Medical

What Are Terpenes?

Terpenes belong to a class of compounds known as aromatic hydrocarbons, and they are made up of chains of linked isoprene units. Isoprene is an abundant naturally occurring molecule with the chemical formula C₅H₈, and terpenes are formed by two or more linked isoprene units. Thus, monoterpenes (C₁₀H₁₆) are formed of two isoprene units, diterpenes (C₂₀H₃₂) from four, triterpenes (C₃₀H₄₈) from six, and so on.  Terpenes are a major component of many plant resins, cannabis being no exception. Most terpenes are strong smelling and often serve the purpose of attracting pollinators or repelling predators. Furthermore, it is thought that certain tree species release terpenes, which react with atmospheric compounds to produce aerosols, which in turn encourage water vapor to form clouds. During hot weather, these trees release higher levels of terpenes, doubling cloud cover and providing a strong cooling effect.

Terpenes Found in Cannabis

Some notable terpenes contained within the cannabis plant include d-limonene, myrcene, pinene, camphene, sabinene (all monoterpenes), squalene (a triterpene), and α-humulene and caryophyllene (both sesquiterpenes, which are made up of three isoprene units and have the chemical formula C₁₅H₂₄). According to one source, cannabis contains 58 monoterpenes and 38 sesquiterpenes. Many related compounds known as terpenoids are also contained within cannabis (such as linalool and geraniol, and even cannabinoids themselves); however, for purposes of simplicity, we will focus only on the true terpenes.

Terpenes and the Endocannabinoid System

Many terpenes were also found to interact synergistically with cannabinoids by directly or indirectly acting on the cannabinoid receptors. Most notably, recent reports have highlighted the likelihood that the monoterpene myrcene interacts with THC to produce the characteristic “couch-lock” effect associated with “indica” varieties. Likewise, earlier research demonstrated that the sesquiterpene caryophyllene (the oxide of which is the compound drug-sniffing dogs are trained to detect) acts as a selective CB₂-receptor agonist and has anti-inflammatory properties via this mechanism.

Dr Ethan Russo (former senior medical advisor at U.K. cannabinoid research company GW Pharmaceuticals) released an extensive review of the existing medical literature investigating the synergy between cannabinoids, terpenes and terpenoids. On the basis of his research and others, the concept of the “entourage effect”—the synergistic biological effects of the various compounds in cannabis—was developed. The entourage effect is the focus of intense research, and it is clear that we are only beginning to understand the complexities of the thousands of potential interactions between these many and varied compounds.

Medical Benefits of Terpenes

Terpenes have been found to have a range of medicinal benefits in their own right. For example, limonene has been shown to have anticarcinogenic properties (Elson et al. 1997); myrcene, limonene and citral have demonstrated sedative and motor relaxant effects (Vale et al. 2002); and myrcene has been shown to have analgesic effects on peripheral pain (Lorenzetti et al. 1991).

A number of studies also observed potential medical properties in the essential oil of various plant species. Essential oils, which are derived from plants via steam distillation or solvent extraction, typically contain terpenes in higher concentrations than any other constituent. For example, a 2008 study (Gilani et al) investigated the essential oil of Nepeta cataria (catnip), which contains the terpenes pinene and α-humulene, and found it to have bronchodilatory and antispasmodic effects. Another study (Farag et al. 1989) demonstrated that the essential oils of six herbs and spices (sage, rosemary, caraway, cumin, clove and thyme) known to be high in various terpenes including pinene, camphene and limonene demonstrated antimicrobial activity against various gram-positive bacteria. Sage and cumin oils exhibited particularly strong antimicrobial activity.  

Possible Synergistic Effects Between Terpenes 

Several studies out there point to a possible synergistic effect between the various terpenes found in plants. For example, a study (Food Chemistry, 2008) compared essential oil extracted from Rosmarinus officinalis L. to its three main components (1,8-cineole, α-pinene, β-pinene) to investigate possible antioxidant effects, and found that the essential oil showed greater activity than its components. 

As well as this, significant evidence is beginning to emerge on the nature of the interactions between terpenes and the endocannabinoid system. Although no research has been done on the specific interactions between pinene and the plant cannabinoids found in cannabis, Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects by Dr. Ethan Russo is an important review. The former senior medical advisor to GW Pharmaceuticals suggested that pinene may interact with CBD, CBN and CBG to provide an enhanced antibacterial effect, specifically for the treatment of MRSA and other drug-resistant pathogens; with THC as a bronchodilator and with CBD as a means of reducing production of sebum and sebocytes. 

Myrcene 

Myrcene is a monoterpene (a class of strong-smelling hydrocarbons with the chemical formula C₁₀H₁₆) with an aroma that is described as “herbaceous, resinous, green, balsamic, fresh hops and slightly metallic” and “like floor-cleaner” at higher levels. It is the principle aromatic compound in hops, along with humulene and caryophyllene (together, the three terpenes constitute up to 80 percent of the oil from hop flowers), and is also present in wild thyme, bay, parsley, lemongrass, verbena and ylang-ylang, as well as in cannabis.

Myrcene is widely used in the perfume industry, although rarely as a fragrant compound in its own right; more commonly, it is used as an industrial precursor to various other terpenes including geraniol, menthol, citral and nerol.

Myrcene is the most abundant monoterpene found in cannabis, and in some strains makes up a surprisingly high proportion of the extracted resin. A recent study conducted by researchers at the University of Leiden in the Netherlands investigated the government-licensed strains of medicinal cannabis marketed as Bedrocan, Bediol and Bedrobinol, and found that myrcene was the fourth, third and second most abundant compound present, respectively.

Myrcene appears to have various medicinal properties in its own right. More than one study has investigated the compound for its anti-inflammatory and analgesic effects, and one study also demonstrated it to have sedative and motor relaxant effects, along with limonene and citral.

It has also been shown that myrcene, linalool and eucalyptol may exert a protective effect against oxidative cell damage that can cause cancer; that limonene, pinene and myrcene may exert directly tumoricidal effects on cancer cells; and that of four terpenes--pinene, carene, limonene and myrcene--myrcene exerted the strongest anti-invasive effect on metastatic human breast cancer cells.

A toxicity study on rats also determined that extremely high doses of 300mg/kg were necessary to produce adverse effects; while equivalent studies have not been performed on humans, toxicity levels are likely to be comparably low.

Pinene is a terpene, and more specifically, a monoterpene. Terpenes have been shown to have important medicinal qualities in their own right, and researchers recently discovered that they exert synergistic biological effects in combination with THC and other cannabinoids.

Pinene

Pinene is a naturally occurring plant compound belonging to a large and diverse class of organic hydrocarbons known as terpenes, which are made up of linked isoprene (C₅H₈) units. Within this class, pinene is a monoterpene, and thus each molecule consists of two linked isoprene units, giving the chemical formula C₁₀H₁₆. 

The pinene molecule naturally occurs in two closely related forms known as structural isomers. For the sake of comparison, an isomer is a natural variant of a molecule; a structural isomer shares the same chemical formula, but the structure of the molecule or its chemical bonds differ; and a stereoisomer shares the same structure as the original molecule but is oriented differently in space. 

The two subtypes of pinene are α-pinene and β-pinene. The two isomers each possess two stereoisomers (more specifically, enantiomers, which are perfect mirror images of the original molecule), either positive or negative. Thus, the four forms of pinene are (+)-α-pinene, (−)-α-pinene, (+)-β-pinene and (−)-β-pinene. 

A recent study (The Journal of Essential Oil Research, 2006) investigated the antimalarial, antimicrobial and antioxidant effects of a range of common plant terpenoids including (+)-α-pinene. It was discovered that (+)-α-pinene, along with (-)-pulegone, (E- & Z-)-(±)-nerolidol and linalyl acetate, exhibited the most potent antimalarial activity.

Evidence suggests that the positive enantiomers of  α-pinene and β-pinene have greater biological activity than the negative, such as a study (Molecules, 2012) that demonstrated that only the positive enantiomers of α- and β-pinene were active against bacterial and fungal cells. An earlier study (Journal of Essential Oil Research, 1999) also noted that the positive and negative forms of α-pinene had differing effects, with the negative enantiomer being more effective against certain bacteria, as well as being more likely to stimulate spasms in smooth muscle tissue.

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