that something big was brewing. Jane Wilson, director of program development for the American Herbal Products Association (AHPA) and author of the article, predicted: “The next few years are anticipated to include continued high levels of legislative activity regarding the Cannabis spp. plant.” Retailers, she said, “can best position themselves to take advantage of the changing legal landscape for Cannabis spp. plant products, and the potential resulting business opportunities, by paying close attention to emerging state and federal legislation and the myriad regulations that impact access to this botanical and its many useful derivatives.”

Wilson was spot-on about the myriad regulations and the opportunities—as well as about the need to pay close attention. The category is huge, evolving and there are pitfalls aplenty. Here, we break it down into 25 things to know right now—plus, go here for 7 questions retailers need to ask before selling any CBD product.

1) The ECS is key to health. “The endocannabinoid system is the body’s largest, and quite possibly, most important neurotransmitter system,” says Jade Beutler, CEO, Emerald Health Bioceuticals, based in San Diego. “It’s activated by both endocannabinoids and phytocannabinoids, which lock into CB1 and CB2 receptor sites located throughout the body. Once locked in, a cascade of communication takes place and the ECS begins its impressive task of creating balance in every cell, tissue and organ. Despite what’s going on in your body or in your environment, the ECS strives to maintain constant homeostasis by enzymatically breaking down cannabinoids based on your body’s current needs.”

Carl Germano, CNS, CDN, VP of Verdant Oasis and author of The Road to Ananda: The Illustrated Guide to The Endocannabinoid System, Phytocannabinoids, Hemp & Your Health adds, “The endocannabinoid system is enormous in what it does and what it regulates and what it modulates throughout the human body. From a global perspective, it is controlling and maintaining health, wellbeing and homeostasis. At the organ level, it governs neurotransmission, inflammatory cycling, pain signaling, insulin sensitivity, bone building and the list goes on and on and on.”

Indeed, adds Rob Maru, founder and co-CEO of Planted Earth in Livingston, NJ, “The endocannabinoid system remarkably regulates just about every function in the body including metabolism, hormone regulation, digestion, reproduction, mood, sleep, memory, immune function, appetite, movement and neuroprotection. The most exciting areas relate to its ability to naturally assist with pain and inflammation.”

2) There’s more to learn. “Researchers did not fully delve into this important system until the last couple of decades, so we’re behind the 8 ball as far as I’m concerned with having done research on one of the most important regulatory systems in the body thus far discovered,” says Cheryl Myers, chief of scientific affairs and education at EuroPharma, Inc., maker of the Terry Naturally and EuroMedica brands, based in Green Bay, WI.

Germano echoes that sentiment. “We are technically in our infancy of research, even though Israel and Europe have been doing this for quite some time, and even though the endocannabinoid system was discovered in the 1990s. Issues surrounding the way cannabinoids were categorized kept a lot of research at bay. Do we have the complete picture? Not entirely, but we have a sufficient amount of data out there to show these retailationships. When the endocannabinoid system suffers, so do you in so many different ways, and each person is different.”

On the upside, the research community received an infusion of cash in May, when an alumnus of Harvard and MIT gave $4.5 million to each institution to support cannabis research.

3) Endocannabinoid deficiency is a growing concern. “The ECS has a series of receptors throughout the body that modulate responses to a variety of stimuli,” Myers says. “In the presence of certain cues, the body responds by sending endocannabinoids to click into these receptors; I think of them as light dimmers that can turn up and turn down. It’s not that there’s a static amount of endocannabinoids and receptors. It’s constantly in flux depending on the needs of the body.” But, she notes, many people are not making optimal amounts of endocannabinoids.

Experts are exploring this in terms of deficiency. Explains Gene Bruno, professor of nutraceutical science for Huntington University of Health Sciences and senior director of product innovation for Twinlab Consolidation Corp., Boca Raton, FL, “There are several subjective pain syndromes that have proven to be resistant to effective and meaningful treatment. Chief among these are migraine, fibromyalgia, and irritable bowel syndrome. Given the similarity in pain and sensitivity symptoms and possible similarities in underlying pathophysiology, researchers have suggested that endocannabinoid deficiency syndrome might be the common factor in their origin.”

What causes inadequate levels of endocannabinoids? “There is no one single answer,” says Bruno. “Recent research suggests that, in some cases, the cause may have to do with genetic variants in the core endocannabinoid system genes. Other research suggest that maternal obesity may result in a fetal syndrome of endocannabinoid deficiency. Also, chronic exposure to glucocorticoids down regulates the endocannabinoid system, as can excessive amounts of arachidonic acid and chronic alcohol intake. A diet low in phytocannabinoids—low in plant foods—may also play a role. The fact is, inadequate levels of endocannabinoids may be associated with their production, metabolism, or the state of cannabinoid receptors.”

Lifestyle Strategies for an Optimized ECS

The buzz over CBD is driving new customers into natural products stores, and that is creating a beautiful opportunity to deliver on the goal of helping people achieve healthier lifestyles overall. “Phytocannabinoids may be part of a health and fitness plan that includes a clean, nutritious diet, exercise, good sleep habits, and things that lift your mindset and spirit like spending time out in nature, and spending time with your loved ones,” says Laura Fuentes, CEO and co-founder at Green Roads.

Speaking of diet, Bruno adds, “Human beings have evolved on a diet that includes various phytocannabinoids-containing foods. For example, grapes, broccoli, cabbage, carrots, parsley, sunflower seeds and peas all contain phytocannabinoids—so does cacoa, from which chocolate is derived, and tea. Likewise, culinary herbs like basil, cinnamon, black pepper, cloves, oregano and rosemary all contain phytocannabinoids, as do medicinal herbs like Echinacea, turmeric, and licorice. Consumption of these foods and herbs can all help to support healthy function of the ECS.”

Beutler outlines ECS-nourishing strategies that retailers can pass along to customers:

Move more. “Exercise can be anything from yoga to walking and swimming. And here’s something fascinating about that famed and fabled ‘runner’s high’: There are studies out disproving the source of an endorphin rush. Instead there is evidence suggesting that the high is a result of a bump up in endocannabinoids in your system.”

Get a massage. “Massage has been found to rev up the endocannabinoids in your body. If you can’t afford to hit the spa every week, a foam roller, massage ball or a gentle neck and shoulder massage can do the trick.”

Go easy on alcohol. “No, you don’t have to give up the enjoyment of a glass of wine at dinner,” he says. “If you’re celebrating and that action is rare, no sweat. But excess alcohol can inhibit and even deaden the signaling you need from your ECS receptors.”

Eat greens. “Not only do leafy greens contain beta-caryophyllene, studies have also found that they activate the CB2 endocannabinoid receptor which may be key for defeating autoimmune disorders and conditions that flare up because of excess inflammation.”

4) Our hectic lives up the risk. “In today’s modern world, we’re managing more daily stressors, acquiring more unhealthy habits and lifestyle choices and are more sedentary than previous generations—and it’s all significantly affecting the functioning of the endocannabinoid system and our overall well-being,” says Beutler. “How can you tell? Well, if you’re experiencing pain and inflammation, not sleeping well or having difficulty with mood, anxiety and stress, or trouble concentrating, your ECS may be out of balance, and it can cause serious health problems. Most of us experience these symptoms on a regular basis, but the reality is, this it isn’t normal! And if left unchecked, these imbalances could develop into Clinical Endocannabinoid Deficiency Syndrome (CEDS), a condition where an individual produces a lower amount of cannabinoids essential for balanced health.” In addition to migraines, fibromyalgia and IBS, Beutler says CEDS has been implicated in mood imbalances, inflammation flare-ups and more—the list grows as research continues.

5) Plant-based cannabinoids can help. “We can prevent [certain health] issues,” Beutler says, “by supporting and nurturing our ECS with the production of endocannabinoids—cannabinoids produced naturally inside the body—and phytocannabinoids—plant compounds that mimic endocannabinoids.”

“The way plants work to augment our health as far as the endocannabinoid system,” Myers adds, “is that they contain compounds capable of attaching to cannabis receptors throughout the body to bring about certain health benefits. And in addition to augmenting your own supply of endocannabinoids with phytocannabinoids, there are also compounds in hemp oil that interfere with the enzymes that destroy our body’s own endocannabinoids.”

Bruno breaks down the science: “The two prominent endocannabinoids that the body produces are anandamide and 2-arachidonoylglycerol. These endocannabinoids bind with receptors within the endocannabinoid system. Despite the fact that these endocannabinoids have valuable effects, there is an enzyme in the body called fatty acid amide hydrolase (FAAH) that breaks down these endocannabinoids.” Enter phytocannabinoids. “When significant amounts of phytocannabinoids are consumed,” Bruno says, “the FAAH will be used to break them down, instead of breaking down the endocannabinoids. This helps maintain healthy levels of endocannabinoids and prolong their action.”

6) CBD and THC act differently. “THC is an activator of the ECS, causing a spike in the manufacturing of anti-stress compounds that, in small amounts, help you deal with a stressful situation or set of circumstances,” explains Rebecca Hall, project coordinator at Pervida, based in Blacksburg, VA. “As with many drugs, this effect is easy to abuse—to ‘get high.’” Then there’s CBD. “CBD is a regulator of the ECS, helping the body to re-evaluate and re-define what it sees as a baseline amount of stress and encouraging the body to balance the levels of these compounds within its own capacity,” Hall says. “The human body responds to stress in so many different ways—this is why you hear stories of people’s blood pressure returning to normal or experiencing the relief of chronic pain in seemingly unrelated parts of the body after taking CBD. Additionally, studies have shown that CBD works best in the presence of other phytocannabinoids due to a phenomenon called the ‘entourage effect,’ meaning that someone who is trying CBD will get a more strongly perceived effect from a full-spectrum oil instead of CBD isolate.” Pervida CBD, she says, has a line of full-spectrum hemp oil-containing products called Pervida Calm. “The hemp oil we use for our products is GRAS and third-party analyzed. We use pomegranate seed oil to address inflammation and the damages caused by stress, and we used full-spectrum CBD as a way to help encourage the mind and body to heal, and manage stress in a less damaging way.”

7) Full Spectrum, explained. “CBD is one of many phytocannabinoids found in hemp,” says Bruno. “Although it is the most prevalent phytocannabinoids, consumption of the other ones alongside CBD results in ‘the entourage effect’—greater overall synergistic activity with greater results. Specifically, full-spectrum phytocannabinoids will result in the activation of the two major ECS receptors, not just one of them, as is the case with just CBD isolate. There is no entourage effect if you’re just using isolated CBD. Full-spectrum hemp extract, conversely, provides a full spectrum of naturally occurring phytocannabinoids, including a defined amount of CBD.” Although CBD isolate is less expensive, he says, it is also less effective.

“I am a huge proponent of full spectrum hemp oil because there’s more than 120 different cannabinoids in hemp and they all work differently,” says Myers. She notes that when we look the broad spectrum of cannabinoids in hemp, “they aren’t just acting independently. There are times when they join hands and all act as a group. There are times when the naturally occurring amounts of CBD in full spectrum hemp oil will behave differently because it is being influenced by its family members, rather than CBD that has been taken out in isolation.”

8) But…the term “full spectrum” may be subjective. “There’s not really a definition of full spectrum, the way there is with isolate,” contends Jake Black, chief scientific officer of Treehouse Hemp, in Longmont, CO. “Isolate means one individual molecule by itself. Full spectrum means a lot of different things to a lot of different people…Some people will take CBD and add some terpenes to it and say that’s full spectrum. Other people say it has to be a raw extract of the plant and if you distill it at all, or process it any further, it’s no longer full spectrum. Other people say as long as there’s two or three other cannabinoids in there, it’s full spectrum. So there is no accepted definition scientifically or in the industry. And that’s a problem. No one is talking on the same level when they talk to each other about this. Our internal definition [at Treehouse Hemp] is that it has to have multiple cannabinoids and terpenes and some of the fatty acids of the plant to make it a full spectrum. Though some people would argue that it’s not because we take the THC out of our process and some people say it needs THC, so that’s yet another definition.”

One thing full spectrum is not, according to Germano: “It is not taking an isolate and dumping it into a cheap inexpensive hemp oil or hemp seed oil that has no cannabinoids in it, and companies are doing that. It’s the wild wild west right now.” Verdant Oasis, distributed by Barrington Nutritionals, based in Harrison, NY, supplies phytocannabinoid-rich hemp stock oil to a number of manufacturers in the industry and has played a major part in shifting the narrative away from CBD and toward full spectrum.

9) “Broad spectrum” explained. The stance at Green Roads, based in Deerfield Beach, FL, is that full spectrum of a hemp plant technically includes THC. “We reduce THC down to non-detectable level,” Laura Fuentes, CEO and co-founder. “We’re committed to transparency, so we use the term ‘broad spectrum’ to acknowledge the absence of detectable THC. However, the CBD experience remains the same. We include the range of compounds that research shows may synergize with CBD and let your body relate to it in a more natural way, hence the use of the term ‘broad.’” Fuentes adds that Green Roads derives CBD from industrial hemp and formulates products designed to let consumers choose their own application method, including oils, gummies, topicals, coffee, tea, and more.

10) Caution is urged with isolates. “FDA has clarified that highly purified and isolated CBD are prescription drugs and not allow to be added to dietary supplements,” says Dr. Duffy MacKay, senior vice president of scientific and regulatory affairs at San Diego-based CV Sciences, makers of PlusCBD Oil. “Marketers of these ingredients are ignoring FDA and taking a significant risk. The intent of the 2018 Farm Bill was to allow farmers to grow agricultural hemp—for example, a tall plant grown on a farm, harvested with a combine, low in resin and cannabinoids, and high in fiber. Products derived from hemp have a moderate amount of CBD, approximately 5 to 15 mg per serving and contain other beneficial cannabinoids, terpenes, fatty acids, and bioactive constituents. In fact, Health Canada, which has been actively regulating hemp and marijuana products, has made a distinction. Hemp extracts that provide a full array of hemp plant constituents are appropriate as supplements—called Natural Health Products in Canada—while products that provide isolated or highly purified compounds are drugs.”

It is prudent, MacKay continues, to work with authentic hemp extracts that are allowed as supplements. “If consumers are looking for drug-like products with drug-like levels of CBD, they should appropriately be referred to a doctor or dispensary. If the emerging hemp industry does not act responsibly while FDA is evaluating how to regulate cannabis products, the industry risks inviting over-burdensome regulations.”

Bruno also stresses, “As the FDA considers a possible path the lawful presence of CBD in dietary supplements, there is considerable risk that CBD isolate will not be part of that path, but that naturally occurring CBD in hemp extracts will be. Of course, we don’t know for sure yet, but consider that the FDA’s current stated reason for not recognizing CBD as lawful for sale as a dietary supplement is that is currently a drug—specifically Epidiolex, which consists of CBD isolate. That being the case, I believe it is safer—and more efficacious—to go with full-spectrum rather than isolate.” He adds that Twinlab’s four full-spectrum phytocannabinoid products provide naturally occurring CBD and a range of other phytocannabinoids. “In addition, these products provide a clove/black pepper extract which contains significant amounts of beta-caryophyllene, a terpene/phytocannabinoid with a great deal of research. The combination of phytocannabinoids helps to assure that more complete ‘nourishment’ of the ECS.”

11) But…some do make a case for isolates. At Louisville, CO-based Bluebird Botanicals, Brandon Beatty, CEO & founder explains why isolates are in the line. “Our most popular products are our full-spectrum hemp extracts, otherwise known as CBD oil,” he says. “These extracts contain the entire array of the 80+ cannabinoids found in the cannabis plant, as well as the additional nutritious compounds like terpenes, flavonoids, fatty acids, etc. We offer these extracts in both oil and capsule forms. We also offer a variety of hemp isolate products, including our CBD isolate, vape oil, and THC-Free CBD oil. These are great choices for those looking to enjoy the benefits of pure CBD.”

Expanding on that, Grace Kaucic, digital marketing specialist at Bluebird Botanicals, says, “Full-spectrum extracts do contain a small amount of THC—less than 0.3% by dry weight per federal regulations. This small amount prevents most people from experiencing its psychoactive effects; however, some consumers may have extra sensitivities to THC. Likewise, civil servants and athletes who undergo rigorous drug screenings may need a product completely purified from THC. For these individuals, we created our THC-Free CBD Oil, which contains CBD isolate emulsified in fractionated coconut MCT oil.”

Warfighter Hemp, in Boulder, CO, offers over 30 products ranging from tinctures to CBD bath bombs. And offerings include both full spectrum and CBD-only products that are derived from an isolate, says company founder Steve Danyluk, Lt. Col (retired), Marines. “A substantial number of people do not want any THC in their product, which is the reason why the isolates remain popular. However, anecdotal evidence suggests that there are many benefits found in the full spectrum products where trace amounts of the 100+ cannabinoids found in the plant can interact and form what is commonly referred to as an ‘entourage effect.’”

12) Synthetics are sneaking in. “Now we have synthetic CBD out there that can be made more cheaply than extracting it,” laments Myers. “Now we have to deal with yet another compound that does not exert the kind of health activity that you get from the full balance of phytonutrients.”

Maru seconds the concern. “The marketplace is being flooded by synthetic isolate CBD which should be avoided at all cost. Research suggests that full spectrum CBD with its vast array of cannabinoids, terpenes and other phytonutrients is superior and more efficacious. We believe whole plant full spectrum hemp that is processed using a clean method such as water extraction is the very best way to get your CBD.” Planted Earth, he adds, offers a quick-dissolve powder with MCT that provides 10mg CBD per serving, along with a CBD liquid 25mg, and 15mg and max potency 25mg capsules, “all of which are powdered by our proprietary EZsol technology which micronizes and emulsifies our CBD for enhanced solubility and absorption.”

13) Consumers may confuse hemp stock and hemp seed. “There are no cannabinoids in hemp seed oil,” says Myers, adding that Europharma’s Hemp Select hemp oil line uses hemp seed oil as a carrier because it has omega-3s in it. “We like to provide a product exclusively from the plant. But for the companies selling hemp seed oil on its own, it has healthy plant-based omega-3s, but does not have any cannabinoids whatsoever. A lot of times consumers are confused because hemp seed oil is very inexpensive, whereas full spectrum hemp stock oil is not inexpensive.”

Hemp History Week!

Hemp Industries Association (HIA) and the hemp industry community celebrate the 10th annual Hemp History Week, June 3-9. During the campaign, natural product retailers, hemp advocates and HIA chapters across the country were set to host over 1,500 unique grassroots and retailer events, featuring educational components, hemp product sampling, speakers, documentary screenings and a letter-writing campaign, as well as community outreach at farmers’ markets, state lobbying days and spring plantings. “This is our opportunity to further illustrate that hemp is not just a counterculture novelty but a mainstream commodity,” said Colleen Keahey Lanier, executive director of HIA. “This Hemp History Week, we come together in support of hemp farmers, in support of healthy, American-made products, and in support of a more sustainable future.” Sponsors include Bluebird Botanicals, Dr. Bronner’s, Manitoba Harvest, Nutiva, PlusCBD Oil and Prana Principle.

14) Cannabis-free phytocannabinoids also deliver benefits: “Until recently, it was believed that only hemp and cannabis could activate the ECS, however scientists have discovered other plants containing phytocannabinoids with the same ability to support this critical system,” Beutler says. With this understanding, he adds, the Scientific Advisory Board at Emerald Health Bioceuticals “identified six powerful cannabis-free phytocannabinoids from a 4,000 plant meta-analysis to create our proprietary PhytoCann Complex. This science-backed, doctor-formulated blend of herbs and botanicals including echinacea, peony, magnolia, clove oil