The Chemistry of Terpenes and cannabinoids synergy

The neighbor’s cannabis is always greener
May 17, 2021

The Chemistry of Terpenes

The set of chemical reactions that constantly occur in cells is called metabolism. Plant cell metabolism is related to the various chemical reactions that occur in plant cells. Through its metabolism, primary metabolites are produced, which are responsible for plant growth and development (amino acids, sugars and nucleotides) and secondary metabolites that have specific action and distribution (limonene, carotenoids and anthocyanins). Plants produce compounds that promote their protection against herbivores, some insects and fungi, and other substances that aim to attract certain pollinating insects.
Terpenes belong to a wide class of secondary metabolites. Also known as essential oils, they have been used for around 3500 years, with application in cosmetics, perfumes, solvents or raw materials for the production of paints, greases, waxes, and as sensory enhancers in foods. Terpenoids are molecules derived or modified from terpenes. Many terpenes are volatile, that is, they are easily released into the air and also perceived by humans through our nostrils, as well as those of other animals - hence the relationship of terpenes with the function of repelling or attracting animals, according to the needs of the plant. Terpenes are also aromatic oils that give plants a variety of flavors and aromas such as citrus, berry, mint and pine. They are secreted in glands, like trichomes, for example.

The benefits of Terpenes

Many studies have shown the use of essential oils, through aromatherapy, can result in excellent health benefits, especially in the reduction of anxiety and stress, two of the biggest problems in modern life. By vaporizing the aromatic essences of essential oils, the therapist is actually administering doses of terpenes to his patient. Despite their long history of use, research on the interaction of aromas and terpenes with each other and with other plant compounds and even their synergistic effects on the human body is recent. When interacting with each other, terpenes form different molecules, with different aromas, giving the famous variations in the smell and taste of flowers.
All terpenes are made up of the union of five carbon atoms, that is, basic isoprene structures (C5H8), which polymerize to form a variety of terpenes. Terpenes can be classified according to the amount of basic isoprene structures. Hemiterpene (C5) which, in addition to being an alkylating agent, is present in plant species such as chrysanthemum, in the form of pyrethrins; monoterpenes (C10) are found in essential oils or essences such as menthol, citral, linalool and aromatic oils; the sequiterpenes (C15) in α-bisabolol, α-humulene, β-farnesene and β-caryophyllene; diterpenes (C20) found in resins such as copaiba; the triterpenes (C30) precursors of α- and β-sitosterol, stigmasterol and phytosterol; tetraterpenes or carotenoids (C40), pigments present in various plants such as peppers, tomatoes, carrots and beets; and the polyterpenes (larger units) found in rubber tree latex.

How Terpenes affect the body

In the food area, the ingestion of terpenes such as carotenoids have physiological functional properties. β-carotene, α-carotene and β-cryptoxanthin are provitamin A. Many substances have a reducing action, reacting with free radicals and genotoxic and/or carcinogenic substances, in addition to making bonds with metals. They can reduce the risk of getting cardiovascular disease and macular degeneration. These factors indicate the great importance in promoting the industry and commercialization of terpenes. Some terpenes promote relaxation and stress relief, while others promote focus and acuity. A single plant species can produce over 100 different types of terpenes, and they also have the ability to interact synergistically with other plant compounds and even components of the human body. Terpenes can offer great additional medical value as they mediate our body's interaction, through our own endocannabinoid system, with therapeutic cannabinoids.
Terpenes bind to receptors in the brain and give rise to various effects in the body. In addition, each type of terpene reacts in a unique way with other molecules in the human body, changing the ways in which our bodies absorb other plant compounds and, consequently, causing various psychoactive and medicinal effects. Myrcene terpene, for example, can reduce resistance at the blood-brain barrier, facilitating the passage of other beneficial chemicals. Beta-caryophyllene, humulene and pinene have anti-inflammatory effects. Pinene helps to counteract the impairment of cognition and memory caused by THC. A combination of pinene, myrcene and caryophyllene terpenes has a direct effect in reducing anxiety. The mixture of linalol and limonene terpenes has shown beneficial effects in the treatment of some bacterial infections.

Other components of the Cannabis plant

In addition to terpenes, Cannabis also contains a number of therapeutically active compounds known as cannabinoids, including Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol (CBN). THC, CBD and CBN are the most researched and best-known cannabinoids. Of the three species of Cannabis studied, we have Cannabis sativa which has high levels of THC and low levels of CBD and CBN, Cannabis indica, which has medium levels of THC and medium levels of CBD and CBN, while Cannabis ruderalis has low levels of THC and high levels of CBD and CBN. THC is considered the primary psychoactive compound because of its analgesic, anti-inflammatory, appetite-stimulating and anti-emetic properties. CBD and CBN have beneficial properties of their own and also tend to inhibit some of the adverse effects of THC. The Cannabis plant is an essential source of full spectrum CBD extracts. There are believed to be over 200 different terpenes in the plant, each with a slightly different chemical structure and, as a result, a unique aroma and unique effect on the human body.

The entourage effect

Dozens of ways terpenes can impact the human body have been studied and observed, including influencing cell membranes, ion channels, receptors and enzymes. However, when considering how many terpenes exist and how complex the human body is, it's not surprising that researchers are still trying to figure out how each compound works. Terpenes exhibit unique therapeutic effects that can significantly contribute to the entourage effect of medicinal cannabis extracts. Interactions between cannabinoids and terpenes could lead to the treatment of dozens of biological diseases, including neurological ones. Although we may not understand all of the interactions that are taking place, terpenes prove to be quite versatile, potentially affecting mood, immune system, sleep and appetite. The importance of terpenes is very great, not only due to their aroma and possible biological effects, but also due to their potential synergy with cannabinoids such as CBD, CBN and CBG. There is evidence to suggest that when cannabinoids and terpenes exist together, their respective biological effects are enhanced. The interaction of terpenes, cannabinoids and other substances present in the Cannabis plant is called the entourage effect and is what makes the molecules found in Cannabis unique. However, even in isolation, studies have shown that terpenes can have significant biological impacts on their own.

The importance of the right extraction method

Terpenes are extracted from cannabis plant material in the same way as cannabinoids, using different extraction techniques. However, terpenes are more sensitive to changes in temperature and pressure, so it is easy to damage them unless you have the necessary equipment and knowledge to safeguard their integrity. Before extraction, the sample must be prepared, drying the plant in forced or natural circulation ovens or in vacuum ovens, it can also be carried out by a drying system using a freeze-drier without heating and grinding it. Regarding the extraction techniques commonly and currently used to obtain bioactive extracts from Cannabis plants, hydrodistillation is highlighted, as well as other methods: steam distillation or water vapor drag distillation of essential oils; the extraction of organic compounds by organic solvent; extraction with cold fat (enfleurage); maceration; microwave extraction; supercritical fluid extraction; extraction by mechanical stirring with a heating plate; extraction by winterization with reactors; percolation extraction; extraction by infusion and boiling; extraction by rotary evaporators; glycerin extraction; extraction through percolation using a heating plate and solvent; extraction by decoction using a heating plate with water solvent until boiling and infusion and the extraction assisted by ultrasound. In CO2 supercritical fluid extraction, extracts are made with carbon dioxide, which is compressed into a supercritical fluid. This fluid mainly extracts the essential oils from Cannabis, in a similar way to what organic solvents do. This method is unique because it has the characteristics of a supercritical fluid that has liquid and gaseous properties, thus allowing the plant to completely dissolve. In this technique, the extracts are left with more terpenes (up to 10%). Due to the fact that it does not use organic solvents and because it presents a higher yield in the concentration of terpenes, the extraction by supercritical fluid CO2 becomes the extraction technique in greatest demand today. At the company Piauhy Labs, headquartered in Portugal, the extraction of terpenes and cannabinoids will be done using the technique of supercritical fluid CO2 extraction, by which we will have a higher concentration of terpenes in the extracts obtained from the extractions. We will also research terpenes that have a lower intensity in the plant.
Elmo Resende
PhD in Analytical Chemistry
Piauhy Labs, Portugal