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Journal of Cannabis Research volume 3 , Article number: 32 Cite this article. Metrics details. As the cannabis industry transitions from a black market to a legal market, product development, and methods of extraction have become a focal point. To date, more than thousands of chemical constituents have been identified from the cannabis plant, all of which possess different chemical properties that require different conditions for preservation during drying and extraction. However, scientific publications that explore these areas for the cannabis plant are currently lacking. This is a narrative review paper which focuses on critiquing drying and extraction methods of Cannabis sativa L. To find relevant papers for this narrative review, 93 papers have been reviewed. Among them, 12 irrelevant papers were discarded. The excluded papers were either about hemp seed oil or hemp fiber and protein. Based on this review, solvent extraction is the most common method for cannabis plants. Although solventless and hydrodynamic extraction are known for their high yield and feasibility, more investigation is needed in these areas. Regarding the drying process, hang-drying is the most convenient method; however, it may be substituted by freeze-drying in the near future. This review analyses various drying and extraction processes to guide the selection of suitable methods for various types of cannabis products and applications. This is done by outlining traditional and modern methods of drying techniques, exploring the importance of solvents for extraction, visiting solventless extraction procedures, and finally comparing conventional and alternative methods of extraction. In conclusion, based on the current knowledge, using organic solvents is the most convenient method for medicinal cannabis extraction. However, more research is needed for some of the drying and extraction methods. Also, developing a green and sustainable cannabis extraction method should be considered for future studies. Cannabis is a flowering plant from the Cannabaceae family and genus Cannabis. Cannabis sativa and Cannabis indica are generally well known, while subspecies Cannabis ruderalis is often overlooked due to its limited ability in producing active compounds Gloss Hybrid species are variable depending on the parent plant; they can be sativa dominant, indica dominant, or balanced. Within the genus, the number of species is disputed, and the traditional nomenclature of sativa and indica may not be correct or useful in determining therapeutic potential. In any case, cannabis is dioicous, meaning it exhibits both male and female reproductive structures in separate individual plants. Female cannabis plants produce more glandular trichomes compared to the male plant. Among all the known compounds in the cannabis plant, cannabinoids and terpenes are the most active compounds with therapeutic potential which largely synthesized in those glandular trichomes. These compounds have shown to have therapeutic effects on a range of conditions such as metabolic disorders, neurodegenerative disorders, movement disorders, anorexia in HIV patients, nausea, and pain after chemotherapy in cancer patients Namdar et al. Traditionally, the dried cannabis flower has been a popular product for the use of smoking and vaping. However, as the industry expands, the need for cannabis products in different forms and higher potency also increases. Currently available products, medicinal or recreational, come in the forms of topicals, edibles, beverages, and vaporization cartridges. Each product type presents its own set of advantages and disadvantages allowing for customization to serve a particular purpose Blake and Nahtigal For pharmaceutical and food applications, the extraction and isolation of active components and combinations of identified cannabinoids are critical steps that should be explored Fathordoobady et al. The separation of bioactive compounds has recently become rapidly sought after by the pharmaceutical and food industries. This is due to the increased understanding of the dynamic nature and potential of diverse bioactive molecules from natural sources Azmir et al. To further continue scientific research on the selection, identification, and characterization of bioactive compounds, the selection of a suitable extraction process is imperative Azmir et al. Failing to designate a fitting method of sample preparation can jeopardize any analytical procedure resulting in unfavorable outcomes. However, the field of extraction is often neglected and is not studied as thoroughly as other processes. This creates a gap in the literature that should be explored more extensively Smith The process of extraction is commonly employed to obtain target bioactive compounds from complex plant matter, yet it can also be altered to cater for many purposes, for instance, increasing the selectivity and sensitivity of bioassays by increasing the concentration of a target compound, as well as providing a potent and reproducible sample matrix Smith Valizadehderakhshan et al. They also reviewed various parameters that affect cannabinoid transformation after extraction Valizadehderakhshan et al. Different methods of extraction will yield varying degrees of extract quality and composition depending on the procedure and substances used Blake and Nahtigal This review focuses on various drying and extraction methods while comparing conventional and most recent methods. For example, conventional methods of extraction including Soxhlet and dynamic maceration have longer extraction time and large amounts of solvent are required to complete the extraction process Agarwal et al. Recent methods including ultrasonic-assisted, microwave-assisted, supercritical fluid, and pressurized liquid extraction processes can be considered as an alternative, slightly greener, options as opposed to the conventional methods. These procedures reduce the need for synthetic and organic solvents, cut down on operational time, and produce a better quality extract with a higher yield Azmir et al. Solventless methods such as dry sieve and water extraction are particularly known to extract entire trichomes. Hydrocarbon extraction methods can be used to avoid unwanted water and pigments such as chlorophyll. Ethanol can extract flavonoids, while carbon dioxide can be manipulated to extract different compounds depending on the conditions Blake and Nahtigal The characteristics of the product must be considered when deciding on a method. For example, depending on the application, cannabinoids can be extracted in either acidic or neutral form. The preservation of acidic cannabinoids requires extraction to be completed at room temperature Citti et al. To decarboxylate acidic cannabinoids into neutral form, high temperatures are recommended for extraction, although a higher temperature may result in the loss of some terpenes and minor constituents Fathordoobady et al. Therefore, the selection of an appropriate extraction procedure will benefit future stages of development by minimizing the requirements for refinements Blake and Nahtigal To further understand the processes and possible outcomes, this review will explore different methods of drying and extraction procedures used for the cannabis plant. This paper is a narrative review paper which focuses on drying, extraction, and post-extraction methods for Cannabis sativa L. The focus of this narrative review was on Cannabis sativa , initially where 93 papers were identified. Papers on various drying and extraction methods specifically for Cannabis sativa L. Overall, 12 papers about cannabis seed oil, hemp seed oil, or hemp plant were excluded as this review focuses on the oil coming from flowers. In the end, 81 related papers about various drying, extraction, and post-harvest processes were carefully reviewed. External factors such as light duration, oxygen, and harvest time floral maturity have been shown to influence the secondary metabolite production in cannabis Liu et al. A 4-year study by Lindholst found that cannabinoid stability is affected by temperature, light, and air. However, it was observed that light was only partially influential. The resin samples that were placed at room temperature, in either light or dark settings, only exhibited little differences in the degradation of neutral THC. The dense color and structure of resin are thought to be the reason behind the reduced light sensitivity of THC. Accordingly, it is suspected that the exposure of light on resin only reaches the cannabinoids on the surface resulting in low degradation levels. This theory is further illustrated when a comparison was done between the degradation levels of both acidic and neutral THC levels in cannabis resin and cannabis extract. It was observed that both the neutral and acidic forms of THC in the cannabis extract degraded significantly more through light exposure. Furthermore, compared to resin, cannabis extract had a 10 times lower half-life 35 days for extract and days for resin , while THCA decreased to nondetectable levels after days. The neutral forms, in the extract, increased during this period, although THC concentrations were reduced to 1. Danziger and Bernstein a , b evaluated the effect of light on three chemovars of cannabis under four different light conditions. In this study, light as the key factor affected the profile and yield of cannabis chemovars. To be precise, using blue to red lights and ratios had the highest yield compared to white LED light. In addition, CBGA as a primary cannabinoid and precursor for many cannabinoids increased by using blue light Danziger and Bernstein a. Defoliation, removing primary and secondary branches, and pruning have been considered as a part of eight various architectural manipulation treatments in different light intensities. Results showed that plant architectural modulation affects cannabinoid profile while no changes has been reported in the decarboxylation of cannabinoids Danziger and Bernstein b. Saloner and Bernstein evaluated the effect of nitrogen supply as an environmental factor on cannabinoids and terpenes. Bernstein et al. Each of the supplements affected the cannabinoid concentrations differently based on the organ and its location in the plant. For this reason, drying is considered an essential step for product development Hawes and Cohen Drying the plant not only prevents the growth of microorganisms that would otherwise rot plant tissue based on ASTM D which is a standard practice for determination of water activity aw in cannabis flower , it would also enable long term storage while maintaining potency, taste, medicinal properties, and efficacy Hawes and Cohen This is done by maintaining the water activity level between 0. Hang-drying or air-drying is considered the oldest way of drying cannabis plants after harvest Fig. Ross and ElSohly applied four treatments for air-drying to evaluate the efficacy of each condition in producing the highest yield of cannabis products. The treatments were extracted immediately, after the flower harvest at room temperature 0. Inconveniences of this method include the manual removal of leaves and buds from the stem as well as the time taken to complete the overall process. The separation is crucial as different parts dry at different rates; therefore, a lack of completing this step may result in uneven drying. Consequently, a disadvantage of removing buds from stems is the possibility of producing a product with a harsher taste. Another detriment of this method is the involvement of gravity. The water from the top part of the plant will absorb into the lower parts leading to a slower and uneven drying process. To speed up the procedure, heaters, fans, and dehumidifiers can be used. However, fast-drying can lead to a harsher taste as opposed to slow-drying which produces smoother tasting products. It is also believed that speeding up the drying process can prevent the plant from reaching peak potency in the curing phase Hawes and Cohen Coffman and Gentner evaluated the effect of drying conditions on the cannabinoid profile. The results were shown that the percentage of total cannabinoids was decreased by increasing time and temperature. To be precise, the percentage mean weight loss of total cannabinoids increased from 7. A faster direct method of drying is the oven-drying approach Mujumdar This method can be carried out in either a vacuum chamber, vacuum desiccator, or in a drying oven with or without air circulation Hawes and Cohen To illustrate the outcomes of the process, an early study tested out four different oven conditions to compare the end products. After extraction with ethanol, gas chromatography showed that the yield of CBD and THC decreased as the temperature and time of drying increased. Additionally, using high temperatures and excessive drying can result in the loss of key components Hawes and Cohen This statement can be the reason for the lack of information about using oven dying in the cannabis industry. This was highlighted in a study that compared the ratio of cannabinoid and by-product produced during vaporization. These approaches had produced intense fragrance which is indicative of the loss of terpenoids and other volatile components Pomahacova et al. Freeze-drying also known as lyophilization has become a popular option due to the increasing demand for high-quality medicinal cannabis. The freeze-drying method holds the cannabis plant at temperatures far below those of air or oven, while removing the water content, in the form of vapor, via sublimation in a vacuum chamber Mujumdar The nascent legal cannabis industry claims that freeze-drying preserves the volatile compounds and acidic form of cannabinoids Tambunan et al. It is generally agreed that the end products of freeze-drying are considered high quality compared to other methods of drying. This is due to the structural rigidity found on the surface of frozen materials where sublimation occurs, preventing the disintegration of the solid matrix and resulting in a porous, unaltered structure Mujumdar When assessing the end product produced by freeze-drying, it was found that the composition is largely unaffected from that found in the plant Tambunan et al. A disadvantage of freeze-drying is the cost of operation. This procedure requires an intense amount of energy to maintain such temperatures, vacuum, and long-running time Mujumdar Comparing the different drying methods, we can safely state that the approach elected will affect the yield and cannabinoid profiles in the extracts. Therefore, the selection of a drying procedure will largely alter the outcomes Coffman and Gentner The process of hang-drying cannabis was found to be time-consuming as it can take several days, while the main factors that increase the rate of drying were determined to be moving air and low humidity Ross and ElSohly In contrast, the oven-drying method was observed to be faster, but readily volatile compounds and neutral forms of cannabinoids decreased in extracts to almost non-detectable concentrations, affecting therapeutic potential Coffman and Gentner To address this issue, freeze-drying is thought to be the preferred method. Freeze-drying enables the preservation of flavor qualities in many foods, themselves often due to the presence of volatile compounds Tambunan et al. In all the drying methods mentioned above, humidity, temperature, ventilation rate, and time are the most important parameters to be optimized. Incorrect drying conditions may cause decarboxylation of acidic cannabinoids and loss of terpenes. The presence of light, oxygen, and heat may also cause degradation in cannabinoids and terpenes and can affect the taste Jin and Chen Curing is the final post-harvest procedure that allows for the development of the maximum flavor in the cannabis plant Vogel Jin et al. Green et al. Curing can reduce the harsh smell and the sense of throat burning during smoking or vaping as well as increasing the shelf life by minimizing mold growth. It is also believed that curing can increase cannabis potency as the number of cannabinoids such as THC and CBN will increase by curing. Although curing is one of the most significant post-harvest stages for the cannabis plant, there are not enough academic investigations around this area. Cannabis extraction can be used to concentrate target components for product development. There are important parameters that can affect the yield of the cannabis extract such as mean particle size, size distribution, temperature, rate of agitation, and extraction time Fathordoobady et al. Solventless, solvent-based, convention, and alternative methods of extraction are explored concerning cannabis extraction. Long-established solventless methods such as dry-sieving, water extraction, and rosin press extraction lack coverage in literature due to outdated techniques and difficulty in scaling despite having simple procedures. The process of dry-sieving begins by beating dried cannabis against a mesh screen and forcing the trichomes to separate and fall off. The final product can either be pressed further into hashish or mixed with dried flowers. This simple procedure is time-consuming and labor-intensive, therefore, not popular for the industrial level. Water extraction produces roughly the same potency of THC as the dry sieve method, although it also depends on the potency of the starting material. The procedure begins by placing the cannabis plant in a mesh bag immersing it in ice water and finally stirring it to knock the trichome off. The trichome is further filtered through a series of screens then allowed to settle before collecting and drying the final product, commonly known as water hash or bubble hash. Similarly, to dry sieving, this process is difficult to upscale as well as limited control of potency Blake and Nahtigal Solventless extraction exploits the fact that cannabinoids are semi-liquid and can be extracted by suitable heating and pressure. Rosin extraction uses compression and heat to obtain oils and rosin. Rosin extraction can be as simple as using a hair straightener for recreational extractions. For more commercial medicinal applications, a modified hat press is adopted. For both methods, high pressure at low temperatures is not achievable; therefore, the retention of terpenes is limited analytical cannabis. To prevent high-temperature changes, a typical pneumatic press can be used, exerting some lower temperatures and preserving the terpenes. Pressures up to Solvent-based extraction methods such as Soxhlet, maceration both static and dynamic, ultrasonic-assisted extraction, and microwave-assisted extraction require a solvent to complete the extraction process. A variety of solvents can be used to extract cannabinoids including ethanol, butane, propane, hexane, petroleum ether, methyl tertbutyl ether, diethyl ether, carbon dioxide CO 2 , and olive oil Dussy et al. Gaseous solvents such as butane and propane can also be used for extraction purposes Raber et al. Gas solvent extractions start in the gas phase at room temperature and are either cooled or pressurized into a liquid state as they run through the sample material Rovetto and Aieta The extracted sample is collected, and the solvent is evaporated Chan et al. The process of pressurizing these flammable and potentially explosive gases poses safety hazards Jensen et al. In addition, the gases used in cannabis extractions are often industrial grade and contain impurities that end up in the cannabis extracts. Moreover, the solvents themselves may become a residue in the final extract Raber et al. The differing solubilities of individual cannabinoids and other phytochemicals are thought to be an important factor that needs to be considered when selecting a solvent. The stickiness and viscosity of cannabis oil result in binding to solvents; therefore, it is important to consider the toxicity, affinity, and temperature profile of the solvents being used Fathordoobady et al. The efficiency of conventional methods of extraction is presented to be heavily dependent on the solvent of choice. Solubility, molecular affinity, mass transfer, co-solvent, toxicity, and environmental safety are major factors that should also be considered during the solvent selection process Azmir et al. Commonly used solvents to extract cannabis can be divided into three groups, low molecular mass organic solvents, vegetable fats oils , and supercritical fluids, notably supercritical carbon dioxide Reichardt and Welton Low molecular mass organic solvents are hydrocarbon-based with limited polarity due to the presence of oxygen. Halogen substituted hydrocarbons are also included in this group. These solvents are known for their ability to dissolve generally nonpolar compounds, following the chemistry adage: like dissolves like. Inspection of cannabinoids in Table 2 shows that they are dominated by carbon and hydrogen, making them generally nonpolar. However, the presence of alcohol and acid groups requires some polarity in extraction solvents and solvent mixtures. Table 2 shows some of the properties of the most popular organic solvents in cannabis extraction. These solvents are observed to have low boiling points and high volatility, indicating their ability to be easily separated from the extract at low temperatures after the extraction process Reichardt and Welton To illustrate how different solvents can affect the yield of compounds from the source material, consider the example of phenolic extraction from grape pomace and elderberry. Phenols are nominally water soluble. The solvent combinations ethanol—water and acetone—water mixtures had a higher yield than ethyl acetate-water mixture Vatai et al. In another example, isopropanol-hexane, chloroform—methanol, and hexane were used as solvents for crude fat extraction from insect, egg yolk, and krill powders in one-step organic solvent extraction. The highest fat yield was achieved with a chloroform—methanol mixture Rose Thus, with a mixture of cannabinoids, terpenes, chlorophyll, carotenoids, and other fat-soluble classes in cannabis flowers, different extraction efficiencies can be confidently predicted. If seeds have matured, the fats triacylglycerols that comprise the energy stored in seeds will also be extractable to some extent. Namdar et al. A mixture of polar and non-polar solvents achieved the highest yield for all the compounds in the cannabis plant Namdar et al. Vegetable oils are routinely extracted from seeds or fruits such as rapeseed, sunflower, or olive, and even brans, making them an inexpensive option. These oils are considered lipophilic due to their nonpolar characteristic, which enables selective dissolving properties. Each of these has a degree of emulsifying capacity that may play a role in cannabinoid extraction. Interestingly, apart from olive oil, some specialized oils, nearly all commercial oils, are refined to eliminate the minor components. Whether this could affect cannabinoid extraction is unknown. Olive oil is a well-known solvent in the cannabis extraction field. It is also one of the least refined oils with characteristically high oleic acid content. Terpenes can be preserved during extraction with olive oil due to their low volatile nature. Romano and Hazekamp used two different protocols with olive oil for cannabis extraction. In the first experiment, 5 g cannabis with 20 ml olive oil and 50 ml water were mixed and heated up to 60 min. In the second experiment, 10 g cannabis with ml olive oil were mixed and heated for up to min. The high yield of terpenes obtained from using olive oil as a solvent is thought to be due to its efficient capabilities in solubilizing and limiting loss of product by protecting the compounds from evaporation Romano and Hazekamp In common with other solvents, CO 2 —which is nominally a polar gas—enters a so-called supercritical state at a defined temperature and pressure. In a supercritical state, distinct liquid and gas phases do not exist. In the case of CO 2 , the critical temperature is Supercritical CO 2 behaves like a non-polar solvent, capable of extracting a broad range of non-polar solutes, cannabinoids included. In comparison, strongly polar water becomes supercritical and useful as a non-polar solvent but at a much higher temperature and pressure, K and Therefore, CO 2 is the solvent of choice due to low critical temperature and pressure. It is also non-flammable, non-toxic, inert, renewable, easy to remove, abundant, and relatively low-cost. As an example, consider supercritical extraction of linalyl acetate from lavender oil compared with its extraction by conventional steam distillation Reverchon et al. The yields for supercritical extraction were The reason proposed was that the higher temperature of steam distillation caused the undesirable hydrolysis of the linalyl acetate to linalool and acetic acid. CO 2 pressure—temperature phase diagram, the critical temperature is Thus, the low base temperature of supercritical CO 2 is probably an intrinsic advantage Reverchon et al. Soxhlet extraction was first proposed by Franz Ritter Von Soxhlet, a German chemist, as a method of extraction of, primarily, lipids. However, over the years, this procedure has become widely employed for various extraction purposes, commonly used for the separation of bioactive compounds from plant matter. Soxhlet is also extensively used as a model for the comparison and development of alternative methods of separation Azmir et al. The process begins by placing a small amount of the dried sample in a thimble that is then transferred to a distillation flask containing a particular solvent. When the overflow level is reached by the solution, a siphon is used to aspirate the solute and unload it into the distillation flask with the extracted analyte carried along into the bulk liquid. For cannabis extractions using the Soxhlet apparatus, Lewis-Bakker et al. These drawbacks were demonstrated by a study conducted by Wianowska et al. The simplicity in methodology alongside the ease of system optimization can result in high sample throughput and yield. The minimal requirement for a trained personal for process operation is also considered advantageous when compared to recently developed methods of extraction. Dynamic maceration is a conventional solid-lipid extraction procedure that is based on soaking a sample in organic solvents solvent varies depending on the polarity of the target compound for a specific time at a specific temperature and followed by agitation Fathordoobady et al. This process of separation is inexpensive and a popular method used to obtain essential oils and bioactive compounds Azmir et al. Recently, the use of vegetable oils e. However, vegetable oils are not volatile and are difficult to remove from extracted isolates Romano and Hazekamp Alternatively, ethanol is suggested as a preferred solvent for cannabinoid extraction. A study conducted by Fathordoobady et al. However, when the recovery of acidic cannabinoids was tested, ethanol had the highest yield. The use of ethanol for maceration extraction of cannabinoids was found to produce the highest yield when used twice compared to other methods of extractions, for instance, ultrasonic-assisted extraction UAE or supercritical fluid extraction SFE Fathordoobady et al. With ethanol as solvent, unwanted chlorophyll was extracted along with the cannabinoids. The unwanted chlorophyll not only added an unpleasant flavor and a green tinge to the end product, but it also demonstrated accounts of interference with gas chromatography—mass spectrometry analysis, hence removal is considered necessary Ciolino et al. To eliminate unwanted chlorophyll, the ethanol extract can be treated with activated charcoal. Consequently, although yields are high with ethanol, the removal of unwanted chlorophyll with charcoal comes at the expense of cannabinoid loss. In respect of toxicity, Romano and Hazekamp found significant amounts of petroleum hydrocarbon residues in the extracts obtained with naphtha and petroleum ether, indicating that special attention must be paid to ensure safe residual concentrations Romano and Hazekamp In the same study, when compared to other solvents, the olive oil extract was shown to contain the largest number of terpenes, making it a superior crude extract. Olive oil is a cost-effective nonflammable solvent that is considered nontoxic when applied topically or consumed orally, and not through the lungs. As an added benefit, Citti et al. A disadvantage associated with olive oil extracts, however, is that extracts cannot be concentrated by evaporation. This means that larger volumes of olive oil extracts need to be consumed to have the same therapeutic effects as other extracts Romano and Hazekamp In another study by Hazekamp et al. For this study, hexane was particularly used as it does not extract chlorophyll and is easily evaporated after extraction Hazekamp et al. Methods to extract chlorophyll from plants generally required acetone as the preferred solvent; however, as acetone is considered carcinogenic, it is not recommended to be used in cannabinoid extraction. The highest yield was achieved with the mixture, but for cannabinoids, the polar solvent was best Namdar et al. Likewise, Brighenti et al. Ultrasound technology is widely adopted in the food and chemical industry for its ability to significantly influence the rate of various processes Chemat et al. The main feature that sets ultrasonic-assisted extraction UAE apart from other processes is the use of sound waves, commonly with frequencies between 20 to kHz. This enables the penetration of solvents into a sample matrix to extract the compounds of interest. This is done during the process of cavitation. Cavitation is described as the formation, expansion, and collapse of bubbles within the solution that allows for intense mass transfer and accelerated solvent access into cell material Azmir et al. The effective mixing ability of the UAE can be explained by the faster energy transfer, micro-mixing, and reduced extraction temperature Otles Factors such as moisture content of a sample, particle size, milling degree, solvent, temperature, pressure, and time of sonication must be considered and manipulated to achieve efficient extractions Azmir et al. A study that employed the ultrasonication method to leach and hydrolyze phenolic compounds presented evidence of low analyte decomposition during the extraction procedure when compared to other methods such as subcritical water, and microwave-assisted and solid—liquid extractions. After assessing the degradation of phenolic compounds, the decrease in decomposition was found to be due to the low energy type produced by the sonication mechanism and the short duration time. However, this was only evident when the exposure time to ultrasound was less than 10 min Herrera et al. De Vita et al. Although low yield was obtained, the ultrasonication procedure had provided extracts using lower temperatures in an environmentally friendly, safe, and energy-efficient way. This study also found that ethanol extract yield was 3 to 4 times higher than olive oil extract De Vita et al. A mix of ethanol, hexane, and isopropanol: hexanes were used as solvents. The results showed that the yield for ethanol and hexane was almost the same, and isopropanol: hexanes achieved the highest yield of the extract. However, an HPLC analysis showed a reverse relationship between the extract yield and cannabinoids: the isopropanol: hexanes product had the lowest cannabinoid content, due to coextracted non-cannabinoid content. The authors also indicated that the acidic forms of cannabinoids four shown in Fig. To optimize the extraction of target cannabis compounds, it is suggested to use UAE as a conditioning step for conventional extraction methods. In , the increasing demand for environmentally friendly and sustainable industrial processes had provoked the development of the Microwave-assisted extraction procedure Otles The electromagnetic energy provided in the form of microwaves, with frequencies between MHz and GHz, is used to produce rapid heating following ionic conduction and dipole rotation Azmir et al. This procedure directly exposes each molecule to a microwave field which is converted to kinetic energy that can break cell walls and release their contents into a liquid phase. The enhanced performance of this green extraction process can be attributed to improved solubility, efficient mass transfer, and increased surface equilibrium. These factors result in a system that uses less energy with fast processes requiring less solvent consumption but also producing a final product with high purity Fig. It was also noted that olive oil had superior properties when compared to ethanol during an MAE De Vita et al. MAE process where the flask is housed in the microwave oven Krishnan and Rajan Placing the flask containing the sample in the microwave, attached to a condenser outside of microwave to capture the solution of interest compounds after distillation. Neutral phytocannabinoids have been established as important for their medicinal properties; therefore, using extraction procedures to obtain these compounds is considered essential. Methods used for the extraction of neutral cannabinoids can be explored by investigating their decarboxylation efficiencies of phytocannabinoid acids. For example, Lewis-Bakker et al. However, only the isolates from the Soxhlet method had completely decarboxylated. Although prolonging the duration time to 30 min in MAE, extracts yielded 0. In this approach, high pressures facilitate the extraction while the high temperatures promote solubility and mass transfer to increase analyte solubility, as well as reduce solvent viscosity and surface tension Azmir et al. Accordingly, altering temperature and pressure enables influence over the solubility of the compound of interest Wianowska et al. This procedure also does not require a filtration step as the insoluble matrix components are contained inside the extraction cell. This feature allows for the process automation for continuous operation Fathordoobady et al. Figure 5 visualizes the PLE process. PLE process using organic solvent as extracting solvent coupled with supercritical antisolvent SAS precipitation process 1 heat exchanger for cooling, 2 pump, 3 heat exchanger for heating, 4 extractor, 5 T-mixer, 6 precipitation vessels, and 7 filter Santos and Meireles When comparing PLE to conventional methods such as Soxhlet, features such as shorter duration, reduced solvent consumption, and decreased sample handling are observed Rodrigues et al. To demonstrate this, Wianowska et al. The data obtained illustrates the influence of parameters such as time and pressure have on the end product. The high pressure applied enables the use of temperatures above the boiling point of the extractant. This increases the penetration ability of the selected solvent into the plant matrix in a short time. Green approaches, such as supercritical fluid extraction SFE , are used to displace conventional methods of pressing and organic solvent extractions. The use of supercritical fluids is advantageous as at room temperature they are in a gaseous, allowing for recovery of extract via simple evaporation Santos and Meireles Under conditions except for supercritical, CO 2 behaves as a polar compound. In instances where supercritical CO 2 is not sufficiently polar to act as a solvent, polarity modifiers, such as alcohols, water, and acids, can be used as co-solvents Rovetto and Aieta Rovetto and Aieta evaluated the effect of pressure and the use of ethanol as a co-solvent on cannabinoid extraction. Extractions were run at 17, 24, and 34 MPa pressure. The yields increased almost linearly to 34 MPa, 0. Increased pressure can increase the solvation power but decreases the selectivity of the extraction, so a higher pressure may not be the ideal condition. Ethanol was indicated to be useful as a co-solvent: When added in pulses, it can increase the rate of supercritical CO 2 extraction of cannabinoids Rovetto and Aieta Omar et al. However, when comparing SFE with other methods of extraction, Brighenti et al. Figure 6 visualizes the supercritical fluid extraction process. Diagram of a supercritical fluid extraction Adopted from Wikiwand. Hydrodynamic cannabis extraction is a recent development within the cannabis industry that can be used to produce full-spectrum cannabis extracts with high bioavailability. There have been accounts of companies, such as IASO Incline Village, Nevada , claiming to have developed a unique extraction system that produces products with high yield and increased potency. This alternative method involves freezing fresh plant material and converting it into a nanoemulsion in water by ultrasonication. Hydrodynamic force is then used to break the cell wall and release its contents. This is followed by liquid—liquid extraction using solvents, centrifugal separation, and finally low-temperature drying. The initial step of freezing the plant matter helps preserve the volatile compounds as well as acidic cannabinoids during the following steps. Hydrodynamic extraction is claimed to exceed conventional methods mainly due to the lack of high temperatures, short contact distillation, and low organic solvent consumption admin, n. Ishida and Chapman used this technique to extract carotenoids from tomatoes and found that the extractable lycopene, other carotenoids, and accessibility of carotenoids significantly improved Ishida and Chapman However, to this date, there has been no scientific publication that explores this method of extraction. Therefore, to fully understand the efficacy of this method, more research is required. Traditionally, the dried cannabis flower was the product of choice; however, as the industry expands, the demand for various products with distinct properties also increases. Therefore, multiple factors should be considered when selecting a drying technique or an extraction method to produce a specific product. Among different drying methods for post-harvest processing, freeze-drying is considered more appropriate when compared to other methods; however, there is currently a lack of academic research and evidence to support this. Hang-drying as a traditional technique is still the most convenient way to reduce the prevalence of mold and bacteria during storage before extraction. Solventless extraction and hydrodynamic extraction are of interest due to their high yield, easy, and fast process but lack the scientific publication to promote their employment for large-scale production. Although for terpenes with more than 15 carbons, non-polar solvents are suggested. Soxhlet and dynamic maceration are being used as traditional methods which are time- and solvent-consuming but accurate enough to be compared with modern techniques. In this narrative review paper, the advantages and disadvantages of various drying and extraction methods have been discussed. The best methods for industries based on the final products have been reviewed and suggested. Some gaps are found in this review paper including the lack of information and knowledge about using freeze dryer for drying plant material after harvest, hydrodynamic extraction method, and a developed green extraction technique in the cannabis research area as well as cannabis industry which needs more investigations in the future studies. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Agarwal C, et al. Ultrasound-assisted extraction of cannabinoids from cannabis sativa L. J Food Sci. Supercritical CO2 extraction of hemp Cannabis sativa L. Ind Crops Prod. Al-Ani RA, et al. Antibacterial activity of clove, cinnamon, and datura extracts against Erwinia carotovora subsp. J Med Plants Res. Azmir J, et al. Techniques for extraction of bioactive compounds from plant materials: A review. J food Eng. Bernstein N, et al. Impact of N, P, K, and humic acid supplementation on the chemical profile of medical cannabis Cannabis sativa L. Front Plant Sci. Article Google Scholar. Blake A, Nahtigal I. The evolving landscape of cannabis edibles. Curr Opin Food Sci. Development of a new extraction technique and HPLC method for the analysis of non-psychoactive cannabinoids in fibre-type Cannabis sativa L. J Pharm Biomed Anal. User characteristics and effect profile of Butane Hash Oil: an extremely high-potency cannabis concentrate. Drug Alcohol Depend. Chemat F, et al. Ultrasound-assisted extraction in food analysis. Handb food Anal Instrum. Commercial cannabis consumer products part 1: GC-MS qualitative analysis of cannabis cannabinoids. Forensic Sci Int. Medicinal cannabis: principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method. Coffman C, Gentner W. Cannabis sativa L. Bull Narc. Google Scholar. Danziger N, Bernstein N. Light matters: effect of light spectra on cannabinoid profile and plant development of medical cannabis Cannabis sativa L. Soxhlet extraction of solid materials: an outdated technique with a promising innovative future. Anal Chim Acta. Comparison of different methods for the extraction of cannabinoids from cannabis. Nat Prod Res. De Vita MJ, et al. Association of cannabinoid administration with experimental pain in healthy adults: a systematic review and meta-analysis. JAMA Psychiatry. Chapter 4—Green analytical methodologies for preparation of extracts and analysis of bioactive compounds. Comprehensive analytical chemistry, vol. Amsterdam: Elsevier; Hemp Cannabis Sativa L. Food Rev Int. Gloss D. An overview of products and bias in research. Green G, et al. The cannabis grow bible, Greg Green. Supercritical extraction strategies using CO2 and ethanol to obtain cannabinoid compounds from Cannabis hybrid flowers. J CO2 Util. Method of drying cannabis materials, Google Patents. Preparative isolation of cannabinoids from Cannabis sativa by centrifugal partition chromatography. J Liq Chromatogr Relat Technol. Ultrasound-assisted extraction of phenolic compounds from strawberries prior to liquid chromatographic separation and photodiode array ultraviolet detection. J Chromatogr A. Effects of a hydrodynamic process on extraction of carotenoids from tomato. Food Chem. Honey oil burns: a growing problem. J Burn Care Res. Article PubMed Google Scholar. Jin D, et al. Cannabis indoor growing conditions, management practices, and post-harvest treatment: a review. Am J Plant Sci. Jin S, Chen J. Krishnan RY, Rajan K. 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Variation in the compositions of cannabinoid and terpenoids in Cannabis sativa derived from inflorescence position along the stem and extraction methods. Optimisation and characterisation of marihuana extracts obtained by supercritical fluid extraction and focused ultrasound extraction and retention time locking GC-MS. J Sep Sci. Acta Scientiarum Polonorum Technologia Alimentaria. Perrotin-Brunel H. Sustainable production of cannabinoids with supercritical carbon dioxide technologies. Pomahacova B, et al. Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhal Toxicol. Understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing. J Toxicol Sci. Application and possibilities of supercritical CO2 extraction in food processing industry: an overview. Food Sci Technol Int. Reichardt C, Welton T. Supercritical CO 2 extraction and fractionation of lavender essential oil and waxes. J Agric Food Chem. Romano LL, Hazekamp A. Cannabis oil: chemical evaluation of an upcoming cannabis-based medicine. Rose A. Characterization of lipids and the protein co-products from various food sources using a one-step organic solvent extraction process. Book Google Scholar. The volatile oil composition of fresh and air-dried buds of Cannabis sativa. J Nat Prod. Supercritical carbon dioxide extraction of cannabinoids from Cannabis sativa L. J Supercrit Fluids. Saloner A, Bernstein N. Nitrogen supply affects cannabinoid and terpenoid profile in medical cannabis Cannabis sativa L. Food Sci Technol. Smith RM. Before the injection—modern methods of sample preparation for separation techniques. Tambunan A, Yudistira K, Hernani. Freeze drying characteristics of medicinal herbs. Dry Technol. Valizadehderakhshan M, et al. Extraction of cannabinoids from Cannabis sativa L. J Food Eng. Vogel A. Transformations of tetrahydrocannabinol, tetrahydrocannabinolic acid and cannabinol during their extraction from Cannabis sativa L. J Anal Chem. Vegetable oils as alternative solvents for green oleo-extraction, purification and formulation of food and natural products. Download references. You can also search for this author in PubMed Google Scholar. Masoumeh Pourseyed Lazarjani has written the first version of this paper. Lidya Kebede added some parts to it and then Masoumeh edited different drafts which were revised by Ali Seyfoddin and Owen Young. The author s read and approved the final manuscript. Correspondence to Ali Seyfoddin. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Lazarjani, M. Processing and extraction methods of medicinal cannabis: a narrative review. J Cannabis Res 3 , 32 Download citation. Received : 17 July Accepted : 29 June Published : 19 July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Introduction As the cannabis industry transitions from a black market to a legal market, product development, and methods of extraction have become a focal point. Method This is a narrative review paper which focuses on critiquing drying and extraction methods of Cannabis sativa L. Result To find relevant papers for this narrative review, 93 papers have been reviewed. Discussion This review analyses various drying and extraction processes to guide the selection of suitable methods for various types of cannabis products and applications. Conclusion In conclusion, based on the current knowledge, using organic solvents is the most convenient method for medicinal cannabis extraction. Introduction Cannabis is a flowering plant from the Cannabaceae family and genus Cannabis. Table 1 Common cannabinoids and their molecular formulas Full size table. Method This paper is a narrative review paper which focuses on drying, extraction, and post-extraction methods for Cannabis sativa L. Results The focus of this narrative review was on Cannabis sativa , initially where 93 papers were identified. Influence of external factors on cannabis External factors such as light duration, oxygen, and harvest time floral maturity have been shown to influence the secondary metabolite production in cannabis Liu et al. Air-drying, also known as hang-drying Hang-drying or air-drying is considered the oldest way of drying cannabis plants after harvest Fig. Air-drying hang-drying of the cannabis plant. Full size image. Table 2 Popular low molecular mass organic solvents Full size table. Table 3 Five protocols to extract cannabis by dynamic maceration Romano and Hazekamp Full size table. Discussion Traditionally, the dried cannabis flower was the product of choice; however, as the industry expands, the demand for various products with distinct properties also increases. Conclusion In this narrative review paper, the advantages and disadvantages of various drying and extraction methods have been discussed. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. References Agarwal C, et al. Google Scholar Rose A. Article Google Scholar Download references. Acknowledgements Not applicable. Funding This study has not had any funds. View author publications. Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. About this article. Cite this article Lazarjani, M. Copy to clipboard. Contact us Submission enquiries: nikki.
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