The hemp industry has seen a surge in products claiming to be “water soluble” and offering higher “bioavailability.” But what does this actually mean for products and consumers of hemp-based wellness products?

This article will help address the different methods used to make cannabinoids water soluble. We’ll also assess the CBD industry claims associated with these methods and bioavailability.

EDITOR’S NOTE: Keith Butler is the founder and lead hemp researcher for Life Patent, one of our Top CBD Brands. After Jessica introduced us to CBD bioavailability, we asked Keith for a more detailed “deep dive” into this fascinating subject. -KO


To understand these terms and their meaning within the context of hemp-based cannabinoids, it would be helpful to start with some basic science.

First, cannabinoids are lipophilic molecules (i.e., oil-based compounds that are not soluble in water). This means that when you place extracted hemp oils into water, they float. Cannabinoids in their natural lipophilic state do not mix with water and they act exactly as if one poured motor oil onto water—they will not dissolve in the water. This has always been the problem for oil-based compounds—because our bodies are up to 60% water, they have difficulty dissolving, and more importantly, absorbing these types of molecules.

The term “water solubility” refers to a compound’s ability to dissolve into water at a specific temperature. The term bioavailability refers to the amount of active ingredient (AI) in the compound which makes it into the bloodstream. If one injects an AI directly into the bloodstream, this is called 100% bioavailability. If a compound is ingested, in almost all cases that compound is subjected to what is known as a first pass metabolism, or first pass through the liver, where the contents from our stomachs are “cleansed” by the liver on the first pass of digestion.

It is here where most of the degradation of AI takes place as enzymes process digested material within the liver. The chances of ANY ingested lipophilic compound passing 100% of the AI into the bloodstream by ingestion is almost zero percent. Decades of pharmaceutical science have tackled this subject with relative success, but no pharmaceutical company claims 100% bioavailability of active ingredients in their formulations of lipophilic compounds.


Why, then, does the CBD industry continue to tout claims of 100% bioavailability of cannabinoids, or other inflated claims about bioavailability?

The simple answer is because they can. The marketing of unregulated products like hemp “allows” companies to print what they want to believe or what they want you to believe. This is simply the nature of an unregulated industry, and unfortunately the hemp CBD industry is overflowing with overzealous assertions and outright misinformation when it comes to water solubility and bioavailability claims.

Vitamin and pharmaceutical companies have developed methods over time which allow lipophilic molecules to be more readily absorbed by our water-based bodies. These methods have included micro and macro emulsions; liposomes; nano particles; and nano emulsions. While each of these methods has its place in the world of solubility, the truth is to date, this author is unaware of any certified research trials testing the resulting efficacy and bioavailability of compounds associated with each of these cannabinoid formulation methods.

We asked an expert to explain CBD water solubility and bioavailability. Photo: Science laboratory test tubes and laboratory equipment

We asked an expert to explain CBD water solubility and bioavailability.

Certified research is available on every form of conversion by the pharmaceutical industry for their products, but few in the hemp industry have done this important work. Very few players in the hemp space have considered blood plasma testing for AI and those who do are mainly working with their own products. There are no independent studies available on this subject without product bias designed to prove one product is better than another. There have been no governing bodies for the industry to guide or implement these studies, and as a result, the public hears unverifiable information created primarily for marketing purposes and providing little insight into the actual efficacy of a product.


What is the truth about bioavailability? How do our ingestion methods correlate to the amount of active ingredient our bodies process when we ingest hemp-based cannabinoids?

To begin, there are a few basic ways to introduce hemp cannabinoids to the body: through inhalation, ingestion, or application.

With bioavailability as the desired target, the most effective and proven delivery method is inhalation. Studies have shown that combustion, be it smoking or vaporizing cannabinoids, produces bioavailability levels from 2%-56% depending on the study and the smoker type, with averages leaning towards the higher side. The high discrepancy in availability is attributed to the experience of the test subject—novice smokers versus experienced smokers who inhale deeper and longer. So simply put, on the higher side of the scale, smokers get a high average bioavailability of cannabinoids around 40% (i.e., less than one half of what they ingest becomes available or quantifiable in their bloodstream). Now that we know this best-case scenario of actual high bioavailability (56% on the highest end), some claims by CBD (cannabidiol) and THC manufacturers may become a little harder to believe.

The truth becomes even more apparent as we move onto other methods.

Sublingual CBD has high bioavailability. Photo: A man takes a tincture.Sublingual CBD

Ingestion (sublingual) offers much lower bioavailability than inhalation, but the effects are longer lasting. Sublingual delivery is when a tincture is absorbed into the body by delivery into the bloodstream through the soft palate located under the tongue. This is considered the preferred method for bioavailability by mouth as the CBD can absorb through the mucosal membrane and enter into the bloodstream more rapidly than by swallowing. It is this action that many “water soluble” claims are based upon to increase the bioavailability to 100%.

But here is the trick: there are no independent published studies (that I am aware of) testing the transfer of CBD sublingually into the bloodstream by evaluating blood plasma test results to assess an increase in availability. There is a published article where sublingual techniques of cannabinoid delivery are discussed in comparison to known oral delivery bioavailability where the scientists believe that sublingual bioavailability is only slightly higher than oral ingestion. However, almost all the known studies involve THC (with exception of the work by GW Pharmaceuticals). With THC, there is a different outcome when ingested. Since the THC molecule undergoes changes in the digestive tract and transforms to 11-OH THC which is believed to be as much as 5 times more psychoactive than Delta 9 THC (the byproduct of D9 THC), the resulting effects—such as a long-lasting high associated with edibles—are magnified.

So, sublingual is perhaps marginally better than oral delivery.  Oral delivery (ingestion by swallowing) is verifiably known to have bioavailability levels ranging from 4% to 20%, with most studies and outcomes falling within the lower range below 10% bioavailability. As a result, we can theorize (because we have virtually no data to confirm this) that sublingual administration of cannabinoids may yield a range somewhere between 10% and 20%, but not much more.

What about rectal CBD?

There is another way for cannabinoids to enter the body: through rectal administration.

Anecdotal evidence and articles would suggest that this method is the most bioavailable as many cancer patients choose this route of administration. However, the only science available was conducted on monkeys and showed about 13.5% availability, much lower than one would expect given the popularity of this method in large dosages. The truth is, rectal administration is basically location specific. Based on the veins and arteries in the rectal area, absorption into the bloodstream is minimal according to existing scientific publications.

Topical CBD and bioavailability

What about the skin? How and why do topical cannabinoids seem to work? Is the skin capable of transferring CBD to the bloodstream to create bioavailability, and if so how much?

You might be surprised to find that, in reality, transdermal delivery of cannabinoids is only a theory, at least for now, but clinical tests are underway. Eventually, science will prevail as topical CBD products proliferate and inquiring minds prioritize this as an area of study. However, testing the transfer of a lipophilic molecule into water-based skin can’t truly be done without complicated scientific practices which are currently rare in the hemp industry. There is only one company that I am aware of (CV Sciences) who has created a transdermal delivery method with any strong science behind it and who was recently granted a patent for this invention.

A person's knee with topical lotion applied in a heart shape.Topical CBD vs. topical THC

There is one thing we do know: THC and CBD act differently as far as the epidermis is concerned, and CBD seems to be far more absorptive through the epidermis than THC.

There is also another reason why cannabinoid topicals seem to work so well for so many people. The skin is the body’s largest organ and is filled with CB receptors, as are our muscles, bones, nerves and tissues. So, it is possible the cannabinoids, given the proper carriers, can cross the epidermal layer and directly affect CB receptors by absorption.

If this is true, it would support the massive collection of anecdotal evidence which supports the general consensus that topicals work. But as a formulator, I can tell you that there is a big gap between those components required to make products that just work, and those that work really well. In developing LifePatent’s topical formulations, I am focused on making sure our products work really well as opposed to the ‘whatever works mentality’ that is prevalent in the industry and that is often opposed to exploring the possibilities of what could work better through dedicated research and development.


Now that we understand how cannabinoids get into our system in different concentrations dependent upon administration methods, we can now start to develop an understanding of the current water solubility methods employed to increase availability, efficacy, or both. We can also now take a look at some of the claims made by certain product lines, and better understand the challenges that consumer’s face when trying to evaluate and differentiate cannabinoid products in the marketplace.

One popular CBD website claims that their ‘Nano Particle Water Soluble CBD’ has a bioavailability of 90% or more. Really? Let’s look at this claim. Our industry is plagued by false or unsubstantiated claims. I have seen no science showing that this company conducted clinical trials comparing their product to others, or comparing blood plasma levels showing their product is 90%+ as effective as an injection into the bloodstream. In addition, this company claims a “patent” on this technology, but do they actually own the patent? Would it be safe to assume the technology is patented and they are buying it from a third-party source who owns the patent and did the blood plasma tests to make the claim that this product works 90+% as well as an injection?

But let’s first understand what this claim is for—it is for a “new” technology which is claimed to be “better” than Nano-Emulsion technology (which this company claims offers an absorption rate of 10-30%). If Nano-Emulsion CBD has a bioavailability rate of 10-30%, and we know that sublingual oil-based tinctures already have a bioavailability rate of 10-20%, where do these claims of increased bioavailability leave us? Confused.

Is anybody confused yet?

If these claims are true, the Nano-Emulsion technology that everybody claimed increased bioavailability by ten-fold is now less than two-fold according to the claims of this particular company because their new “patented” technology claims to be superior to Nano Emulsion. The new science? Nano Particles, which producers claim are smaller and therefore work better.

That seems to be the ‘science’ in our industry: if its particles are smaller, they absorb better—which is somewhat true. A glass of shaved ice, which has a much higher surface area than a glass of ice cubes, will cool down and melt faster due to the greater surface area. Translating this into the skin-blood barrier, smaller particles may pass through the skin easier, but this does not ultimately change the way the body metabolizes or digests lipophilic compounds. Smaller particles just allow a greater surface area in which to transfer the active ingredients through carriers into the body where they still undergo the ‘first pass metabolism’ and where a large percentage of the active ingredients are destroyed by enzymatic processes.

So, is anybody confused yet?

Although it is confusing, now that we have the basics of administering cannabinoids, let’s look at the science behind today’s applications to improve their water solubility.


To achieve fine dispersion of oil into water, the water must be kept in a continuous phase while the oil is in a dispersed phase. This requires the use of an emulsifier or surfactant to assist in the dispersal. There are three common ways to achieve this.

  1. Macro emulsions, which utilize large 1 micron plus droplets, with the carrier oil and surfactants added. Macro emulsions are rather unstable. Think of this as the mixing of cannabis or hemp oil with lecithin (such as animal fats), and mixing it in a drink at home. This method probably works as well as a good sublingual dosage, and maybe even a little better.
  2. Micro emulsions are done on a smaller scale, with droplet sizes 1/10 of the size of a macro emulsion. Micro are more stable than macro. Unfortunately, like macro emulsions, the current science is lacking. Additionally, the number of surfactants used can overwhelm the taste buds or can exceed allowable limits for consumption.
  3. Liposomic transfer by spherical structures that are either man made, or available in nature, which have a water attractive (hydrophilic) outer layer and in inner cavity which is capable of encapsulating the cannabinoid molecules and pass them literally “inside” themselves. There are a variety of carriers out there available in the pharmaceutical industry which are approved to do this job. I expect over time there will be CBD manufacturers who reach out to the pharmaceuticals for help, or technology.

I’m excited to be a part of all of this! I can’t wait to one day unveil what my team and I have been able to create in our labs, starting with our solid dose pill. I’m sure others out there have great dedication for the cannabis sciences and are creating the future as well.


Probably the most well-known method of enhancing solubility is through the use of Nanoparticles or Nano Emulsions. These two terms are completely different things, so let’s first discuss the differences between emulsions and particles.

Nano Particles are generally carrier and active ingredient particles dispersed or disrupted with the use of sound waves or frequencies where the particle size of the intended target (the CBD and carrier) is disrupted into smaller and smaller pieces by ultrasonication (sound waves). Nano-sized particles are created by this process. These very small (nano) particles composed of carrier and active ingredients are much smaller than their non-disrupted selves. They’re capable of passing through membrane walls easier as a result of the highly diminished particle size.

Nano emulsion is a mixture of those nanoparticles with emulsions of surfactant droplets, which are also extremely small, and are designed to enter the body more efficiently. Nano emulsion is currently (theoretically) the most bioavailable option out there. But how much better is it? If you listened to some of the companies who sell it, they claim the bioavailability of nano emulsions is over 90%. By now, I’m hoping we all realize that this is doubtful. Considering known administration types, like sublingual or oral ingestion, can be boosted from 20% bioavailability in a best-case scenario to 90+% of that through an intravenous injection, I would be really surprised if a study could ever prove such efficacy for traditional delivery methods.


Returning to nano water soluble claims of 100% absorption, we can see this simply cannot be true unless the water-soluble products on the market today could be (and were) injected directly into the bloodstream. As a result, how do we express the relative bioavailability of products that our industry supplies comparative to the science?

Photo: A researcher holds up CBD oil and a hemp leaf.

More research will be needed to determine the truth about different forms of CBD and bioavailability.

Firstly, we do the science and get the answers before we make claims. LifePatent filed patents in 2017 for water solubility and bioavailability of cannabinoids. We’ve still yet to make a claim of any kind other than the discovery of “nature’s delivery method” for cannabinoids. Our technology has been in testing for over a year. Once all the evidence is in and verified we will speak.


At LifePatent, we encourage all CBD and hemp cannabinoid users to do the research. The unregulated marketplace is the ‘wild west’ but eventually the wild west was regulated.

As time passes, I expect to see changes from both consumers and regulatory agencies. This will encourage the proliferation of real science and genuine products. Unfortunately, in our world today we only have the word of mouth and product reviews to make our choices. Tomorrow we may have science and technology to support those referrals and reviews.


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