Medical Research

Cocrystallization of Cannabinoids in Pharmaceuticals

Written by Lisa Rennie

Cannabinoids have shown great promise in the medical world, given their potential therapeutic properties. However, there are certain challenges in terms of cannabinoid chemistry that can impede their pharmaceutical development.

That said, a revamped technique from over a century ago may help to resolve some of these issues.


Challenges of Cannabinoids in Pharmaceuticals

The following are a couple of issues that the pharmaceutical industry faces with developing cannabinoids into medicinal products.


Low melting point semisolids
Most cannabinoids are semi-solids with low melting points. This physical makeup comes with certain challenges. For instance, many cannabinoids have stability limitations as a result of their lipophilic physical nature. Acidic cannabinoids are particularly vulnerable to decarboxylation, a chemical reaction that removes a carbon atom from a carbon chain.

Even neutral cannabinoids that lack a carboxyl group may be unstable when heat is applied. The low melting point semi-solid nature of most cannabinoids makes it more difficult to administer them as tablets in the world of pharmaceuticals.


Lack of water solubility

The lipophilic nature of cannabinoids also means they are not water soluble. As such, their absorption and bioavailability in the body is lacking, which is a significant issue when attempting to transform them into pharmaceuticals.

Cocrystallization as a Potential Solution to Cannabinoid chemistry Issues

Fortunately, these obstacles may be overcome through “cocrystallization,” a phenomenon that was initially studied and used in the 19th century. Unlike traditional crystallization, cocrystallization is a technique that involves the intermolecular non-covalent bonding of molecules, such as cannabinoids, with neutral molecules, or “conformers,” to crystallize the pair in a well-defined and recurring cocrystal lattice.

The pharmaceutical industry has recently become very interested in modern cocrystal technology as a way to improve drug stability and bioavailability. Over the past decade, researchers have discovered signs that cannabinoids may also form cocrystals. For instance, the flavonoids luteolin and quercetin from the cannabis plant were shown to produce cocrystals with isonicotinamide. Isonicotinamide is an isomer of nicotinamide and is soluble in water and ethanol.

The goal of this research was to improve the water solubility and bioavailability of these substances, and cocrystal chemistry could affect cannabinoids. This technology may also be useful in identifying cocrystal pairs of minor cannabinoids to purify them from other cannabis components.

Thanks to its potential to mitigate cannabinoids’ above-mentioned chemistry issues, cocrystal chemistry is now experiencing a resurgence in interest among researchers and the pharmaceutical industry over a century after its discovery. As such, we may be seeing more and more cocrystal technology in the pharmaceutical development of cannabinoids.


Image source: LPARRO via Pixabay



  1. Filer, C.N., “Cannabinoids as Cocrystals“, Med Cannabis Cannabinoids, January 2022; Vol.5:7–8.

About the author

Lisa Rennie

Lisa Simoneli Rennie has been working as a freelance writer for more than a decade, creating unique content dedicated to informing consumers. She enjoys sharing her knowledge and experience with others, and in her spare time, Lisa enjoys trying funky new recipes, spending time with her dog, and of course, reveling in the joy of family.