What is ‘water-soluble’ CBD? Difference Between Water-Soluble CBD & Oil-Soluble CBD

An average adult body is around 50–60% water. So, it’s natural that anything that’s water-soluble will be easily absorbed by the human body. 

But CBD oil is mostly oil-based. And, we all know that oil and water don’t mix. So, in our attempts to make the most of CBD, we usually consume it along with fatty foods, so that it is metabolized properly. 

When vaped or used sublingually, oils don’t pose much of a problem in allowing the CBD to be absorbed into the bloodstream. However, we all know how CBD’s effect reduces when consumed orally and routed through the digestive system. 

So, to maximize its impact, we are advised to eat fatty food along with CBD, so that in the process of metabolizing the fats, CBD too is metabolized and gets absorbed into the systemic channel. 

But, what if this no longer remained an issue? Can we increase the efficacy of ingestible CBD? 

Water-soluble CBD: What is it?

What do you understand by a substance being water-soluble? 

In general terms, it means that the substance can dissolve in water, i.e. the gaps within the molecules of water are filled up by those of the substance, hence creating a bond. This is only possible when that substance breaks down into its molecular level and each of its individual molecule bonds with each molecule of H2O. 

Note that a certain volume of water can only dissolve a certain volume of a water-soluble substance. That is why, if you add too much salt or sugar (both of which are water-soluble) to water, a certain portion of the former just doesn’t dissolve. It remains at the bottom of the container in its normal crystalline form. 

The reason for that is there is simply no more space left between the molecules of water to be substituted by the salt or sugar molecules. 

However, that isn’t exactly what happens in the case of CBD. CBD is, as we know, an oil-based chemical compound. So, how does CBD dissolve in water? Or does it? 

What has come to be commonly known as water-soluble CBD isn’t exactly soluble in water; it is miscible in water. This means that “water-soluble” CBD does really dissolve in water, it “mixes” with water to form a homogenous liquid. 

In this case, two miscible liquids – CBD oil and water – essentially becomes a homogenous mixture without forming internal, electrical bonds with each other. The best part with this kind of “mixing” is that they both can completely mix no matter how much of each liquid is being used. That is no residual liquid remains unmixed. 

But how does that happen with CBD? It is, after all, an oil-based substance. Well, it’s nanotechnology – a recent development in science that is helping many industries these days overcome the usual hurdles. 

And, CBD is not alone in this new age drug delivery science. A lot of pharmaceutical drugs these days are also being prepared to be water-miscible. Simply said, the oil that CBD is emulsified is created such that CBD can mix in it and so can water. 

Let’s find out how “water-soluble” CBD was created. 

What led to the development of water-soluble CBD products

We’ve all heard about CBD-infused edibles and capsules having lower bioavailability. We know that most of it get wasted along the way as it passes through the digestive system, getting metabolized by the liver enzymes, before getting absorbed into the bloodstream. 

But why does its efficacy or bioavailability lower while getting metabolized in the stomach, and not get absorbed directly into the bloodstream as it does in case of tinctures (through sublingual glands under the tongue) or vape juices (through alveoli of the lungs). 

The reason is “First Pass Metabolism”. What is First Pass Metabolism? 

First Pass Metabolism [1] or first-pass effect is a physiological phenomenon, known in drug delivery science, as one that occurs in a human body when a person consumes some plant extract-based substance, in which the concentration of the substance ingested reduces substantially before reaching the systemic circulation.

Obviously when the strength of the substance reduces, so does its efficacy or bioavailability. 

Almost 40% of all new drug compounds are hydrophobic and have the same oral bioavailability issues as CBD. It is commonly seen in medicinal compounds, like morphine, curcumin (from turmeric), lidocaine, nitroglycerin, besides cannabinoids.

When these compounds are ingested in their natural oil state, they can’t effectively get absorbed into the hepatic portal vein system. But the first-pass effect is no longer an issue if: 

  • The substance is used in some other way, like topically, under your tongue (sublingually) or inhaled; 
  • The substance is no longer in the natural oil form that inhibits it from getting dissolved in water and, hence, absorbed into the bloodstream more readily.

While the former option is well-utilized by many CBD users, it is the second option we’re talking about here. If we must use CBD orally, through the digestive system, where the first-pass metabolism will come into play, a water-soluble substance has a better chance of making it into the bloodstream with all its strength. 

This is why some scientists devised a way to bypass the first-pass effect and came up with this novel chemistry technique that has now become common in drug delivery science. Thus was invented the “water-soluble” CBD powder or water-miscible CBD fluid that increased the bioavailability of this substance when ingested. 

CBD Bioavailability & why it matters

In case of certain medications (or supplements for that matter), like CBD oil, the dose of the substance you ingest and the dose that eventually reaches your bloodstream isn’t the same. It actually reduces in strength. 

This strength is the bioavailability that is lost due to the first-pass metabolism. Mind you, our bodies are around 60% water, and CBD oil doesn’t mix with water (hydrophobic), and hence fails to get absorbed into the bloodstream effectively enough.

In simple terms, CBD bioavailability is the strength of the substance that enters the bloodstream when introduced into the body. When it goes through the digestive system, (as we discussed) it reduces in strength and, hence, has a lesser effect than what it would have had if the original dosage reached the bloodstream. This is why bioavailability of drug matters. 

That is why you may have noticed that CBD Calculators show a requirement for a higher dose of CBD when it is ingested than when it is inhaled or taken through the sublingual route, as in tinctures. 

How’s “water-soluble” CBD produced?

“Water-soluble” CBD generally utilizes a newly invented method of manipulating matter on an atomic, molecular, and even a supra-molecular scale, known as nanotechnology. 

This technology utilizes sound waves to break down CBD oil into micro-sized nanoparticles, each being smaller than 100 nanometers. For your reference, one nanometer is only one-millionth of a millimeter.

At this size, CBD oil particles are more susceptible to getting mixed in water-friendly oils or water molecules themselves. At this stage, CBD particles are emulsified in a hydrophilic (water-friendly) carrier oil, creating “water-soluble” CBD oils. To make the perfect blend, a surfactant is used to reduce the surface tension between the two liquids – oil and water.

Different types of water-soluble CBD products can be created with the help of this method. 

Types of Water Soluble CBD

Some of the common methods used to create water-soluble oils for pharmaceutical purposes, especially CBD, are:

  • Nanoemulsions: One of the best methods of creating water-soluble CBD oil, this method has already been explained in the above section. Such CBD oils can be easily added to smoothies or other such drinks without being visible separately, as such CBD oils are translucent in nature. 
  • Microemulsions: A lesser-used method and a lesser-available CBD oil, microemulsions creates droplets that are 100 to 5000 nanometers in size. This method solubilizes CBD oil in water with the help of a chemical process that requires a high amount of surfactants that can cause other undesirable side effects for the user – the reason why it is not often utilized in the CBD industry.
  • Liposomes: This type and method of making water-soluble CBD are a little more common than the above method. But what are “liposomes”? These are spherical structures, filled with water and ranging from 50-5000 nanometers in size. The surface of each compartment is hydrophilic but enwrapped in a hydrophobic (water-insoluble) bilayer. The CBD extract, in this case, is stored in this bilayer membrane. However, this process is a highly complex one and also needs high levels of surfactants.

What are the benefits of water-soluble CBD?

Water-soluble (or miscible) CBD is simply the more efficient and effective form of CBD extract. This naturally gives us an idea as to how this form of CBD can be better for users. Nonetheless, we will still give you an all-encompassing idea of why water-soluble CBD is better than the natural oil-based CBD that is available in the market. 

Advantages of water-soluble CBD

  1. Higher bioavailability, hence far more effective than oil-based ones, when ingested. 
  2. Less wastage, hence you need much less! Since even the slightest dose of water-soluble CBD reaches in its almost intact strength, you need much less. That’s a good thing because let’s face it, CBD is expensive
  3. Quicker action, in fact, 10 times more effective than oil-based options, as they easily get absorbed into the body. 
  4. Broadened the purview of CBD use, and made CBD-infused edible more viable and easily usable through drinks and foods. 
  5. Possibly better option over tinctures for people who don’t like the taste of CBD oil
  6. Eventually, we can expect a rise in CBD-infused beverages and edibles in the market, making edible CBD products more popular in the near future

Is there any Scientific Proof to these statements?

While you would have understood the basic science surrounding the logic behind using water-soluble CBD extracts for making CBD-infused edibles, we would still want to ponder over what the scientists have found out so far. 

According to a 2017 study [2], published in Journal of Controlled Release, nano-emulsion leads to substantially higher levels of absorption of both THC and CBD – cannabinoids found in Cannabis plants, when compared to Sativex (an aromucosal spray containing cannabis whole-plant extract). 

Scientists, led by Cherniakov I from The Hebrew University of Jerusalem, carried out two-way crossover, single administration clinical study on nine healthy volunteers and analyzed the comparative bioavailability of a CBD/THC nano-emulsion and Sativex. It must, however, be noted that the nano-formulation used for this experiment included Piperine, a natural absorption enhancer. 

Another study, carried out by another group of Israeli scientists later that year, also confirmed the results of the former experiment. This study, which was published in another peer-review science magazine, Journal of Pharmaceutical Sciences, involved 14 healthy male volunteers. 

To confirm the hypothesis, they collected blood samples from the volunteers after they consumed either the CBD nano-formulation or Sativex. They found that the nano-formulation took much less time to achieve maximum absorption than Sativex, besides leading to an overall higher absorption of cannabinoids.

The researchers concluded that this finding “justifies further, larger-scale clinical studies with this formulation”. 

Final Takeaway

We all know how potent CBD’s therapeutic effects are on our bodies. And if technology could remove the little hindrances that we face while using CBD, wouldn’t that be great? 

Well, scientists have certainly cleared one step towards that goal by creating water-soluble (or water-miscible to be more precise) that has higher bioavailability compared to oil-based CBD oils when ingested. 

Let’s hope that scientific fraternity can soon overcome all the other hurdles and make CBD a more convenient drug for common use by working on ways to ensure…

  • No more hempy taste of CBD oil tinctures, 
  • No side effects (even the mild ones), 
  • No pulmonary issues from inhaling CBD vape juices, 
  • No more THC in any CBD product (by finding better techniques to remove THC from CBD oils, so no more false positives are reported), 
  • No more trial and error with CBD (by finding the right CBD dosage)
  • No possibility of drug interactions
  • Even better, more convenient techniques of using CBD, etc. 

Perhaps someday, we can hope to see governments all over the world accept CBD more openly and legalize its use as a therapeutic supplement so that everyone can benefit from its natural powers. 


Research Citations: 

  1. First-pass elimination. Basic concepts and clinical consequences; Clinical Pharmacokinetics; Jan-Feb 1984; Pond SM & Tozer TN; https://www.ncbi.nlm.nih.gov/pubmed/6362950 
  2. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration; Journal of Controlled Release; September 8, 2017; Cherniakov I, Izgelov D, Barasch D, Davidson E, Domb AJ, Hoffman A; https://www.ncbi.nlm.nih.gov/pubmed/28890215 
  3. PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers; Journal of Pharmaceutical Sciences; December 26, 2017; Atsmon J, Cherniakov I, Izgelov D, Hoffman A, Domb AJ, Deutsch L, Deutsch F, Heffetz D, Sacks H; https://www.ncbi.nlm.nih.gov/pubmed/29287930 


Author Details
Senior Editor & Researcher , Greenthevoteok
Matt Hansel is a Medical Practitioner, who has been writing and researching about cannabis since 2014.  His popular quotes which we like are: \"Don\'t use CBD oil for a cure, use it as a precaution\"  \"CBD should be considered as any other vitamin supplement and your body needs it!\"