The Entourage Effect and Whole Plant Extracts: A Patient’s Guide
You’ve more than likely heard of THC and CBD – tetrahydrocannabinol and cannabidiol, respectively. Maybe you’ve heard them discussed on the news, seen them listed as ingredients in cannabis oils, or discussed them yourself. You’ve likely learned that the two compounds are primarily responsible for the various effects of cannabis; that THC and CBD provide therapeutic relief for a range of medical conditions. This is certainly true, but it’s nowhere near the whole picture.
Aside from THC and CBD, we know that there are as many as 112 other cannabinoids that provide therapeutic benefits. What’s most interesting, though, is the synergy between these cannabinoids and the hundreds of other chemicals found in cannabis. The interaction of these chemicals is called the “entourage effect.” The entourage effect has sparked the use of whole plant extracts in cannabis oils and analgesics intended for pharmaceutical use. Stay tuned, we’ll get to that soon.
It is true that THC and CBD are the compounds responsible for the most therapeutic effects of cannabis, so it’s understandable that pharmaceutical companies out to create patentable medicines would isolate them. Just as morphine was isolated from opium poppies and cocaine from coca leaves, both THC and CBD have been singled out for use in medicines. However, many researchers, including Raphael Mechoulam – the Israeli scientist who determined the structure of CBD and first isolated THC – believe that all components of cannabis provide some therapeutic effect. While we don’t know exactly what each compound contributes, there is compelling evidence that these compounds work better in tandem than in isolation.
Synergy and the Entourage Effect
Raphael Mechoulam and colleague Shimon Ben-Shabat proposed the concept of the entourage effect in a paper published in 1999. Mechoulam said, “Investigations of the effect of the active component in the presence of its ‘entourage’ compounds may lead to results that differ from those observed with the active component only.” Simple: the effects of cannabis are shaped by the interplay of the various chemicals found within the plant.
Researchers have identified over 400 different chemicals in cannabis. More than 100 of these chemicals are cannabinoids (the group that includes THC and CBD). But there are many other compounds found in the plant, including nitrogenous compounds, amino acids, ketones, and terpenes, among others. Recent research suggests that the synergistic effects of the compounds in cannabis – with terpenes in particular – often counter the less-desired effects of cannabis. For example, linalool, a terpene found predominantly in lavender, helps reduce anxiety induced by THC.
Ethan Russo described interactions between terpenes and cannabinoids to counter a host of conditions, such as pain and inflammation, insomnia, epilepsy, depression and even cancer. One study demonstrated the use of an essential oil created from black pepper reducing nicotine cravings in cigarette smokers. Black pepper is high in the terpenes myrcene, pinene and caryophyllene – so is cannabis. It stands to reason that cannabis oils or flowers could yield similar results.
This position has given rise to designer extracts – cannabis oils tailored to replicate particular therapeutic effects of cannabis. This calls to mind the practice of nutrients from vegetables, like in the case of Vitamin C supplements. But as any nutritionist will tell you, you’re better off eating broccoli than taking supplements to replicate the nutritional benefits. Research suggests that the same applies to cannabis. That brings us to the next point; whole plant extracts.
What is the Entourage Effect?
Ever heard of the phrase “the whole is greater than the sum of parts?” Well, this phrase that was coined by the famous Greek philosopher has some applications in plant medicine. The phrase “entourage effect” was popularized by a founding father of cannabis as medicine called Dr. Ethan Russo. Russo described how different compounds in hemp and cannabis work synergistically to produce a powerful and sustained therapeutic effect that is greater then what would have been produced if the units were working individually. This is what forms the basis of full-spectrum cannabis.
The Mechoulam-led study of 2014
The core idea of cannabis synergy was first discussed by Dr. Robert Mechoulam in a paper that was published in 1998. However, the term cannabis synergy was coined in 2011 by another founding father of medicinal cannabis- Dr. Ethan Russo.
In 2014, a team of researchers from the Hebrew University of Jerusalem led by Dr. Mechoulam conducted a study that demonstrated the superiority of full-spectrum cannabis extracts over pure cannabinoid isolates. The study was titled:
“Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol.”
It had been observed that pure cannabidiol extracts formed a bell-shaped response curve where the CBD benefits would taper off after hitting a certain climax. At this point, no additional benefits are appreciated in spite of more cannabidiol being consumed.
The Mechoulam led study demonstrated that a full spectrum extract was able to overcome this plateau effect. The result was a sustained and stronger therapeutic effect.
What Is Cannabis Synergy?
Cannabis synergy defines the interaction between cannabinoids, terpenes, and flavonoids in the cannabis plant to produce a stronger and longer-lasting therapeutic effect. If these terms are strange to you, here is a brief breakdown:
Cannabinoids: The cannabis plant has over 140 known cannabinoids. Cannabinoids are the compounds that give cannabis the beneficial effects that we know it for. The most popular cannabinoid is tetrahydrocannabinol, or THC, which is responsible for the psychoactive properties of weed. The other popular cannabinoid is cannabidiol, or CBD, which offers therapeutic effects without causing the typical marijuana high. Arguably, CBD is the emerging poster child of medical marijuana.
Terpenes: There are over 200 terpenes present in the cannabis plant. These compounds are responsible for the unique scents in cannabis and other plants as well. They also offer significant therapeutic benefits.
Flavonoids: There are at least 20 flavonoids present in the cannabis plant. Flavonoids give color to plants, for example, anthocyanin is responsible for the purple color in Purple Kush. They also play a key role in boosting cannabis synergy.
When these three are mixed in a product the healing effect produced, say anxiety relief, will be appreciated for a longer time. Also, it will take a smaller dose of the product to achieve significant relief. These are the benefits of cannabis synergy.
What are Whole Plant Extracts and Why Should I Care About Them?
Whole plant extracts are, well, exactly what they sound like. Instead of synthesizing or isolating active compounds, growers are breeding plants to have high concentrations of specific compounds. The extracts from these plants make for effective medicinal cannabis oils and analgesics. Dr. Sanjay Gupta says, “Unlike other drugs that may work well as single compounds, synthesized in a lab, cannabis may offer its most profound benefit as a whole plant, if we let the entourage effect flower.”
A 2015 study by researchers in Israel showed the superior anti-inflammatory and pain reducing effects of CBD-rich whole plant extracts over pure, single-molecule compounds. The researchers attributed their results to the entourage effect of CBD with other chemicals in the plant.
We don’t yet understand all the ways chemicals in cannabis work together, or how they interact with the human body. We know that certain compounds, in combination with cannabinoids, produce the various effects of cannabis. However, we don’t know that other chemicals in the plant aren’t contributing to or improving these effects. Take for example limonene, a terpene found in lemons as well as cannabis. In combination with CBD, limonene is an effective antidepressant. It seems logical to isolate limonene and CBD to create an antidepressant medicine. The science, however, suggests that whole plant extracts are more effective – the whole is more than the sum of its parts. That brings us to the next important bioactive molecule in cannabis namely terpenes.
Terpenes and the Entourage Effect
You may be thinking that using whole plant extracts instead of designer concentrates diminishes the ability to emphasize certain synergies. Russo’s answer to this: is selective breeding, focusing on the desired terpene. Growers have graduated from selectively breeding only for THC and CBD content to emphasizing terpene concentration. Researchers and growers alike see terpene-rich whole plant extracts as the future of medical marijuana. Don’t fall behind – opt for whole-plant cannabis.
Terpenes can help determine effects the plant might have when used. Lavender has been used for its calming effect for years. Linalool main ingredient is also found in Some Hemp.
What are Terpenes?
Terpenes are a fragrant, diverse group of organic compounds that are found all throughout nature. There are over 200 terpenes that exist in nature and hemp plants are just one of many plants that create terpenes.
Terpenes are responsible for the unique scents that are found in cannabis. For example, myrcene which is the most abundant terpenes produces a grassy scent which is common in most hemp and cannabis strains.
Terpenes, just like cannabinoids, have therapeutic potential. Researchers are now looking into how this potential can be harnessed to support cannabinoid-based therapies.
Myrcene
This is the most abundant terpene in most cannabis strains. It accounts for almost 60% of the terpene profile of indica strains. It produces a strong herbal and musky aroma.
- Aids digestion
- Anti-fungal
- Reduces inflammation
Pinene
This terp is found commonly in cannabis as well as in pine tree’s. It has a pine-like aroma.
- Increase focus
- Anti-bacterial
- Bronchodilator
- Anti-inflammatory
Linalool
Commonly found in lavender and has a floral aroma. It is often identified for its relaxing & calming aroma.
- Relieves pain
- Promotes sleep
- Reduce stress
- Sedating
Other common terpenes in cannabis include the following:
- Beta Caryophyllene
- Limonene
- Terpineol
- Humulene
- Terpinolene
- Valencene
- Bisabolol
- Camphene
- Phytol
- Carene
- Pulegone
- Eucalyptol
- Phellandrene
- Sabinene
- Ocimene
The Whole Is Greater Than the Sum Of Parts
What happens when all these compounds come together? You get a full-spectrum hemp extract. Earlier on it was believed that CBD acting alone would produce stronger healing effects. However, some later studies showed that the reverse is true. When terpenes, flavonoids, and extra cannabinoids are combined the healing effect produced is more powerful and lasts for longer. Therefore, the effect is not equal to the sum of parts but greater than the sum of parts.
This was illustrated clearly by a study conducted by the University of Jerusalem in 2015. This study demonstrated that when CBD is administered alone, the effects plateau after hitting a certain climax. Further administration of CBD does not lead to greater effects. However, when a full-spectrum extract is used, the effects overcome the plateau effect and become stronger and more sustained. By now you should know that this is what is referred to as the entourage effect.
What Kind of CBD Oil Should I Choose ?
CBD oils are usually made up of a hemp extract (CBD) and a carrier oil. They can also come with other ingredients to provide higher bioavailability than other CBD forumations.
The difference between broad spectrum, full spectrum and CBD isolate is simply the chemical compound content found in each of the products. Full spectrum CBD contains all of the cannabinoids and other plant compounds. When referring to CBD,this refers to other cannabinoids and terpenes.
In a nutshell.
Broad spectrum CBD contains all cannabinoids and plant compounds other than THC. CBD isolate only contains CBD and is often found in crystal or powder form. Full spectrum CBD contains a mix of cannabinoids (THC included) and terpenes. However, full spectrum CBD MUST contain less than 0.3% THC.
Isolate CBD oil
CBD isolate is a great way to consume a high amount of CBD. CBD isolate is an all-natural cannabinoid supplement made from the process of isolating the CBD out of whole plant extract. This process removes the remaining oils, wax, chlorophyll and other plant compounds, like other cannabinoids (THC) until you are left with CBD refined to the highest level of purity
Full Spectrum CBD oil
Full Spectrum products contain not only CBD but other cannabinoids + terpenes that naturally occur in the hemp plant. These include but are not limited to Cannabigerol (CBG), Cannabinol (CBN), Cannabinol (CBN), and trace amounts of Tetrahydrocannabinol (THC). Each of these cannabinoids offers different therapeutic benefits and when combined create an entourage effect. Full spectrum oil is most effective in more severe or advanced ailments such as excessive inflammation and major stress.
Broad spectrum CBD oil
Broad Spectrum, like full spectrum oils, contains CBD plus some combination of terpenes and cannabinoids. Importantly, broad spectrum oil should always contain zero THC. These products are therefore a great compromise for consumers who want to enjoy a good range of cannabis compounds, but never to be exposed to even small amounts of THC.
Nano CBD oil
CBD is lipophilic; it does not mix with water naturally. This affects how CBD is absorbed in the body. The CBD space is embracing different technologies to get past this hurdle, and nanotechnology is one of them.
Nanotechnology breaks down the CBD into nanoparticles. By shrinking the CBD particle down it makes it small enough to blend with water molecules, making it 4-7x more bioavailable than Other CBD Oils.
Our bodies are made up of water and thus some intervention is required for effective CBD absorption. In short, nano CBD hds (CBD) is produced when the plant grows and is found primarily in the bud, leaves and stems. As the hemp plant grows it becomes more susceptible to disease and infection. When this occurs the plant triggers the release of CBD to protect itself. This is the plant’s natural defense against viruses, bateria/bugs and even UV rays.
Every time we consume CBD Oil, we are borrowing the plant’s personal medicine cabinet for our own therapeutic purposes. Science is making great strides in understanding the CBD Oil by the day. These discoveries are poised to revolutionize how modern human and animal medicine is practiced in the 21st century.
Is hemp oil the same thing as CBD oil?
As much as hemp seed oil is nourishing, it’s not the same thing as CBD oil. CBD Oil is extracted from the leaves, buds and stems of the hemp plant. On the other hand, hemp seed oil is extracted purely from hemp seeds. Phytocannabinoids are found in the buds, leaves, and stems of hemp but not the seeds. Therefore, hemp seed oil does not have any cannabinoids. In other words, hemp seed oil is free of CBD.
Will Full-spectrum Hemp Oil Make Me high?
Full-spectrum hemp oil will not make you high. This is because it contains negligible amounts of THC (always less than 0.02%). Cannabis strains that cause psychoactive effects usually contain over 10% THC. So the amount of THC, if any, in full-spectrum hemp oil never cuts the threshold for causing a change in mental status.
For all its goodness, there are many complex things about the cannabis plant. The journey towards understanding this plant has brought us to many exciting spaces, cannabis synergy is just one of them. This simple discovery gave us an about-turn in our understanding of cannabis and even transformed the cannabis marketplace. Sure enough, most CBD companies dropped their isolates in favor of the new trend: full spectrum products.
The Rise And Fall Of Cannabis Isolates
If you have gone through the product catalogs of most cannabis businesses you will notice that full-spectrum products are being given greater coverage as compared to isolates. This reflects on what the companies believe to be superior and also what the customers are asking for.
A few years back, this was not the case. Companies would go the extra mile to refine their cannabinoids (cannabidiol and tetrahydrocannabinol) to come up with a pure extract. Creating a pure extract means peeling off other cannabinoids, terpenes, and flavonoids from the extract to achieve an isolate with 95%-99% purity levels.
For a long time, pure isolates were the in-thing because they offered higher levels of a particular cannabinoid. It was imagined that a CBD isolate with 99% purity levels would do a better job at knocking out that pain, stress, nausea, etc as compared to a full-spectrum extract. However, somewhere in the late 1990s, a few scientific discoveries changed the way the world views cannabis isolates.
What Is The Difference Between Full-Spectrum And Broad-Spectrum Cannabis Extract?
Both broad-spectrum and full-spectrum cannabis extracts offer synergy benefits. The only difference that exists between the two is the presence or absence of THC.
Broad-spectrum CBD contains a mix of cannabinoids, terpenes, and flavonoids but lacks THC. Full-spectrum CBD contains a mix of all cannabinoids, terpenes, and flavonoids-plus THC.
THC has psychoactive properties meaning that it causes an alteration of mental status. Because of this, THC is outlawed in many states, only 11 states have allowed recreational use of marijuana. Following, some CBD companies prefer to completely exclude THC when creating synergy focused CBD products. The result is a broad-spectrum product.
A Few Applications Of Synergy
What happens when you mix CBD with THC?
We still don’t have the full picture of how CBD interacts with cannabinoid receptors. However, a few studies have shown that CBD can mitigate the psychoactive effects of THC by displacing it from the CB1 receptor. This means that taking a full spectrum containing both THC and CBD will give stronger healing effects with less psychoactive effects.
What happens when you mix Myrcene with CBD?
Myrcene is the most abundant terpene in most cannabis strains. It gives cannabis that earthy, musky, or skunky scent.
CBD relieves pain, fatigue, stress, and any other symptom that may cause insomnia. Myrcene, on the other hand, has direct sedative effects. A full-spectrum extract with both myrcene and CBD will have enhanced sedative benefits.
References
- Larsen, C., & Shahinas, J. (2020). Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials. Journal of clinical medicine research, 12(3), 129–141. https://doi.org/10.14740/jocmr4090
- Gallily, R. , Yekhtin, Z. and Hanuš, L. (2015) Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy, 6, 75-85. doi: 10.4236/pp.2015.62010.
- Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M. H., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V., & Mechoulam, R. (1998). An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European journal of pharmacology, 353(1), 23–31. https://doi.org/10.1016/s0014-2999(98)00392-6
- Russo E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British journal of pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x
- Pertwee R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British journal of pharmacology, 153(2), 199–215. https://doi.org/10.1038/sj.bjp.0707442
