The Entourage Effect, Cannabis, and You

Cannabis and its constituents have been revered across time and culture. No doubt do to its versatility in use as medicine, textile, food, and ritual. All of these things would be impossible without the large host of terpenes and cannabinoids. Cannabinoids are oils formed by many plants but there are many specific only to cannabis. Terpenes, however, are responsible for all smells in nature. This is because, all plants, many fungi, and even some insect release terpenes into the air. The cannabis plant produces possibly more than 400 different cannabinoids, each with its own unique set of properties.

This fascinating herb also produces anywhere between 100 to 200 different terpenes. So now that we have established what both cannabinoids and terpenes are; why exactly does this majestic plant create these amazing compounds? These compounds are produced for a variety of reasons. They act as antibiotics, preventing pathogenic molds and mildews from taking hold on the surface of the plant. They are also useful for deterring pests and attracting beneficial insects.

Endocannabinoids

Now, why would we care about these smelly oils you might ask? These oils just so happen to be synergistic with the human body and have a ton of health benefits!  Cannabinoids, in particular, have been part of a unique co-evolution with humanity. Endocannabinoid receptors or Endogenous Cannabinoid receptors line our entire body. Endogenous being a fancy word meaning: Originating or produced within an organism. Your body synthesizes endogenous cannabinoids just like cannabis plants produce phytocannabinoids Phyto meaning produced by a plant!

Anandamide or AEA for short is one such endogenous cannabinoid. AEA is often called the bliss molecule and is responsible for a huge number of bodily functions. A few of these functions are stimulating appetite, giving you feelings of blissful happiness and making you sleepy. Sound familiar? That’s because AEA is essentially endogenous THC. Yeah, you heard me right, your body produces an endogenous version of THC!

There are two types of endocannabinoid receptors in the body CB1 and CB2. CB1 receptors are found primarily in the central nervous system and the brain. However, CB2 receptors are found in your immune cells and lymphatic system. The fact that our bodies produce cannabinoids just like cannabis explains why it is such a potent herb! When terpenes and cannabinoids combine we get what is called the entourage effect or the ensemble effect. In short, the entourage effect describes how cannabinoids and terpenes work together to complement each other’s health benefits.  Raphael Mechoulam “the father of cannabis” and the man who discovered cannabinoids coined the term entourage effect in 1998. The term resurfaced in 2011 when another team of researchers utilized the term again. They used the term in a comprehensive comparison of cannabinoids and terpenes [1][2]

Chemical and Enzymatic Production of Cannabinoids

Next, I would like to give a brief rundown of how cannabinoids are synthesized. It all begins inside of very small hairs on the cannabis flowers called trichomes. All cannabinoids are formed through various chemical and enzymatic reactions inside trichomes. This process creates a diverse spectrum of cannabinoids. Now there are three precursor molecules and they are geranyl pyrophosphate (GPP), divarinic acid (DVA), and olivetolic acid (OLA). So as GPP reacts with either OLA or DVA, cannabinoid mother compounds are produced.

The first two synthesize cannabigerolic acid (CBGA), and the latter stimulates the production of cannabigevarolic acid (CBGVA). Once that has taken place a series of enzymes break CBGA and CBGVA into three main cannabinoids. CBGA is converted into Cannabidiolic Acid (CBDA), Tetrahydrocannabinolic Acid (THCA),  and Cannabichromenic Acid (CBCA). CBGVA gets broken down in similar ways but gives yield to Cannabichromevarinic acid (CBCVA), Cannabidivarinic Acid (CBDVA), and Tetrahydrocannabivarinic Acid (THCVA). [1] The fact that all these cannabinoids form from the same molecules explain how their interactions form the entourage effect. Each cannabinoid bringing a unique piece of the puzzle.

Stabilizing Through Decarboxylation

 The part of the process that is most important to take note of is that the cannabinoids at this stage are all acids. These acids aren’t very stable, so to become stable, they undergo decarboxylation to lose a carbon dioxide molecule (CO2) and a hydrogen atom (H) to become a more neutral and therefore stable compound. In chemistry when CO2 and H atoms bond it forms a carboxyl group, the reaction that removes this group is called decarboxylation.

Now when decarboxylation takes place THCA becomes ∆9-THC (Delta-9 Tetrahydrocannabinol) the cannabinoid that is known for its psychoactive effects on users generally when referring to THC this is the compound being discussed. Adversely CBDA converts to CBD (Cannabidiol) this is the compound found in high concentrations in our 1000mg Full-spectrum tincture and is the major cannabinoid found in hemp. The diagram above shows the conversion from mother compounds into full-fledged cannabinoids, while this table makes sense of the hectic amount of acronyms present in this article. [1]

Terps and Terpenes

Terpenes or terps for short are the next constituents we will be talking about. As previously stated these are the oils that make up the aroma of basically everything in nature. These oils are very potent and can be active in our bodies in concentrations as small as ng·kg−1. There are more than 20000 fully characterized terpenes. Cannabis expresses over 200 of them. A few of the terps we will be highlighting are the monoterpenes MyrceneLimonene, and Pinene. A monoterpene is a precursor in the production of many other terpenes and terpenoids.

Limonene!

Let’s start with Limonene! The peels of citrus fruits contain high levels of Limonene. Being one of the most abundant terpenes found in nature, A-Limonene is what gives lemons their distinct smell. D-limonene is responsible for the smell of oranges, and B-limonene is responsible for limes’ distinct differences.

Several studies with citrus oils and mice show that limonene has powerful anxiolytic properties, meaning that it reduces anxiety! In one study, they found that citrus essential oil increased serotonin in the prefrontal cortex and dopamine in the hippocampus. Very Compelling data from clinical studies verified this finding in humans. Citrus oil, diffused near depressed hospital patients caused normalization of Hamilton Depression Scores. 9/12 patients exposed were then able to discontinue antidepressant medications. Researchers also observed immune system stimulation.  “The treatment with citrus fragrance normalized neuroendocrine hormone levels and immune function and was rather more effective than antidepressants.” [1]

These results are no doubt partially because limonene is highly bioavailable to humans with up to 70% pulmonary uptake. It also behaves as a metabolite in the human body. A few other very cool functions of limonene are, it causes apoptosis in breast cancer cells. Limonene has been patented for use in relieving gastro-oesophageal reflux. Citrus essential oils mimicking those in cannabis demonstrate strong free radical scavenging properties. Frankincense, celery, dill, sage, and all citrus fruits contain Limonene.

Myrcene

Next up Myrcene! This amazing monoterpene has a myriad of different actions including diminishing inflammation and relieving pain (analgesic). Employed as a sleep aid in Germany, since it is a sedative that combines with THC for the “couch-lock” effect. My favorite example of the entourage effect between terpenes and cannabinoids is that myrcene thins the blood-brain barrier. Meaning that myrcene compliments any and all of their effects as well as increases therapeutic potential.

Another function of myrcene in the body is that it inhibits certain metabolic pathways. These pathways are responsible for inflammation effectively reducing it and no doubt lending to its analgesic (pain-relieving) properties. It can block the development or tendency to cause liver cancer (hepatic carcinogenesis) from aflatoxin exposure. Some strains of aspergillus fungi produce a deadly mycotoxin called aflatoxin. Mangoes, bay leaves, hops, eucalyptus, and lemongrass all contain Myrcene. [1]

Benefits of Pinene

Pinene like Limonene is highly bioavailable. This terpene is rapidly metabolized and redistributed through the body. Showing up to 60% pulmonary uptake in humans. Found in all coniferous trees pinene is the most abundant terpene in nature. However, It is also present in many culinary herbs and innumerable other plants as an insect repelling agent. Pinene shows efficacy as a powerful antibiotic. Likewise, Pinene has also shown high activity in the treatment of MRSA. [1]

This amazing terpene is also highly active against Propionibacterium Acnes bacteria one of the main causes of acne. As a matter of fact, its power as an anti-inflammatory is no doubt why it is so effective against skin conditions! Pinene is a powerful gastroprotective agent. Pinene reduces the volume and acidity of gastric juices and increases gastric wall mucus. Also, another study has shown pinene to be a potential aid in the treatment of schizophrenia. Rosemary, basil, parsley, and all coniferous trees contain Pinene.[1]

Bring In The Entourage Effect

Alright, alright, alright! I will now discuss a few of the fun combinations of terpenes and cannabinoids that demonstrate the entourage effect. This Symphony of interactions is present in every plant we humans use even food. Let’s just jump right into one of my favorite cross-species entourage effects between delicious mangoes and cannabis!!! Mangoes contain a decent amount of myrcene, and its ability to open your blood-brain barrier combines amazingly with cannabis.

Eating a mango 45 minutes before consuming cannabis will increase the speed of onset. Moreover, this interaction will intensify the overall therapeutic effects of the THC and other major cannabinoids and terpenes. Basically, myrcene is like the key that opens your blood-brain barrier to allow all the other goodies easy access. Combine this with Cannabidiol or CBD’s potential to reduce b-amyloid. Beta-Amyloid is the plaque that causes Alzheimer’s. Meaning that a high CBD strain containing myrcene is a potential treatment for the prevention and alleviation of Alzheimer’s symptoms. Myrcene coupled with the effects of caryophyllene, limonene, pinene, and linalool could offer great relief to those affected by Alzheimer’s.

The essential oil of Sideritis Erythrantha and Salvia Rosifolia containing high amounts of pinene are highly effective in combating MRSA. CBN has a highly sedative effect. This cannabinoid is more prominent in older cannabis samples as THC oxidizes into CBN. CBN can be an anticonvulsant and anti-inflammatory when combined with THC. CBN also increases stem cells in bone marrow suggesting promotion of bone regeneration and also showed high activity against MRSA. So in essence, pinene, CBN, and CBGs’ antibiotic properties; coupled with myrcene and caryophyllenes skin softening may yield a potent and safe topical antibiotic!

More Entourage Effect!

We all know THC gets a bad reputation for causing memory loss in those who consume high levels. However, Pinene improves memory by actively blocking certain enzymes. Also, the short term memory deficit often caused by THC can be halted and reversed with CBD. A-pinene and CBD also both act as anxiolytic agents meaning they have been shown to reduce anxiety.[1][2]

Over the centuries there have been a few “cures” to THC overdose. One of which is Calamus root a plant that contains β-asarone an enzyme inhibitor similar to pinene. Another reported cure for the undesirable effects of THC Lemons due to high levels of limonene. So, in theory, cannabis with balanced THC to CBD and high a-pinene content could help improving memory deficit. In combination, this should increase overall therapeutic effects while reducing memory loss and anxiety. Other cannabis-specific terpenes that also display sedative and anxiolytic effects are β-Caryophyllene, Limonene, Linalool, Myrcene, a-Pinene, Phytol, a-Terpineol, and Terpinolene.

Let’s Wrap This Joint Up!

So far we have learned some of the interactions that take place in your body between terpenes and cannabinoids. Isn’t it impressive how many ways it can be a beneficial addition to your everyday health regimen? More research is needed to fully understand the mechanisms by which these compounds function. However, we can tell that terpenes and cannabinoids have promising therapeutic benefits especially when you factor in the entourage effect. These compounds could also provide relief from, or aid in the efficacy of many other drugs in today’s society.

A special thanks to Raphael Mechoulam for coining the term entourage effect. I can’t think of a better way to describe the symphony of interactions that takes place when you consume cannabis. Cannabis gets a bad rep but it is quite obviously a plant with many uses. Not to mention we haven’t even touched on textiles, but that for another blog. Until next time thanks for stopping by! I hope you have a better understanding of cannabis and the entourage it brings with it to the party. Hopefully, the next time you hear someone talking down about this amazing plant you can explain some of the benefits. Or skip the hassle and send them here so they can learn more themselves.

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