DARWIN Origin Series

A How-To Guide to Microdosing Cannabis

A How-To Guide to Microdosing Cannabis

It is a common misunderstanding that one must feel “high” or intoxicated in order to reap the therapeutic benefits associated with cannabis consumption. But…::drumroll::… this is not necessarily the case!  More and more individuals are becoming familiar with the concept of microdosing, which is the use of very small or sub-therapeutic doses of cannabis to gain medicinal benefit without mind-altering effects.  In fact, when dosed properly, microdoses of cannabis can be consumed throughout the day without impediment to productivity and focus, allowing the consumer to reap the value of consumption without psychological impairment.

In the pharmaceutical world, microdosing is certainly not a new concept.  It is a general practice to prescribe a dose of drugs using the minimal amount necessary to elicit a therapeutic effect. Think about any medication that requires titration or an increase in dose over time, such as antidepressants, or can be taken in a variety of doses depending on the endstate needed, like over-the-counter versus prescription-strength ibuprofen. On the flip side, the “dose makes the poison,” meaning, too much of anything, no matter how beneficial it’s perceived, can lead to serious, adverse effects.  Cannabis is no different, and all of these aspects are important when delivering the right amount of cannabis for the intended purpose. So how do we get there, and can we use even less?

Did you know?

Microdosing is used in pre-clinical studies to analyze a drug’s concentration-time effect, giving researchers a starting point for initiation of a clinical trial.  It allows scientists to analyze how a drug affects the way a cell functions in its presence, allowing for the collection of real, human pharmacokinetic and pharmacodynamic information. Over time, an equal and effective amount of the drug will be present in the bloodstream, and by gathering these data, the lowest effective therapeutic dose can be determined.  In the end, a consumer can reap constant and consistent benefits while minimizing unintended and unwanted adverse effects.

Many also associate microdosing with the recreational use of psychedelic drugs such as LSD and mushrooms.  Many have found positive and sustaining effects on symptoms related to depression and anxiety.  Positively, the consumption of cannabis is following suit, with practitioners and patients using the lowest effective dose of THC to help individuals suffering from chronic pain and mood-related disorders.

At this point, you may be asking yourself… what do I need to know about microdosing cannabis, and how do I get started?

DARWIN Origin Series

 

Is microdosing the right thing for me?

  • Microdosing is a great way for new patients to engage with cannabis for the first time. In addition, it is also ideal for consumers who need to remain focused, alert and mentally clear, but choose to consume cannabis throughout the day for whatever their intended treatment plan is.

What are the major benefits of microdosing?

  • As stated above, microdosing allows consumers to function while simultaneously benefitting from the therapeutic value of using cannabis. Benefits include pain relief, stress reduction, mental clarity, and mood enhancement. In addition, new consumers can more confidently engage with cannabis without the fear of over-medicating and having a negative experience due to some of THC’s adverse effects.  By utilizing a variety of CBD-to-THC ratios, a new consumer can find their ideal starting dose with less stress, and therefore have an overall better experience while tailoring the amount consumed to their individual needs.

Do all microdoses contain THC? Or, can microdosing be applied to CBD and hemp oil, too?

  • The concept of microdosing does technically focus on the use of THC, but it is not always warranted or necessary depending on the pathological condition of focus because a variety of cannabinoids have therapeutic value. If a consumer is using CBD, whether it be from hemp or cannabis, like any other cannabinoid or drug, the lowest effective dose is ideal.  Keep in mind that CBD does have an effect on mood and can be pharmacologically considered psychoactive, though not intoxicating.

 

So… How do I get started?

Step 1:  Choose your method of consumption.

  • Microdosing is easiest when using an ingestible formulation of cannabis, like an edible or tincture, because they are easier to dose, but other formulations can be used as well, such as vape cartridges. Look around and ask your local budtender for a reputable product that produces consistent and reliable products, such as Darwin Brands in Arizona.

Step 2:  Choose your dose.

  • Start low and go slow, especially if you are new to cannabis or are aware that you have a low tolerance for THC.  Don’t be afraid to begin with 1 mg of THC to see how you personally react. If you consume an edible, it may take up to two hours to notice any effects, so it is recommended to refrain from consuming more before then.

Step 3:  Construct a dosing schedule.

  • This will be different for orally-ingested products versus inhaled or other formulations that are absorbed directly into the bloodstream, like vaporized oil and transdermals. Once you figure out your preferred formulation and how much of that formulation you need to consume to get the effects you seek, make a note of how long the effects take to kick in, as well as how long they last. You can then design a schedule based on your personal dosing needs.

 

What are examples of some reliable products to try?

  • Darwin Brands’ Origin Series Caramel Hard Candies come in a dose of 20 mg CBD with 2 mg THC, a wonderful starting place for those looking for a balanced and clear-headed experience without the intoxicating effects. Because the caramels contain 20 mg of CBD, the typical adverse effects associated with THC, such as paranoia and anxiety, is highly mitigated.

 

If 20 mg of CBD is too much, Darwin also offers their Seriously Good Gummies in a dose containing 10 mg CBD and 2 mg THC.  One great benefit of their edibles is the homogeneity that results from their strict production process.  Feel free to cut them in half and expect half the dose!

 

Happy Microdosing!

By: Jennifer Corso, BA, MA
Biochemical Exercise Physiologist

CannabisCBN

CBN: The Inconclusive Conclusions

By: Jennifer Corso, BA, MA
Biochemical Exercise Physiologist

How about a bit of trivia: Do you know the first cannabinoid structure that was identified and isolated?  If you guessed it was THC because of its iconic and superior identity with cannabis, think again (and take a puff… games are fun!) It was actually cannabinol (CBN), discovered in the year 1899, structurally mapped by chemist Robert Cahn in the 1930s, and then synthesized by Nobel Laureate and organic chemist Lord Alan Todd.  Only a few years later, THC and CBD were isolated and quickly swept CBN in cultural popularity, political manipulation and therapeutic understanding. But, don’t dare underestimate the OG – CBN has it’s own psychosomatic uses and is a very interesting molecule.

A Little Botany

CBN is known as a product of cannabis degradation; it forms slowly when weed is harvested and left exposed to the typical ambient environment. When THC is exposed to UVA/B light, oxygen and heat, it undergoes an oxidation reaction and loses four hydrogen atoms, creating This change in molecular structure also changes the way CBN binds to endocannabinoid receptors, further altering how it elicits its effects within the body.

THC and CBN

But CBN is not just a product of THC or THCV degradation (yes, there exists CBNV, or cannabinovarin). It is also formed normally throughout the plant growth cycle just like other cannabinoid acids such as CBDA and THCA. Cannabinolic acid (CBNA) is present predominantly in chemovars that are reported to cause sleepiness or sedation. Don’t mistake this for an Indica-only association. An example? Purple Sour Diesel, a Sativa-dominant strain and cross of Sour Diesel, Purple Kush, and SR-71, is known for its dose-related energizing effects and high-concentration of THC, but it is also causing notable sleepiness due to the fact it contains CBN, or so we think.

What We Think We Know:

CBN has historically been classified as a mildly intoxicating phytocannabinoid, significantly less than that of THC and its analogs, and less than THCV in higher doses. In contrast, many researchers consider CBN to be non-intoxicating on its own, and it’s still up for debate.  CBN is a weak CB1 and CB2 agonist, and when metabolized into 11-OH-CBN through first pass liver metabolism, its affinity or agonism when interacting with CB1 receptors in the central nervous system increases slightly, but the effects are still thought to be generally mild.

It is widely known for its claim to produce sedating effects and has even been reported to be a 2:1 mg equivalent to diazepam (Valium), a drug commonly prescribed for anxiety (this will be discussed later).  When used in a synergistic fashion with THC, CBN has been stated to increase mental and somatic sedation, as well as increase overall intoxicating effects.  It’s also been reported to help alleviate pain and inflammation.  But how much of the current medical literature supports its therapeutic value?  Does CBN actually do what we all believe?

CannabisCBN

When administered as an isolated molecule, the majority of the scientific body of literature does not conclusively support claims that CBN is responsible for causing sedation. Surprised? One specific and commonly cited study published in 1975 does conclude that orally-administered CBN enhances feelings of drowsiness, drunkenness, dizziness and a “drugged” feeling, but only when combined with THC.  In addition, the study only recruited five subjects, making the statistical analysis very underpowered and likely significant by chance.

What about the circulating claim relating CBN to diazepam?  This relationship was actually reported by Steep Hill Labs and quickly went viral as a claim by many to cure sleeplessness. But no clinical data exists to support this, and the page stating Steep Hill’s conclusions has been recently removed. There is actually more evidence comparing the use of THC and diazepam in relation to their comparative effects on drowsiness and anxiety. Further, more data support a dose-response relationship between THC and sleepiness when compared to CBN alone. With regard to CBN, the support favors more of an entourage effect, where its potential is seen as a synergistic relationship with other cannabis constituents than of one in isolation.

A not-so-fun fact for the males out there: The NEJM published a study in 1974 concluding that marijuana use may decrease plasma testosterone levels (say what?) Though the mechanism was thought to be linked to hypothalamic and pituitary gonadotropin hormone production, it led to further investigation.  In 1978, an in vitro animal model study published in the journal Pharmacology Biochemistry and Behavior concluded that both THC and CBN may decrease testosterone secretion by the testes. Further, different mechanisms may exist between THC and CBN’s negative effect on testosterone production, with THC’s effects being more pronounced and having a negative impact on sexual activity. Another study in 1979, one in 1980, another in 2015, concluded similarly regarding CBN’s effects on testosterone suppression. Yikes!

Based on the current body of literature, what are the forward-looking statements?

Cannabinol has been positively supported to be an important pain-relieving cannabinoid, as well as an anti-inflammatory. There is also limited evidence supporting CBN’s ability to stimulate the appetite.  Several studies have also considered the potential antioxidant role of CBN in delaying symptom onset associated with amyotrophic lateral sclerosis (ALS), a motor neuron disorder, as well as its help with motor relaxation.

Aside from the flower strains discussed above, if you’re in the market for products that have harnessed the effective and supported uses of CBN, be sure to check out Darwin Brands’ Chillax + CBN vape cartridge. Not only does the triple-distilled oil include a consistent and effective 4% CBN in each cartridge, it features a unique blend of terpenes crafted to promote a relaxing mind and body effect. The carefully designed synergism between the aromatics, THC and CBN yields a tasty and effective solution to help you unwind.

As the ability to conduct cannabis-focused research expands, the scientific community will be able to deliver more concrete, evidence-based directives on CBN and the therapeutic value it holds. Stay tuned!

Darwin Photos 5.22.19-13161

Purity and our Cannabis Products

What is CO₂-Extracted Cannabis Oil?

As vaporizing cannabis oil becomes an increasingly popular method of cannabis consumption, many consumers are looking to make the switch from traditional smoking to vaping. One of the most significant factors that draw consumers to vaping is the dramatic difference in the taste and experience. Rather than inhaling the sometimes harsh, lung-irritating smoke, many people prefer the cleaner, smoother effect of vapor from CO₂-extracted cannabis oil instead.

With the growing popularity of cannabis comes the demand for safer and more health-conscious options. Consumers looking for highly pure, premium quality cannabis products are moving away from hydrocarbon-extracted oil, such as BHO, which uses butane as the primary extraction solvent. Due to the flammability of hydrocarbons like propane and butane, these extraction processes have a historically-supported risk of explosion if proper safety protocols aren’t in place. But even with improved extraction technology, the resulting oil may contain residual solvent if not properly purified before being sold to patients. For the discerning cannabis consumer, CO₂extracted cannabis oil has quickly gained attention as an ideal option.

Why use a CO₂ Extraction Process for Cannabis Oil?

CO₂extracted cannabis oil is an alternative to the more traditional industry extraction methods such as butane or ethanol. The CO₂ extraction process allows for a cleaner, purer final product that eliminates the use of more dangerous and unappealing chemical solvents. This oil may then be used to make a variety of concentrates, may be purified and used in a vaporizer, or as an ingredient in topicals and edibles.

What is CO₂ Cannabis Extraction?

The CO₂ extraction process is what lends CO₂extracted cannabis oil its name. It is a type of supercritical fluid extraction (SFE), which shares attributes of both a gas and a liquid. Gaseous CO₂ is pumped through a temperature- and pressure-controlled system, which transforms it into a supercritical fluid. This fluid is then passed into a chamber containing cannabis plant material or biomass, where it easily passes through the plant cell membranes, dissolving the active compounds. The following phases allow for the separation of compounds such as terpenes, cannabinoids, plant waxes, and lipids, as well as the removal of the remaining CO₂. The resulting product is an unpolluted cannabis extract that can then be used in a variety of medicated products.

Benefits of Using CO₂ During Extraction

CO₂ is used in cannabis extraction for a few different reasons. Not only is it an abundant and naturally occurring compound, but it’s also among the safest non-polar solvents – far safer than options like hydrocarbons. It also transforms more easily than other solvents, which means the solvent properties of supercritical CO₂ can be changed to extract different compounds from cannabis plant material.

Our Vape Products

Choose your series based on the MG per Dose.

CO₂-Derived Products in the Cannabis Industry

The cannabis industry has welcomed CO₂-derived products with open arms, particularly those made using high-quality cannabis and a carefully-crafted process. Darwin is among the top names in the cannabis industry providing a range of CO₂-extracted cannabis products, including their Origin, Evolution, and Voyager Series distillate cartridges and edibles.

To learn more about CO₂extracted cannabis oil, how to consume CO₂ oil, and how you can incorporate it into your cannabis experience, visit www.darwinbrands.com or ask about Darwin products in your local dispensary.

What is CBD

CBD, Cannabidiol – What does it actually do?

By: Jennifer Corso, BA, MA
Biochemical Exercise Physiologist

Our nation is struggling to treat lifestyle constructs that foster chronic disease, an opioid crisis, and the existence of an obesity epidemic. Further, according to the National Institute of Mental Health (NIMH), 6.7% of U.S. adults have suffered from a major depressive episode at least once in their life, and another 19.1% have suffered from anxiety in the past year. That’s more than 45 million people at any given time!

Why a population with access to advanced medical research and technology is scrambling to maintain its own well-being is a lengthy discussion ripe with conflict between science, time and fiscal interest. But in contrast, fueled by the end of a prohibition on hemp and legal acceptance of medical marijuana by many states, CBD has been embraced by an ever-rising populus for its ability to do good within the body. Some are going so far to consider it a historically-proven panacea.

But if you’re new to cannabis or wanting to update your education on the topic of CBD, you may ask yourself the following: How does CBD actually illicit the sought-after mental and physical changes we hear about, and what don’t we know? CBD is consumed for a multitude of reasons – to promote a better mood, combat side-effects of THC, and help decrease pain. But of the supporting research that exists, many studies are underpowered, lack good control of variables, don’t include human subjects, and have yet to provide substantial evidence of efficacy, despite the mounting evidence of CBD’s widespread, therapeutic promise.

What is CBD?

First, it is important to understand what CBD is, and what it is not. Cannabidiol (CBD), in its neutral and “activated” form, is the second most abundant phytocannabinoid produced by the cannabis plant. It trails only behind ∆9-tetrahydrocannabinol (THC), the neutral, active component that most people associate with marijuana.

CBD is often referred to as a non-psychoactive (and therefore more socially acceptable) cannabinoid – a technical misrepresentation. By definition, any substance that elicits a change in psychological state or mood can be classified as pharmacologically psychoactive. (Psychoactive should not be confused with intoxication, a term synonymous with being “high,” like after consuming THC.)

What makes CBD psychoactive?

It is used by many individuals to treat non-clinical depression and/or anxiety, both classified by the medical community as mood disorders. A 2010 study published in BJP supports the notion of CBD as an antidepressant because it may activate 5-HT1a (serotonin) receptors. Serotonin is an important neurotransmitter responsible for regulating mood and the sleep/wake cycle. CBD’s agonistic properties may act similarly to serotonin, promoting mood balance like an antidepressant. Further, its interaction with the larger 5-HT receptor family may support its use as a panicolytic (anti-panic) drug, which may provide benefit for those suffering from panic attacks.

The strongest example in support of CBD’s psychoactivity can be illustrated by the 2018 FDA approval of Epidiolex, a cannabis-derived CBD drug for use in the treatment of Lennox-Gastaut and Dravet syndromes, two serious forms of epilepsy. A solid scientific consensus has yet to be reached, however, its mode of action as an anti-epileptiform and anticonvulsant is thought to be due to a combination of cumulative effects. These include effects on inflammation, 5-HT serotonin receptors (like described above), and the ability to modulate GABA channels. (GABA is a neurotransmitter that prevents overstimulation of the nervous system, and its receptors are often the target of certain types of anti-anxiety drugs, like Xanax and Valium.)

At this point, it is clear there’s much more to CBD’s interaction within human physiology than we understand. The compound has been praised by many for its anti-inflammatory properties, potentially leading to pain relief and assisting in amelioration of some of the aforementioned disorders.

〉Nerd alert! As an immunoregulator, it’s thought that CBD has an effect on the production and action of various cytokines responsible for regulating inflammation. According to several studies, CBD may increase the activity of interleukin-10 (IL-10) and regulate the pro-inflammatory effects of IL-6, both glycoproteins responsible for regulating inflammation. Though more investigation is warranted, the compound may be useful in treating pain and both Type II diabetes.

CBD’s Effect On THC Intoxication

CBD has been shown to assist in the prevention and counteract several adverse effects of THC intoxication, such as anxiety and memory loss. According to a 2013 article published in Frontiers in Psychiatry, CBD may inhibit these unwanted effects by preventing the reuptake of anandamide, an endogenous and abundant cannabinoid made by our own bodies. Anandamide has a stronger affinity for (or connection to) CB1 receptors than THC – it’s a better fitting key to unlock its own effects the endocannabinoid system. Less anandamide reuptake means more of it is available to be used by the body, trumping THCs ability to make us “high.”

〉Did you know? CBD’s ability to decrease intracellular calcium concentration by way of T-type calcium channel inhibition may also help prevent the neurotoxic effects of high or prolonged use of THC. This mechanism may also play a role in CBD’s anticonvulsant properties.

The understanding of CBD’s psychological and physiological activity within the human body has progressed far beyond this publication. It is being investigated to treat psychosis in Parkinson’s disease, and according to a study being conducted at the University of Miami, may promote recovery in individuals who have suffered from sustained concussion and traumatic brain injury (TBI). Regardless of personal perspective, there does exist a small but growing database of respectable scientific research on its therapeutic potential, and it can only grow from here… stay tuned!

The Scientific Effects of CBD [Cannabidiol]

Cannabidiol [may be a] promising nonpsychotropic therapeutic to prevent the recruitment of microglial cells at neuroinflammatory lesion sites.” Walter, Lisa, et al. “Nonpsychotropic cannabinoid receptors regulate microglial cell migration.” Journal of Neuroscience 23.4 (2003): 1398-1405.

Sources:

450mg Engage + THCV

The Therapeutic Value of THCV

450mg Engage + THCV

THCV is rumored to be a new therapeutic power player, with positive impacts on health both mentally and physically. Many consumers state that cannabis strains and products containing tetrahydrocannabivarin (THCV) help them focus and improve mental engagement, as well as decrease their appetite while medicating. But what’s even more intriguing about this cannabinoid is the supporting evidence surrounding its use to potentially improve insulin sensitivity and some other significant underpinnings associated with diabetes. Let’s dig in!

What is THCV?

THCV is a structural analog of Δ9-tetrahydrocannabinol (THC). This means that the molecular structures are very similar to one another, but a differentiating component exists, such as one or more atoms or structural group. (The image below illustrates the difference between the molecules.) Certain chemovars of cannabis express a gene that produces the compound divarinolic acid, which combines with geranyl pyrophosphate (GPP) to form CBGVA instead of CBGA, and therefore THCVA instead of THCA. Other “varin” cannabinoids exist as well, such as CBDV, CBCV, and CBGV.

THCV vs THC

THCV and THC are analogs. The circled portions of the molecule highlight the subtle difference between the two.

The Therapeutic Value of THCV

THCV is classified as a CB1 “receptor neutral antagonist,” which in a general sense means it has no direct effect or slight opposing effects on the endocannabinoid system (ECS). It differs from CB1-activating compounds like THC. Because of this, THCV may turn down ECS activity, potentially decreasing and preventing unwanted effects like memory impairment, the inability to recall vocabulary and thoughts, a slower perceived reaction time, as well as paranoia.

It also binds strongly to CB2 receptors, having a slight agonistic, or activating effect, opposite than when interacting with CB1 receptors. This unique combination of cellular interactions allows THCV to do what it does best!

The unique compound may be classified as one of a few psychotropic and intoxicating cannabinoids found in cannabis, however, the experience is not synonymous with that of THC, and its actions may be regarded as dose-dependent. This means, as the dose increases, it is thought that THCV may switch and become a partial agonist, or activator of the entire ECS, activating both CB1 and CB2 receptors. Anecdotal evidence supports the onset of activity is much quicker, milder and of a shorter duration, and it may be assumed that less is required for therapeutic effect (you’d be lucky to find a strain containing 0.5% – a little goes a long way).

Research supports the notion that THCV may combat the adverse effects associated with being sensitive to or consuming too much THC. Its mechanism of action suggests this based on how it binds to ECS receptors, predominantly when the two cannabinoids are consumed together. That being said, evidence further states THCV may be effective in combating anxiety and short-term memory impairment. Patients prone to anxiety when consuming cannabis may be able to worry less about using strains and products containing it.

Appetite Suppression

What is even more intriguing? THCV may help combat the munchies, so unless you’re using cannabis to help you gain weight, this could be a major benefit. Diving a bit deeper, several studies have shown the effects of neutral antagonists, like synthetic cannabinoid AM4113, to block endocannabinoid tone and lead to a decrease in appetite. The mechanism of THCV is similar, though more research needs to be conducted in support of these claims.

Insulin Sensitivity

A very compelling animal study was published in a 2013 edition of Nature’s Nutrition and Diabetes, illustrating the positive effects of THCV on insulin sensitivity. In the study, both genetically obese (ob/ob) mice and dietarily-induced obese mice were placed on different THCV dosing regimens, both alongside control groups that received a placebo treatment. The research team tracked body mass, blood glucose and insulin levels were measured (among other biomarkers). Overall, THCV reduced glucose intolerance in all mice, improved insulin sensitivity in some of the mice, and restored insulin signaling in liver cells.

In 2016, the support for these findings increased significantly after the American Diabetes Association published a study conducted using patients with untreated type II diabetes. The results? THCV significantly reduced fasting blood glucose levels and improved pancreatic β-cell function (the cells responsible for producing insulin).

What does this mean for diabetics? THCV could be a potential drug useful in controlling blood sugar and perhaps treating the underlying causes associated with diabetes and metabolic syndrome. These findings are important and promising on many levels, and more clinical trials investigating the therapeutic potential in those with diabetes are warranted.

Where can I find THCV?

Some strains that express the gene leading to THCVA production (thus THCV) include Durban Poison, Jack the Ripper and GSC. However, if you come across a strain that includes one of these as a cross, it doesn’t guarantee that the gene was expressed in the chosen phenotype that causes the plant to produce THCV, so do your homework. And don’t expect to find it frequently or in high potency (even 0.5% in cured flower isn’t typical). There are a few cannabis products that contain THCV and are specifically formulated to maximize its therapeutic benefits. One such product is the Engage + THCV vape cartridge produced by Darwin Brands. The oil contains about four times more THCV than the higher potencies found in naturally grown strains of cannabis flower, ensuring the consumer gets the desired and consistent effect, maximizing the therapeutic value of this awesome cannabis compound. Happy medicating!

900MG THC Engage+THCV VapeCartridge

Sources:

Jadoon, K. A., Ratcliffe, S. H., Barrett, D. A., Thomas, E. L., Stott, C., Bell, J. D., … & Tan, G. D. (2016). Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care, 39(10), 1777-1786.

McPartland, J. M., Duncan, M., Di Marzo, V., & Pertwee, R. G. (2015). Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. British journal of pharmacology, 172(3), 737-753.

Wargent, E. T., Zaibi, M. S., Silvestri, C., Hislop, D. C., Stocker, C. J., Stott, C. G., … & Cawthorne, M. A. (2013). The cannabinoid Δ 9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & diabetes, 3(5), e68.

a-humulene

All About Aroma: The Therapeutic Value of Terpenes

By: Jennifer Corso, BA, MA
Biochemical Exercise Physiologist
Darwin Brands

The cannabis plant is comprised of much more than cannabinoids like THC and CBD.  It is rich in many phytochemicals, including terpenes and terpenoids.  These volatile, odorous organic compounds act as antioxidant, anti-fungal and anti-bacterial agents, protecting plants against disease and infection, and are shining in the current spotlight for their therapeutic value. But what exactly are they?

Phytochemicals are a group of biologically active compounds found in plants that provide some type of health benefit. They are not required by the human body to sustain life, however, many of them have proven to aid in the prevention of disease and reduce the risk of developing cancer.  Terpenes, along with polyphenols, phenolic acids, antioxidants, and flavonoids are all types of phytochemicals, and they are just a few of many classifications that are currently accounted for.

What are Terpenes?

Terpenes are among several groups of low molecular weight chemicals responsible for the aromas associated with flowers, citrus, and conifers – they can be attributed to why lilies and lilacs smell distinctly sweet and floral [(E)-𝛃-ocimene], and that nug of Lemon Train Haze has a delicious, citrus-y zing to it (D- and L-limonene).  The variety of odors attract pollinators and fight off consumers, assisting plants in both reproduction and survival.

Cloud Nine Cartridge

Caption:  Darwin’s Cloud Nine cartridge contains valencene, for a tasty, mood-uplifting experience.

Nerd alert! Terpenes and terpenoids are classified as lipids, similar in structure to steroids, squalene, and cannabinoids. They are biologically synthesized from isopentenyl pyrophosphate (IPP), a molecular intermediate created in the HMG-CoA reductase pathway (the same pathway that produces cholesterol).  Every terpene contains a multiple of five carbons and eight hydrogen atoms, with variations such as the inclusion of an oxygen atom or cycling rings (This is called the C₅ Rule or Isoprene Rule, discovered in 1953).

The Scientific Classification of Terpenes and Terpenoids

Terpenes are classified based on the number of carbon atoms they are comprised of. Hemiterpenes are the smallest units and contain only five carbon atoms.  Monoterpenes contain 10 carbon atoms and are volatile and fragrant, the chief constituents of essential oils.  Sesquiterpenes are the most diverse group of terpenes, each containing 15 carbons and found is essential oils and resins. As the number of isoprene units increases, diterpenes, sesterterpenes, triterpenes, carotenoids are formed, and eventually rubber (>100 isoprene units).

 

 Biosynthesis of terpenes

Caption: Biosynthesis of terpenes, from Egbuta, M., McIntosh, S., Waters, D., Vancov, T., & Liu, L. (2017). Biological importance of cotton by-products relative to chemical constituents of the cotton plant. Molecules, 22(1), 93.

As stated earlier, phytochemicals may aid in disease prevention. There is substantial scientific support for this notion, although the variety of chemicals is vast and there many mechanisms we have yet to understand. Because terpenes are found in anything from eucalyptus to blood oranges, they are easier to study, legally and independently from cannabis.

It wasn’t until 1998 that researchers began investigating the therapeutic potential of terpenes in cannabis and applying them toward what we refer to as the entourage effect. This is the synergistic interplay of phytochemicals within the plant that may elicit a response different or greater than individual compounds themselves.  The effect is seen most clearly between cannabinoids CBD and THC, and is most supported by researchers such as Dr. Ethan Russo, who published a notable article on the idea in the British Journal of Pharmacology in 2011.  Curious about learning more?  Here is a spotlight on three interesting terpenes found in cannabis and supporting scientific evidence on their therapeutic value.

Three Terpenes Found in Cannabis and their Therapeutic Benefits

Alpha-humulene

Alpha-humulene was first discovered in the lupulin glands (trichomes) of the flower or cone of the female hop plant, Humulus lupulus, playing a notable role in the plant’s characteristic smell. Cannabis’ sister-from-another-mister, hops are bred to elicit a plethora of different aromatic and flavor profiles. Because of the antiseptic ability of the acids, hops were historically incorporated in beer as a preservative, but they also balance the sweetness of the malt sugars in cooked wort. Many varieties are created and used specifically to bitter beer because of their high 𝛂-acid (humulone) content, giving them a zesty, bitter flavor and odor.  The more aromatic varieties, like noble hops, are lower in 𝛂-acids and higher in aromatics like 𝛂-humulene – up to 40%, delivering a sensory experience familiar to both beer and cannabis connoisseurs alike.

  • Classification and chemistry: A monocyclic sesquiterpene and farnesyl diphosphate (FPP) derivative, with the molecular formula C₁₅H₂₄. Also known as 𝛂-caryophyllene, an opened-ring isomer of 𝛃-caryophyllene. A primary terpene in cannabis essential for growth and development.
  • Aroma and flavor: Robust, woody, spicy; also found in common sage, ginger and ginseng.
  • Cannabis strains high in 𝛂-humulene: White Widow, Original Glue, GSC
  • Main effects:
    • Anti-inflammatory, illustrated through the reduction of eosinophil migration and inhibition of IL-5, NF𝛋B and AP-1 in the lung during aerosol application; similar to dexamethasone
    • Antineoplastic by inducing cytotoxicity through increased ROS production and decreased cellular glutathione concentration. May also work synergistically with the chemotherapeutic agent doxorubicin in certain ovarian cancer cell lines.
    • Antiseptic (antibacterial, antifungal)
  • Entourage effect: May work synergistically with trans-caryophyllene as an anti-inflammatory and anti-cancer May work with tetrahydrocannabivarin (THCV) to suppress appetite.

 

a-humulene

Valencene

Valencene – you guessed it – is primarily found in valencia oranges, and is the precursor to the notable odorant found in grapefruit, nootkatone. Looking to combat the skin-deep signs of aging? An interesting study published in 2016 illustrated the effects of valencene on UVB radiation.  The researchers found that valencene interacts with TRPV1 and ORAI1 calcium channels, assisting in the regulation of photoaging and prevention of skin pigment changes and inflammation.  There is some say that valencene may also assist in promoting a calm mood, but more research needs to be done in this area in particular.

  • Classification and chemistry: A bicyclic sesquiterpene, (+)-valencene has the molecular formula C₁₅H₂₄. It is used widely to synthesize nootkatone and may be biotransformed by various microorganisms through oxidation, as well as CYP-450 found in the liver.
  • Aroma and flavor: Sweet citrus, oranges, grapefruit
  • Cannabis strains containing (+)-valencene: ACDC, Agent Orange, Tangie
  • Main effects:
    • Antiproliferative: In two lines of ovarian cancer, and two lines of lymphoblast cancer, valencene was shown to successfully enhance the effects of chemotherapeutic agent doxorubicin by increasing the accumulation of the drug in the treated cells. It’s also been shown to improve efficacy in colon cancer treatment.
    • Antioxidant activity, highest as a constituent of sweet orange oil, however successful as an isolated compound. May have cytotoxic effects.
  • Entourage effect: May work best as an antioxidant with terpenes such as linalool and octanal.

 

Valencene

Nerol

Nerol was originally discovered as a constituent of the prized essential oil neroli, which is extracted and steam distilled from the delicate and sweet blossoms of the bitter Seville orange tree.  The molecular structure is close to muguet – change the location of one methyl group and the aroma changes from sweet citrus to lily of the valley.  It is known for its stress-relieving properties and has been shown to reduce anxiety in mice through decreases in motor activity, similar to the effects of diazepam.  Found in small amount in cannabis, nerol has been shown to be an effective insect repellent, assisting in plant defenses. And if you’re a fan of wine, nerol, along with its stereoisomer geraniol, is an important part of the flavor nuances in young Muscat varieties.

  • Classification and chemistry: A linear, volatile monoterpene and alcohol with the molecular formula C₁₀H₁₈O. Nerol is the cis (2Z) stereoisomer of geraniol. It can be synthesized from pyrolysis of 𝛃-pinene, and from 𝛃-myrcene.
  • Aroma and flavor: fruity, sweet rose, citrus, raspberry, deep; also found in lemongrass, rose, orange blossoms, lavender.
  • Cannabis strains containing nerol: There aren’t any strains that feature nerol in high concentrations, however, may be present in strains containing geraniol, such as Lavender.
  • Main effects:
    • Anxiolytic – the mechanism may be similar to the CNS-attenuating effects of benzodiazepines on GABA channels.
    • Antibacterial against several strains of Gram-(+) and Gram-(-) bacteria, to include Escherichia coli, Mycobacterium tuberculosis, and Salmonella typhimurium, among others. More info, here.
  • Entourage effect: May work synergistically with linalool and geraniol to induce a relaxing/sedating effect, and also ameliorate the onset of anxiety associated with THC.

 

nerol

 

Until next time… smell ya later!

Sources:

https://truphys.com/antioxidants-and-training/

https://www.scientificamerican.com/article/why-do-flowers-have-scent/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785529/pdf/bph0158-1074.pdf

https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2003-39695

https://www.ncbi.nlm.nih.gov/pubmed/28632185

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/pdf/i1524-5012-13-2-214.pdf

https://www.researchgate.net/profile/Alan_Pollnitz/publication/10878787_Quantitative_analysis_of_geraniol_nerol_linalool_and_a-terpineol_in_wine/links/0c9605366d82151aaf000000/Quantitative-analysis-of-geraniol-nerol-linalool-and-a-terpineol-in-wine.pdf

https://www.sciencedirect.com/science/article/pii/S0254629910001559#bbib95

https://www.tandfonline.com/doi/abs/10.1080/10412905.2007.9699283

https://www.researchgate.net/publication/228897917_Cannabis_and_cannabis_extracts_Greater_than_the_sum_of_their_parts

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1750-3841.2012.02924.x

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152637/pdf/molecules-22-01021.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/

darwin-caramel-hard-candy-edibles

How Should I Consume Weed for the First Time?

For those in the early stages of incorporating cannabis as a part of your lifestyle, it can often feel overwhelming to consider the various options for consumption. From cannabis-based edibles and topicals to smoking and vaping, there are many different ways to ingest the herb. However, the cannabis product recommendations for first-time consumers have increasingly leaned towards vaping or edibles.

If it’s your first time-consuming weed, tips often encourage you to keep it simple and to avoid overcomplicating the process to make the learning curve a bit less steep. This will enable you to maximize the benefits of cannabis without requiring you to struggle through a more complicated consumption process, such as rolling a joint, allowing you to simply enjoy experiencing the herb. For those wondering, “How should I consume weed for the first time?”, vaping is often a clear front- runner for many different reasons. If you’re not a smoker nor interested in smoking, edibles are an excellent way to consume cannabis as well.

Improved Taste, Efficacy, and Smell

Recent studies have shown that many cannabis consumers prefer vaping weed extract through a vape pen over smoking a joint, attributing it to a higher-quality flavor, the distinct lack of a lingering smoke smell, and stronger effects.

Low dose edibles are a good way to consume cannabis without the “marijuana” taste. Also, this way to consume cannabis also means no marijuana smells.

User-Friendly

Unlike smoking, vaping allows the user to inhale the vapor in small, short puffs instead of deep breaths. For many consumers, particularly those who are just getting started with cannabis, vaping is a far easier method.

Edibles are another user-friendly way to consume marijuana, as there is no need to master the use of a vape pen. Gummies, for example, are small, tasty,  and easy to consume.

Highly Discreet

With the growing popularity of vaporizers and e-cigarettes, utilizing the devices for vaping weed has become a highly discreet way to consume cannabis – especially when compared to traditional smoking.

Just like eating a piece of candy, gummies or hard candy style edibles are perfect for a quick bite with results kicking in within 25-45 minutes after consuming. If you are consuming an edible for the first time, be careful to watch your dose. It’s recommended to start with 2mg of THC and wait two hours before consuming any more THC.

Seriously Good Gummies DARWIN Brands

DARWIN Seriously Good Gummies

Getting Started with Vaping Weed or Quality Edibles

One of the most important steps you can take in your cannabis journey is to choose high-quality products that have been expertly crafted so you can enjoy them with confidence. Instead of starting your cannabis journey with products you’ll find lacking in quality, effectiveness, and user-friendliness,  enjoy a confident experience with premium-quality products from a company you can trust, such as Darwin. If you plan to try vaping weed, a distillate cartridge system like Darwin’s Origin Series is an ideal set-up for your first vape and beyond. If you’re interested in going the edibles route for consuming marijuana for the first time, take a look at Darwin’s Origin Series’ Seriously Good Gummies.

To learn more about how you should consume weed for the first time, and products that can provide you with an enjoyable, confident experience, visit www.darwinbrands.com or ask about Darwin products in your local dispensary.

The antioxidant properties of CBD.

CBD and Exercise: Deciphering Fact vs. Fiction

The antioxidant properties of CBD.

“If exercise could be packed into a pill, it would be the single most widely prescribed and beneficial medicine in the nation.” – Dr. Robert Butler, Founder, National Institutes on Aging

If asked, I wonder what Dr. Butler would say about cannabidiol (CBD), or the combined use of CBD to supplement exercise? The market is booming with an array of choices for just about anybody’s body – CBD tinctures, capsules, CBD-enriched protein powders, some of them full-spectrum, some with CBD only, each with their own claim on how CBD can provide therapeutic value. One niche is promoting the use of CBD as a supplement touted to give a better workout or active experience and help recover from exercise. It leads to more gains, right? Before we chalk it up to either the best thing since sliced bread or opposite, the likes of a trendy fad diet, the concept of using CBD as a training aid deserves some scientific attention.

According to research, CBD may be anti-inflammatory, antioxidant, a 5-HT1a (serotonin receptor) agonist, and GABA channel agonist. This means it may play a role in attenuating inflammation and associated pain and reduce the effects of stress and mood disorders such as anxiety and depression. Physical activity is also a stress – not the way most people think about it unless you dislike it (then, of course, it’s stressful!) But physiologically, exercise creates reactive oxygen species (ROS, similar to “free radicals”), causes inflammation and may leave you sore and fatigued. However, these are all necessary signals to tell your body to adapt and progress in training.

It seems like CBD would be a useful supplement for anyone who moves, whether its a focused athlete or an active individual who suffers from chronic pain. Does it assist with training gains, maintenance and/or recovery? The last thing a physically active individual desires is to kill the very chemical messengers that tell their body to increase muscle mass or improve their aerobic capacity because it would all be for nothing, and that’s not an option. Let’s take a look!

First thing’s first. There are a LOT of factors that comprise physical activity. The health and fitness statuses vary among individuals, including how frequently they are active. The intensity of activity is important, and so is the duration of the workout. The type and purpose of exercise matters also. Going on daily walks, training for a marathon and powerlifting are three completely different modalities of exercise with different benefits and effects. All of them recruit different types of muscle fibers and use different types of fuel to provide energy to do work.

Understanding recovery is also important – if not more important, as you can’t train if you don’t recover. It involves replenishing and refueling the body, not just after a workout, but for the next one as well. In addition, getting adequate amounts of rest, not overtraining, and long term, adapting to all the chemical signals produced in response will all effect training gains.

Antioxidants Paskenta

Signalling Cascades – Don’t Kill the Messenger!

CBD is a potent antioxidant. In fact, some research shows it may be more effective than vitamins C and E when it comes to providing protection against neurotoxic damage and can assist in protecting the heart in diabetic cardiomyopathies. Antioxidants are very important as they keep ROS at bay, preventing damage to cell membranes and combating the onset of a host of age-related chronic diseases and cancers. To do so, our body produces its own endogenous antioxidants: superoxide dismutase (SOD), catalase, and glutathione peroxidase to name three first-line defenders. We also get them from food (some vitamins, for example) and from cannabis, like CBD.

But consuming more is not always better. Many athletes and coaches misunderstand the role of antioxidants and their use during training, CBD included. In healthy adults, supplemental antioxidants may actually slow adaptations to training by killing the signal that ROS delivers to produce more mitochondria, the “powerhouse of the cell.” More mitochondria basically allow for more fuel turnover and energy production, and therefore improvements in aerobic capacity and endurance. Slowing this process down through antioxidant use will cause adaptations to take longer. Several studies support this concept, showing an attenuation to adaptation when athletes use vitamin C and E supplementally while training and those are just two examples. If CBD is more effective than the aforementioned vitamins, then the dampening on gains could perhaps be even more profound. (You can read more in-depth about antioxidants, training and mitochondrial biogenesis, here.)

A similar mechanism may exist with inflammation. Like ROS, inflammation is also a signal to repair stressed tissue and synthesize more protein. A few studies have shown CBD to be a cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor, therefore dampening the production of prostaglandins involved in the natural inflammatory response. This is the same target that non-steroidal anti-inflammatory drugs use to work their magic. In addition, CBD may inhibit the production of interleukin-6 (IL-6), a pro-inflammatory cytokine produced post-workout, as well as tumor necrosis factor-ɑ (TNF-ɑ), another important inflammatory marker involved in training response. Unfortunately, there exists supporting data showing that using NSAIDs to treat post-workout muscle soreness may inhibit adequate protein synthesis, slowing metabolic changes, and adaptation to training. (Many actually think that NSAIDs are an ergogenic aid). CBD may have the same effects, as it has an inhibitory effect on messengers important in acute and long-term training gains, although training studies on both healthy and sedentary adults need to be conducted.

COX Prostaglandin Pathway

CBD Still Has Potential

You may be discouraged at this point, but all may not be lost! Several studies on various disease states in cardiac and neural tissues have investigated the effects of CBD on the regulation of the PI3K-Akt-mTOR pathway. mTOR (mammalian target of rapamycin) is an important regulator of cellular metabolism, growth, and survival. One of its roles is to signal skeletal muscle cells to increase protein synthesis in response to strength training, leading to strength gains and muscle hypertrophy. There are conflicting data, some suggesting that CBD downregulates this pathway, and others suggesting the opposite. If the latter is true, it may be a useful supplement to enhance protein synthesis, but the jury is certainly still out.

In addition, nitric oxide (NO) has an important role in maintaining vascular and cardiac tissue health, causing vasodilation (relaxation) when it is released as well as a cascade of responses to signal mitochondrial biogenesis in muscle. Exercise is a trigger for NO production, and there exists conflicting conclusions on CBD’s role in stimulating or inhibiting its production.

Overall, it is unclear the long-term effects of CBD use on training adaptation. It is true that more research needs to be conducted, and of the body of evidence that exists, the majority of it is investigating its use in different disease states. What we could possibly conclude, however, is for healthy adult athletes, CBD supplementation may have a negative impact on training progression. For active individuals using physical activity to improve or maintain health, without a training goal, and perhaps treat inflammation-related pain or other researched conditions, CBD may be just the thing you need to succeed.

Sources:

Corso, J. (2017). Antioxidants and Training: Friend or Faux?. [online] truPhys. Available at: https://truphys.com/antioxidants-and-training/ [Accessed 21 Mar. 2019].

Hampson, A. J., Grimaldi, M., Axelrod, J., & Wink, D. (1998). Cannabidiol and (−) Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences, 95(14), 8268-8273.

Jie, L. I. U., Bin, G. A. O., MIRSHAHI, F., SANYAL, A. J., KHANOLKAR, A. D., MAKRIYANNIS, A., & KUNOS, G. (2000). Functional CB1 cannabinoid receptors in human vascular endothelial cells. Biochemical Journal, 346(3), 835-840.

Rajesh, M., Mukhopadhyay, P., Bátkai, S., Patel, V., Saito, K., Matsumoto, S., … & Haskó, G. (2010). Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology, 56(25), 2115-2125.

Trappe, T. A., Fluckey, J. D., White, F., Lambert, C. P., & Evans, W. J. (2001). Skeletal Muscle PGF2αand PGE2 in Response to Eccentric Resistance Exercise: Influence of Ibuprofen and Acetaminophen. The Journal of Clinical Endocrinology & Metabolism, 86(10), 5067-5070.