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)-????-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 ????-acid (humulone) content, giving them a zesty, bitter flavor and odor.  The more aromatic varieties, like noble hops, are lower in ????-acids and higher in aromatics like ????-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 ????-caryophyllene, an opened-ring isomer of ????-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 ????-humulene: White Widow, Original Glue, GSC
  • Main effects:
    • Anti-inflammatory, illustrated through the reduction of eosinophil migration and inhibition of IL-5, NF????B 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 ????-pinene, and from ????-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.

Celebrate this 420 with FREE* WEED!