In Australia, thousands are prosecuted every year for Cannabis use while driving. Research at the University of Sydney Lambert Initiative for Cannabinoid Therapeutics suggests the devices currently used return both false positives and negatives. This new research calls into question the reliability of the two devices used for mobile ‘drug’ testing (MDT) in New South Wales (NSW) and other Australian states. These devices were used in the prosecution of almost 10,000 Cannabis users for ‘drug driving’ in NSW in 2016 (the last year for which data are available).
In the United States in 2011, the Centers for Disease Control and Prevention declared an ‘opioid epidemic’. This announcement came on the heels of two decades of medical over-prescribing practices, leading to opioid misuse and abuse, resulting in soaring rates of overdoses across the US. Too little, too late? Addiction isn’t a new problem. The human body is inherently vulnerable to addiction through the action of dopamine in the brain. Dopamine, a prominent chemical messenger, is released in response to rewarding and pleasurable events. Its role is to reinforce biologically relevant and necessary behaviours, including eating, sleeping and sex.
However, humans and other animals are at risk of becoming dependent on the dopamine ‘rush’ and can, therefore, develop an addiction to these behaviours whereby their body becomes dependent on the increased dopamine to function at baseline. Just like food or sex, substances like alcohol and opioids can lead to dopamine release. Opioids are derived from the poppy plant and are a key component of illicit drugs (like heroin) and pain medications (like oxycodone). While opioid medications have been used for many years to treat pain, a few crucial factors converged in the late 1990’s and early 2000’s that led to an opioid-addicted US.
In 1996, healthcare professionals were urged to pay closer attention to the pain reported by their patients – a recommendation bordering on being a requirement, prompting recognition of pain as the ‘fifth vital sign’. The Joint Commission on Accreditation of Healthcare Organisation heightened the urgency to treat pain in their published guidelines and US Congress declared the first decade of the 21st century to be the “Decade of Pain Control and Research”. These events and associated policy changes sent a jolting ripple effect through the medical community that resulted in greatly increased prescriptions for pain medications.
Concurrently, Purdue Pharmaceuticals, the manufacturer of OxyContin®, began aggressively marketing their prescription opioids, spending $200 million on advertising. Their tactics included down-playing the potential risk of addiction and dependency caused by opioid medications. As a result, OxyContin® sales soared from $48 million in 1996 to almost $1.1 billion in 2000. While Purdue eventually faced criminal and civil charges, by then, the damage to America had already been done. In 2017 there were 47,600 opioid-related deaths in the US. While prescription opioids certainly contributed to these statistics, many of these deaths involved heroin; those who take opioid medications are at significantly higher risk of using heroin, due to its lower cost and easier access.
In fact, the nature of the opioid epidemic fundamentally shifted the way addiction is viewed in the US. Government initiatives have invested in strategies to reduce access to prescription opioid medications but this does nothing to help patients with chronic pain who need treatment, nor those recovering from addiction. Fortunately, there is an overwhelming amount of data supporting Cannabis as both an effective agent for pain relief and an aide in helping people recover from opioid addiction. The idea of using Cannabis to treat pain is not new – in fact, ancient Chinese civilisations used Cannabis for joint pain and inflammation before it came to the West (Cannabis is one of the ancient Chinese ‘50 Fundamental Herbs’).
Opioids, derived from the poppy plant, have also been historically used for pain control; however, unlike Cannabis, those who used opioids quickly learned of the risk of addiction. Cannabis shares some physiological similarities to opioids, as short-term use increases dopamine to relieve pain. However, Cannabis increases dopamine via cannabinoid receptors, while opioids increase it via opioid receptors. Additionally, the increase in dopamine levels from Cannabis does not persist over time and, therefore, the risk of possible dependence is significantly lower.
The effects of Cannabis on pain have been demonstrated across many studies. A meta-analysis of 28 clinical trials conducted on Cannabis and pain ranging from 1948-2015 reported positive findings, concluding Cannabis is effective in treating pain with a reasonable safety profile. Cannabis has therefore been approved to treat chronic pain in the majority of US states where its use is legalised. But, what about treating opioid addiction and not just pain? US states with legalised ‘medical’ Cannabis have significantly lower levels of opioid use and opioid-related deaths.
A study in 2016 found a 64% reduction in opioid use in American patients who used Cannabis for their chronic pain. Studies have shown Cannabis may be effective in reducing craving for opioids and easing withdrawal symptoms. Based on this evidence and the unrelenting opioid crisis, New Jersey and Pennsylvania added opioid addiction as a qualifying condition for ‘medical’ Cannabis and other states like New Mexico, Maryland, Connecticut and Ohio are drafting similar policies. New York and Illinois allow patients prescribed opioids to receive ‘medical’ Cannabis instead.
These policies certainly represent tremendous progress toward helping patients use ‘medical’ Cannabis to treat their pain and potentially aid them in recovery as they transition off opioids. However, Cannabis still remains a Schedule I substance at the federal level in the US, which restricts patients’ access to it and continues to slow critical research. Despite growing awareness and recognition of the potential for Cannabis in alleviating the epidemic caused by opioid addiction, ending prohibition entirely is the only way to further progress and alleviate the opioid crisis in the United States.
Cannabinoids interact with each cannabinoid receptor type in the body, sometimes in tandem and sometimes in competition. Each activation gives a response to dampen pain stimuli and reduce inflammation. Cannabinoid receptor types, CB1 and CB2, are proteins embedded in cell membranes. These surface proteins attach to another protein which determines signalling direction: activation or inhibition (tetrahydrocannabinol (THC), for example, activates). The signal that goes out depends on which molecule binds to the receptor. Cannabinoids also activate many other receptors in the human body.
CB1 and CB2 receptors are the most common. The main difference between the two is in their distribution throughout the body: CB1 is highly expressed in neurons within the brain (except the respiratory centre, where it is almost non-existent). CB2 is present in 100-fold lower numbers in the central nervous system and mainly expresses on immune cells, including those of the brain (microglia). The classical effects, in the brain, for CB1 activation are reductions in neuro-transmitter release. CB2 activation dampens microglial activation and reduces neuro-inflammation. These are the basic mechanisms to reduce pain (anti-nociception).
A unique feature of CB1 and CB2 receptors is their ability to “team up” with other neuro-receptors, such as dopamine, opioid, orexigenic (appetite regulator) and adenosine. This cooperation changes their neuro-transmission. In the periphery of the body (outside the central nervous system), reduction of inflammation and neuropathic injury has been primarily ascribed to the activation of CB2. CB2 receptors are present in the peripheral nerves, as well as within the inflamed lining of joints and skin. Reduction of colitis in rodents, for example, has been possible using cannabinoids that act through CB2 receptors. Doctors also managed it with cannabigerol (CBG) acting through CB2.
The GPR55 receptor, a more recently discovered cannabinoid receptor of the non-classical type, regulates neuro-inflammatory responses. GPR55, like CB1 and CB2 attaches to the cellular membrane. It associates with an effector protein inside the cell. GPR55 is part of the central nervous system, expressed in the hypothalamus, thalamus and mid-brain. It modulates anti-nociceptive responses in animals. GPR55 activation can either be pro- or anti-nociceptive depending on the type of injury.
For example, co-activation of CB2 and GPR55 increases microglia activity and neuro-inflammation, while CB2 alone decreases these responses. The anti-inflammatory and pain relieving effects of cannabidiol (CBD) come from how CBD is an inhibitor (antagonist) of GPR55, coupled with the fact that it activates CB2. The effect of THC is a bit cloudier. Knowledge of GPR55 potential in therapeutic applications is still in its infancy and needs many more studies to explore its effects further.
Another non-classical type of cannabinoid receptor is PPARg, which operates by completely different modes of action compared to CB1, CB2 and GPR55. It belongs to a nuclear hormone receptor family, which, when activated, makes alterations at the level of gene expression. Unlike classical receptors that embed in the cellular membrane and exert their actions via activation of signalling cascades within the cell, PPARg directly affects expression of genes involved in inflammation. Scientists have found it in many tissue types, including adipose, muscle, brain and in immune cells. The endocannabinoid anandamide also interacts with PPARg.
Isolation of THC led to the discovery of the Endocannabinoid System (ECS), an atypical neuro-transmission system that modulates release of other neuro-transmitters and participates in many biological processes, including the cascade of inflammatory responses. Due to a myriad of neuro-protective, anti-neuro-inflammatory and anti-oxidant actions, cannabinoids have been cogitated as possible therapeutic agents for neuro-degenerative disorders that combine inflammatory responses, such as Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Huntington and Parkinson Diseases. AD sufferers exhibit increased microglial CB1 and CB2 receptor expression, suggesting a role for cannabinoids.
THC competitively inhibits the enzyme acetylcholinesterase (AChE). A common feature in the AD brain is the presence of AChE. Multiple in vivo studies have also shown CBD reduces neuro-inflammation in dementia and AD. Some suggest the mechanism of action involves CBD acting as PPARg agonist. When CBD activates PPARg, there is reduced gene expression in inflammation from oxidative stress. This decreases neuronal cell death in studies and promotes neurogenesis. A 2017 study in the British Journal of Pharmacology, showed the acid form of THC, tetrahydrocannabinolic acid (THCa), found in the raw plant, has a similar effect on PPARg. THCa activates PPARg with more potency than its decarboxylated counterpart THC. THCa also improves motor deficits, prevents neuro-toxicity and reduces neuro-inflammation.
Cannabinoids also exert their actions on the ion channel, TRPV1. This ion channel is different from usual cannabinoid receptors in that it allows passage of specific ions (sodium and calcium), that trigger a painful burning sensation. Known activators of TRPV1 include temperature above 43oC (which is a protective mechanism that will make us seek strategies to cool off), acidic conditions (such as when we eat a hot chilli pepper), or eating a compound in wasabi. Furthermore, CB1 occurs along with TRPV1. TRPV1 ion channels have desensitisation potential. This explains why we build tolerances to increasingly spicy food.
An interesting application of the interaction between Cannabis, TRPV1 and capsaicin (an extract from chilli peppers with analgesic properties) involves the purported ‘Cannabis Hyperemesis Syndrome’, which is actually Azadirachtin poisoning and not a clinical disorder at all, a complete misdiagnosis and total misnomer! Capsaicin is a neuropeptide releasing agent selective for primary sensory peripheral neurons, producing desensitisation analgesia and as such when used topically, capsaicin aids in controlling peripheral nerve pain.
The severe nausea and vomiting that characterise poisoning by Neem products can be ameliorated in part by rubbing capsaicin on the skin. Cessation of Cannabis treated with Azadirachtin or increasing use of untreated Cannabis are both effective treatments for the toxic effects of the otherwise seemingly harmless Neem. The full characterisation of the interplay between TRPV1, capsaicin and hyperalgesia (enhanced pain response) has not been completed yet, but will prove useful.
In many states of the United States and across Canada, dispensaries and health food stores have shelves lined with little amber or blue glass dropper bottles. Easy to purchase and use, tinctures offer a tried-and-true mode of Cannabis consumption that has been around since long before the days of legalisation. A dropper or two of a liquid tincture placed under the tongue is a solid sub-lingual delivery mechanism that can lead to quick absorption and lasting effects. But what exactly is in a tincture? Tinctures have been used in ancient and modern herbalism for centuries and are, at a basic level, an alcohol extract of an herb.
The two necessary ingredients to any tincture are thus alcohol and an amount of the botanical from which to derive an extract. In the case of Cannabis tinctures, this means the most basic ingredients are alcohol and Cannabis. Ethanol, or grain alcohol, is the most common base for a tincture, but the extract can also be done by soaking plant material in oil or in vegetable glycerine under normal ambient conditions. A saturated MCT oil, such as coconut oil, is a common carrier for this type of tincture. A vegetable glycerine tincture is the least common due to the availability of glycerine and the fact it can lead to a less potent tincture.
Cannabis tinctures are made by soaking Cannabis flowers (buds) in alcohol (leaf trim, hash and kief can also be used). The alcohol extracts the terpenes, cannabinoids and other compounds from the Cannabis (for the full ‘Entourage Effect’), into a liquid that contains a high concentration of active compounds. Alcohol preserves the compounds, which is important since it takes longer to consume tinctures as opposed to other forms of Cannabis. A DIY or homemade tincture would involve soaking raw Cannabis in a strong grain-derived alcohol and leaving it to soak in a dark glass container for several weeks.
Tinctures are often darker than post-processed concentrates which have undergone clean-up steps like winterisation to remove undesirable plant molecules like waxes, lipids and chlorophyll that are soluble in the alcohol. A commercial application would involve a similar process while using laboratory equipment to adhere to standards and regulations for cleanliness and quantity. Cannabis should be decarboxylated prior to being placed in the alcohol (or oil/glycerine) solution if the intent is to consume the activated THC instead of the inactive THC-A. While a strict tincture only consists of the carrier liquid and herb base, many tinctures available for public consumption in North America contain other ingredients.
Many additions are based on flavour and/or recipe desires and are not essential in the creation of a tincture. Honey, Mint, Lavender and many other herbs can be added to a Cannabis tincture and are often included to make a more proprietary blend that brands can use to distinguish themselves in the marketplace. Cannabis tinctures are usually stored in glass dropper bottles, which help preserve the tincture for longer by blocking out sunlight. One of the benefits of using tinctures is the alcohol allows the body to absorb the medicine faster. Most tinctures are taken by placing a few drops under the tongue, known as sublingual administration.
When you take a tincture sublingually, the cannabinoids are absorbed rapidly by the blood vessels lining the inner tissues of the mouth, resulting in a quick onset of effects. Tinctures can also be ingested orally, such as by swallowing or mixing it with food. If you consume a tincture orally, the cannabinoids must be absorbed through the stomach and gastrointestinal tract and through the liver (in particular) and take significantly longer to enter the bloodstream. Depending on whether the Cannabis is decarboxylated first, tinctures may contain tetrahydrocannabinol (THC) in its active form or non-active form (THCa). Most people choose to decarboxylate their Cannabis before making a tincture, allowing them to take full advantage of the medical benefits of THC.
While medical uses of THC are still being researched, there is evidence it can be helpful in treating a wide range of conditions and disorders, including nausea, vomiting, poor appetite, pain, multiple sclerosis, cancer, Crohn’s disease, PTSD, anxiety, depression, Parkinson’s disease, Alzheimer’s disease, sleep apnoea, glaucoma, diabetes, cardiovascular disease and many others. However, if you do not decarboxylate your Cannabis, you will receive the benefits of tetrahydrocannabinolic acid, THC acid or THCa, found in the flowers, leaves and stems of young Cannabis plants.
Biosynthesised by the trichomes, THCa plays a critical role in protecting the trichomes, and thus the plants themselves, from insects and other predators. Furthermore, THCa is no more ‘psychoactive’ than CBD, thus allaying parental concerns about getting their children ‘high’ (an unfounded, prohibitionist-driven fear). THCa is one of the cannabinoids primarily found in fresh Cannabis, although in variable amounts, according to CannLabs. Once the Cannabis plant is exposed to heat, such as vaporising, THCa decarboxylates to THC. What happens on a molecular level is that the carbon dioxide in the Cannabis is released; as a carbon atom in the acid is lost, THCa is converted to neuro-active THC. THCa acts as a cannabinoid receptor agonist and in so doing, also provides neuro-protective (brain protection) effects.
North American Recipes
- How to Decarboxylate
- Traditional Cold Method
- Traditional Warm Method
- Hot Method (Green Dragon)
- Rick Simpson’s Hemp Oil (Dosage information from Phoenix Tears)
Australian Recipes (Nimbin HEMP Embassy)
- How to Make Medicinal Cannabis Preparations (Fifth Edition 2018)
(including Cold and Hot Methods, Glycerine and Oil-based Methods)
Tinctures can be felt as quickly as 15 minutes after dosing and the effects last for a shorter period of time compared to edibles. Tincture efficacy usually peaks about 90 minutes after consumption and can last 4 to 8 hours, depending on the dose. Because the effects can be felt so quickly, dosing with a tincture is easier than dosing with an edible. As with any form of Cannabis, you should start with a small dose to gauge your tolerance and to avoid any possible, initial, unwanted effects of ‘over-consuming’. If you’re taking a Cannabis tincture for the first time, start off with about 1 ml and adjust (upwards or downwards) as necessary.
There are three ways to consume Cannabis tinctures: sublingually, orally or with food. To take a tincture sublingually, drop desired dose under the tongue and hold for 30 seconds before swallowing. This method will produce quicker, stronger effects because the tincture is absorbed into the bloodstream through the inner lining of the mouth. You can take Cannabis tinctures orally by adding a few drops to a beverage such as a smoothie, juice or even a ‘mocktail’. Alternatively, you can swallow the tincture on its own like any liquid medicine. When you take a tincture orally rather than sublingually, it must be absorbed through the digestive system, so it will take longer to feel the effects.
Tinctures taken orally have a similar effect to edibles and can take up to an hour to start working. Tinctures can also be combined with food to make a tincture edible. The difference between a tincture edible and a fat-based edible is the latter is harder to dose and can produce a longer, more intense effect (including euphoria). If you consume a tincture mixed with food, it will take the digestive system more time to absorb than if you took the tincture sublingually. Cannabis tinctures may be added to a variety of foods such as puddings, ice creams, dressings and sauces.
There are many advantages to taking Cannabis tinctures, with a major one being how easy they are to make at home. You can make your own Cannabis tincture (links above) and, while there are many different recipes, these are some of the most popular. When preparing a Cannabis tincture, you usually must decarboxylate (or ‘decarb’) your plant material. Decarboxylation is the process of heating Cannabis to activate the compounds in the plant. Specifically, this will convert THCa into THC and allow you to experience all the effects of whole-plant Cannabis. If you choose to skip this step, your tincture will mostly contain THCa.
Epsilon Apothecaries, (California, US) has a downloadable Extraction Basics Guide (pdf), the Epsilon Essentials Guide Series, comprises a novice approach to the creation of three special supplements: tincture extract of Cannabis, essential extract of Cannabis and supplemental extract of Cannabis. Readers can learn how to create therapeutic grade supplements at home, following in the footsteps of Epsilon’s decade-long track record of success in a variety of cases. The Epsilon Essentials Guide is free of charge, the company’s website says, “All we ask is your respect in return”.
Beta-caryophyllene or β-caryophyllene (βCP), is a natural bicyclic sesquiterpene commonly found in:
- Basil (Thai, in particular)
- Black Caraway
- Black Pepper
- Cinnamon (true)
- Copaiba Oil
- Ylang Ylang
With a rich spicy odour and flavour it is present in all Cannabis strains. Strains that have tested high in βCP are Sour Diesel, Skywalker OG, Chemdawg, Rockstar, Bubba Kush and OG Kush. Caryophyllene oxide takes part in the defence system of plants, functioning as an insecticide and an anti-fungal. Drug sniffing dogs use caryophyllene oxide to identify Cannabis, it is also an approved food additive used for flavouring. Various studies have shown βCP’s therapeutic uses to include:
- Alcohol craving reduction
- Analgaesic – pain relief
- Anti-coagulant (properties)
- Anti-fungal – Caryophyllene and Cannabichromene (CBC) join in defence against fungi; 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-nociceptive (blocking detection of painful or injurious stimulus by sensory neurons)
- Anti-oxidant – prevents oxidation damage to other molecules in the body
- Anti-proliferative – inhibits cancer cell growth
- Anxiolytic – relieves anxiety
- Gastric protection effects
- Neuroprotective – slows damage to the nervous system and brain
And, much like the cannabinoid cannabidiol (CBD), this terpene can be a good combatant for deemed ‘uncomfortable’ amounts of tetrahydrocannabinol (THC) in the system. The medical establishment stands poised to accept Cannabis and its active constituents as legitimate medicinal compounds. An article in the Journal of the American Association of Orthopedic Surgeons advocated for increasing the scrutiny of cannabinoids as a potential alternative to narcotics and anti-inflammatory steroids in the modulation of pain. βCP, has shown potential in recent years as a modulator of pain and inflammation. There are two main cannabinoid receptors in the human body, so-called CB1 and CB2, βCP has been shown to selectively activate the CB2 receptor. While CB1 is especially localised in the central nervous system (CNS), CB2 can be found mainly in the peripheries, especially in white blood cells that mediate inflammation and cellular immunity.
It’s hypothesised that by βCP binding to and activating the CB2 receptor, it mediates and enhances the same activity as that caused by the cannabinoid class of compounds, providing some scientific rationale for the often bespoken entourage effect. To that effect, a European study was conducted to see how βCP modulates the pain-relieving capabilities of both strong opioids and molecular mimics of THC termed CB2-agonists. It successfully demonstrated (in mice) that βCP does indeed work through the CB2 receptor and that it even enhances the pain-relief provided by morphine. The authors postulated that this may illuminate the path towards making a combinatorial βCP and narcotic pharmaceutical mixture to administer for relief of cancer-induced pain. Besides the anti-nociception activity described above, βCP specifically alters several key pathways important for cancer development. Therefore, a pharmaceutical mixture that not only provides pain-relief, but also actively down-regulates the cancer from developing itself, obviously represents a win-win situation.
An astrocyte grown in tissue culture stained with
Glial Fibrillary Acid Protein (GFAP) and Vimentin.
Switching gears to a discussion of a different terpene and system, another study aimed at testing molecular targets of brain cells that have become actively inflamed. The brain contains two main types of cells: neurons, or excitatory cells and glial, or non-excitatory cells. The purpose of the glial cells is, generally speaking, to support the neurons. Astrocytes (see above) are a type of glial cell that carry out a lot of the metabolic activity required to 1) feed neurons, and 2) keep the local electrolyte environment of the neuron well-adjusted. When the CNS undergoes injury, a healing process called gliosis, meaning inflammation of the surrounding glial cells, takes place. The study, which was done in cells in a lab rather than a living being (in vitro), examined the effects of how Linalool affects the ability of astrocytes to become less inflamed and the results showed promise. There is a large and growing body of research that is exploring the use of terpenes for treating all kinds of pain, from neuropathic and muscular all the way to headaches and migraines. We think that terpene formulations providing tangible relief for pain are going to hit the market hard, and soon.
Red Seal chef John MacNeil
A chef earns a Red Seal accreditation by demonstrating superior skills, knowledge and passing a national exam. Canadian John MacNeil is from Cape Breton, Nova Scotia, but worked at Michelin-rated restaurants in Europe and then made a name for himself in Calgary, where he was an executive chef of the award-winning Italian restaurant, Teatro Ristorante.
He opened The Black Pig Bistro in the city’s trendy Bridgeland area five years ago. He later sold it to his business partners and started reTreat Edibles, which sells baking mixes formulated to accommodate the addition of Cannabis. He starts by emphasising the importance of origin. “You should only use legally produced Cannabis to ensure it’s clean and safe” he says. “People don’t scrutinise Cannabis the way they scrutinise food, but they should”.
How does Cannabis affect the flavour of a dish?
Like wine grapes, Cannabis comes in countless strains with various flavours including, for example, citrus, berry, mint and pine. These flavours are created by aromatic oils called terpenes, which are secreted in the same glands that produce Cannabis compounds including Tetrahydrocannabinol (THC) and Cannabidiol (CBD). Terpenes form part of the flavour profile of a Cannabis-infused dish so it’s important to select ones that complement the other ingredients.
How much Cannabis should be included in a dish?
MacNeil compares learning how much Cannabis to include in a dish to learning how to cook steak properly. You overcook then undercook before learning to make it just right. It takes practice to find out where the sweet spot is, he says. Dosing varies from one individual to the next depending on a person’s previous history of Cannabis consumption, gastrointestinal factors, and the sensitivity of his or her endocannabinoid system.
Most experts recommend a starting dose of no more than 2.5 mg of bud for beginners. However, since effects vary based on each person consuming, MacNeil does not make dosing recommendations. Also, it takes awhile for edibles to take effect so beginners often make the mistake of ingesting too much too soon. MacNeil and other experts advise beginners to wait around two hours before deciding whether to take a second dose.
What is one of the most popular Cannabis-infused items people make at home?
Many people express an interest in Cannabis-infused brownies. MacNeil recommends using Thai coconut milk and French chocolate. To infuse Cannabis into chocolate brownies and other baked goods, many people use the whole plant, drying, curing and then grinding it into a flour-like substance and combining it with cooking oil or butter.
Cooking with Cannabis Recipes by Chef John MacNeil
- Kale Burger and Cannabis Infused Mayonnaise
- Coconut Steel Cut Oats with Mango Blueberry Lime Gremolata
Adapted from, Cooking with Cannabis: Tips From a Red Seal Chef
The majority of research on Cannabis has been conducted on the two most familiar compounds – cannabidiol (CBD) and tetrahydrocannabinol (THC). However, the lesser-studied terpene constituents, also produced in the trichomes, have been shown to possess key biochemical properties that make them well-suited for therapeutic applications. Terpenes are also believed to interact with cannabinoids to produce an “entourage effect” – a synergy of biochemical interactions that provide holistic medicinal benefits. While terpenes are essential components of Cannabis, they are by no means exclusive to it, as they can be found in flowering plants. Limonene contributes to the fragrance of citrus and Linalool, lavender. The shared chemical properties across terpenes and their physiological effects have provided clues as to the specific medicinal properties of Cannabis-derived terpenes. Pre-clinical trials have shown that certain terpenes possess anti-oxidant properties.
While many consumer products are labelled as “antioxidants” to promote health, only substances proven to prevent the oxidation of fundamental biological compounds such as proteins, carbohydrates and fats, are scientifically considered “antioxidants”. When oxygen is broken down in the body, it produces free radicals, or atoms with unpaired electrons. An abundance of free radicals can causes damage, as they are highly reactive and unstable – this is called oxidative stress. The damage caused by oxidative stress has been linked to multiple conditions, including autoimmune and cardiovascular diseases. Nitric oxide (NO), an essential signalling molecule in the body, is a free radical and during the process of creating NO, additional free radicals are produced. NO levels have been linked to increased oxidative stress and associated disease. While erroneous (or exaggerated) claims abound, several terpenes, such as those found in Rosemary, are proven to possess antioxidant properties through inhibition of NO production.
Similar effects have been found for Cannabis terpenes. One study evaluated three Cannabis chemotypes and analysed their terpenoid content. Applying high concentrations of different terpenes inhibited production of NO in cell cultures and reduced production of reactive oxygen intermediates, byproducts of oxygen metabolism. These terpenes also reduced swelling and pain perception (measured by muscle retraction) in an animal model of paw inflammation. Another study found that Myrcene significantly reduced NO production in a cellular model of osteoarthritis. However, this effect was exclusive to Myrcene; while Limonene produced a smaller degree of inhibition, E-caryophyllene showed no effect. These results indicate that some terpenes may possess more potent effects on oxidative stress than others. Additional research is necessary to better understand how terpenes impact NO production, as well as other forms of oxidative stress, to better evaluate how they could be potentially used as antioxidants.