Using Chromatography to Purify Cannabidiol for Medical Applications

We look at the importance of chromatographic purification in the production of medical-grade cannabidiol (CBD) for modern therapeutics.
Demand for CBD in Medical Research and Treatment

The legalization of cannabis for both medicinal and recreational purposes is a hot industry topic in 2020, as pros and cons of its de-criminalization continue to be debated across the globe. The discovery of specific cannabinoids, such as CBD, that demonstrate promising characteristics for medical treatments, has resulted in an increasing demand for highly purified, safe cannabis-derivatives. This has prompted a need for robust analytical methods of purification that can provide reliable results for both manufacturers and consumers alike.
What is CBD?

CBD, the colloquial term for Cannabidiol, is one of at least 100 active compounds (cannabinoids) that can be found in hemp or marijuana cannabis plants. These chemical compounds join to the cannabinoid receptors of the body and brain, also known as the endocannabinoid system, to produce different effects.

CBD is a non-psychotropic cannabinoid, so it doesn't create a "high" sensation. Instead, it demonstrates effective pain relief and anti-inflammatory properties, resulting in a growing interest in its potential medical applications. There is currently no evidence to suggest that there is any dependence potential of CBD and it is not associated with any major side effects.

A lot of focus is given to separating CBD from THC (or tetrahydrocannabinol), another cannabinoid derived from the plant. This is to remove the psychoactive effects of THC that have led to its status as a controlled substance in many countries worldwide. Both cannabinoids, although chemically similar, interact with the body's endocannabinoid system in very different ways. THC binds with the CB1 (cannabinoid 1) receptors in the brain to produce a sense of euphoria, or a "high". In contrast, CBD has a very low affinity to the CB1 receptors. This interaction with the body's cannabinoid receptors affects the release of neurotransmitters. These chemicals play a part in pain, pleasure and memory amongst many other bodily functions. The indirect effect of CBD on the endocannabinoid system enhances the body's natural levels of endocannabinoids through occupying select enzymes. The limit for THC content in cannabis-derived products is currently 0.2 % in the EU, 0.3 % in Canada and set at similar levels around the world, meaning that removal of THC from CBD is a requirement for commercialization.
Applications of CBD

The US FDA has, to date, approved one medical product containing CBD. Epidiolex, which contains a purified form of the drug substance CBD for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. This means that the FDA has concluded that this particular drug product is safe and effective for its intended use. The FDA has resources available that address their stance on cannabis products like CBD. You can view these resources here for more information.

CBD is also showing encouraging results in the treatment of:

  • Chronic Pain Relief
  • Inflammation
  • Epilepsy
  • Neurological disorders such as Alzheimer's disease
  • Cancer treatment
  • Anxiety
  • Acne

Extraction and Purification of CBD through Chromatography

Chromatography is proving the most effective method in the purification of cannabidiol as it acts as the cleaning stage once the CBD has been extracted. But achieving highly pure CBD for medicinal applications requires numerous pre-treatment stages to ensure the removal of impurities that could potentially foul the resins used in chromatography. This can include shredding the plant, drying, extraction, decarboxylation and distillation before the chromatography step can be performed. The removal of contaminants from cannabinoids is a prominent manufacturing challenge, but chromatography is becoming the leading purification method because of its quick and evident results.
CBD extraction

Extraction is usually the first step in the preparation of CBD. If the product contains both CBD and THC, then the extraction process becomes more complex. There are different methods of extraction available, but the three most common methods used are CO2, solvent and olive oil extraction. CO2 extraction is considered the most effective of these methods due to the production of consistent high quality concentrations of CBD. Although this demonstrates effective separation of cannabinoids, it is not enough to achieve the purity now required by manufacturers.
Reverse Phase Chromatography

Reverse phase chromatography is a widely utilized analytical method for purification because of its ability to separate compounds of varying hydrophobicities. This is effective in the separation of tetrahydrocannabinol from CBD, as THC has a greater hydrophobicity, allowing efficient removal of small amounts of THC from a CBD-dominant product. The larger the separation peaks identified in this method, the better the purification will be from a higher number of sample loads.
High Performance Liquid Chromatography (HPLC)

Liquid chromatography is considered an important method for determining concentrations of cannabinoids within the cannabis plant. High performance liquid chromatography (HPLC) is probably the most commonly used method for the separation (or remediation) of THC from CBD. It offers the ability to test for THCA, a compound normally untraceable in other methods. It is also a reliable choice for potency determination, allowing you to identify cannabinoids with similar structures in just one accurate analysis.
Chromatography Resins for CBD Purification

As we have seen, the pre-treatment of CBD before its purification is extremely important in order to provide cannabidiol-based treatments. Our range of Chromalite chromatographic resins offer an affordable and effective method to separate THC from CBD. The chemical and physical strength of these compounds means that traditional silica media can be damaged during chromatography, resulting in the need for expensive replacements. After vigorous testing of their mechanical stability, Chromalite resins show a much lower breakdown over time than equivalent competitor resins. As a result, they are stable for a long lifetime and will withstand tough conditions of use.

Our PCG600M and PCG600C resins have a smaller pore structure, creating wider peaks and a larger time gap between the peaks making the purification process much simpler. Alternatively, our PCG900M and PCG900C resins have a larger pore structure, giving sharper peaks and a smaller time gap. Our PCG1200M and PCG1200C resins are also being used in these applications.

Ready to enhance your CBD purification process? Order your Chromalite resin here.

Click here to view the full scientific poster.