Terpenes make up a diverse class of organic molecules produced mainly by plants and fungi. They (and their more complex derivatives, terpenoids), are the major representatives in plant essential oils, and are particularly profuse as a component of plant resin. Resins are famously found in conifers, but are produced by many plants, including such famous medicinal specimens as frankincense, myrrh… and cannabis!
The effects of cannabis in humans are substantially variable, thanks to its alterable and complex chemistry. As is the case with plant/fungus medicines generally, the various components in cannabis appear to act in synergy. This means that while one component is considered “active”, and has effects when administered in isolation (i.e. as a single extracted chemical compound; pharmaceutical drug), other components of the plant contribute to this. The result is that the total effect of the combination is greater than that of the components alone. This effect is being explored in cannabis as the entourage effect.
Briefly, the human body has receptors in just about every tissue type (if not all!) that interact with cannabinoids. The first compounds discovered in this class were from the cannabis plant, hence their name. However, we naturally produce our own members of the cannabinoid family endogenously! Anandamide is the famous one, named after the Sanskrit word for bliss. This signalling system of endogenous cannabinoid molecules and receptors is now recognised as the endocannabinoid system (ECS), and it is a hot topic for researchers currently, due to its vast potential regulatory effects throughout the body. It has become increasingly difficult to define the ECS exactly, as the more we learn, the more complicated it becomes! Therefore it is understood to maintain overall homeostasis as a master system. This is because the downstream effects of endocannabinoid function have broad regulatory action on many aspects of our health, which are beyond the scope of this article (to be reviewed in future!). (2)
Terpenes have the capacity to bind to these same cannabinoid receptors, however they do not generally bind at the active site where cannabinoids do. Receptors are not quite the simple lock and key, on/off switches they are often simplified to be. Endogenous cell signalling chemicals and/or exogenous chemicals (i.e. from plants, fungi or drugs) that connect with the active sites of receptors can indeed agonise (cause an effect), or antagonise (block an effect), and some can cause only a partial effect, or can dampen an effect. This means that any given receptor may produce various potential results depending on the specific chemical in the active site. Receptors are more complex than this even, and have other points of binding beyond the primary site of action, known as allosteric sites. These additional binding sites can collect information from other molecules. These change the shape of the receptor, thereby altering the effects of the active site. Terpenes are thought to offer this allosteric modulation capacity, altering the effects produced by cannabinoid receptors. This is known as the entourage effect, something that is being enthusiastically explored in scientific research currently.
Because our cannabinoid receptors respond to our own cannabinoid molecules, we can potentially affect the primary binding sites already. With what we understand about the terpene entourage effect, it makes sense that terpenes work in isolation by offering similar enhancements on the activity of our endogenous cannabinoids that they do when taken combined with phytocannabinoids (plant sourced cannabinoids). We can therefore theoretically use their allosteric modulator capacity to tweek the effects of our own endogenous cannabinoid molecules.
The terpene content of plants is often complex, and cannabis is no exception. Having been domesticated and selectively bred for over 5000 years, the species now exhibits a fascinating array of chemovars, each varying in chemical composition. Over 150 different terpenes have been identified in cannabis resin, and the various combinations, in various quantities, are part of what makes up the distinctive aroma of each variety (1). Serious cannabis users will generally have a preference for certain aromatic qualities that they have identified as being correlated with enhancement of certain effects. For instance, a heavy muskiness or clove note is often associated with a stronger sedative quality, while cannabis with the distinctive smell of pine is likely to be favoured by those looking for mental clarity/alertness, etc. The theory here is that because the terpenes are considered key contributors to the volatile aromatics, their signature in the smell can be used to identify their rough proportions within each chemovar. Eventually users begin to see patterns of effects from certain terpene combinations, identified simply by nose. This indicates terpenes must somehow affect the way the body interprets signals from the more obviously active components in cannabis, the cannabinoids.
Here we will briefly acquaint ourselves with some of the popular cannabis terpenes. Be aware that most the research for terpene use is in its infancy, so few human studies are yet available. The preclinical data summarised below gives us an idea of the kinds of effects to expect.
Mycerne
This is the most prevalent terpene in cannabis chemovars being commonly grown in Europe and the USA today. Mycerne is most famous for a sedative effect, with skeletal relaxing properties (cannabis users might associate it with the “couch-lock” effect). However, it also appears to offer protection in the form of anti-inflammatory, analgesic, antioxidant and neuroprotective effects in preclinical studies. (3)
Linalool
This famously psychoactive sedative terpene has some of the most solid research to date, with established sedative, anxiolytic, antidepressant and immune function potentiating effects, with anticancer activity being currently explored. Further, it appears to offer significant potential as an anticonvulsant, interacting with glutamate regulatory mechanisms. Finally, it displays some analgesic activity, including a local anaesthetic action topically. (3)
Limonene
A beautifully uplifting terpene found very commonly in nature, limonene has demonstrated anxiolytic and antidepressant activity, in part by modulation of serotonin levels. A strong cellular protective capacity is also apparent, with antioxidant, anti-inflammatory and anticancer activity. As a result, limonene holds promise in a variety of disease states with broad potential indications currently ranging from cataract risk, to gastroesophageal ulceration, reflux, and colitis, to mitochondrial and metabolic disturbances. (3)
Pinene
This sharp, fresh terpene occurs as two structural isomers that have differing activity in the body, α-pinene and β-pinene. The former’s effects are described as “legion” for they appear to be abundant. The antibiotic & antibiofilm potential is substantial, seeming to affect a range of pathogenic species. Other research has found anti-inflammatory, bronchodilator, neuroprotective, and anxiolytic effects, with some anticancer potential. Meanwhile β-pinene is far less researched to date, but so far demonstrates some similar antimicrobial actions and the potential to induce apoptosis in cancer cells (3).
Beta-Caryophyllene (BCP)
The most common terpene in cannabis extracts on the whole, BCP has one of the widest ranges of known applications. Setting it apart is its ability to potently agonise cannabinoid 2 receptors, offering significant antioxidant and anti-inflammatory support with broad application for various inflammatory and painful conditions such as inflammatory bowel disease and arthritis. Preclinical studies indicate it offers substantial cellular protection in many organ tissues including liver, kidneys, stomach, heart and more. Immunomodulatory and antimicrobial activity appear likely, and it even has the potential to support mental health by reducing anxiety, depression and drug dependency. (3)
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References:
- Booth JK, Bohlmann J. Terpenes in Cannabis sativa - From plant genome to humans. Plant Sci. 2019 Jul;284:67-72.
- Di Marzo V, Piscitelli F. The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics. 2015 Oct;12(4):692-8.
- Russo EB, Marcu J. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Adv Pharmacol. 2017;80:67-134.