Why Terpenes are Essential to Cannabis Therapeutics

An Introduction to the Role of Terpenes in Cannabis Metabolism and Plant Medicine

Terpenes are aromatic hydrocarbons that occur naturally in plants and some animals. They are mainly secreted as secondary metabolites and give plants their characteristic scents. Terpenes protect plants from infectious germs, animal grazing or attract pollinators. 

Cannabis based terpenes have received a good level of interest thanks to the numerous therapeutic potentials of cannabinoids. Terpenes can synergize with cannabinoids and alter their metabolism. Cannabis-based terpenes can, to some extent, determine ahow cannabinoids interact with receptors and even provide some therapeutic benefits by themselves in addition to enhancing or enabling the full effects of the major cannabinoids. 

Terpenes are a big deal in the pharmaceutical industry. They represent an estimated 55,000 chemical entities, most of which are known to be very therapeutic. They are directly involved in aromatherapy and the development of medications like Taxol (an anticancer drug) and Artemisinin (anti-malaria) generating over $2 billion in 2002. 

Combining terpenes with cannabinoids is a good choice as these compounds promote cannabinoid medicine and also determine how well these cannabinoids can interact with their receptors. 

Terpenes vs Terpenoids

While it is commonplace to use terpenes and terpenoids interchangeably, it is pertinent to note that they are not the same. Terpenoids are modified terpenes with an additional functional group usually, an oxygen containing molecule. Terpenoids are a natural constituent of essential oils and oxidized forms of terpenes, just like CBGA and CBG. 

Terpenoids are formed when terpenes are oxidized during the attachment of different functional groups at specific positions in the molecules. While terpenes are primarily present in the plant as natural molecules, the terpenoids are mostly responsible for the therapeutic potentials of the compounds. 

Terpenoids are classified as monoterpenes, sesquiterpenes, diterpenes, sesterpenes and triterpenes depending on the carbon units. They are biologically active and play important roles in the treatment of diseases like cancer, malaria and more. Industrially, terpenes are used as flavoring agents.  

Terpenes and Cannabinoid Medicine

Terpenes and cannabinoids have gradually evolved into an inseparable duo. They exhibit an excellent level of interaction that makes them a natural part of cannabis-based products. Note that the cannabis plant contains about 400 terpenes, most of which are known to exhibit an excellent activity on the endocannabinoid system. The endocannabinoid system consists of drug targets that play important roles in modulating cognitive activities. 

Terpenes and cannabinoids have successfully created a strong bond in the provision of entourage effects and therapeutic activities. Cannabis-based terpenes, when used by themselves, can mimic the activities of cannabinoids to provide pain-relief and other benefits. When combined with cannabinoids, the effects are found to be amplified without an increase in the negative effects of the molecules. Just like cannabinoids that mimic endogenous compounds, terpenes can mimic activities of cannabinoids at the receptor sites. 

Terpenes are cannabimimetic. Research data show that almost all terpenes can activate the CB1 receptors while a few of them have a relatively important activity on other cannabinoid targets. This may explain why they can suppress the psychoactive effects of THC and other psychoactive cannabinoids. This was reported in a paper titled, Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity. The findings of this research shows that cannabis-terpenes can provide conceptual support for the entourage effect and may serve to enhance the therapeutic properties of cannabinoids. 

Terpenes have been used thousands of years ago as antimicrobials, analgesics, anti-inflammatory medicines. Information from research shows that terpenes can modulate the activities of cannabinoids as seen in its interaction with the CB1 and Adenosine A2a receptor (A2a receptor). A2a receptors belong to the family of G protein-coupled receptors (GPCRs) and are responsible for a broad range of physiological processes like regulating the immune system, promoting sleep and angiogenesis (formation of new blood vessels). Just like other cannabinoid receptors A2a, is a potential drug target for several pathophysiological conditions including dementia, cancer, and sleep disorders. 

This pharmacological effect of terpenes and cannabinoids can come in handy in selectively modulating the impact of cannabis/cannabinoid therapy. When combined, terpenes and cannabinoids can provide an additive effect thus enhancing the overall therapeutic benefits of cannabis-based products. As terpene targets, CB1 and A2a provide a detailed role of the terpenes as cannabimimetic compounds thus allowing terpenes to enhance the analgesic properties of cannabis/cannabinoid therapy without worsening the side effects. With the right terpene-cannabinoid combinations, users can maximize the therapeutic index for a particular disease thus, providing an improved human therapy with cannabis-based medications. 

Terpenes were found to activate the CB1 just like THC thus suggesting a cannabimimetic activity. 

Is terpene profile important?

Yes, terpenes are just as important as the overall cannabinoid profile when it comes to cannabis as a therapeutic. That’s why cannabis strains with similar potency will have vastly different psychoactive and therapeutic effects. It comes down to the terpenes. While there are over 400 terpenes present in the cannabis plant, the following are the few with medical importance. Note that these terpenes were chosen based on their abundance in the cannabis plant, interaction with the cannabinoids and the cannabinoid system.

  • alpha-Humulene 

Humulene or alpha-caryophyllene is a natural constituent in ginseng, sunflower, tobacco, pine trees and orange orchards. It was first observed in hops plants (Humulus lupulus) hence the name. It has a long history in providing energizing effects. It is responsible for the characteristic aroma of cannabis. It has a strong anti-inflammatory effect and has been shown to exhibit a cannabimimetic activity on CB1, and A2a receptors. Unlike β-caryophyllene, its isomer, humulene lacks a CB2 activity but possess an excellent anti-inflammatory and analgesic property when administered orally, topically and by aerosol. There are also reports on how it can promote wound healing. 

  • β-caryophyllene

This is described as an agonist of CB2 receptors. It is the first known dietary cannabinoid with a GRAS status (generally regarded as safe) and approved by the FDA for food use. It is responsible for the spiciness of pepper and is a common constituent of cannabis, copaiba, rosemary, hops and cloves. 

β-caryophyllene (BCP) is one of the first cannabis derived compounds and can bind directly to the cannabinoid receptors like the CB1 and CB2. It is often associated with the psychoactive effects of some cannabinoids like THC and is directly beneficial for disease conditions like anxiety and depression, colitis, diabetes, cerebral ischemia and liver fibrosis. It can also improve the bioavailability of orally administered cannabis products. CB2 agonist. After binding to CB2 receptors, BCP can inhibit adenylate cyclase (an enzyme responsible for modulating regulatory roles in organisms). As a CB2 agonist, BCP also can increase immune responses in users. It can also activate Peroxisome proliferator-activated receptors (PPARs) and is speculated to play an important role in trinity of infection, immunity and inflammation associated with Covid-19. BCP also shows a good activity as tissue protective and can modulate several signaling pathways. It can produce Anti-allodynic effect, anti-diabetic effect, antioxidant, analgesic, antidepressant and anxiolytic effects, as well as antitumor, and neuroprotective properties. 

  • Beta-pinene

Pinene is responsible for the earthy, woody and fresh aromas of pine and resins in many non-edible plant parts. They exist as alpha and beta pinene and provide some therapeutic potential. Pinene is highly concentrated in the cannabis plant and found in other plants like turpentine, rosemary, frankincense, mastic tree, myrtle, rock rose, juniper, camphor, and conifers, fir, and guinea grains.

Although it does not interact with the CB1 and CB2 receptors, pinene can interact with other cannabinoid receptors like GABA, 5-HT1A to protect against brain damage, analgesic, anticonvulsant, anti-inflammatory, anxiolytic, antidepressant and sedative properties. Although its mechanism of action is not fully understood, pinene may play important roles in cannabis reaction with the listed receptors. Pinene can produce additive effects by interacting with the A2a receptors. 

  • Limonene

Limonene is responsible for the distinct citrus aromas in cannabis products. It was reported to possess some anti-cancer properties in mice and may directly interact with the CB1 receptors. It produces antinociceptive, anti-inflammatory and gastroprotective characteristics. It plays a critical role in neurodegenerative diseases like Alzheimer’s disease, epilepsy, anxiety, multiple sclerosis and stroke. Limonene is speculated as one of the cannabis terpenoids that can activate the CB2 receptor thus, producing analgesic effects. 

  • Linalool 

Cannabis with Linalool comes in handy in handling stress since the terpene can increase the activity of TRPA1 receptors. TRPA1 is a cannabinoid receptor that functions as a mechanical and chemical stress sensor. Apart from interacting with this receptor, linalool is also found to possess some antimicrobial activity. 

  • Myrcene 

This terpene is responsible for the earthy, fruity and clove-like smell of cannabis and comes with some levels of therapeutic use in treating dysentery, diarrhea, hypertension and diabetes. It is believed to synergize the activities of terpenes and other compounds in several ways. Some researchers have reported the high permeability of myrcene in penetrating the Blood-brain barrier (BBB), thus aiding cannabinoid transports into the brain. It also enhances transdermal penetration of administered cannabinoids

Bottom Line

The benefits of cannabis, either psychoactive or purely therapeutic, depend on terpenes. Anyone who’s serious about cannabis as a therapeutic should stay up to date on terpene science.