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Terpenes

​Terpenes are aromatic molecules found in plant resins.
There are thousands of terpenes found in the plant kingdom, and more than one hundred compounds found in cannabis alone.

As a cannabis plant matures from fertility to senescence, the resins containing terpenes change in composition and viscosity. Cannabis terpenes are typically divided into two chemical classifications, monoterpenes and sesquiterpenes, the former being more volatile.

Beta-Myrcene is the monoterpene that is most commonly produced in cannabis.
The words terpene and terpenoid are becoming more and more interchangeable in the industry, although the two represent different chemical classifications. Terpenes are various sized, aromatic hydrocarbons that can be found in plant resins, whereas terpenoids are terpenes with the addition of a functional group such as alcohols, ketones, and esters.


Importance of terpenes
Terpenes account for the vast array of smells and flavors in cannabis flowers and extracts, and provide the notable aromas of cannabis varieties.

Some of the medical and physiological benefits found in cannabis have been attributed to terpenes.

Genetic and environmental factors, as well as drying and curing processes, determine the types and levels of terpenes present in usable cannabis.

It is in the process of the drying and curing that terpenes are oxidized and denatured to form terpenoids.

β-Myrcene

Myrcene, specifically β-myrcene, is a monoterpene and the most common terpene produced by cannabis (some varieties contain up to 60% of the essential oil). Its aroma has been described as musky, earthy, herbal – akin to cloves. A high myrcene level in cannabis (usually above 0.5%) results in the well-known “couch-lock” effect of classic Indica strains. Myrcene is found in oil of hops, citrus fruits, bay leaves, eucalyptus, wild thyme, lemon grass and many other plants.

Myrcene has some very special medicinal properties, including lowering the resistance across the blood to brain barrier, allowing itself and many other chemicals to cross the barrier easier and more quickly. In the case of cannabinoids (like THC), myrcene allows the effects of the cannabinoid to take effect more quickly. More uniquely still, myrcene has been shown to increase the maximum saturation level of the CB1 receptor, allowing for a greater maximum psychoactive effect.

Myrcene is a potent analgesic, anti-inflammatory, antibiotic and antimutagenic. It blocks the action of cytochrome, aflatoxin B and other pro-mutagenic carcinogens. The Bonamin et al study focused on the role of β-myrcene in preventing peptic ulcer disease. The study revealed that β-myrcene acts as an inhibitor of gastric and duodenal ulcers, suggesting it may be helpful in preventing peptic ulcer disease. Its sedative and relaxing effects also make it ideal for the treatment of insomnia and pain.

Since myrcene is normally found in essential oil from citrus fruit, many claim eating a fresh mango about 45 minutes before consuming cannabis will result in a faster onset of psycho activity and greater intensity. Be sure to choose a mango that is ripe otherwise the myrcene level will be too low to make a difference.

Linalool

Linalool is a non-cyclic monoterpenoid and has been described as having floral and lavender undertones. Varieties high in linalool promote calming, relaxing effects.

Linalool has been used for centuries as a sleep aid. Linalool lessens the anxious emotions provoked by pure THC, thus making it helpful in the treatment of both psychosis and anxiety. Studies also suggest that linalool boosts the immune system; can significantly reduce lung inflammation; and can restore cognitive and emotional function (making it useful in the treatment of Alzheimer’s disease).

As shown by the Ma, J., Xu et al study, linalool may significantly reduce lung inflammation caused by cigarette smoke by blocking the carcinogenesis induced by benz[α]anthracene, a component of the tar generated by the combustion of tobacco. This finding indicates limonene may be helpful in reducing the harm caused by inhaling cannabis smoke.

Linalool boosts the immune system as it directly activates immune cells through specific receptors and/or pathways. The Sabogal-Guáqueta et al study suggests linalool may reverse the histopathological (the microscopic examination of biological tissues to observe the appearance of diseased cells and tissues in very fine detail) hallmarks of Alzheimer’s Disease and could restore cognitive and emotional functions via an anti-inflammatory effect.

The Environmental Protection Agency has approved its use as a pesticide, flavor agent and scent. It is used in a wide variety of bath and body products and is commonly listed under ingredients for these products as beta linalool, linalyl alcohol, linaloyl oxide, p-linalool and alloocimenol. Its vapors have been shown to be an effective insecticide against fruit flies, fleas and cockroaches.

Linalool has been isolated in several hundred different plants. The Lamiaceae plant and herb family, which includes mints and other scented herbs, are common sources. The Lauraceae plant family, which includes laurels, cinnamon, and rosewood, is also a readily available source. The Rutaceae family, which contains citrus plants, is another viable source. Birch trees and several different plant species that are found in tropical and boreal climate zones also produce linalool. Although technically not plants, some fungi produce linalool, as well. Linalool is a critical precursor in the formation of Vitamin E.

D-Limonene

Limonene is a monocyclic monoterpenoid and one of two major compounds formed from pinene. As the name suggests, varieties high in limonene have strong citrusy smells like oranges, lemons and limes. Strains high in limonene promote a general uplift in mood and attitude. This citrusy terpene is the major constituent in citrus fruit rinds, rosemary, juniper and peppermint, as well as in several pine needle oils.

Limonene is highly absorbed by inhalation and quickly appears in the bloodstream. It assists in the absorption of other terpenes through the skin and other body tissue. It is well documented that limonene suppresses the growth of many species of fungi and bacteria, making it an ideal antifungal agent for ailments such as toenail fungus. Limonene may be beneficial in protecting against various cancers, and orally administered limonene is currently undergoing clinical trials in the treatment of breast cancer. Limonene has been found to even help promote weight-loss.

Plants use limonene as a natural insecticide to ward off predators. Limonene was primarily used in food and perfumes until a couple of decades ago, when it became better known as the main active ingredient in citrus cleaner. It has very low toxicity and adverse effects are rarely associated with it.

α-Pinene
Pinene is a bicyclic monoterpenoid. Akin to its name, pinene has distinctive aromas of pine and fir. There are two structural isomers of pinene found in nature: α-pinene and β-pinene. Both forms are important components of pine resin. α-pinene is the most widely encountered terpenoid in nature. Pinene is found in many other conifers, as well as in non-coniferous plants. It is found mostly in balsamic resin, pine woods and some citrus fruits. The two isomers of pinene constitute the main component of wood turpentine. Pinene is one of the principal monoterpenes that is important physiologically in both plants and animals. It tends to react with other chemicals, forming a variety of other terpenes (like limonene) and other compounds.

Pinene is used in medicine as an anti-inflammatory, expectorant, bronchodilator and local antiseptic. α-pinene is a natural compound isolated from pine needle oil which has shown anti-cancer activity and has been used as an anti-cancer agent in Traditional Chinese Medicine for many years. It is also believed that the effects of THC may be lessened if mixed with pinene.

α-Terpinolene

Terpinolene is a common component of sage and rosemary and is found in the oil derived from Monterey cypress. Its largest use in the United States is in soaps and perfumes. It is also a great insect repellent. Terpinolene is known to have a piney aroma with slight herbal and floral nuances. It tends to have a sweet flavor reminiscent of citrus fruits like oranges and lemons.

Terpinolene has been found to be a central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. Further, terpinolene was found to markedly reduce the protein expression of AKT1 in K562 cells and inhibited cell proliferation involved in a variety of human cancers.

Camphene

Camphene, a plant-derived monoterpene, emits pungent odors of damp woodlands and fir needles. Camphene may play a critical role in cardiovascular disease.

The Vallianou et al study found camphene reduces plasma cholesterol and triglycerides in hyperlipidemic rats. Given the importance that the control of hyperlipidemia plays in heart disease, the results of this study provide insight into to how camphene might be used as an alternative to pharmaceutical lipid lowering agents which are proven to cause intestinal problems, liver damage and muscle inflammation. This finding alone warrants further investigation.

Camphene is a minor component of many essential oils such as turpentine, camphor oil, citronella oil and ginger oil. It is used as a food additive for flavoring, and also used in the preparation of fragrances. It is produced industrially by catalytic isomerization of the more common α-pinene.

Terpineol

α-Terpineol, terpinen-4-ol, and 4-terpineol are three closely related monoterpenoids. The aroma of terpineol has been compared to lilacs and flower blossoms. Terpineol is often found in cannabis varieties that have high pinene levels, which unfortunately mask the fragrant aromas of terpineol.

Terpineol, specifically α-terpineol, is known to have calming, relaxing effects. It also exhibits antibiotic, AChe inhibitor and antioxidant antimalarial properties.

Phellandrene

Phellandrene is described as pepperminty, with a slight scent of citrus. Phellandrene is believed to have special medicinal values. It has been used in Traditional Chinese Medicine to treat digestive disorders. It is one of the main compounds in turmeric leaf oil, which is used to prevent and treat systemic fungal infections.

Phellandrene is perhaps the easiest terpene to identify in the lab. When a solution of phellandrene in a solvent (or an oil containing phellandrene) is treated with a concentrated solution of sodium nitrate and then with a few drops of glacial acetic acid, very large crystals of phellandrene nitrate speedily form.

Phellandrene was first discovered in eucalyptus oil. It wasn’t until the early 1900s that it was actually constituted and shown that phellandrene from eucalyptus oil contained two isomeric phellandrene (usually referred to as α-phellandrene and β-phellandrene), and on oxidation with potassium permanganate gave distinct acids, concluding that the acids had been derived from two different isomeric phellandrene. Before that, phellandrene was mistaken for pinene or limonene. Today, we are aware of many essential oils where phellandrene is present. It is, however, a somewhat uncertain terpene as it can only be detected in the oils of some species, especially in Eucalypts, at particular times of the year.

Phellandrene can be found in a number of herbs and spices, including cinnamon, garlic, dill, ginger and parsley. A number of plants produce β-phellandrene as a constituent of their essential oils, including lavender and grand fir. The recognizable odors of some essential oils depend almost entirely upon the presence of phellandrene. Oil of pepper and dill oil are composed almost entirely of phellandrene. The principal constituent in oil of ginger is phellandrene. Phellandrene, particularly α-phellandrene, is absorbed through the skin, making it attractive for use in perfumes. It is also used as a flavoring for food products.


Carene

Delta-3-carene is a bicyclic monoterpene with a sweet, pungent odor. It is found naturally in many healthy, beneficial essential oils, including cypress oil, juniper berry oil and fir needle essential oils. In higher concentrations, delta-3-carene can be a central nervous system depressant. It is often used to dry out excess body fluids, such as tears, mucus, and sweat.

It is nontoxic, but may cause irritation when inhaled. Perhaps high concentrations of delta-3-carene in some strains may be partially responsible for symptoms of coughing, itchy throat and eye afflictions when smoking cannabis.

Delta-3-carene is also naturally present in pine extract, bell pepper, basil oil, grapefruit and orange juices, citrus peel oils from fruits like lemons, limes, mandarins, tangerines, oranges and kumquats.

Carene is a major component of turpentine and is used as a flavoring in many products.

Humelene

Humulene is a sesquiterpene also known as α-humulene and α–caryophyllene; an isomer of β–caryophyllene. Humulene is found in hops, cannabis sativa strains, and Vietnamese coriander, among other naturally occurring substances. Humulene is what gives beer its distinct ‘hoppy’ aroma.

Humulene is considered to be anti-tumor, anti-bacterial, anti-inflammatory, and anorectic (suppresses appetite). It has commonly been blended with β–caryophyllene and used as a major remedy for inflammation. Humulene has been used for generations in Chinese medicine. It aids in weight loss by acting as an appetite suppressant.

Pulegone

Pulegone, a monocyclic monoterpenoid, is a minor component of cannabis. Higher concentrations of pulegone are found in rosemary. Rosemary breaks down acetylcholine in the brain, allowing nerve cells to communicate more effectively with one another.

An ethnopharmacology study indicates pulegone may have significant sedative and fever-reducing properties. It may also alleviate the side effects of short-term memory loss sometimes associated with higher levels of THC.

Pulegone has a pleasant peppermint aroma and is considered to be a strong insecticide.

Sabinene

Sabinene is a bicyclic monoterpene whose aromas are reminiscent of the holidays (pines, oranges, spices). Results of an ongoing study by Valente et al suggest that sabinene should be explored further as a natural source of new antioxidant and anti-inflammatory drugs for the development of food supplements, nutraceuticals or plant-based medicines.

Sabinene occurs in many plants, including Norway spruce, black pepper, basil and Myristica fragrans (an evergreen indigenous to the Moluccas)—the Spice Islands of Indonesia. The seeds of the Myristica fragrans are the world’s main source of nutmeg. Sabinene exists as (+)- and (–)-enantiomers.

Geraniol
Geraniol produces a sweet, delightful smell similar to roses. This makes geraniol a popular choice for many bath and body products. It is also known to be an effective mosquito repellant. Medically, geraniol shows promise in the treatment of neuropathy.


The FDA and other agencies have generally recognized terpenes as “safe.” Terpenes act on receptors and neurotransmitters; they are prone to combine with or dissolve in lipids or fats; they act as serotonin uptake inhibitors (similar to antidepressants like Prozac); they enhance norepinephrine activity (similar to tricyclic antidepressants like Elavil); they increase dopamine activity; and they augment GABA (the “downer” neurotransmitter that counters glutamate, the “upper”). However, more specific research is needed for improved accuracy in describing and predicting how terpenes in cannabis can be used medicinally to help treat specific ailments / health conditions.

 

Synergistic Effects

The Carlini et al study demonstrated that there may be potentiation (a form of synaptic plasticity that is known to be important for learning and memory) of the effects of THC by other substances present in cannabis. The double-blind study found that cannabis with equal or higher levels of CBD and CBN to THC induced effects two to four times greater than expected from THC content alone. The effects of smoking twice as much of a THC-only strain were no different than that of the placebo.

This suggestion was reinforced by a study done by Wilkinson et al to determine whether there is any advantage in using cannabis extracts compared with using isolated THC. A standardized cannabis extract of THC, CBD and CBN (SCE), another with pure THC, and also one with a THC-free extract (CBD) were tested on a mouse model of multiple sclerosis (MS) and a rat brain slice model of epilepsy.

Scientists found that SCE inhibited spasticity in the MS model to a comparable level of THC alone, and caused a more rapid onset of muscle relaxation and a reduction in the time to maximum effect than the THC alone. The CBD caused no inhibition of spasticity. However, in the epilepsy model, SCE was a much more potent and again more rapidly-acting anticonvulsant than isolated THC; however, in this model, the CBD also exhibited anticonvulsant activity. CBD did not inhibit seizures, nor did it modulate the activity of THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. anti-spasticity), THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb is due to the THC content.

Dr. Ethan Russo further supports this theory with scientific evidence by demonstrating that non-cannabinoid plant components such as terpenes serve as inhibitors to THC’s intoxicating effects, thereby increasing THC’s therapeutic index. This “phytocannabinoid-terpenoid synergy,” as Russo calls it, increases the potential of cannabis-based medicinal extracts to treat pain, inflammation, fungal and bacterial infections, depression, anxiety, addiction, epilepsy and even cancer.

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