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Ways to take CBD - Explaining Bioavailability and Metablosim - BWell

Ways to take CBD… Explaining Bioavailability and Metabolism.

July 14, 2019  •  By Jason Avent

Ways to take CBD… Explaining Bioavailability and Metabolism.

CBD comes in a dizzying array of product types, each with its benefits and drawbacks. Here is a breakdown on the best ways to take CBD… and an explanation on the real science behind it.

This is a long read but very worth it. Please take it all in 🙂 We research and write so that you can make educated purchasing decisions!

These include liposomes, edibles, oil-based products, emulsions, powders, vaporizers and topical formulations.

Each of these has its own advantages and disadvantages with regards to bioavailability, palatability, duration of effect and speed of onset. The science surrounding these many facets is called: Pharmacology.

There are also effects of the matrix where cannabidiol is appreciated as a more “well-rounded” product with some more potent and longer-lasting effects. The matrix is a term that describes all of the things other than CBD that make it act the way that it does and can affect every aspect of pharmacology through interactions.

There are benefits to including more than just CBD from the plant. Most research studies are done with isolate, which means scientists can get a very clean picture of the effects without other confounding factors.

With full spectrum, the results are generally better and sophisticated consumers who have tried both isolate and full spectrum come to appreciate what has been termed “the entourage effect”. The entourage can include other cannabinoids (these share a structural similarity to CBD) or terpenoids, small, often aromatic molecules that enhance absorption or make the metabolism of CBD change in favorable ways.

The potential downside can be that the product will have flavors that may be unwanted by the novice consumer.

We, at The BWell Market, have found that if you understand the functionality that these flavors provide, it is much easier to tolerate and even appreciate these novel flavors.

Often described as “an acquired taste” almost any flavor can become desirable when it is paired with pleasant outcomes, such as the relief of pain or anxiety. We can also use these sensory cues of flavor and smell as valuable indicators of product quality. Often, freshness can be a major factor in how potent a product is, and without these characteristic flavors and smells, we may be using expired product without knowing it, and then we don’t receive the therapeutic benefits.

Flavor and Smell as an Indicator of Quality

One classic example of flavors that are perceived as unpleasant at first and then become an “acquired taste” is the flavor of hops in beer. These bitter compounds are not something most people desire without an experience with them, but as the flavor of hops becomes associated with the feelings that the beer provides, the flavor is “colored” by our memory to be a pleasant indicator of the beer buzz to come.

Mentally appreciating the function of the flavor as you experience it is one way to accelerate the process of developing an acquired taste and using it to your benefit.

For example, hops has more than a flavor to give to beer, it can also act as a valuable indicator of quality. When beer is exposed to light, photooxidation destroys the antioxidants inside it, and one of those hops compounds becomes a “skunky” flavor.

Without the hops in beer, the destructive effects of photooxidation may go unnoticed and the beer gets a reputation as poor quality for no other reason than it is abused by users and transporters, but the end consumer doesn’t taste “skunked beer” because the skunk precursor flavor has been taken out by a manufacturer with a poor understanding of its function. In the attempt to make beer less bitter, they actually removed the indicator of oxidation that would lead to skunky flavor.

So, the next time you taste full spectrum CBD flower you will appreciate that you have some real sensory information about quality and consistency.

*NOTE: One way to ensure the quality and consistency of the CBD products you use is to keep them at a controlled temperature, and never leave them in a hot car or in direct sunlight.*

Explaining Oral Bioavailability

Bioavailability has several interacting factors. When the product is put into or on the body, there is either absorption or it can be excluded from the body.

For instance, when you swallow it, most may pass all the way through your system – ending up in the toilet 😢 💩

Expensive excrement is not the goal!

Quality CBD should be used sparingly and with great care to ensure that what you pay for is what you get. This also prevents wasteful misuse that leads to a used up supply and unnecessarily high prices.

We believe that the potential of this wonderful active ingredient to change lives is so great that our goal is to only stock products that make the price for an effective dose low enough that more people in the world can afford it and make sure that there is enough to go around.

You’re welcome.

Even for the CBD that does enter the body, some may be metabolized (broken down) before it can have its desired effect.

Most of this “work” is done by something called the Cytochrome P450 (CYP450) system in the liver.

This is a valuable detoxification system (people who live in polluted areas have more CYP450 activation than people from the countryside), but in the case of cannabidiol this metabolic represents significant losses before there is any therapeutic effect. Much like the soldiers who die in overloaded boats on the way to battle, there is little sense in sending CBD to its demise simply because it is convenient to swallow it and absorb it in the same way we absorb food.

The portal blood system delivers everything absorbed from the digestive system to the liver first. CYP450 is one of the “grinders” in the liver that leads to the wastefulness of first pass metabolism.

To confound things further, CYP450 is also responsible for the metabolism of other drugs, and consuming a capsule of CBD along with another medication may mean that both last longer in the system than we are prepared for.

This is called a “metabolic interaction” between drugs and is one of the classic forms of drug interaction. When a pharmacist is dispensing multiple drugs to a patient, metabolic interactions are one of the red flags that they look for.

When using CBD, it is important to let your pharmacist know that this is something that may interact with your other medications. In the best of circumstances, it may actually lead to lower doses of the other medication, especially if the dosing of CBD is co-ordinated to occur before the other medication is taken. Other times, it may lead to blood levels that are too high and can cause discomfort or increased side effects.

The science of drug interactions is tricky, and even foods can have effects upon the metabolic rates of the liver, a classic example is grapefruit, which has so many drug interactions and is such a powerful metabolic moderator that people taking statins are told they cannot eat them.

The furanocoumarins in grapefruit stop CYP3A from doing its job. Since CBD has also been shown to be a potent inhibitor of CYP3A, statins and CBD are likely to have an interaction similar to the interactions between statins and grapefruit.

Since metabolism is so very complex, it is important that you pay attention to what you eat and what drugs you dose and how this coordinates with the effects you feel.

We are still in the infancy of knowing all of the effects of CBD, and there are a dizzying array of possible interactions, so, please be careful and be observant.

Many drugs of abuse have been shown to have higher levels in the brain after use of CBD, so please be careful when driving machinery (yes, that means a car) if you don’t have experience with a CBD combo.

We find that playing a video game is an excellent way to measure your hand-eye coordination in an objective way, but you can probably think of others.

Here is an excellent presentation on the effects of cannabinoids and drug interactions from the department of health (D.O.H.).

The Food Matrix Effect

The combined route of food and therapeutics also lead to confounding “food matrix” effects; a fatty meal may make things absorb more slowly and over a longer period of time than a dose taken on an empty stomach. This is a problem, because it is difficult enough for most of us to eat right, and attempting to coordinate our food and drink consumption with a therapeutic like CBD means there will be inevitable variability in onset of CBD action and how long it lasts in the system.

Some people have a very analytical and observant nature; they may notice slower onset or longer duration of effects. EVERYONE is different.

These people were probably the ones who helped develop the modern concepts of pharmacology.

For most of us, keeping track of our daily work and family needs takes up most of the mental “free time”. For the majority, the burden of tracking what we eat and when we are taking a CBD dose to avoid interactions will be hit and miss. Especially when the benefits of CBD are absolutely critical, it may be advantageous to have a quick acting route of administration for “rescue” in case of metabolic tolerance or food matrix interaction. Small volumes of CBD absorbed in the mouth or by inhalation (vaporizer) can offer a good “safety net”.

Metabolic Tolerance

Presenting a target such as CBD to CYP450 isn’t a simple thing.

In experiments with rodents, the oral dosing of CBD led to a doubling of CYP450 enzymes in the liver. Remember, the CYP450 enzyme is responsible for breaking down the CBD so that it can be absorbed by your body.

This may be part of the problems that have been experienced by people who have to take escalating doses of CBD, eventually resorting to a “holiday” or off cycle to bring their tolerance down.

"Holiday" effect

Especially with limited budgets or limited opportunities to administer a dose it can become quite burdensome to have to take CBD four times a day because the clearance from the system becomes so rapid. In general, more frequent dosing means more mistakes, and for a therapeutic that is difficult to “feel” like CBD it can mean you go out of the optimum therapeutic range before you realize it. Medication reminder apps can be very helpful for these situations, and you may want to track what sort of important events are in your day to optimize the dosing regimen and amount taken at each administration.

If care is taken to circumvent the liver’s attack on CBD, the therapeutic effects may last longer and take much less than the “brute force” method of swallowing it and then having to take more of it and take it more and more frequently. We encourage you to explore dosing systems that are more targeted to the problems you have and more local to the places you want it to go. Swallowing CBD may be appropriate for some users who need whole-body effects or long lasting effects. An example would be for sleep, where the ideal dose has onset at bedtime and is completely cleared by the time you want to wake up. In contrast, if you are treating knee pain, we suggest you use a topical (on the skin) application that uses less and can often provide longer-term pain control while also being more cost effective. Also, if you don’t need to medicate your hand, a CBD application glove may be useful for eliminating off-target effects and wasteful absorption of the product in a place where it isn’t needed.

CBD’s Metabolic Cost – Oxidation

When metabolism is considered, there is a metabolic cost to destroying the things we ingest that are not fuel. When the liver destroys a molecule like CBD, it must use oxidative enzymes. This is akin to having an incinerator in your home; the cost of destroying trash is air pollution, sparks escaping and getting burned. In the liver, the oxidative enzymes that break down CBD exact a cost of their own in the form of escaping free radicals. In a parallel example, we know that much of the problem with drinking is oxidative stress in the liver caused by alcohol metabolism; this has led to the commercialization of many pre-hangover remedies that are antioxidants.

In a study of the livers of mice following CBD administration there was evidence that the metabolism of CBD carried with it the consequence of free radicals and cellular toxicity.

“The present results suggest that CBDHQ formed during hepatic microsomal metabolism of CBD is capable of generating ROS and inducing cell toxicity.”

This can lead to a conundrum, you want the positive effects of CBD, but don’t want to create an inflammation issue while doing it… We take a holistic approach and compensate the metabolic cost of CBD breakdown by adding antioxidants to the CBD formulation. This way, there is a net 0 or slightly positive effect and means that the costs of neutralizing free radicals are “paid for” with an antioxidant-rich formulation of CBD. Similar to the way that an antioxidant-rich mixed drink will prevent your hangover; we can take a similar thoughtful approach to the metabolic consequences of CBD consumption during formulation.

CBD Stability before it Gets to You and After You Open it…

This antioxidant addition has another valuable effect. Antioxidants in foods and herbal formulations have been an important strategy for prevent degradation of the active ingredients while in the package awaiting consumption. The antioxidants you see in foods are often denoted in the ingredient list “to preserve freshness”. In this case, “freshness” can directly translate to pharmacological potency and consistency.

Many poorly thought out formulations of CBD start out with great potency, but as you consume them over the course of days or even months, the formulation may fade in its efficacy. Sometimes, the big bottle can be a much poorer value because the act of taking the therapeutic also means oxygen gets into the bottle. The dose that was effective when the product was new may not be effective as time and oxygen take their toll. This could be through direct degradation of the active ingredients, or it could be through the breakdown of the carrier molecules that help the CBD cross the barriers on the body exterior and get to the bloodstream.

As formulations become more sophisticated, the problems of oxidation may have multi-layered effects. One of the reasons a full-spectrum CBD product is desirable is that many of the products extracted from the plant may have protective effects. Because we don’t hold CBD isolate products in -80°C freezers the way scientists do, many people find that these products don’t have the same longevity and potency as full spectrum or antioxidant fortified versions do.

Full spectrum products naturally compensate for the real way these products are handled and used and therefore may have much greater consistency and longevity compared to isolate. These more expensive products are often produced using harsh methods and solvents to achieve purity and leave the CBD as the only target for oxidation.

Much like the beer that has no bitterness, the longevity of isolate products is highly dependant upon the supply chain and the consistency of handling.

Capsules and Tablets, is there an Alternative for Oral Administration?

The “obvious choice” for administration is swallowing a capsule or tablet; after all, this is how we get nutrients into our bodies. The problems with oral administration and swallowing are substantial. Some people simply don’t swallow pills well. Even for those of us experienced with the process, there is the occasional mis-timed swallowing, the pill stuck in your throat or other uncomfortable scenarios.

Small children have to be taught how to swallow pills without chewing, and chewing is an innate and instinctive thing to do when putting things into our mouths.

Many of the people who could receive some potent benefits from CBD (such as autism) have difficulty being taught to take doses by swallowing something whole. For the young and the disabled, chewable tablets and liquid forms of “children’s” medicines have been formulated for many therapeutic products.

Sorta-oral Administration A.K.A. Sublinguals

Sub-lingual absorption is a good compromise to swallowed products. This does mean tasting the formulation, and it does mean that you will taste the product for a longer time than with a “normal” food experience. When administering CBD sublingually, the goal is to hold the product in the mouth and under the tongue (hence the term sub-lingual).

Saliva production starts to fill the mouth and the innate desire to swallow often defeats the ambition to hold the formulation in the mouth long enough to absorb it through the mouth’s mucosal membranes. I like asking someone a question or making a joke right after they take a sub lingual; the result is awesomely funny, even though can sometimes become a tad wasteful.

Sub-lingual is a combination of absorption in the mouth and absorption via the digestive system. There is a decided benefit to taking a small volume of material that is highly potent. Absorption in the mouth is proportional to the surface are of the mouth, so a large volume of a dilute sublingual will be less effective than the same amount of CBD contained in a micro-volume. Two to three drops is an ideal sublingual volume or a very small dissolving tablet.

The goal is to “paint” the mouth with a single layer of the CBD and then give it as much time as possible to absorb. Once you have given it the best chance to absorb by holding it in your mouth, you eventually swallow. This gives a quick effect via the mucosal absorption followed by a slower absorption via the digestive system.

A pre-treatment of the mouth before consumption of a sub-lingual will have beneficial effects upon the rate and quantity of absorption. Brushing your teeth will take away all of the nonspecific binding sites in the plaque and food particles within your mouth and the abrasion of the mouth’s tissues will open up the membranous absorption surface area. Mouthwash (or hard liquor) can be swished in the mouth in a small volume prior to sub-lingual dosing. This strips oils away from the surface of the membranes in a way that makes those sites for the absorption have a higher affinity for the oily nature of the CBD.

Likewise, since there is a limited surface area, larger doses may be absorbed more effectively if broken up into smaller amounts. i.e. If you want to take 20 milligrams of CBD sublingually, but the volume of the solution is large, consider breaking up the administration into three smaller doses, each involves a cleanse of the mouth, administration of the dose, holding the dose and swallowing, then repeat.

Understanding the ideal methods of absorbing these products can lead to much lower total consumption and greater efficacy of the dose-both in terms of peak potency and duration of the effects. Obviously, lengthy procedures are not ideal, but they do lead to some creative thinking about how to optimize dosage volume and application method. A spray of a fine mist may have much faster bioavailability versus a glob of liquid, but does that mean that a spray is superior? It all comes down to what you want and we have dosage forms that interlock in order to provide you with a smooth and convenient experience.

Your CBD product suite should cover your short and long-range options so that you have something that accomplishes the “just enough” dosing you want at the rate you want to administer it. Some people, for instance will choose long-lasting dosing forms for work or to send them off into sleep, while someone working from home on days that may trigger more or less anxiety may opt for a more frequent “As needed” dosing form that gets to its peak quickly and gets them over the hump with as little CBD as possible consumed. Varying the dosing to be exactly enough can greatly reduce the metabolic burden of CBD metabolism and reduce its potential for drug interactions.

Rectal Suppository

Same story as oral absorption, has shown some very good bioavailability and slow absorption effects without first pass metabolism.

Vaginal suppository

Similar to rectal in many ways. May have some valuable benefits for sexual function due to the antioxidant effect and how this influences the stability of nitric oxide (NO). NO is destroyed by free radicals and can be protected with a coating of topical antioxidant. Whether CBD or other active antioxidants in a mixture are responsible for the preservation of NO it means better erection of the tissues.

Erections, vagina? Am I in the wrong section? Yes, women get erections, but the effect isn’t the same as the erection of the penis. The tissues inside the vagina associated with the clitoris have all of the same spongy tissues that exist inside a penis. Instead of making a rod-shaped organ erect, these tissues tighten the vaginal walls, making sensation to and from a penis much more pleasurable. Often, inflammation steals sexual satisfaction from women, and they are unaware that drugs like sildenifil can actually help them.

The problem is that for a woman, there is no marketing of these well-understood drugs for female sexual satisfaction. If a woman were to read the following study and go to their urologist (OBGYN?) with a complaint about sexual satisfaction and a request for an erection medicine, the use would be considered “off label”.

Significant improvements in FIEI questions 2 (p = 0.017) and 4 (p = 0.015) were noted with sildenafil compared with placebo. For women with FSAD without concomitant hypoactive sexual desire disorder (HSDD) sildenafil was associated with significantly greater improvement in 5 of 6 FIEI items compared with placebo (p <0.02).”

It is a sad defect of our medical system that we treat the exact same disorder of the erectile tissues as if it is a different thing happening on a different planet when it happens in one gender versus another. It is almost as ridiculous as if we were to rename every disorder with two very different names, one in men and one in women. In spite of the homology of male and female physiology and anatomy, we see the problems of men and the problems of women as unelated in spite of the fact we all start out development as females and the grow our sexual organs from a female scaffold of “parts”.

Unfortunately the lack of obvious “equipment failure” means many women have a treatable disorder and don’t know that they should ask a doctor. After all, without an ad imploring us to “Ask your doctor if ______ is right for you.” We can’t possibly know how to find out what we have or how we might treat it…

Obviously, this is facetious quip. We live in a new era of information; we have the ability to experiment and use the resources of the scientific literature. This science is at all of our fingertips with an internet connection and a device to reach the searches. The barriers to science such as jargon and paywalls obscure scientific literature, but only partially.

While a Viagra might well help many women, the mechanism of action is clumsy. Viagra is a blunt instrument causing ripple effects of side effects like headaches and vision changes. While Viagra acts to amplify a paltry signal that is sent by the stragglers of the nitric oxide army, CBD acts to preserve the nitric oxide from oxidative destruction, allowing the local signal of NO to reach the smooth muscle and relax the vessel walls; allowing the blood to engorge the clitoris (which is much larger than the part we can see). The clitoris is like an iceberg… These inner structures expand against the walls of the vagina, squeezing and giving a sensation of pressure that both a man and a woman can appreciate, but without altering signaling in the rest of the body the way a pharmaceutical does.

We have yet to see large scale studies of CBD in female sexual function as a suppository, but the summation of the anecdotes available leads me to hope we will see more studies in the future for the underserved goals of women’s sexual health and sexual pleasure. Unfortunately, with fertility as a major goal of our medical and religious organizations, erections are seen as an urgent problem to solve- because you can’t easily get pregnant without an erection.

When it comes to a women’s engorgement, there is not a real problem with fertility, so the necessity of such a treatment is less likely to become covered by insurance.

We do have some indication that Cannabanoid receptor systems are important for female sexual arousal.

Results revealed a significant relationship between endocannabinoid concentrations and female sexual arousal, whereby increases in both physiological and subjective indices of sexual arousal were significantly associated with decreases in arachidonoylethanolamide (AEA), and increases in subjective indices of sexual arousal were significantly associated with decreases in 2-arachidonoylglycerol (2-AG).”

Certainly, many women experience anxiety that prevents sexual arousal, and CBD has many anti-anxiety effects. CBD action upon 5-HT1A receptors has been shown to moderate anxiety. Obviously CBD has actions at a host of other receptors, and this makes it hard to nail down why one thing happens or another, but this is a powerful lens through which we can reveal the nature of CBD’s many synergistic effects.

“The activity of CBD at 5-HT1A receptors may drive its neuroprotective, antidepressive, and anxiolytic benefits…”


Liposomes are a clever way to make the insoluble oils like CBD and carrier oils into a water-suspension that can be taken into the body much more rapidly. Oils have a tendency to create coherent coatings, clogging up the pores that would act as portals. When a liposome is made, it uses phospholipids to form its outer shell. Phospholipids make up cell membranes we use the disrupted cell membranes of oilseeds to provide our phospholipids for liposome manufacturing.

The oils separate from the water cocooned in phospholipids, so that little droplets of the oily CBD is carried into the water as a suspension of small particles. In a CBD liposome, the phospholipid is in a bilayer, where the polar head groups are facing both inward and outward in the sphere.

This is identical to the structure of a cell membrane and water is on both sides. A CBD liposome has only one place where the CBD can stay, and that is among the tail regions of the phospholipid bilayer. This offers a very small volume of hydrophobic (water-repelled, oil-loving) real estate for holding CBD. In order for the CBD held in a liposome to be absorbed, the bilayer has to come apart and be disassembled by the digestive system’s enzymes and bile (bile is like soap in many ways).

The micelle is slightly different from typical liposomes, because it has just one layer of phospholipids. Their polar (water soluble) head groups face outward, while their tails face inward toward a droplet of hydrophobic CBD.

Image source:

Figure to be made Here is an illustration of a liposome, a micelle and a bilayer sheet. It would be ideal to remake this image with more color and an example of a single phospholipid in the picture labeled head and tail and showing the water associated with the head and an oil-y structure like CBD hanging out at the tail. 

Liposomes offer a really powerful method for travelling past the barrier layers of the body. These can often be made with additives that can cause digestive upset, such as polyethylene gycol (PEG). You may be familiar with PEG from the more common use as antifreeze in car radiators. PEG causes a great number of problems when ingested, including diarrhea. It has toxicity of its own, something that prompted manufacturers of antifreeze to add bitter flavors to their products so that children wouldn’t drink it.

In the very small amounts of PEG that would coat a liposome, there would be little reaction or digestive upset, but the problem is that the manufacturers of these liposomes are taking a shortcut and not clearing the excess away from the liposomes once they have been formed. The result is that a lot of PEG is ingested along with PEGylated liposomes, and this excess ingredient causes some people to have unpleasant experiences. We understand that it is frustrating to get product from people who half-understand the recipes and take shortcuts.

We take pride in out post-production purification and concentration of our aqueous formulations. This means a small volume contains a high level of active ingredients while not having the unpleasant “leftover” ingredients that make an otherwise good product intolerable. This is the difference between “wild west” idiots and real scientists who have taken the time to understand what all of the steps are and why they are done. Often, it is easy to skip steps of purification, since it seems unnecessary.

The reason why most manufacturers of water soluble CBD (really better described as an aqueous suspension) use liposomes is simple… They are following directions in a cookbook and don’t know the underlying chemistry and physics of what they are making. The products work, and some work very well, but you are paying for large quantities of highly purified phospholipids to carry very small amounts of CBD.

Starting with a basic understanding of biochemistry, it is obvious that a micelle would carry a much larger quantity of the CBD to be delivered and in much smaller particles, which enhances their penetration through the body’s epithelium barrier layers. This led me to investigate micelles, only to find that very little work has been done on them. The formulations of phospholipids force the formation of liposomes with micelles being a minor “accidental” product. The starting materials favor liposomes rather than micelles, much the same way that using ingredient lists for pie crust will only occasionally cause a bread-like structure

The problem is that the literature is full of liposome talk, mostly as a way to deliver water soluble drugs through the skin or to make them last longer in the bloodstream. Lipophilic (AKA hydrophobic) therapeutic molecules are actually a rarity in the world of pharmacology, so CBD and other cannabinoids are delivered via the “secondhand technology” of liposomes.

Liposomes enhance penetration into the body regardless of the route of administration. They can often lead to a shielding of the internal payload from the damaging effects of first pass metabolism. These can also allow the therapeutic molecules to circulate widely in the body so that even though a local area is treated on one part of the body the effects of the formulation are felt everywhere. In contrast, some topicals that are desirable to not migrate may have tremendous effects on the small areas where they are applied with little systemic effect.

Topical Application for Targeted Release

If you want pain relief in your elbow, you may find more relief when rubbing CBD directly on the elbow because you avoid the first pass metabolism that the liver inflicts upon everything that is swallowed. If you can absorb CBD through your mouth, you may be able to limit how much is destroyed in first pass metabolism, but you still have the CBD diluted throughout the body, which means you have more consumed than would be absolutely necessary for your elbow pain.

Topical formulation with quick release liposomes may help to combine the best of both worlds, allowing penetration through the resistant skin and then releasing in an oil form to the tissues below, where the slowly moving lipid ingredients can offer a long-lasting reservoir of pain-relieving CBD.

It becomes the work of clever formulation to avoid the “dangerous neighborhoods” of the body and deliver the CBD to the places where it will do the most good. Much like the weapons of war, there are immediate “bombs” and late to trigger “grenades” with the “no man’s land” of the liver to make the strategy a finely tuned process with perils, solutions and problems.

In Conclusion

There is a lot that goes into deciding which type of product is best for your needs. Please, please, please do your own research so that you don’t waste your money!

P.S., use the code “WELCOME” to receive 20% off any product before August 15th, 2019.


Jason Avent