Deep Dive: Medical Cannabis Extraction Techniques

This Deep Dive serves as a summary of a 2022 detailed study about the chemical characteristics and safety profiles of the major extraction techniques employed in the cannabis and hemp industries. It teaches students about the various technologies and technical approaches behind the creation of cannabis extracts and concentrates.

A January 2022 research study entitled "A Comprehensive Review on the Techniques for Extraction of Bioactive Compounds from Medicinal Cannabis" that was published in the journal Molecules investigated and summarized the most common cannabis extraction methods.

"We comprehensively analysed the current literature and drew a critical summary of the extraction methods implemented thus far to recover bioactive compounds from medicinal cannabis," reported the study. It also discussed "critical factors affecting extraction yields" and proposed considerations for future extraction methodologies.

The study reported that "numerous factors have influenced the extraction efficiency of phytochemicals from plant materials, including cannabis," and that these factors include environmental elements such as temperature and pressure, the exact extraction technique employed, the length of the extraction period, the nature of the plant materials input, the exact solvent used, the pH level (acidity) of that solvent, the material-to-solvent ratio, and the presence and level of agitation.

The extractability of phytochemicals such as cannabinoids and terpenes from hemp and cannabis varies considerably "depending on the type of material."

"Understanding these factors can help establish the optimal conditions for the cost-effective extraction of the target compounds from the plant matrix," noted the scientists. They explained that cannabis extraction companies cannot, unfortunately, form precise operational procedures (standard operating procedures) due to the fact that "each plant material has specific matrix, structure, and phytochemicals."

The study reported that the extractability of phytochemicals such as cannabinoids and terpenes from hemp and cannabis varies considerably "depending on the type of material." In addition, the precise part(s) of the cannabis plant from which these chemical compounds are being extracted—including leaves, stems, roots, and flowers—significantly influences results.

"In addition, fresh, dried, or ground plant materials with small particle sizes have different extraction efficiencies when the extraction is performed under the same conditions," reported the study's authors.

A variety of solvent substances can be used to separate cannabinoids and terpenes from the nearly microscopic glandular trichomes that produce them and appear most abundantly on the flowers of the female plants. "Solvents are known to directly affect the extraction efficiency of phytochemicals from plant materials," reported the research.

However, the stability of phytochemicals can decrease when they are exposed to high temperatures for a long time because most phytochemicals are sensitive to heat. Higher temperatures also decrease the stability of phytochemicals such as terpenes and cannabinoids. Terpenes are particularly volatile (fragile).

It is "important to determine the most suitable temperature and length of extraction to extract a high level of phytochemicals with minimum degradation."

The study determined that it is "important to determine the most suitable temperature and length of extraction to extract a high level of phytochemicals with minimum degradation." While these two factors are critical, also important in achieving maximum extraction efficiency is agitation and pressure. "Studies have reported that agitation significantly increases the extraction efficiency of phytochemicals compared to non-agitation," noted the scientists. In addition, "high pressure has improved the extraction efficiency of phytochemicals."

The study's authors categorized cannabis and hemp extraction techniques into two major groups, "conventional" and "advanced." While many of the advanced techniques demonstrate greater efficiency than conventional approaches, "the cost of setting up on a commercial scale is a major limitation for the advanced techniques."

The study reported that conventional cannabis extraction methods include "Soxhlet extraction, maceration, and dynamic maceration." As with all systems or approaches, different types of cannabis extraction feature distinct pros and cons. "Studies have revealed the caveats of using conventional extraction methods, such as the extraction of unwanted substances and degradation of heat-sensitive compounds due to extraction under high temperature," reported the research.

The study explained that the cannabis plant species "contains 125 individual cannabinoids, but Δ9-THCA and CBDA are the most predominant." It noted that these acidic precursor cannabinoids experience a chemical process called decarboxylation in which they convert to their infamous neutral versions (sometimes called the "active" versions), delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD).

"Ethanol is an effective solvent in extracting cannabinoids," but its efficiency is "significantly lower than that of the advanced microwave-assisted extraction."

The scientists reported that "ethanol has been found as an effective solvent in extracting cannabinoids using hot maceration," but noted that the efficiency of this technique is "significantly lower than that of the advanced microwave-assisted extraction."

They explained that the advantages of conventional cannabis extraction technology is "simple procedures, easy operations, and affordability," but that the disadvantages include "longer extraction times and the demand for larger solvent volumes," both of which lead to increased operational costs "and harmful environmental impact compared to modern techniques."

The research cited a recent study that extracted CBD from cannabis flowers using methanol as a solvent and a supercritical fluid extraction process (categorized by the scientists as an advanced technique) that revealed that "conventional extraction obtained a higher oil yield but lower CBD in comparison with supercritical fluid extraction."

The study reported that "ethanol, acetonitrile, and hexane are the common solvents used to extract cannabinoids" in conventional methods. It noted that ethanol is better at extracting acidic cannabinoids (using dynamic maceration) than other organic solvents (including hexane, acetone, and methanol), but that it is equal in efficiency to other organic solvents when extracting acidically neutral cannabinoids.

A CO2 extraction machine from Waters Corporation

Research from 2013 revealed that "olive oil is more effective in extracting cannabis oils containing cannabinoids and terpenes than ethanol" and that a disadvantage of the latter is that it also extracts "chlorophylls, imparting a distinct green colour and unpleasant taste in the final product." Cannabis extracts made using olive oil as a solvent were also shown to involve a much slower degradation rate compared to those made using ethanol.

Terpenes are the special compounds that deliver both aroma and flavor to cannabis (along with a slew of other types of molecules). "Terpenes such as α-pinene, β-pinene, β-myrcene, limonene, terpinolene, linalool, α-terpineol, β-caryophyllene, α-humulene, and caryophyllene oxide are known as the major constituents of cannabis essential oils," reported the study.

"Hydro-distillation and steam distillation were less effective than the advanced supercritical fluid extraction at a lower temperature."

"Distillation techniques such as hydro-distillation and steam distillation have been implemented to extract essential oils (terpenes) from cannabis," reported the study. However, it noted that these approaches "were less effective than the advanced supercritical fluid extraction at a lower temperature."

One study cited by the current research investigation revealed that "steam distillation at 130° C [266° F] and hydro-distillation at 110° C [230° F] [both conventional extraction techniques] showed 37 and 35 terpenes, respectively." However, use of supercritical fluid (an advanced extraction technique) at 45° C [113° F] "showed only 30 terpenes."

A 2019 study cited by the current research employed a mixture of "ethyl acetate, ethanol, methanol, and chloroform/methanol" as a solvent to remove terpenes and reported that "ethyl acetate was the best solvent to recover terpenes from cannabis."

Vape cart with butane hash oil (BHO)

The study also revealed that mixes of different organic solvents "are generally more effective for extracting terpenes from cannabis than individual solvents." A 2018 study cited by the current research found that a solvent mixture of hexane and ethanol (at 7:3) "is more efficient in extracting terpenes compared to hexane or ethanol alone."

A 2020 study cited advocated against the use of high temperatures in cannabinoid extraction, particularly when seeking maximum terpenes, concluded that "cannabis should be macerated at room temperature to obtain the optimal terpene and cannabinoid yields."

"Cannabis should be macerated at room temperature to obtain the optimal terpene and cannabinoid yields."

In addition, a 2021 study cited reported that drying method can have a significant impact on the terpene yield volume of an extraction effort. "Gentle drying with a nitrogen stream can retain monoterpenes and sesquiterpenes in the cannabis extract," reported the research. These results prompted the authors of the current study to conclude that "dehydration of samples before extraction should be optimised to prevent the degradation of terpenes."

The study explained that butane is "one of the cheapest and most efficient solvents that offer the most desired final product," but that it also features many disadvantages, including being more difficult to handle in larger batches and the fact that it is highly flammable, colorless, and odorless (making it difficult to detect and, thus, less safe). However, more advanced closed-loop extraction machinery provide a "more stable and environmentally friendly platform for dealing with volatile butane to create butane hash oil (BHO)."

Advanced cannabis extraction techniques, as defined by this particular study, include closed-loop systems that employ a variety of solvents, including butane. Some modern extraction machinery models strategically employ multiple solvents in an effort to extract maximum volumes of cannabinoids, terpenes, and other phytomolecules such as flavonoids (along with chlorophyll, responsible for a cannabis plant's pigment, but have nothing to do with its flavor).

Also common in the advanced extraction category are "subcritical carbon dioxide (CO2) extraction systems with specialised pressure and controlled temperature." The research reported that "carbon (IV) oxide is also an effective method to extract CBD oil, with up to a 90 percent extraction efficiency."

Of the two types of CO2 extraction, supercritical and subcritical, the scientists reported that supercritical fluid extraction "is more effective compared to subcritical CO2 extraction systems." The researchers emphasized that many factors other than solvent type or volume effect extraction efficiency, including "temperature, pressure, and sample types."

The scientists reported that supercritical fluid extraction "is more effective compared to subcritical CO2 extraction systems."

Other advanced cannabis extraction techniques include "dynamic maceration (DM), ultrasound-assisted extraction, and microwave-assisted extraction." The study reported that the DM cannabis extraction technique "focuses on maceration of the cannabis in organic solvent, then concentrating the extracted solution by removing the solvent under reduced pressure, high temperature, and acid." The disadvantage of this approach is that "final target compounds can change during the extraction process."

Another advanced cannabis extraction technique is nonthermal pulsed electric field-assisted (PEF). The research revealed that this cannabis extraction approach involves "less risk of thermal degradation of the phytochemicals" (something to which terpenes are especially sensitive). The study reported that PEF has been found to exhibit "higher extraction efficiency with better oil quality," but that the main disadvantage is that it requires high-voltage pulses."

Enzyme-assisted extraction (EAE) is an advanced cannabis extraction approach that involves enzymes such as pectinase or cellulose (either alone or in a mixture). A 2018 research study cited found that "EAE increased the recovery of cannabinoids from cannabis." The scientists explained that two types of EAE exist: "Enzyme-assisted cold pressing and enzyme-assisted aqueous extraction." The disadvantage of EAE is that it is expensive, but the study called it a "very promising" cannabis extraction technology.

The study's authors summarized that previous studies "have demonstrated that the yield and bioactivity of phytochemicals are primarily influenced by the extraction techniques implemented." They reiterated the complexity of the topic and the myriad inputs that must be controlled or understood to gain maximum extraction volumes to best meet the bottom line of for-profit businesses. These inputs include the exact extraction technology employed, the solvent, its pH, the temperature and pressure involved, and the plant material-to-solvent ratio.

Because the "optimization of these factors can be highly expensive, time-consuming, and labor-intensive, the utilisation of mathematical prediction models could accelerate the optimization process for both conventional extraction techniques (including Soxhlet extraction, maceration, hydro-distillation, and steam distillation) and advanced approaches.

The most common advanced extraction methods are "pressurised liquid, subcritical CO2, supercritical fluid CO2, nonthermal pulsed electric field-assisted, microwave-assisted extraction, ultrasound-assisted extraction, and enzyme-assisted extraction."

The study noted that the most common advanced cannabis extraction methods employed in the nascent industry are "pressurised liquid, subcritical CO2, supercritical fluid CO2, nonthermal pulsed electric field-assisted, microwave-assisted extraction, ultrasound-assisted extraction, and enzyme-assisted extraction.

Of note, the research also noted that further factors can impact the efficiency of cannabis extraction techniques, including the annual season during which cultivation occurs, its geographical location, and the precise "strain, chemotypes, and chemovars" of cannabis biomass from which the exaction is being made.

View the original study.