The “Entourage Effect”: How Terpenes Can Intensify CBD’s Healing Power
Israeli scientist Raphael Mechoulam has made studying cannabis his life’s work.
Starting out as a young postdoctoral student in the 1960s, his research has spanned decades and produced some of the world’s most influential studies on cannabis.
For example, in 1963 he determined the structure of cannabidiol (CBD), the non-psychoactive component in cannabis that is now being regarded as the new wonder drug of our times.
A year later, he became the first person to isolate delta-9 tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana.
Over the next 50 plus years, the now 80-something Mechoulam was able to isolate numerous compounds from the cannabis plant with his research teams. The cannabis plant, known as Cannabis Sativa, contains over 480 chemical compounds of which over 80 are terpenophenolic compounds called cannabinoids. Cannabinoids are the chemical compounds that provide relief to an array of symptoms including pain, nausea, and inflammation. These compounds can imitate the compounds our bodies naturally produce, called endocannabinoids, which activate to maintain internal stability and health.
According to a report by CNN medical correspondent, Dr. Sanjay Gupta, “(Mechoulam’s) work also went a long way toward illuminating how the drug works in the brain. When Mechoulam’s team identified the first known endogenous cannabinoid, a chemical actually made by the brain itself, he named it “anandamide.” In the Sanskrit language, ananda means “supreme bliss,” which gives us some insight into what Mechoulam thinks of cannabinoids overall.”
But although Mechoulam’s research has produced groundbreaking studies into the medicinal qualities of cannabis, one of his most important discoveries is what’s known in cannabinoid science as the “entourage effect”.
An Entourage Effect: The Power Of Whole Plant Cannabis
In a combined study with researchers from Israel and Italy that was published in 1998, Mechoulam and his team discovered that the healing power of a binding molecule called 2-Arachidonylglycerol was increased when combined with related chemical compounds. More importantly, they also discovered that these compounds showed no significant activity when they were tested alone.
In other words, Mechoulam and his team discovered that these compounds – while not special when tested alone – worked synergistically when they were combined to intensify the healing power of the binding molecule. After this revelation, Mechoulam coined the term the “entourage effect”.
So far, no one has really figured out the exact role or mechanism these various compounds play in producing the entourage effect. Perhaps multiple individual compounds play a role. Or maybe compounds interact in certain ways inside the body. Or perhaps it’s a combination of both.
But similar to how eating whole foods like meat, fruits and vegetables will provide better nutrition than taking protein supplements and multivitamins, we’re learning that whole plant preparations of cannabis are more therapeutically beneficial for the human body than just isolated compounds.
Of course, that implies that finding the right combinations of compounds could be a way of supercharging the healing power of cannabis.
Terpenes and CBD: A Potent Combination
The entourage effect has been shown to enhance the healing power of certain cannabinoids when taken as a whole instead of in isolation. The combination of terpenes and CBD oil in particular could be one of the most powerful pairings found in cannabis.
Terpenes are potent, aromatic, naturally occurring hydrocarbons which are primarily found in the essential oils of a variety of plants. They often have a strong odor and play a vital role in the plant kingdom.
In cannabis plants, they deter herbivores with bitter sesquiterpenoids, repel insects with monoterpenes such as limonene and pinene, and attract predators and parasites of herbivores. The combination of mono- and sesquiterpenoids determine the stickiness of cannabis which can trap insects.
Closely related to terpenes are terpenoids which are terpenes that have been chemically modified. The two terms are often used interchangeably. There are over 200 reported terpenoids found in cannabis.
Because terpenes are flavor and fragrance components common to humans, they have unique therapeutic effects that may contribute to the entourage effects of extracts like CBD on the human body. This is especially true when considering treatments for pain and inflammation.
For example, the cannabis plant produces the terpene β-caryophyllene which is generally the most common sesquiterpenoid. β-Caryophyllene selectively binds to the CB2 receptor and acts as a full agonist (or stimulant). This terpene is commonly found in black pepper, cinnamon, clove, and other spices.
Orally administered β-caryophyllene has been shown to produce strong anti-inflammatory and analgesic effects. It also helps with reducing neuropathic pain, and promotes an immune response that plays a critical role in neuroinflammation, sensitization, and pain. In cases of difficult-to-control pain, combination therapy that includes non-psychoactive cannabinoid receptor agonists like β-caryophyllene may provide better relief than with just cannabinoids alone.
Other terpenoids that could produce an entourage effect include:
- d-limonene, found in the lemon and other citrus essential oils, is the second most widely distributed terpenoid in nature. Studies suggest it to be a powerful anxiolytic (anxiety-inhibiting) agent that can increase serotonin and dopamine in the brain. The citrus fragrance has also been shown to help improve depression and reduce the dependency on antidepressant medication. Limonene produces cell death of breast cancer cells, produces anti-stress effects in brains, treats gastro-esophageal reflux, is effective against dermatophytes (a fungus that causes ringworm), and has strong radical scavenging properties (antioxidant).
- β-Myrcene is another common monoterpenoid in cannabis. It has been shown to diminish inflammation, and block the formation of cancer in the liver by cancer causing chemicals. Myrcene has analgesic, sedative, and muscle relaxant properties and is a prominent sedative terpenoid in cannabis.
- α-Pinene is a bicyclic monoterpene and the most widely encountered terpenoid in nature. It plays an insect-repellent role and works as an anti-inflammatory and bronchodilator in humans. Pinene also seems to be a broad-spectrum antibiotic. Perhaps most compelling, however, is that it can help in improving memory.
- D-Linalool is a monoterpenoid alcohol, common to lavender. Linalool has anesthetic, analgesic, sedative, anxiolytic and anticonvulsant properties and is a powerful anti-leishmanial agent. Leishmaniasis is an infectious disease caused by parasites that can present with fever, low red blood cells, and enlarged spleen and liver.
- Nerolidol is a sesquiterpene alcohol found in orange and other citrus peels. It has sedative properties and could be helpful in treating fungal growth. Nerolidol also has anti-protozoal parasite control benefits and is a potent antimalarial and anti-leishmanial agent.
- Caryophyllene oxide is a sesquiterpenoid oxide found in lemon balm, and eucalyptus. It serves as an insecticidal/anti-feedant and as broad-spectrum antifungal. Fun fact, caryophyllene oxide is also how drug-sniffing dogs are able to identify cannabis.
- Phytol is a diterpene present in cannabis extracts. The presence of phytol could account for the alleged relaxing effect of wild lettuce (Lactuca sativa), or green tea (Camellia sinensis), despite green tea’s caffeine content.
How Terpenes Can Intensify CBD’s Healing Power
There are many potential combinations of different terpenes and CBD that can produce an entourage effect.
One possibility for synergy includes treatment for acne in which new acne therapies utilizing whole hemp oil extracts can be more therapeutic than single isolated compounds.
Other possibilities include treatment for depression, anxiety, insomnia, dementia, and addiction where there may be several possible therapeutic synergies and entourage effects with different combinations.
A phytocannabinoid-terpenoid preparation, such as a citrus scent (which has been shown to be effective for depressed patients) combined with CBD (a known antidepressant), could have an entourage effect for treating depression.
For anxiety, a combination that includes anxiolytic (anxiety-inhibiting) limonene and linalool could contribute to the clinical efficacy of CBD and boost its effectiveness for treatment.
For dementia patients with Alzheimer’s disease, the anti-anxiety and anti-psychotic effects of CBD are known to be beneficial. Researchers have found that CBD, when present in significant proportion to THC, can improve cognition and memory. CBD may also have primary benefits on reduction of β-amyloid in Alzheimer’s disease. Psychopharmacological effects of limonene, pinene and linalool could combine with CBD to help improve the mood in patients.
For insomnia, CBD is viewed as a potential treatment because of its anxiolytic properties. Meanwhile, terpenoids with pain-relieving, anti-anxiety and sedative effects may supplement such activity with caryophyllene, linalool and myrcene.
And finally there’s the exciting possibility for treating addiction. Drug addiction and alcohol addiction are chronically relapsing disorders characterized by the compulsive desire to use the substances and a loss of control over consuming the substances.
CBD has been shown to modify or control various neuron circuits in the brain involved in addiction and can exert an anti-addiction benefit and help prevent addiction relapse. CBD has shown promise in fighting addiction to cocaine, amphetamines, heroin, and nicotine.
Terpenoids also have anti-addiction properties as well. In a study with 48 smokers, researchers discovered that black pepper essential oils helped reduce nicotine cravings significantly. The terpenoids myrcene, pinene, and especially caryophyllene (through CB2 agonism) may have contributed to its effectiveness. When you take these factors into account, CBD extracts that contain caryophyllene, and possibly other terpenoids, could revolutionize addiction treatment in the future.
Readers’ Choice: CBD With Terpenes
As you can see, CBD and terpenes that work together through the entourage effect are much more powerful in treating a variety of conditions than single isolated compounds.
Although there is still a lot of research to be done, scientists like Raphael Mechoulam are steadfast in their beliefs that all the components of the cannabis plant likely exert therapeutic effects better as a whole plant – rather than in isolation.
That’s why for consumers, it’s important to look for whole plant CBD preparations with terpenes in order to get the full benefit of CBD’s healing power. Please view our CBD product reviews to find out which products are right for you.
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