Water-soluble vs oil-soluble for cannabis products: what are the key differences and why should I care?

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We love speaking to all our current and potential clients because it keeps us ultimately "on the pulse" of the cannabis conversation globally, with a particular focus on Europe and the UK. In these conversations, time and time again, clients ask us the question in our headline: what's the difference between oil and water-soluble, and why should I care (i.e. – what version is best for the product I'm developing, how do I explain this to consumers, how do I ensure that my product is as effective as possible etc etc.….)?

With that in mind, we thought we'd take some time to provide our view – focussing on a couple of core areas – hoping we can clarify a few points and help make this tricky decision somewhat easier!

Of course, and as always, we're here to talk, so please use what follows as a starting point for a conversation, and please get in touch with us to discuss your specific needs.

Key Considerations When Choosing Between Water-soluble and Oil-soluble Cannabinoids

For today, we’re focussing on the following key considerations:

1.     Mechanisms of absorption - water vs oil soluble cannabinoids

2.     Bioavailability and fat solubility - in nutrition and cannabis consumption

3.     Factors affecting bioavailability of cannabis compounds - from literature findings

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Mechanisms of absorption - water vs oil soluble cannabinoids

• Water-soluble cannabinoids are absorbed quickly into the body, as they are small enough to absorb directly into the hepatic portal vein, which transports nutrient-rich blood from the gastrointestinal tract to the liver. Cannabinoids go through chemical conversions in the liver before distributing them throughout the body in the bloodstream.

• Oil-soluble chemicals are too large to absorb directly into the bloodstream. Instead, fats have an indirect absorption mechanism, which is first absorbed into the lymphatic system and incorporated into chylomicrons (transporter molecules). Within the lymphatic system, the fats will be digested into smaller molecules before entering the venous blood supply and transported to the liver.

• After processing in the liver, the chemically converted cannabinoids can be delivered throughout the body via the bloodstream and able to interact with our internal endocannabinoid receptors.

• Oil-soluble cannabinoids will therefore absorb more slowly and stay in the body slightly longer than water-soluble cannabinoids. Thus, the onset of action of oil-soluble cannabinoids takes longer, but the therapeutic effect will also be longer.

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Bioavailability and fat solubility - in nutrition and cannabis consumption

• Remember the adage from your school science lessons: "like dissolves like." For example, fats dissolve in fats, and polar compounds (molecules with both positive and negative electrons) dissolve in polar solvents (such as water).

• The majority of fat digestion happens once it reaches the small intestine - this is also where the majority of nutrients are absorbed.

• Your pancreas produces enzymes that break down fats, carbohydrates, and proteins.

• The cannabinoids THC and CBD are lipophilic, meaning they need fats to dissolve and become bioavailable to humans. They work with the fatty tissues and endocannabinoid systems in our own bodies to enhance the effects.

• Water-soluble vitamins like vitamin C and B-complex dissolve rapidly in water, allowing any excess amounts of these substances to be excreted through the kidneys.

• We can conclude from this that saturated fats are better at increasing the bioavailability of cannabis compared to unsaturated fats.

• As a side note - MCT oil has 50-90% saturated fats and is often used in CBD oils for this reason. (see Boost your health with CBD and MCT Oil: the perfect combination)

• Whilst excess amounts of water-soluble compounds will therefore be quickly flushed out from the body, oil-soluble ones will tend to be stored by the body for 30 days or more – again suggesting to us that the longevity of these products is greater.

Factors affecting bioavailability of cannabis compounds - from a variety of sources

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• Water-soluble powder has been found to be approximately 4.5 times more bioavailable than the lipid-soluble form.

• But note that the lipid soluble form was given to the individuals without an additional fat source and on an empty stomach; both factors that greatly reduce bioavailability for oil soluble CBD.

• Peak CBD concentration was reached in 54 min for the water-soluble formulation and in 90 min for the oil-soluble formulation. The water-soluble sample was metabolized faster compared to the oil soluble formulation.

• By consuming fat (~10 g, easily consumed by a standard meal) while ingesting CBD the mechanism in which CBD is transported through the body changes so that the bioavailability of CBD is 3 times higher.

• If a person consumes a cannabis-infused edible that contains a high-fat ingredient, or consumes it alongside a relatively high-fat meal, the fats in the food seem to activate the intestinal lymphatic system. As a result, the compounds dissolved in the fats are transported into the bloodstream by this secondary lymphatic system, thereby making them available to the body.

• ‍Cannabidiol (CBD) has low oral bioavailability (6%), which increases about fourfold when it is co-administered with a high-fat meal. This low bioavailability can be ascribed to incomplete gastrointestinal absorption coupled with extensive hepatic pre-systemic metabolism.

• ‍Because CBD behaves as a high hepatic clearance compound, drug–drug interactions affecting its metabolism are likely to have a prominent impact on its systemic exposure after oral administration.

Our conclusions: Considerations for Choosing a Delivery Metric for Cannabinoid Products, Prioritizing End Consumers

Thus far, unhelpfully, there doesn't seem to be a "right" answer here. However, considering the pros and cons of each delivery metric leads us to conclude that producers, brand owners and business leaders must always consider the end consumer. What do they want to feel? How does your product address their particular need? How will you explain to them how it works? Does a long-term or shorter-term effect suit your product story better?

All of these questions – and more – need to be considered before deciding which route to take, and as ever, our team of experts is here to help you carefully consider your parameters and define the best way forward.

However, we believe in the potential of developing improved CBD formulations with greater oral bioavailability and reduced susceptibility to food effects. Our mantra as a business is to solve problems, and the problem of increasing the "efficiency" of consuming cannabinoid products is one that we're working on all the time! So get in touch to find out more.

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Sources used:

What is Water Soluble CBD and how does it work?

TNL What is a need state?

‍Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

Critical Aspects Afecting Cannabidiol Oral Bioavailability and Metabolic Elimination, and Related Clinical Implications  

Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation

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