THC and CBD are very chemically similar organic compounds found in the cannabis plant. Their chemical structure is C21 H30 O2. They mainly differ in one chemical bond causing an open ring in CBD and closed ring in THC. They both have aromatic benzene rings and hydrocarbon tails with only a couple hydroxyl groups that makes them predominately lipophilic and fat soluble, like many other hydrocarbons they are also not very water-soluble. Petroleum is actually a hydrocarbon found in the earth from decomposing organic matter and as you can imagine petroleum is a very oily substance that does not dissolve in water.
In general, hydrocarbons are not polar compounds. That means they are neutral, essentially having no charge. Water, on the other hand is very polar. That is why oil and water don’t truly mix and form a homogenous solution. And while water molecules can surround oily non-polar hydrocarbon macromolecules to form an emulsion, these compounds do not truly dissolve into one another, in the true sense.
With respect to medicinal chemistry, all of this affects the use and availability in creating formulations of THC and CDB as a drug. Since humans are predominately made up of approximately 60%  water (though somewhat dependent on age and sex), water is the solvent of choice for new drug development. This insolubility in water poses a challenge, especially in oral formulations. Oral ingestion of medications are the most convenient and preferred method of taking any medication. When there is poor water solubility there is potentially slow oral drug absorption and that can cause variable bioavailability which can become a rate-limiting step to achieve therapeutic plasma concentrations and ensuing pharmacologic response. It is estimated that about 40%  of newly discovered compounds are lipophilic and don’t ever make it to market due to their poor water solubility.
However, there is much research in the pharmaceutical industry aimed at improving drug delivery and water solubility for hydrophobic compounds. One technique called solid dispersion, uses a mixture of drugs with water soluble carriers, which are a compound consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug inside it. For example, using sugar molecules called cyclic oligosaccharides which have an outer surface that is hydrophilic and an inner cavity that is hydrophobic has been used as a vehicle to deliver these lipophilic drugs in a more water-soluble form.
Another technique called nanosuspension technology, takes poorly water-soluble drugs and breaks them down into tiny particles between 200-600nm and suspends them in a colloid dispersion mixture to improve solubility, bioavailability to improve pharmacokinetics, efficacy and safety.
And within the cannabis industry further research continues to improve the availability of oral THC and CBD by improving its water solubility. A Colorado company created a patent pending process creating a water-soluble powder. They generally describe it as an emulsification of a high-quality CO2 distillate slurry that breaks down into very tiny particles that are then coated with a food grade surfactant which is then dried into a powder. This powder can then supposedly be mixed into liquids such as water, coffee, tea or any recipe for cooking.
Solubility to form a homogenous solution continues to be one of the most important parameters to achieve efficacious concentrations of that compound in our systemic circulation for its desired pharmacological response and one of the bigger challenges that the cannabis industry faces as it works to create medicinal oral formulations.
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Dr. Leigh Vinocur is a board certified emergency physician, who also has a cannabis consulting practice for patients and industry. She is a member of the Society of Cannabis Clinicians. And in the inaugural class for the first Masters of Science in the country in Cannabis Science and Therapeutics at the University of Maryland School of Pharmacy.
This blog is not written or edited by Hearst. The authors are solely responsible for the content.