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Terpenes and the entourage effect

Despite whole cannabis and hemp plant extracts typically containing a combination of over 400 different cannabinoids and terpenes, most research on the topic use either synthetic and/or single molecule cannabinoids. 


We know that many of these compounds work together synergistically to create an end result in which the individual effects and benefits of each molecule enhances the effects and benefits of the other compounds. This is what scientists are calling the “entourage effect”. 


The question then arises, what conclusions can we really draw regarding the data obtained from typical cannabinoid research that uses single molecule isolates? In other words, what impact does the entourage effect have on the efficacy of medical cannabis based medicines?

The entourage effect: cannabinoids and terpenes

Before delving into the entourage effect, let’s first take a look at the players involved in creating this synergistic effect - cannabinoids and terpenes.

Cannabinoids

The cannabinoids found in the cannabis plant each have their own set of potential benefits and therapeutic effects. The effects of each is primarily due to the way in which they interact with the endocannabinoid system (ECS) as well as how they modulate, bind to and affect the cannabinoid receptors located throughout our brain and body. 


For instance, THC’s effects mainly arise because it acts as a partial agonist for CB1 and CB2 receptors. This is the underlying cause behind many of its properties and benefits, including psychoactive analgesic, muscle relaxant, antispasmodic, neuroprotective, antioxidant, and anti-inflammatory properties. 


On the other hand, CBD has no binding affinity with either of CB1 or CB2 cannabinoid receptors. This accounts for its unusual pharmacological versatility and its ability to modulate the behavior of a variety of other, non-ECS receptors, genes and enzymes. 


Tetrahydrocannabivarin (THCV), an analogue and modulator of THC, is a powerful anticonvulsant and anti-inflammatory in addition to producing weight loss, decreased body fat and serum leptin concentrations. CBD’s analogue, cannabidivarin (CBDV), is also a powerful anticonvulsant, anti-inflammatory and analgesic. And cannabigerivarin (CBGV), CBG’s analogue, is thought to have analgesic and anti-inflammatory properties. 


Cannabichromene (CBC) is an anandamide uptake inhibitor showing pronounced antidepressant effects while cannabigerol (CBG) inhibits gamma aminobutyric acid (GABA) uptake suggesting that it has muscle relaxant, analgesic and anti-erythemic effects. 


Finally, CBN, a by-product of THC deterioration, is a powerful anticonvulsant, anti-inflammatory and antiviral agent that can help promote bone formation and inhibit breast cancer growth.

Terpenes

Terpenes are volatile, odiferous and oily compounds responsible for repelling insects, prevent fungal and bacterial infections as well as attract pollinators. There are around 200 terpenes found in the cannabis plant and is what gives different cannabis strains their unique smell characteristics. 


The most notable of these is beta-caryophyllene that binds directly to the CB2 cannabinoid receptor in the same way cannabinoids do. It is considered a promising therapeutic compound for inflammatory and auto-immune conditions as well as a great help in fighting neuropathic pain. 


Below is a list of some other common terpenes found in cannabis and a summary of their positive properties:

Terpenes

Properties


Limonene


Immunostimulant, anxiolytic, anti-bacterial, anti-cancer


a-Pinene


Anti-inflammatory, bronchodilator, aids memory


b-Myrcene


Anti-inflammatory, analgesic, hypnotic, muscle relaxant, sedative


Linalool


Anxiolytic, sedative, anaesthetic, analgesic, anti-convulsant


Nerolidol


Sedative, antimalarial, antimicrobial


Terpinolene


Anti-fungal, antibacterial, antioxidant

What is the entourage effect?

The first to speak of a potential synergistic effect between THC and CBD, was cannabinoid researcher Ethan Russo in the British Journal of Pharmacology. He recognized an entourage effect between cannabinoids as well as the various terpenes found in the cannabis plant. In his review of the potential benefits of using CBD with THC, Russo makes the case that CBD has the ability to tame many of the unwanted side effects (e.g. acute intoxication, anxiety and feelings of panic) of THC by modulating its psychoactivity.


Further support for the cannabinoid-cannabinoid entourage effect is when scientists investigated the effect of full-spectrum extracts vs CBD isolates on dose-responses. They found that when a CBD isolate was given to rats for the treatment of pain, dosages needed to steadily increase in order to remain effective, eventually reaching a ceiling of effectiveness. However, when a full-spectrum CBD oil was administered, the analgesic effect remained constant, without required dosage increases or ceiling effects.

A study on the effects of medical cannabis on human breast cancer cells showed that full-spectrum extracts were more effective in reducing tumor size than THC alone. The researchers theorized that this was due to the entourage effect and the presence of small amounts of other cannabinoids, such as CBG and tetrahydrocannabinolic acid (THCA). 


Likewise, in a study investigating the anticonvulsant effects of CBD, scientists compared the effects of five types of full spectrum extracts. Each of them contained the same amount of CBD but had different cannabinoid and terpene profiles. Their results mirrored those of previously mentioned research as they found significant differences between the effectiveness of each extract with regards to seizure development. 

Similar to synergies between cannabinoids, there is also evidence of a potential synergy between cannabinoids and terpenes. Research shows that a cannabinoid-terpene entourage effect can increase blood flow, hence enhancing cortical activity and kill antibiotic-resistant pathogens like MRSA. Similarly, it also has the potential to enhance the treatment of pain, inflammation, anxiety, depression, seizure disorders, fungal and bacterial infections. It can also buffer THC’s psychoactivity in combination with CBD. 


Scientists theorize that the cause of an entourage effect lies in the ability of each cannabis plant compound to act on different parts of the body in different ways and therefore to produce varying effects. However, at the same time, they also work together to enhance the benefits of each, especially with cannabinoid-terpene interactions. This is because some terpenes can assist cannabinoids in penetrating the blood-brain barrier that influences the amount of each cannabinoid that passes through that barrier.

Final thoughts on terpenes and entourage effects

The entourage effect is very real and makes a case for research scientists to investigate cannabis compounds holistically as well as in different combinations. This is the only way to fully understand the pharmacological effects of medical cannabis on different conditions. It is also a crucial step in developing truly and consistently effective phytopharmaceutical cannabinoid medications.

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