Terpenes and Cannabis: A Summary

Plants produce terpenes for interactions with other organisms, to help protect them against pathogens like mould, fungus and bacteria, and to attract pollinating insects or repel herbivores. Thousands of terpenes have been found across the plant kingdom, but some are concentrated in certain families such as Cannabaceae, which includes Cannabis sativa and Humulus lupulus (hops). Terpenes found in both Cannabis and hops, or more precisely, in their essential oils (EOs), are mainly mono- and sesquiterpenes: up to 99% of all terpenes found in the EO of hops and up to 98% in Cannabis EO fall into this category. Cannabis and hops produce and accumulate a terpene-rich resin in glandular trichomes, which are most abundant on the surface of female inflorescences (clusters of flowers). Thus, the flowering parts have been utilised in remedies for millennia. Today, it is increasingly common to test the terpene content of Cannabis used for medicinal purposes.
Terpenes

The Cannabis plant’s terpene profile contributes to the medicinal properties. It is also noted that recreational users commonly describe different effects for different “strains” (let’s say “chemovars” from now on to be more accurate). In addition to cannabinoid content, it is now widely believed the terpene content of Cannabis plays a part in the effects reported. It is worth noting that a complete flowering Cannabis plant contains terpenes in amounts of 2-4% of total dry weight; the question is whether that amount is enough to provoke medicinal effects, or the differences in effects between chemovars reported by recreational users. A review paper on this subject, published in the European Journal of Medicinal Chemistry, by Tarmo Nuutinen, PhD, discusses what the scientific literature does and doesn’t say about some of the most common terpenes found in Cannabis and hops along with what the effects could be for each individual terpene and, moreover, if there really is a synergistic function with cannabinoids; known as the “Entourage Effect” the theory popularised by Cannabis research veteran Ethan B Russo.

MyrceneMyrcene, one of the most abundant terpenes in Cannabis, is worthy of specific attention. Recreational users report and sometimes assume that myrcene is responsible for the “couch lock”, an immobilising effect of some Cannabis chemovars. Scientific literature, however, does not support this assumption: only with doses as high as 200 mg/kg do we see an increased barbiturate-induced sleeping time and motor relaxation in mice. Interestingly though, it seems that recreational chemovars are commonly rich in this terpene. Whether this is just coincidence, i.e., founder effect, or because of unintentional selective breeding remains unclear, but the link between the couch lock effect and concentration of myrcene is certainly not proven. Myrcene possesses anti-inflammatory and pain-relieving properties, but again this would only be attainable with myrcene concentrations that are impossible to achieve by smoking Cannabis.

Humulene

Humulene is another suspect for the relaxing and sleep-inducing effects of Cannabis and hops; this is because humulene-containing plants have traditionally been used for the treatment of insomnia, depression, nervousness, delirium, anxiety and digestive disorders. Although not yet recognised by modern science, humulene and its molecular derivatives may show anti-allergic, anti-inflammatory and anti-cancer potential with “reasonable” doses. A molecular relative, β-caryophyllene, is sometimes the predominant terpenoid in Cannabis and interestingly, it is the only molecule outside of the cannabinoid family that has an affinity towards cannabinoid receptors. Surprisingly though, β-caryophyllene does not resemble any other ligands (molecules that bind to, usually, a larger molecule) of cannabinoid receptors. Nevertheless, we can calculate that it could have anti-inflammatory effects on the central nervous system (CNS) with just a single dose of 200 mg of Cannabis inflorescence for the average person. This could point to beneficial effects in the treatment of Multiple Sclerosis and suggests the potential for treating other neuroinflammatory diseases such as Parkinson’s, indeed there is an animal study that supports this idea.

Linalool

Linalool, various in vitro (literally means “in glass”) and in vivo (in the living) studies have shown that linalool has anti-tumour, anti-convulsant, antinociceptive (process of blocking detection of a painful or injurious stimulus by sensory neurons), sedative, anti-depressant, anti-inflammatory, antioxidative, neuroprotective, hepatoprotective (prevent damage to the liver) and anti-microbial properties. The CNS effects are likely to be mediated by neuropeptides, noradrenergic and glutamatergic systems along with the 5-HT1A receptor and altered blood flow in the brain. It is not yet established whether these effects could be achieved by Cannabis consumption.

Grapefruit Oil

Limonene can promote wound healing and anabolism (biosynthesis), it can also ameliorate stress, depression, inflammation, oxidative stress (imbalance between free radical production and ability of the body to counteract or detoxify through neutralisation by antioxidants), spasms and viral infections. In addition, limonene shows a variety of anti-cancer and anti-tumour mechanisms: some of these effects may be due to its conversion to perillyl alcohol in the gastric system. Of note is that limonene is used in Brazil as a cancer drug, especially in the treatment of brain tumours. Finally, its derivatives can be powerful anti-convulsants via GABAergic action (Gamma-aminobutyric acid, GABA, a neurotransmitter, sends chemical messages through the brain and nervous system; regulating communication between brain cells). Thus, as for many other terpenes, it is a target of drug design.

Pineneα-pinene, according to the studies referred to in the review, show anti-metastatic and anti-tumour activities. However, again this is only true in high doses and systemic intake. Moreover, it seems to be anti-inflammatory, anti-oxidant and an anti-allergic bronchodilator and can produce anxiolytic (anxiety reducing) and hypnotic effects via the GABAergic system. Finally, it provides a molecular basis for the development of novel CB2 ligands. In contact with air, α-pinene is oxidised to pinocarveol and myrtenol amongst other molecules and is easily converted to other terpenes in industrial processes; conifers are a well-established source of α-pinene as they produce this terpene in abundance. β-pinene (at 100 mg/kg) showed anti-depressant and sedative activities in mice with several experimental models. In addition, a study indicated that β-pinene (100 mg/kg) produces its anti-depressant effect through the monoaminergic system (includes the dopaminergic (DA), noradrenergic (NA), serotonergic (5-HT) and histaminergic (HA) circuitries). β-pinene reversed the antinociceptive effect (process of blocking detection of a painful or injurious stimulus by sensory neurons) of morphine in a degree equivalent to naloxone, indicating that it is a partial agonist of the µ-opioid receptors. β-pinene, when complexed with β-cyclodextrin, provoked an antihypertensive (anti high blood pressure) effect and vasorelaxation (reduction in tension of blood vessel walls) in rats. It showed synergistic interactions with a classical cancer drug against non-small-cell lung cancer cells. These results indicate that β-pinene, as with many other terpenes, can enhance the medicinal properties of other drugs. Moreover, it exhibits anti-viral activity against herpes simplex and could be used to support the medicinal properties of other anti-viral drugs.


Secondary metabolites

For other common terpenes see the review. Cannabis contains rare terpenes which can actually be responsible for some benefits at relatively low doses. These have not yet gained much attention in popularised science. These terpenes include nerolidol, ocimene, perillyl alcohol, terpinolones, fenchone, geraniol, borneol, α-bisabolol, and α-phellandrene among other less studied terpenes. As for many other terpenes, effective doses are unlikely achievable by the consumption of Cannabis chemovars. It is claimed that terpenes, together with tetrahydrocannabinol (THC) or cannabidiol (CBD), evoke a so-called ‘entourage effect’, which means that the terpenes could have synergistic actions with these cannabinoids. Especially, myrcene is claimed to induce strong synergistic sedative/immobilising action with THC. However, the study referenced in the review did not find any support for this or for the ‘entourage hypothesis’ in general. Thus, it may be possible that the yet-to-be-understood effects of some cannabinoids explain most of the different subjective effects reported by Cannabis users.

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For example, CBD is known to antagonise psychotomimetic (mimics symptoms of ‘psychosis’) action of THC, among its properties in its own right. In addition, there are several other cannabinoids with distinct physiological effects. Cannabinoids; cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), Δ9- tetrahydrocannabivarin (Δ9-THCV), cannabivarin (CBV) and cannabidivarin (CBDV) among other less abundant cannabinoids have been shown to act, not only on the classical cannabinoid receptors CB1 and CB2, but also on other receptors like PPARγ, 5HT3A, A1A adenosine receptor, α2 adrenergic and on a variety of Transient Receptor Potential (TRP) channels and the non-classical cannabinoid receptors G protein-coupled receptors GPR55 and GPR18. Thus, it is not yet known whether different chemotypes of Cannabis show their different effects through this complex interplay or by the support of terpenes or both. If terpenes do contribute to the sedative effects of Cannabis, then limonene, terpinolene, nerolidol, bisabolol, isopulegol, borneol, linalool, linalyl acetate and ocimene may be the more probable candidates.

Terpenes

Early studies, where animals or human subjects were exposed to inhalation of terpene odours, showed that terpineol, pinenes and linalool were able to alter activity. Interestingly, β-eudesmol was found to increase appetite and gastric emptying in rodents with supplementation of only 0.14 ppb in drinking water, which is comparable to the concentrations found in beer. This could, at least partly, explain why some recreational chemovars make some consumers hungrier than others. Importantly, it might have several different molecular targets in the nervous system and effects could be cumulative or synergistic: for instance, unlike with the entourage hypothesis, a study found that some terpenes might have both synergistic and antagonistic effects on each other in the cholinergic system.

Terpenes - Pepper

Aromatherapy has been suggested to provide a potentially effective treatment for a range of psychiatric disorders by double-blind, controlled and randomised studies. Sedative, anti-depressant, anxiolytic (anxiety reducing) and analgesic effects are most commonly reported by subjects undergoing Cannabis aromatherapy treatments. Similarly, studies in mice showed the inhalation of 27 mg linalool or 23 mg linalyl acetate decreased the motility (independent movement) of normal mice and reversed caffeine-induced over-agitation. Administration of only 0.05–0.1 ml/kg of essential oil (EO) of Eugenia caryophyllata (clove), comprised of 77% eugenol and 10% β-caryophyllene, suppressed tonic electroshock-induced convulsions and mortality in mice. In rats, 0.3 mg/kg of Tagetes minuta (commonly known as Stinking Roger) EO (containing mostly ocimene) displayed anxiolytic (anxiety reducing) and anti-depressant effects, while in chickens, administration of 0.04–0.45 mg/kg of the EO exhibited anxiogenic (causing anxiety) effects.

Cannabis Terpenes

In summary, terpenes found in higher amounts in Cannabis may not be solely responsible for the claimed medicinal properties of these compounds. Actually, we infer that popular web pages exaggerate the medicinal properties of the most abundant terpenes. Of course, we are aware of their strong medicinal properties, but those effects are not commonly attainable with consumption of Cannabis products. Moreover, the popular ‘entourage effect’ hypothesis is currently devoid of scientific proof. This does not necessarily mean it is untrue, merely that more trials are needed. On the other hand, some minor terpenes can have substantial effects in small amounts. It is also prudent to say that the potential of β-caryophyllene has been overlooked. In order to overcome the obstacle of low concentrations in consumable Cannabis products and obtain effective doses, one could purify terpenes by steam-distillation for example, this utilises the fact that Cannabis and hops are high-yielding plants in comparison to many other plants used for essential oil production. By selective breeding, which is easy with unisexual plants like Cannabis, the content could be improved to meet the best medicinal effects. Although there have been numerous studies on terpenes, more studies are needed to elucidate the medicinal properties at low doses.

Terpene Chart 2018

Tarmo Nuutinen (2018): “Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus”. European Journal of Medicinal Chemistry, 157:198-228, Cannabis and Terpenes: What Do We Really Know? and Terpenes and Testing Magazine with Extraction Magazine

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Mad About Saffron

spices that interact with the endocannabinoid system

Modern science is starting to catch on to the wisdom of our ancestors, who knew a lot about using aromatic herbs and spices for medicinal purposes. The use of spices for cooking, healing and dyeing fabric has shaped much of human history. In ancient times these highly precious commodities were traded along well-travelled spice routes throughout Asia, the Middle East, Northern Africa and Europe. Some spices were literally worth their weight in gold. Yet, it’s only recently that scientists have discovered the bio-active constituents and molecular mechanisms of several common kitchen spices, shown to reduce oxidative stress and inflammation while modulating multiple healing pathways simultaneously. A number of scientific studies confirm the health-promoting properties of various spices are mediated by the same receptors in the human brain and body that respond pharmacologically to Cannabis.

Saffron: Nerve Tonic

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A 2013 report in Pharmacognosy Review  examined the neuro-protective effects of Saffron extracts, which inhibited the build-up of beta-amyloid plaque in the brain in animal models of Alzheimer’s. The same article noted that Saffron extracts could “prevent retinal damage and age-related macular degeneration”. An Italian research team subsequently showed Saffron can counteract effects of continuous bright light exposure in lab rats by enhancing retinal blood flow. Saffron “engages” both the CB1 and the CB2 cannabinoid receptors “in order to afford retinal protection” the Italian scientists concluded. Described as “the most expensive cultivated herb in the world” Saffron (Crocus sativus) is a much-revered food seasoning and a natural colourant.

Cultivated originally in Persia and Asia Minor, this legendary spice comes from a light purple flower with thread-like red-orange stigma that contains 150 bioactive components, including carotenoids, flavonoids and other potent polyphenols. A rich source of riboflavin (vitamin B-2) and free-radical scavengers, saffron has a long history of use as a folk medicine for treating cancer, convulsions, headaches, skin conditions, asthma, ulcers, premenstrual distress and other diseases. The Ebers papyrus (1550 BC) refers to Saffron as a “cheering cardiac medicament” and a cure for kidney problems. Scientific studies indicate Saffron improves learning and memory by inhibiting the breakdown of acetylcholine. Saffron also enhances the functioning of the GABA receptor, which explains in part its efficacy as a relaxant and nerve tonic. Clinical trials evaluated the anti-depressant properties of Saffron and concluded it was more effective than a placebo and equivalent to Prozac.

Turmeric: Holy Powder

ImageTurmeric (Curcuma longa), a perennial plant of the Ginger family, has a safe 6,000-year track record as a medicinal herb, a culinary spice and a dye for fabric and food. The fleshy rhizome of this all-star botanical is ground into a deep orange-yellow powder and used to season South Asian cuisine. It is a significant ingredient in most commercial curries, as well as a staple of Ayurvedic medical practice, which utilises Turmeric (typically in combination with other herbs) to treat indigestion, throat infections, metabolic dysfunction, common colds and many other ailments. Known as “the holy powder of India”, Turmeric is also applied topically as an antibacterial and anti-fungal remedy for skin sores and to clean wounds. The United States Food and Drug Administration (US FDA), perennial handmaiden of Big Pharma, recognises Turmeric as a food-colouring agent but not as a therapeutic substance, despite more than 5,600 peer-reviewed studies of Turmeric and its main polyphenolic component, Curcumin, that document numerous healing attributes. There is more evidence-based scientific literature (1,500 science articles) supporting the use of Curcumin against cancer than any other nutrient, including vitamin D.

Much like Saffron, Curcumin is a potent antioxidant that confers neuro-protective effects through multiple molecular channels. Turmeric protects against alcohol-induced brain damage, improves insulin sensitivity and cardiovascular function, inhibits platelet aggregation and facilitates the clearing of beta-amyloid plaque associated with Alzheimer’s dementia. It’s worth noting the incidence of Alzheimer’s and other neuro-degenerative diseases among people living in the Asian subcontinent, where Turmeric is ubiquitous, is significantly lower than in North America. Turmeric’s versatility as a medicinal herb derives in part from its interaction with the endocannabinoid system, which regulates numerous physiological processes. In May 2012, Neurochemical Research Identified the CB1 cannabinoid receptor as a mediator of Curcumin’s antidepressant effect: “treatment with Curcumin”, the report notes, “results in the sustained elevation … of endocannabinoids”. In December 2013, the European Journal of Pharmacology disclosed that Curcumin reduces liver fibrosis by modulating cannabinoid receptor transmission.

Peppercorn: Black Gold

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Employed since antiquity as both a food seasoning and a folk cure, Black Pepper (Piper nigrum) is the world’s most traded spice. Touted as “black gold”, the dried fruit of this woody vine, the peppercorn, was considered such a valuable commodity, it served as a substitute for money in business transactions. During the Middle Ages in Europe, Black Pepper was a luxury item only the wealthy could afford. Today, it is one of most commonly used spices on the planet. The manifold therapeutic properties of Black Pepper have been validated by modern science. Essential oil of Black Pepper reduces nicotine cravings and eases withdrawal symptoms. An anti-spasmodic and anti-convulsant, it can also lower blood pressure and relieve digestive distress. Piperine, Black Pepper’s principal bioactive constituent (an alkaloid), has been shown to inhibit cancer cell proliferation in animal models of osteosarcoma, and also potentiates anti-tumoural and apoptotic effects of Turmeric by enhancing the bioavailability of Curcumin. When co-administered, Piperine and Curcumin interact synergistically to confer a stronger antidepressant effect than either compound delivers on its own.

In addition to Piperine, Black Pepper contains vitamin K, iron and manganese along with a robust array of aromatic terpenes, which should be familiar to Cannabis connoisseurs: Pinene, Limonene, Linalool … Black Pepper is particularly well endowed with the sesquiterpene Beta-caryophyllene, an important medicinal component of many Cannabis strains. Beta-caryophyllene is the only terpene known to bind directly to CB2, the cannabinoid receptor that regulates immune function, peripheral nervous system, metabolic tissue activity and other physiological processes. Black Pepper’s potent anti-inflammatory effect is mediated by the CB2 receptor. THC binds directly to the CB2 receptor, although this is not what causes a person to experience euphoria when he or she consumes Cannabis. That’s because CB2 receptors are not present to a significant degree in the brain and central nervous system. Beta-caryophyllene is a significant component of several other common kitchen spices, including Clove, Cinnamon and Oregano.

Nutmeg: Cannabinoid Booster

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Nutmeg (the dried kernel of Myristica fragrans) does not directly activate the CB1 cannabinoid receptor in the brain or the CB2 cannabinoid receptor in immune cells. This commonly used kitchen spice can have a powerful impact on the endocannabinoid system as a 2016 study in Pharmaceutical Biology reported, Nutmeg interacts with the endocannabinoid system by inhibiting certain key enzymes that catabolise (break down) the two main endocannabinoids, anandamide and 2AG. Likened to the brain’s own Cannabis, these short-lived endogenous cannabinoid compounds bind to CB1 and CB2 receptors. This triggers a signalling cascade on a cellular level that protects neurons against toxic insults (stress) and promotes neurogenesis (creation of new stem cells in adult mammals). Two catabolic enzymes, fatty acid amide hydrolase (FAAH) and monoglycerol lipase (MAGL), are involved in the breakdown of anandamide and 2AG, respectively.

Simply put, less FAAH  and MAGL means more anandamide and 2AG. So by inhibiting these catabolic enzymes, Nutmeg raises the level of anandamide and 2AG in the brain and boosts cannabinoid receptor signalling throughout the body. FAAH and MAGL  inhibition has proven to be beneficial for easing pain, anxiety, hypertension and various inflammatory conditions in preclinical research, which lends credence to traditional medical uses of Nutmeg. Ayurvedic healers in India utilise Nutmeg as an anxiolytic or anxiety-reducing agent. But there are conflicting accounts of Nutmeg’s effect on anxiety and depression; higher doses cause a biphasic response, exacerbating mood disorders and triggering hallucinations. Nutmeg has long been known for its central nervous system activity. In an article in Nature (1966), Alexander Shulgin identified “myristicin as a psychotropic substance”.  Many prison inmates, including Malcolm X before his conversion to Islam, sniffed and swallowed Nutmeg to ‘get high’. Now we know how and why Nutmeg has a neuro-active effect; it stimulates cannabinoid receptor transmission by suppressing the enzymes that break down the brain’s own Cannabis.

Ecological medicine

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Herbs and spices are ecological medicines that 75-90% of the world’s rural people still rely on as their primary mode of healthcare. Numerous plants, not just Cannabis, are endowed with compounds that interact directly or indirectly with the endocannabinoid system. The health benefits of many common kitchen spices are mediated by the same cannabinoid receptors in the human brain and body that Cannabis activates. Scientific research into Cannabis’ effects on the brain has opened the door to whole new vistas of understanding human biology and physiology. As we welcome Cannabis back into the pantheon of approved medicinal herbs, perhaps we should rethink our ideas about the endocannabinoid system, so named after the plant that led to its discovery, and stretch its boundaries to encompass an abundance of botanicals.

Adapted from an article by MARTIN A. LEE, Director, Project CBD, author Smoke Signals: A Social History of Marijuana — Medical, Recreational and Scientific

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Copaiba – Natural Anti-inflammatory – Better Than Cannabidiol

CBDThere is a lot of hype around Cannabidiol (CBD), for very good reasons. CBD is one of two well-known major cannabinoids, potent substances with enormous therapeutic potential, causing quite a buzz among scientists, health professionals and patients who are using CBD-rich products to treat a wide range of conditions including anxiety, antibiotic-resistant infections, cancer, cardiovascular disease, chronic pain, Crohn’s, diabetes, multiple sclerosis, PTSD, rheumatoid arthritis, schizophrenia and more. However, legality, purity and potency get in the way of many realising any real relief from CBD. As a completely legal alternative, Copaiba (Copaifera reticulate) essential oil (EO), has the highest known botanical content of one of the most commonly found terpenes in Cannabis, beta-caryophyllene (BCP). Terpenes are produced in special secretory cells within the trichomes of the Cannabis plant, the nearly microscopic resinous stalks that cover the flowers and leaves. This is also where all cannabinoids, like THC and CBD, are created. About 20,000 terpenes exist in nature; around 200 have been identified in Cannabis.

bcp

BCP was first synthesised in 1964, but it wasn’t until 2008 that European scientists discovered it had cannabinoid-like properties. CBD has significant impacts on human health but doesn’t bind to cannabinoid receptors. BCP has many of the same health benefits as cannabinoids do, without binding to CB1 receptors. CB2 receptors are found throughout the body to which BCP’s bind, as evidenced in the 2013 study, Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception (antinociception is the process of blocking detection of a painful or injurious stimulus by sensory neurons). The abstract of the 2008 study, Beta-caryophyllene is a dietary cannabinoid, concludes;

This natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional non-psychoactive CB2 receptor ligand in foodstuff and as a macrocyclic* anti-inflammatory cannabinoid in Cannabis”.

*Relating to or denoting a ring composed of a relatively large number of atoms, such as occur in chlorophyll and several natural antibiotics.

CB1 CB2 receptors

Due to targeting CB2 receptors, BCP is an effective way to medicate while avoiding any alteration in perception or motor skills. It can be used to treat several inflammatory disorders, including arthritis, multiple sclerosis and colitis. BCP has been shown to fight cancer, reduce anxiety and is gastroprotective, meaning it can be used to treat ulcers. There is a mountain of evidence to support the use of BCP for easing tension and discomfort, providing protective effects for kidney and liver systems, providing protection against auto-immune disruptionseasing depressive feelings and even helping to abstain from unhealthy habits such as alcohol dependence. Copaiba also shows skin-enhancing benefits. Applied directly to acne pimples and scars, it reduces inflammation and speeds up skin healing. 

1pain_reliefCB2 activation is correlated with the concentration of BCP’s. CBD oil is 35% BCP while Copaiba is 55%. This means even using high quality Cannabis oil it may be BCP doing all the work in easing health issues. Switching to Copaiba may afford even more relief and due to there being no THC, it won’t give a false positive on a drug test. BCP’s are in plenty of foods and other essential oils but nowhere near the concentration nor purity found in Copaiba. According to Dr Ethan B. Russo in his 2011 study, published in the British Journal of Pharmacology, Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects;

β-Caryophyllene is generally the most common sesquiterpenoid encountered in cannabis … Caryophyllene is anti-inflammatory … comparable in potency to the toxic phenylbutazone and an essential oil (EO) containing it was on par with etodolac and indomethacin. In contrast to the latter agents, however, caryophyllene was a gastric cytoprotective, as had been claimed in the past in treating duodenal ulcers in the UK with Cannabis extract. Caryophyllene may have contributed to antimalarial effects as an EO component. Perhaps the greatest revelation regarding caryophyllene has been its demonstration as a selective full agonist at CB2”.

Copaiba

To get the amazing benefits of BCP from Copaiba EO, use it aromatically, apply topically to affected areas or internally, for example, use as a calmative before sleep, applying a few drops under the tongue (sublingually). CBD oil produced from hemp might not actually have much CBD whilst oils derived from Cannabis might contain THC and heavy metal traces, depending on the soil it was grown in and extraction techniques employed. If you want access to similar health benefits of as those provided by cannabinoids, a 15 ml bottle of Copaiba EO is competitively priced, hugely discounted in comparison to a 15 ml bottle of CBD oil!

Copaiba oil extractionCopaiba is a stimulant oleoresin obtained from the trunk of several pinnate-leaved South American leguminous trees found in the Amazon. Its medicinal use dates back to the 16th century when natives of Brazil used it as folk medicine. Today, Brazil produces approximately 95% of this oil-resin, exporting more than 500 tons each year. Sales of Copaiba are increasing, at least in part because more than 54 million American adults suffer from some form of arthritis and 23.7 million are limited in their usual activity primarily due to pain.

In Australia, 3.5 million (15% of) people have a form of arthritis, with the majority of those affected being of working age or younger. The conventional way to treat arthritis is using nonsteroidal anti-inflammatory drugs (NSAID’s) as well as cyclo-oxygenase-2 inhibitors (COXIB’s), which are not without adverse events like gastrointestinal bleeding, heart attacks and stroke. The side effects of NSAID’s and COXIB’s as well as warnings on the risks of gastrointestinal side effects, bleeding and cardiovascular disease all suggest the need to test novel therapies with potential clinical benefits and fewer side effects than available pharmaceuticals.

ClovesSo, what plants are high in this CB2 agonist BCP? Well the James Duke ARS databse  identifies many plants that have signficant amounts of BCP with the very highest being Celery. Herbs with BCP include Basil (Ocimum basilicum), Oregano (Origanum vulgare), Rosemary (Rosemarinus officinalis), Sage (Salvia officinalis) and Thyme (Thymus vulgaris). Spices as a source of BCP include Black Pepper (Piper nigrum), Cinnamon (Cinnamomum varieties) and Cloves (Syzgium aromaticum). If you’re working on inflammatory problems in the body, try a combination approach; combining CBD from hemp with traditional anti-inflammatory herbs. Alternatively, just include all of the above in your diet to support a healthy endocannabinoid system (ECS) response using food!

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Expanded from Five Reasons Copaiba is Better Than CBD Oil with Copaiba: Silver bullet or snake oil?BCP (Beta-Caryophyllene) : a potent CB2-agonist (anti-inflammatory) cannabinoid from food and Beta Caryophyllene (BCP): Cancer-Fighting Terpene

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Cannabis Terpenes and their Benefits – Linalool

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Many are familiar with the major cannabinoids found in the Cannabis sativa L., (cannabis) plant, tetrahydrocannabinol (THC) and cannabidiol (CBD), which have great efficacy for conditions like depression, PTSD and epilepsy. But cannabinoids are only part of the picture. More than 200 terpenes are available in cannabis, while over 20,000 exist in nature. Primarily responsible for aroma and flavour, terpenes are secondary metabolites, fragrant oils which also offer a wide range of therapeutic benefits. Like amino acids, terpenes are powerful building blocks within plant physiology that aid in production of vitamins, hormones, pigments, resins, and cannabinoids in cannabis.

leavesTerpenes are secreted alongside cannabinoids like THC and CBD, with both biosynthesised in the glandular trichomes, small resin glands primarily observed on the surface of the flowers and leaves of cannabis plants. Terpenes are very volatile, delicate molecules, easily destroyed by heat and oxidation and cannabis plants release more terpenes when temperatures are higher (one reason they emit stronger aromas during the peak of harvest).

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As discussed in a previous article, Cannabis Terpenes and Their Benefits – Limonene, ancient cultures have used terpenes from a variety of aromatic herbs including cannabis for millennia to treat a wide variety of conditions. More modern research has confirmed the beliefs of ancient civilisations, revealing strong medicinal efficacy. There are about ten primary and twenty secondary terpenes that occur naturally in significant concentrations. β–Linalool (linalool), a monoterpene, has a boiling point of 198°C (388°F) and is best known for the pleasant floral scent reminiscent of spring flowers, with spicy overtones, it gives hundreds of different plants including lavender, citrus, cinnamon, laurel, birch, coriander, clary sage and rosewood.

Humans have inhaled the scent of certain plants, including many containing linalool, since ancient times to help lower stress levels, fight inflammation and combat depression. Linalool is a calmative and sleep aid (partly responsible for sedative effects of certain cannabis strains) and is a critical precursor in the formation of vitamin E. Linalool is found in highest concentrations (30-40%) in the essential oil of lavender and to a lesser extent in more than 200 species of aromatic plants, many of which are used traditionally as analgesic and anti-inflammatory remedies. Linalool is the ‘sweetness’ detected in many essential oils.


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Twenty-five drops of lavender essential oil delivers around 0.3 grams of linalool. 



The Lamiaceae plant and herb family, which includes mints and other scented herbs, is a common source of linalool. The Lauraceae plant family, which includes laurels, cinnamon and rosewood, is also a readily available source. The Rutaceae family, which contains citrus plants, is a third viable source. Birch trees and several different plant species found in tropical and boreal climate zones also produce linalool along with some fungi. Linalool is used in a wide variety of bath and body products and is commonly listed under ingredients as beta linalool, linalyl alcohol, linaloyl oxide, p-linalool and allo-ocimenol. Widely used (around 80% of all products) as a fragrance in cleaning and hygiene products, in the chemical industry and as an insecticidal vapour against flies, fleas and cockroaches.

Thyme spice

Linalool serves many roles in relieving symptoms, including pain, depression, seizures, inflammation (similar to limonene) and even insomnia (acts as a sedative) and its tranquillising effects are helpful for those suffering with many types of psychosis. Many linalool-producing plant species are traditionally used as sedative, analgesic, hypnotic or anxiolytic (anti-anxiety) remedies in traditional medicine. The sedative, anxiolytic and anti-seizure effects have their mechanism of action based on the modulation of the glutamate and GABA neurotransmitters (glutamate is the main excitatory and GABA the main inhibitory neurotransmitter in the mammalian brain), similarly to the way cannabinoids act. Thus, a cannabis plant with both THC and linalool will probably produce a significant sedative and analgesic effect, due to the synergy between the two compounds. However, a cannabis plant with CBD and/or THCv and/or CBDv and linalool will probably produce a synergistic effect as an anti-seizure medication, which would be useful in cases of epilepsy, even as a preventive measure.

Linalool’s therapeutic effects include:

  • Analgesia – a pain killer, as elucidated in a 2003 study, ‘Linalool produces antinociception in two experimental models of pain’. Antinociception is the action or process of blocking detection of a painful or injurious stimulus by sensory neurons. In another more recent study (2016), ‘Odour-induced analgesia mediated by Happy Farmerhypothalamic orexin neurons in mice‘, noted that linalool, “… significantly increased the pain threshold and attenuated pain behaviours … findings reveal central analgesic circuits triggered by olfactory input in the mammalian brain and support a potential therapeutic approach for treating pain with linalool odour stimulation“. The essential oil of lavender eases burns (topically) due to its antiseptic, anti-bacterial and circulatory stimulating properties and has been shown to reduce opiate intake when inhaled by patients undergoing post-operative pain treatment. Combined with cannabinoids of the same efficacy, linalool can be a reinforcing agent in managing painful conditions like Multiple Sclerosis (MS), dystonia, arthritis and other chronic conditions.

  • Anti-anxiety – anxiolytic effects on a comparable level to local anaesthetics such as lidocaine or menthol. 2008 research published in the American Association of Nurse Medicinal holy basil or tulsi leavesAnesthetists Journal supported the sedative qualities of linalool. The study estimated 19 million Americans suffer from anxiety-related ailments, with 16% aged 18-54 being patients of one or more anxiety conditions, which sometimes lead to substance abuse and mood disorders. This study revealed linalool to be a powerful sedative that delivers real efficacy to those who suffer anxiety disorders and a most common side effect, insomnia. Concluded the study: “Our data … suggested that linalool modulates the central nervous system by producing unconsciousness and degradation of motor movements”. It has also been used in the treatment of psychosis.

  • Anti-convulsant – seizures afflict those with conditions other than epilepsy, including traumatic brain injury, brain tumours and hydrocephalus, for example. Seizures featuring a duration of less than two minutes, typically do not cause lasting linaloolharm, although very painful and exhausting for sufferers. A 2010 study involving mice that employed three different sub-types of linalool found it to be an effective anti-convulsant, showing significant promise for those who suffer seizures. Reported the study, “Linalool … was effective in preventing tonic convulsions induced by trans-corneal electroshock in … animals”.

  • Anti-depressant – more than 20 million people in the United States (US) and at least one million (annually) in Australia suffer from debilitating depression. This common psychological ailment can negatively affect education, career choices, personal relationships and physical health. Linalool, when combined with cannabinoids like THC, help alleviate depression. A 2015 study, ‘Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway‘, indicated both linalool and β-pinene produce an antidepressant-like effect.

  • Anti-inflammatory – sufferers of inflammation-based diseases, Crohn’s, arthritis, Alzheimer’s, asthma, fibromyalgia, dermatitis, IBS, lupus and Parkinson’s, among many others, gain benefit from the anti-inflammatory activity of linalool. A 2002 study in the Journal of Phytomedicine revealed linalool is a major anti-inflammatory
    coriander-leaves-and-seedsagent, potentially helping with a variety of inflammation-related ailments, such as
    cancer, arthritis and Crohn’s disease. The same research team, in a 2003 study, found linalool to also be an analgesic ( pain killer). In 2006 another linalool study further reinforced its use as a powerful anti-inflammatory. Linalool reverses the histopathological hallmarks of Alzheimer’s (2016 study) and restores cognitive and emotional functions via an anti-inflammatory effect. Linalool can also significantly reduce lung inflammation caused by cigarette smoke as shown by a study in 2015, ‘Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation’.

  • Anti-leukaemia / Chemo-preventive – shown to have anti-leukaemia spectrum and molecular lavender-1117274_640mechanisms inhibiting tumour cell growth. In a 2010 study it was demonstrated linalool preferentially induced growth arrest and apoptosis of a variety of human leukaemia cells, but spared normal cells. The findings warrant further investigation of this class of natural product for developing novel therapeutic agents for leukaemia. A 2016 study, ‘The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis …’, evidenced topical or intraperitoneal treatment with linalool prevented acute UVB-induced hyperplasia, oedema formation, lipid peroxidation and antioxidant depletion, in mice.

  • Anti-seizure – linalool has properties that inhibit glutamatergic activity and also decrease the release of neurotransmitters of the neurons under glutamate stimulation. The abstract of a 2001 study, ‘Effects of Linalool on Glutamate Release and Uptake in Mouse Cortical Synaptosomes‘, states; “Linalool, a monoterpene compound prevalent in essential oil of plant species traditionally used as sedatives, has been characterised as anticonvulsant in several experimental models … linalool significantly reduced potassium-stimulated glutamate release as well as glutamate uptake, not interfering with basal glutamate release. The data indicates that linalool may interfere with several relevant elements of the glutamatergic transmission …“. 

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  • Anti-chemotherapy-induced nausea and vomiting (CINV) – a 2016 study in the Journal of Pharmacology and Experimental Therapeutics, ‘Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modelling’, summarised the research outlining how they used nonlinear mixed-effects modelling to show the oils citral, eucalyptol and linalool inhibit 5-HT3 receptors via noncompetitive mechanisms. Compounds that selectively antagonise 5-HT3 receptors are the current gold-standard for treatment of chemotherapy-induced and post-operative nausea and vomiting and have potential for the treatment of a range of other conditions.linalcool-500x500
  • Sedative / Sleep Aid – an estimated 10-30% of people suffer from insomnia at some point in their lives, with 10% reported to experience chronic and severe sleep deprivation. Cannabinoids like CBN, when combined with terpenes such as linalool, help patients get the sleep they require to maintain homoeostasis (balance) and good health. Adequate sleep is critical for patients to most effectively fight their condition or disease. Linalool has been the subject of many studies, including one in 2009 in the Journal of Agricultural and Food Chemistry, ‘Stress Repression in Restrained Rats by … Linalool Inhalation and Gene Expression Profiling …’ during which scientists allowed laboratory rats to inhale linalool while exposing them to stressful conditions. Linalool returned elevated stress levels in the immune system to near-normal conditions. In tests on humans who inhaled lavender essential oil, it caused severe sedation. In tests on laboratory rats it reduced their activity by almost 75%. 

Sativa

Cannabis strains* that frequently display high levels of linalool include 9lb Hammer, Amnesia Haze, Bubblegum, G-13, Lavender, LA Confidential, Master Kush, Pink Kush, OG Shark and Tangerine Dream.

Expanded from Myrcene, Linalool, and BisabololTaming THCAntitumor Activity of MonoterpenesLinalool Cannabis TerpeneLinalool produces antinociceptionCannabis Terpenes and How They Affect YouTerpenes, Chemistry and analysis of phytocannabinoids, Cannabinoids and Terpenes as Chemotaxonomic MarkersPlant terpenesWhat is the terpene Linalool found in cannabis?Linalool … Shown to Have Anti-Cancer EffectsRelationships of linalool, linalyl acetate and oxygenated derivatives

*Not every batch of any given strain will have high levels of any particular terpene as they are subjected to variable growing conditions. The only way to be sure is through a lab’s terpene analysis.

Cannabis Terpenes and their Benefits – Limonene

terpenes-oidsAs discussed in a previous article, Cannabis Terpenes and Their Benefits – Caryophyllene, Geraniol and Humulene, terpenes form a large group of phytochemicals, responsible for the organoleptic (aroma and flavour) characteristics of different Cannabis sativa L., strains under human domestication. Terpenes are secondary metabolites, fragrant oils secreted in trichomes (cannabis resin glands) alongside cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD). Part terpenoid, part phenol, both types of compounds are biosynthesised in the glandular trichomes of the leaves and flowers of the cannabis plant. Terpenes not only dictate the smell of cannabis and other plants, they also modify their effects.

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Terpenes are very volatile, delicate molecules, easily destroyed by heat and oxidation. Popular cannabis concentrates, like BHO and CO2 oil, are mostly void of terpenes. One extraction method called live resin preserves the terpene profile of cannabis plants. This process involves cryogenically freezing plants immediately after harvest and then using a laboratory extraction process to remove and isolate a more accurate representation of a particular plant’s mix of cannabinoids and terpenes. There are about ten primary and twenty secondary terpenes that occur naturally in significant concentrations. D-limonene (limonene) as its name implies, provides an aroma of citrus and is found not only in cannabis, but also oranges, grapefruits, lemons, limes and some other herbaceous plants.

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terpene icon limoneneIf you’ve ever wondered what gives cannabis strains like Super Lemon Haze, Chernobyl and Tangie that sweet citrus aroma, it’s limonene. Some strains tend to express higher levels of this terpene and often it’s the lemon scent that gives it away. Whereas THC levels typically make up 10-20% of a cannabis flower’s biomass, limonene occurs in trace amounts, generally none at all to 1-2%. Some strains exhibit higher levels than others but these levels can vary widely. One Jack Herer may test for high levels of limonene while another will demonstrate a disappointing lack thereof. The only way to know for sure is through lab-tested batches.

linalool cannabis terpeneLimonene is a dominant terpene in cannabis strains with a pronounced sativa effect, appearing most often in sativa strains, but that doesn’t mean there aren’t indica strains with high limonene potential. Berry White exemplifies this. Jack Herer is a favourite with high levels of limonene and a palette of other terpenes like pinene and myrcene, which promote alertness and relaxation respectively. OG strains tend to have a lemony-pine aroma, which is limonene. It can be detected in Durban Poison, a high-energy sativa, even though not immediately apparent in its subtle sweet, earthy aroma, but you’ll feel its uplifting, stress-relieving effects. The presence of limonene in name and aroma is obvious with Super Lemon Haze, an uplifting sativa strain with a sweet lemon flavour.

Limonene can be vaporised at or around the terpene’s boiling point of 176°C (349°F).

grapefruit-oil

A cyclic carbohydrate monoterpene, limonene is a main component of the essential oil of lemons, which is where its name comes from. It is present in citrus essential oils commonly used in Australia and widely used as a flavour and fragrance additive in cleaning and cosmetic products, food and pharmaceuticals. It is also a biodegradable, organic and environmentally friendly solvent for 3D printing and cleaning.

A major reason for limonene’s widespread use is its very low toxicity. While non-toxic to humans, an ‘allergic reaction’ (sensitisation and/or contact dermatitis) to limonene and linalool are more common than previously thought. Limonene may be related to α-pinene and some limonene products, oxidised by contact with air, provoke skin and mucous irritation. This leads to 3% of people exposed to high doses for a long period of time, such as workers in the paint industry, suffering from contact dermatitis. The second most widely distributed terpene in nature, limonene has a history in medicine and some studied therapeutic benefits include:

  • Aiding digestion – treats indigestion and heartburn, prevents gastric distress by neutralising gastric acid and supporting normal peristalsis (digestive movement). Gastro-oesophageal reflux (GERD) is prevented.
  • Anti-asthmatic – a 2010 study examined anti-inflammatory effects and found it to be a potential treatment for bronchial asthma due to its ability to inhibit cytokines.
  • Anti-bacterialnaturally used by plants to kill pathogens and has anti-bacterial properties as discussed in a 2006 study.
  • Anti-cholesterol – solvent of cholesterol; cholesterol-containing gallstones dissolve and “fat sludge” is cleaned from the Gallbladder. A 2011 study verified inhibition of the activity of an enzyme which plays a central role in the production of cholesterol. dlimonene-300x172
  • Anti-depression – relieves symptoms and elevates mood. A 2012 study examined it’s role and found it to be notable and a significant way to treat depression.
  • Anti-fungal – natural remedy for athlete’s foot and yeast outbreaks.
  • Anti-inflammatory – a potent anti-oxidant, studies from 2006 and 2010 explore such as an anti-inflammatory agent. A 2013 study went so far as to recommend using as a dietary supplement due to powerful anti-inflammatory effects on the intestines (controlling colitis).
  • Anti-insomnia improves sleep patterns and induces sedative effects.
  • Anti-proliferative, chemo-preventive (prevents, rolls back and protects against cancer), inhibits cancer cell growth and helps fight the spread of various cancers (glioblastoma, prostate, pancreatic, breast and skin [melanoma]) – anti-carcinogenic activity in rat mammary carcinogenesis was evidenced in a 1993 study. In another 1993 study, evidence suggested chemo-preventive activity. It’s been known for over two decades it exhibits multiple anti-tumourigenic effects (1994). In 1995 collaborators re-evidenced it’s anti-carcinogenic ability. In a 1996 study, it was suggested it might be a chemo-preventive agent for colonic carcinogenesis. Shown in 1996 to inhibit carcinogen-induced lung tumourigenesis, a 1998 study suggested an association to anti-cancer activity in intercellularlimonene communication. Numerous studies and a clinical trial (1998) found it effective at beating advanced cancers and recommended further research. In 2002 effects were further investigated as a chemo-preventive agent against liver cancer and in a 2003 study it was demonstrated chemo-preventive. A 2007 study established chemo-preventive activity against many types of cancer including breast and colorectal. A selective anti-proliferative action on tumour lymphocytes was shown in 2008 along with inhibited metastatic progression of some melanoma cells. A 2010 study found a constituent increased the survival rate of glioblastoma patients and had virtually no long-term side effects. In 2010, citrus oil rich in limonene was verified to induce apoptosis (cell death) and act as an anti-angiogenic with a preventative effect on colon cancer. This effectiveness is being tested in clinical trials on breast cancer cells. A 2012 study found it to have strong enough inhibition of inflammation to actually be chemo-preventive. A 2013 study promoted the identification of pro-apoptotic, anti-inflammatory, anti-proliferative, anti-invasive and potential anti-angiogenic activities. A 2015 study demonstrated anti-cancer properties with effects on multiple cellular targets at varying potency.
  • Antiseptic – has therapeutic effects in certain diseases and antiseptic properties, mainly against the bacteria responsible for acne.extract-limonene-oranges-800x800
  • Anxiolytic (Anti-anxiety) – a 2012 study found it exhibited anxiolytic-like effects so potent and with such mild side-effects it was recommended as a new treatment for anxiety. Studies suggest it causes a rise of serotonin and dopamine neurotransmitters in the brain. Dispersal of it in the environment produces a decrease in depressive symptoms (trialled on hospital patients) in addition to a strong immuno-stimulation. It is quickly absorbed by inhalation or by the skin and it is metabolised quickly.
  • Pre-Diabetes/Diabetes and weight loss – dietary use prevents and alleviates insulin resistance and works against development of the metabolic syndrome associated with non-alcoholic fatty liver disease (NAFLD). It acts as a mild appetite suppressant and prevents weight gain.
  • Transdermal patches – improves absorption of other terpenes and chemicals by way of the skin, mucous membranes and digestive tract. Is being researched for use in dermal patches to improve transdermal absorption of other active substances as it aids in the biosynthesis of terpenes through the skin and mucous membranes (helps penetrate the skin).
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Dietary Supplement that comes with a Warning

essential-oil-research-limonene-has-great-potential-for-breast-cancer1A person consuming one to two servings of citrus fruits per day is likely to get 15-40 milligrams (mg) of limonene; if the peels are consumed in some way this level may increase to 50-90 mg. The recommended dosage varies depending on the condition being treated, but most suggest taking 1,000 to 3,000 mg per day with meals. It is therefore deemed best to take limonene as a daily supplement to meet the daily dose required. Dietary supplements and essential oil blends of limonene are typically produced from the peels of oranges. Since using tinctures or undiluted essential oils can irritate the digestive passages, capsules are generally recommended for internal use. Typical brands sold at a health food store or online will contain between 250 to 1,000 mg per capsule.

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People who have gastric ulcers or those who take medications which interact with grapefruit should consult their doctor before taking limonene. Higher doses than 3,000 mg or more (capsules) may cause the following:

  • Feeling tired due to its calming and anti-anxiety properties
  • Loose stools in some as it helps peristalsis (digestion)
  • Could move stagnant bile rapidly into digestive tract, which may induce nausea (it clears sludge from the gallbladder)

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Expanded from Myrcene, Linalool, and Bisabolol: What are the Benefits of These Cannabis Terpenes?, Limonene Safety FactSheetTerpenes, Limonene,  d-Limonene – Effective for Lowering Cholesterol Naturally and Much MoreAntitumor Activity of Monoterpenes Found in Essential OilsInfographic: What are Cannabis Terpenes and How Do They Affect You?, TerpenesChemistry and analysis of phytocannabinoids and other cannabis constituentsEvolution and Classification of Cannabis sativa (Marijuana, Hemp) in Relation to Human UtilizationCannabinoids and Terpenes as Chemotaxonomic Markers in CannabisPlant terpenes: defense responses, phylogenetic analysis, regulation and clinical applicationsd-limonene attenuates blood pressure and improves the lipid and antioxidant status in high fat diet and L-NAME treated ratsWhat is Limonene and Chemical profile, antifungal, antiaflatoxigenic and antioxidant activity of Citrus maxima Burm. and Citrus sinensis (L.) Osbeck essential oils and their cyclic monoterpene, DL-limonene

Cannabis Terpenes and Their Benefits – Caryophyllene, Geraniol and Humulene

Terpenes form a large group of phytochemicals, with more than 200 molecules identified in Cannabis sativa L. Terpenes are responsible for the organoleptic characteristics (aromas and flavours) of different strains and have therefore contributed to the selection of strains under human domestication. Terpenes are classified in diverse families according to the number of repeating units of 5-carbon building blocks (isoprene units), such as monoterpenes with 10 carbons, sesquiterpenes with 15 carbons and triterpenes derived from a 30-carbon skeleton.

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Terpene yield and distribution in the plant varies according to numerous parameters, such as processes for obtaining essential oil, environmental conditions, maturity of the plant. Mono- and sesquiterpenes have been detected in flowers, roots and leaves of Cannabis, with the secretory glandular hairs as the main production site. Monoterpenes generally dominate the volatile terpene profile (from 3.1-28.3 mg flower dry weight) and include mainly D-limonene, β-myrcene, α- and β-pinene, terpinolene and linalool. Sesquiterpenes, β-caryophyllene and α-humulene in particular, occur to a large extent in Cannabis extracts (from 0.5-10.1 mg flower dry weight). Triterpenes have also been detected in hemp roots, as friedelin and epifriedelanol, in hemp fibres as β-amyrin and in hemp seed oil as cycloartenol, β-amyrin and dammaradienol.

Hemp trichome types. (A) Unicellular non-glandular trichome; (B) cystolythic trichomes; (C) capitate sessile trichome; (D) capitate-stalked trichome; (E) simple bulbous trichome; (F) complex bulbous trichome.

Terpenes are secondary metabolites, secreted alongside cannabinoids, which are a class of terpenophenolic (part terpenoid, part phenol) compound, which provide plants with aromas and flavours. Both types of compounds are biosynthesised in the glandular trichomes of leaves and flowers of the Cannabis plants and are accumulated in large proportions in the exuded resin. It seems certain non-capitular glandular trichomes, which are more abundant in the leaf surface, are specialised in synthesising terpenes. It has been shown the ratio between monoterpenes and sesquiterpenes in leaves and flowers is rather different due to the dominance of sessile trichomes in leaves, which are more specialised in synthesising terpenes, while capitate trichomes are more abundant in flowers and are specialised in the synthesis of monoterpenes and cannabinoids. The proportion of terpenes in the plant is normally less than 1%, potentially achieving up to 10% of the resin composition.

Terpenes play a vital Oregano, Basil and Rosemary plants with name tags in flower pots, shovel and watering can on woodenrole in the plant kingdom; they deter insect predation, protect plants from environmental stresses and act as building blocks for more complex molecules, such as cannabinoids. Many terpenes act synergistically with other varieties of terpenes and some either catalyse or inhibit formation of different compounds within a plant. While much research has yet to be done on terpenes, their potential to offer unique benefits to medical patients has heightened the interest of both medicine and science. Understanding how terpenes function allows scientists to manipulate cannabinoids to desired ratios.

There are around ten primary and twenty secondary terpenes that occur naturally in significant concentrations. Alphabetically, the first three of the primary terpenes found in Cannabis are caryophyllene, geraniol and α-humulene.

terpene icon-caryophyllineCaryophyllene is a sesquiterpene, made of three isoprene units, which makes it larger than the monoterpenes, pinenelimonene and myrcene (made up of only two isoprene units). α-caryophyllene (α-humulene), β-caryophyllene (BCP, the main component of essential oil of black pepper and Copaiba balsam) and caryophyllene oxide which resists decarboxylation (the terpene  most commonly found in Cannabis extracts and detected by sniffer dogs).

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Thai basil

This sesquiterpene is found in many other plants including Thai basil, cinnamon, cloves (known remedy for toothache), hops, oregano and rosemary. With a rich spicy odour and flavour it is present in all Cannabis strains. Caryophyllene oxide takes part in the defence system of plants, functioning as an insecticide and an anti-fungal. BCP is the only terpene known to interact with the body’s Endocannabinoid System (ECS) via cannabinoid receptor 2 (CB2).

 

Therapeutic uses:

  • Alcohol craving reduction
  • Analgaesic – pain relief.
  • Anti-bacterial Slows bacterial growth.
  • Anti-coagulant properties
  • Anti-depressant – Relieves symptoms of depression.
  • Anti-fungal – Caryophyllene and Cannabichromene (CBC) join in defence against fungi and caryophyllene oxide has shown clinical effectiveness against certain fungal infections
  • Anti-inflammatory on two levels, one is blocking prostaglandins’ inflammatory pathway (also occurs with myrcene and pinene), the other is as a CB2 agonist
  • Anti-oxidant – Prevents oxidation damage to other molecules in the body.
  • Antiseptic
  • Anti-proliferative – Inhibits cancer cell growth.
  • Anxiolytic – Helps relieves anxiety.
  • Gastric protection effects
  • Neuroprotective – Slows damage to the nervous system and brain.

 

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What makes caryophyllene chemically unique is the inclusion of a cyclobutane ring, a rarity in nature making it an attractive candidate for biotech research. As BCP has also been shown to have cancer fighting properties it could be a viable candidate for a new chemotherapy drug. Caryophyllene isn’t only unique for being a cyclobutane, but for being both a terpene and a ‘dietary cannabinoid‘, a food-stuff which acts as a cannabinoid and binds to CB2 receptors.

Cannabinoids as a terpenophenolic compound, trigger the body’s endocannabinoid receptors. A 2008 study, which first identified caryophyllene as a cannabinoid, found it had numerous medicinal benefits. Some sources speculate BCP is so powerful it could threaten existing pharmaceuticals and synthetic cannabinoids currently being developed, which could be why BCP is being so heavily studied.

Boiling Point: 160°C (320°F). LD50 (Lethal Dose): >5g/kg for rats. Compare to Nicotine: for mice – 3mg/kg, for humans – 40–60 mg/kg. Strains known to exhibit high levels of Caryophyllene include hybrids Chemdawg, OG Kush and Skywalker OG; Indica’s Bubba Kush and Rockstar; and Sativa, Sour Diesel.

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Cloves, dried bud of the flower of the Syzygium aromaticum tree

 

terpene icon geraniol Geraniol (also known as lemonol) is present in citronella, geraniums, lemongrass, lemons and roses and emits a floral, rosy, occasionally fruity (passionfruit, peach) scent that makes it a popular perfume additive. It is an effective mosquito repellent but interestingly, geraniol is produced by bees as a means of marking their hives and flowers and as such it is a bee attractant.
What is the cannabis terpene geraniol?

Wood Cranesbill or Woodland Geranium (Geranium sylvaticum)

Geraniol is a monoterpene alcohol that boils at about 230˚C (447˚F) and frequently occurs in strains that also produce linalool. It is used frequently as a fruity flavouring agent and shows up in an array of bath and body products. Geraniol, like valencene, is known to repel mosquitoes. Potential therapeutic benefits include:

A few strains said to test high in geraniol include indica Lavender, sativa’s Amnesia Haze and Great White Shark, Afghani, Headband, Island Sweet Skunk, OG Shark and Master Kush currently test highest in geraniol.

BG7ATW / Flower - Rose

terpene icon humulene
Humulene, also commonly called α-humulene or α-caryophyllene is one of the predominant terpenes in Humulus lupulus (common hops), from which it gets its name. Also found in basil, Cannabis, clove, coriander, ginger, ginseng, common sage and spearmint. While humulene is related to β-caryophyllene it is a different isomer with distinct properties and it has yet to be recognised as a dietary cannabinoid. Like caryophyllene, humulene is a sesquiterpene. Humulene is unique because, like THCv, it acts as an appetite suppressant, making it promising for weight loss treatments.

Humulene exhibits potent anti-inflammatory and analgesic activity. It also displays anti-cancer properties. It carries a subtle earthy, woody aroma with spicy herbal notes. Humulene’s potential therapeutic effects include:

  • Analgesic Relieves pain.
  • Anorectic Appetite suppressant, promotes weight loss.
  • Anti-bacterial  long been known and used in folk medicines but little research had been done to verify claims. 2006 study looked at the essential oil of balsam fir trees and humulene was one of the compounds in the oil which fought bacterial infections.
  • Anti-cancer/tumour – first highlighted in a 2003 study, may have to do with ability to produce Reactive Oxygen Species (ROS). ROS have various roles in cancer, contributing to death of cancer cells through apoptosis. A wonderful demonstration of the Entourage Effect can be seen in this 2007 study, which showed β-caryophyllene potentiates the anti-cancer effects of humulene.
  • Anti-inflammatory –  2007 study found anti-inflammatory properties of humulene comparable to dexamethasone, a steroidal anti-inflammatory. A 2008 study found topical and systemic anti-inflammatory properties and found it to be an antinociceptive (has analgesic properties). This 2009 study looked closer at the anti-inflammatory properties and found them quite notable and present when taken either orally or by aerosol. This research, taken as a whole, shows humulene as a powerful anti-inflammatory in all forms tested, whether topical or internal.
  • Anti-Proliferative Inhibits cancer cell growth.
  • Interleukin-8 (IL-8) Secretion – 2004 study, humulene shown to increase rate of IL-8  secretion. IL-8 is a chemokine (a signalling protein) secreted by human cells which has various functions in the body. One major role of IL-8 is promoting angiogenesis (blood cells split to form new ones; core comHappy Farmerponent in cancer, particularly transition from benign to malignant tumours). The greater the level of angiogenesis, the faster the cancer grows, so generally angiogenesis is inhibited to fight cancer. It is possible that these effects on angiogenesis are tied in to humulene’s ability to promote ROS production, which also has effects on angiogenesis. More research is required to know for certain.
  • Pharmacokinetic – the study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, bio-transformation and excretion.

Boiling Point: 198°C (388°F). Some strains known to test high in humulene include the hybrids White Widow, Girl Scout Cookies and Headband, along with Pink Kush, Sour Diesel and Skywalker OG.

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Expanded from Benefits of Cannabis Terpenes: Terpineol, Valencene, and GeraniolCannabis Terpenes: The Benefits of Humulene, Caryophyllene, and Trans-NerolidolTerpenes, Infographic: What are Cannabis Terpenes and How Do They Affect You?, TerpenesChemistry and analysis of phytocannabinoids and other cannabis constituentsEvolution and Classification of Cannabis sativa (Marijuana, Hemp) in Relation to Human UtilizationCannabinoids and Terpenes as Chemotaxonomic Markers in CannabisPlant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications, Terpene.info