Where the Grass is Greener: Novel Solvents for the Environmentally Friendly Extraction of Phytocannabinoids

With many U.S. states and countries moving to relax their laws restricting medicinal and recreational cannabis use, the incidence of cannabis analysis and monitoring to protect consumer safety is also on the rise. With this rise in mind, it is important that these analyses are conducted in safe and environmentally clean ways as much as possible.

The analysis of cannabis plant matter is carried out to examine the chemical composition of cannabis strains, look for potential contaminants and, test plant matter that has been seized by law enforcement. Primarily, these tests are looking for the presence of phytocannabinoids, namely, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), as well as their neutral counterparts, tetrahydrocannabinol (THC) and cannabidiol (CBD). Studying the presence and relative ratios of these phytocannabinoids in a strain can give insight into the potential effects of the strain on the human body.

In order to carry out analytical tests on a sample, the phytocannabinoids must first be extracted from the plant matter. For many years, this extraction has been done using a 9:1 mixture of methanol and chloroform. The use of chlorinated solvents is considered a potential risk to animal and environmental health, with many chlorinated solvents being linked to increased risk of developing cancer in humans and the contamination of groundwater in some areas. As such, in recent years, there has been a focus on finding alternative solvents for phytocannabinoid extraction that are safer and greener.

Much of the research into greener extraction solvents has focused on the use of alcohols such as ethanol. Ionic liquids have also been studied as a possible avenue for further development, but the high cost and toxicity of some ionic liquids has proved a barrier to wider use. 

Deep eutectic solvents for cannabinoid extraction 

A collaboration of researchers in the Czech Republic recently published a study examining the potential for the use of deep eutectic solvents (DES) as phytocannabinoid extraction solvents. DES systems are made up of a mixture of hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs), typically using renewable compounds such as amines and carboxylic acids. The hydrogen-bonding interactions behave in such a way that the freezing-melting point of the solvent is greatly reduced. This gives DES systems the benefit of low volatility, as well as low toxicity and low cost due to the use of the renewable precursors.

Previously, DESs with hydrophilic properties have been used to extract polar bioactive compounds from plant material. In order to widen this to include nonpolar compounds, the Czech researchers produced multiple hydrophobic DESs of differing compositions and studied their effectiveness for phytocannabinoid extraction.

Initially, the non-toxic compound menthol was used as the HBA. It was combined with a variety of carboxylic acid HBDs in a 1:1 ratio to form a series of hydrophobic DESs. The researchers found that typically, as the alkyl chain length of the HBD increased towards six carbons in the longest continuous chain (C6), its extraction yield for the four main phytocannabinoids fell. Between the chain lengths C8-C12 a slight increase in extraction yield was observed, but not to the same efficiency level as the shorter alkyl chain lengths. This was put down to the competing effects of increasing viscosity negatively affecting mass transfer and longer chains promoting the extraction of compounds with a high partition coefficient, such as the phytocannabinoids. Of the menthol: HBD combinations tested, it was found that menthol: formic acid had the best extraction yield for THC specifically, but menthol: acetic acid had the highest extraction efficiency over all four main phytocannabinoids concerned in the study.

Non-menthol based DESs were also assessed. Four different terpenes (terpineol, linalool, geraniol, and borneol) were used as HBAs with acetic acid as the HBD to create a new class of DES, but none of the four DESs synthesized had an overall extraction efficiency that could beat those of the menthol-based DESs. 

The study also went some way towards comparing the efficiency of the menthol-based DES to the more established methanol: chloroform, methanol, and ethanol extraction solvents. During the comparison, the menthol-based DES was found to be more efficient than all of the mainstream extraction solvents across all four phytocannabinoids in question, but it was also noted that due to each comparison only being repeated three times further work is required.  

This first-of-its-kind study represents a step forward into the creation and proliferation of safer and greener solvents for use in cannabis analysis. Further steps may include the synthesis of a wider range of hydrophobic DESs created from different renewable feedstocks and in turn assessing their efficiency and selectivity of extraction across the phytocannabinoids.