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by Uwe Blesching on October 18, 2021
An Evidence-Based Overview
Terpenes are compounds that are abundantly produced by plants but also occur as a metabolic product in other organisms such as bacteria, fungi, insect, and mammals.1 Not dissimilar to flavonoids, terpenes contribute in a multitude of ways to endow the plant kingdom with support, protection, a means of communication, and of course, its abundant taste, color, and especially, its fragrance. Indeed, terpenes are not just essential for healthy plant life but play critical structural and functional roles in most life forms on Earth.2 For instance, the terpene squalene is one component used to form cholesterol, which in turn plays an essential role in the building of the skin of each of our individual cells, our cellular membranes.3 In contrast, the terpene phytol is able to induce several functional effects associated with its antioxidant, anti-inflammatory, or anti-microbial activity.4 But before we explore the role of terpenes in the context of health, healing, and well-being in detail, it is helpful to briefly review the scientific underpinnings about how we experience scent itself, how the experience can dramatically differ between people, and how it affects our bodies, minds, and emotions.
For several decades now biologist thought they had figured out all the intricacies of how scent works. The orthodox model takes our previous “lock and Key” analogy a step further by literally naming the process by which scent molecule fit into corresponding nasal olfactory chemoreceptors in the nose, the “lock and key” mechanism. In this basic model once the connection between a receptor and a fitting key is made, a signal is sent to a specific portion of the brain that recognizes this specific scent and we become aware of it or in other words, we experience its smell. The scent of lemon (from the terpene limonene) is a key that fits into one unique receptor while the terpene pinene fits into another and both correspond to different portions of the brain that differentiate between them. As such, the effects that they induce are different from each other.
However, the process of experiencing scent is perhaps more complex than can be explained by the lock and key mechanism alone. In fact, quantum experiments have added an additional layer of complexity to the lock and key model by showing that beyond that of matching scent or key molecule with a specific scent receptor, the nose also listens to scent molecules in a process that is not unlike the process of hearing (acoustic resonance). In other words, it isn’t just the shape of the keys that are responsible for the experience of a specific scent but also the movement of electron (vibration) jumping between the elements that form each key molecule and as such bind the elements together with novel characteristics. In this context, limonene vibrates at one frequency while pinene, at another. The marvel of this theory is that our experience of smell and by extension the effects to body, mind, and emotion it engenders, has to do with the vibration of molecular bonds and their wavelike behavior and not just the shape of a particular key or scent molecule.
The Subjective Nose
Unlike our other senses, smell has a direct anatomical and functional link with the limbic system responsible for emotion and behavior. As such, scent can directly affect how we feel and behave. And, while the lock and key mechanism will be similar between humans, the resulting associations each scent can trigger can vary greatly. In other words, while many terpene-based scents tend to primarily induce a pleasurable experience for one person, the same scent can trigger discomfort in another. As such, the way we individually experience scent has a cascading secondary influence over our corresponding internal reality. A scent that causes us stress can lead to an increase in stress hormones (e.g. cortisol, various pro-inflammatory cytokines, epinephrine). In contrast, a scent that induces relaxation may work by enhancing serotonin, oxytocin, dopamine, or anandamide levels. Furthermore, the unique ways we experience scent can directly affect our choices and behavior. Will we choose to respond with compassion or act out aggressively? Which may explain, in part, why cannabis is not going to work the same for every single person but is optimized by an individual approach to matching specific cannabis constituents with the needs of each person. In other words, one type of cannabis that resonates well with one person may not vibe well with the next. And, while scent-based effects tend to vary between people here are a few examples where scents have shown to mostly induce measurable therapeutic effects.
The Therapeutic Nose
Scent molecules reach the brain primarily via two distinct pathways: by interacting with either the olfactory or the respiratory systems. Numerous mechanisms have been proposed by which scent molecules reach the brain including:1
In the therapeutic setting once scent or scent-induced signals reach the brain, they readily induce specific cellular events we experience as a reduction in stress,2 improvements in mood,3 or as physiological changes associated with potent anti-inflammatory,4 anti-oxidative, 5 and neuroprotective6 effects for example. More specifically, consider the data from 29 clinical trials that have examined terpene-induced beneficial effects across numerous chronic patient populations (see annotated list below).
Middle Ear Infection2
|Eucalyptol||Anxiety and Panic Disorders4
Chronic Obstructive Pulmonary Disease7
Menstrual Pain and Associated Conditions8
|Geraniol||Irritable Bowel Syndrome9|
Anxiety and Panic Disorders16
Menstrual Pain and Associated Conditions19
Post-Traumatic Stress Disorder20
Severe Stress Reaction/Oxidative Stress21
Stress and Life Management Difficulty22
|Pinene||Chronic Obstructive Pulmonary Disease23
Stress and Life Management Difficulty26
Menstrual Pain and Associated Conditions28
Nicotine Dependence and Withdrawal29
Most terpenes can be detected by the human nose. However, that does not mean that each plays an equally important role in producing a measurable therapeutic effect. Some may not concentrate in large enough amounts to be considered pharmacologically relevant. However, that does not mean they are irrelevant, especially in producing full-spectrum synergies that are perhaps too subtle to be consciously experienced. They too may still play a role in contributing to subtle cascading events with potential effects to our health.
When looking at the currently available scientific evidence about a minimum of terpene concentration it would take to produce a noticeable or measurable effect, we are left with little data to make more discerning decisions. However, in the expert opinion of some researchers and, based on current analytical limits and technological measuring capabilities, a threshold of terpene concentrations of 0.05% or higher is a reasonable mark to expect pharmacological effects in humans.1
Of Practical Relevance: Monoterpenes tend to dominate and may represent up to 10% of fresh trichome content but after cannabis flowers have been dried actual monoterpene yield of most dried flower is significantly less than 1% while sesquiterpenes such as ß-caryophyllene remain stronger in comparison.2
Terpenes — Terpenoids — Volatile Oil — Essential Oil
The usage of terpenes, terpenoids, volatile oil, and essential oil (EO) are often used interchangeably to mean the same or a different thing, which may produce some confusion. The following distinctions clarify the important differences and similarities.
What all four terms have in common is that each:1
How do they differ:2
Terpene vs Terpenoid: Conceptually terpenes in their most basic form exist as hemiterpenes formed by a single isoprene unit (see graphic below) whose chemical backbone are 5 carbon atoms. It takes 2 hemiterpenes to make one fully formed terpene called a monoterpene. More complex forms of terpenes are produced by a process called biosynthesis where plants add or combine repeating sets of additional hemiterpenes. For example, the backbone of the monoterpene borneol is formed using two hemiterpenes while the sesquiterpene β-caryophyllene requires three of them. Terpenes are hydrocarbons because they only contain the elements carbon (C) and hydrogen (H) and no oxygen. In contrast, while terpenoids are also formed from single isoprene units, they are not considered hydrocarbons due to a change (aka oxidation) that occurs during the drying process for instance after which in addition to containing the elements C and H they now have gained an additional oxygen element (O).
Terpene and Terpenoid Building Block: A hemiterpene or single isoprene unit
EO of cannabis is produced most frequently by steam distillation. It is very rare and one of the most expensive essential oils. EO of cannabis is primarily used in very diluted forms and often mixed with carrier oils for topical applications. It takes large quantities of flowers to produce a drop of essential oil of cannabis. More specifically, it takes 1,000kg of fresh flowers to produce 1.3L of cannabis essential oil, or 1kg to produce 1.3gm.1
Terpenes in Cannabis
Terpenes (like cannabinoids) are present in the small mushrooming, hair-like features or tiny outgrowths (trichomes) of the outer layer of the cannabis flowers and to a lesser degree on the leaves. Trichomes can be seen with the naked eye and upon closer inspection with a magnifying glass can reveal a crystalline structure beneath a coating of sticky, shiny, glass-like appearances.
Depending on specific environmental conditions cannabis will produce different types of terpenes to meet its needs and as such, each terpene is transformed to have unique properties and functions to realize protection against pests, excessive sunlight, or herbivores. Cannabis growers will often adapt the grow environment to maximize the yield of those terpenes they value the most, either to create a specific scent and flavor experience or to work toward specific patient outcomes (see chart of terpenes and conditions that may benefit from their use).
Terpenes Confirmed in Cannabis
Regarding the quantification of cannabis-based terpenes different sources tend to arrive a different total. However, by 2021, 120 cannabis-based terpenes (aka isoprenoids) with the correct chemical structure had been confirmed.1 Terpenes are named according to the number of individual isoprene units used to comprise them. While there are more classes of terpenes in general, here we list only cannabis-based terpene and the class of terpenes to which they belong (alphabetically according to class):
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