Green Analytical Chemistry 13 (2025) 100270

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Green Analytical Chemistry

journal homepage: www.elsevier.com/locate/greeac

Recent advances in cannabidiol (CBD) extraction: a review of potential

eco-friendly solvents and advanced technologies
Saranya Selvaraj a , Nazeefa Nawfer b, K.V. Surangi Dharmawansa c , Ali Ali Redha d,e,* ,
H.P. Vasantha Rupasinghe c
a
Department of Chemistry, Faculty of Applied Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka
b
Postgraduate Institute of Science, University of Peradeniya, Peradeniya, Sri Lanka
c
Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia B2N 5E3, Canada
d
The Department of Public Health and Sport Sciences, University of Exeter Medical School, Faculty of Health and Life Sciences, University of Exeter, Exeter EX1 2 LU,
United Kingdom
e
Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation (QAAFI), The University of Queensland, Brisbane, QLD 4072,
Australia

A R T I C L E I N F O A B S T R A C T

Keywords: Cannabinoids, particularly cannabidiol (CBD), have been gaining attention for their numerous potential health
Cannabis sativa benefits and are employed in various industries. However, there are unresolved challenges in CBD extraction
Phytocannabinoids including low yields, impurity issues, and environmental concerns, suggesting the requirement for green
Green extraction
methods. Hence, our review objectives are to assess the efficacy, and the impact of novel solvents used for CBD
Deep eutectic solvents
Supercritical CO2
extraction, considering green and sustainable techniques. The traditional extraction methods such as maceration
and Soxhlet extraction used for CBD extraction have limitations such as low efficiency, long extraction times,
high energy consumption, and substantial CO₂ emissions, raising environmental concerns. Emerging green
extraction techniques, such as supercritical fluid extraction, deep eutectic solvents, and microwave-assisted
extraction, offer promising alternatives by reducing solvent use, minimizing processing time, and enhancing
extraction yields. Supercritical CO2 extraction, utilizing supercritical fluids’ unique properties offers efficient and
safe CBD extraction. Emerging green solvents such as ionic solvents and deep eutectic solvents provide promising
alternatives for CBD extraction due to their properties such as no or low toxicity compared to the traditionally
used solvents. Pressurized liquid extraction, such as subcritical water extraction, and techniques like microwave-
assisted and ultrasonic-assisted extraction provide rapid and efficient alternatives for CBD extraction. To fulfill
the growing demand for CBD extracts, future research can aim at developing efficient and sustainable extraction
techniques while reducing the potential degradation of CBD, removing impurities produced during extraction,
and considering concepts of sustainability and the One Health approach.

1. Introduction been identified, with the two most well-known being non-psychoactive
CBD and psychoactive 9-Δ-tetrahydrocannabinol (THC), CBD and THC
Cannabis sativa, one of the plants that humans cultivated at the are the most extensively studied cannabinoids due to their pharmaco­
earliest times of civilization, is an oleaginous plant valued for its non- logical significance, while distinguished by their particular relationship
edible fiber content and therapeutic biologically active compounds a. to the mammalian endocannabinoids [4,5].
k.a. bioactives such as cannabinoids [1,2]. The rediscovery of CBD has gained significant interest in its diverse pharmaceutical
non-intoxicating phytocannabinoids found in cannabis such as canna­ applications. CBD exhibits anti-inflammatory, analgesic, neuro­
bidiol (CBD) and cannabinol (CBN) have led to a burgeoning market for protective, and anticonvulsant properties, making it a promising ther­
Cannabis-based products. There has been a significant increase in apeutic agent for various medical conditions. It has been approved by
research, including numerous peer-reviewed articles published annually the Food and Drug Administration (FDA) and the European Medicines
on beneficial cannabinoids [3]. A total of 150 phytocannabinoids have Agency (EMA) in the form of Epidiolex, an oral solution for treating

* Corresponding author.
E-mail address: [email protected] (A. Ali Redha).

https://doi.org/10.1016/j.greeac.2025.100270
Received 20 November 2024; Received in revised form 23 February 2025; Accepted 14 April 2025
Available online 14 April 2025
2772-5774/© 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

epileptic disorders such as Dravet syndrome and Lennox-Gastaut syn­ Cannabis has been used for medicinal purposes for about 5000 years
drome [6]. Additionally, CBD has shown potential in managing chronic since then the extraction of CBD from Cannabis biomass has been a
pain, multiple sclerosis, and arthritis, due to its interaction with the critical step in the production of CBD-based therapeutic products,
endocannabinoid system (ECS) and transient receptor potential (TRP) including oils, tinctures, edibles, topicals, and pharmaceutical formu­
channels, which regulate pain perception and inflammation (Bergama­ lations [20,21]. The common steps involved in producing CBD from
schi et al., 2011). In neurological diseases, CBD’s antioxidant and Cannabis is illustrated in Fig. 1. Extraction makes it feasible to separate
anti-apoptotic effects contribute to its role in treating Alzheimer’s, and concentrate CBD from pulverized dried hemp inflorescence [22],
Parkinson’s, and Huntington’s diseases (Iuvone et al., 2009). Emerging leaves [23], from other parts of plants such as root, stem, seeds [24] and
studies suggest its efficacy in psychiatric disorders, including anxiety, from flower buds [25], preserving the finished product’s high potency
depression, and post-traumatic stress disorder (PTSD), attributed to its and purity. The chemical characteristics of CBD represent one of the
modulation of serotonin receptors (5-HT1A) and reduction in cortisol factors influencing the efficiency of CBD extraction. The choice of sol­
levels (Blessing et al., 2015). Moreover, CBD has shown anticancer po­ vent plays a crucial role in CBD extraction efficiency. According to the
tential, inhibiting tumor cell proliferation and inducing apoptosis in literature, both polar and non-polar organic solvents have been
various cancers, including glioblastoma, breast, and prostate cancers employed for this purpose. Non-polar solvents such as hexane and
(McAllister et al., 2011). Ongoing clinical trials continue to explore its chloroform [26]. CBD is a lipophilic compound, meaning it is soluble in
broad therapeutic potential, positioning CBD as a promising candidate non-polar solvents such as ethanol, butanol, hexane, and supercritical
for personalized medicine and innovative drug formulations aimed at carbon dioxide (sCO2). However, CBD also exhibits some solubility in
safe and effective therapies for complex diseases. polar solvents, such as ethanol and water, particularly under acidic
In 1964, the primary psychoactive component of Cannabis, THC was conditions either individually or in combination, depending on the
isolated based on the pharmacological characteristics of the plant [7]. extraction conditions. These solvent choices impact yield, purity, and
This discovery led to the more recent finding of the endocannabinoid overall extraction efficiency [27]. Therefore, the selection of solvent and
system (ECS), which regulates pain in physiological conditions. Princi­ extraction method is crucial for maximizing CBD yield and minimizing
pally as a source of resinous intoxicant, the plant and the medications impurities in the extracts [28,29].
created from it are often referred to as "marijuana", while stem fiber Green Analytical Chemistry (GAC) focuses on minimizing the envi­
(both the plant and the fiber) is labelled as "hemp" [8]. Industrial hemp ronmental impact of chemical analyses by adopting eco-friendly sample
varieties often contain higher levels of CBD compared to marijuana preparation techniques [30]. One key strategy is reducing or eliminating
strains bred for recreational or medicinal purposes. The CBD material hazardous solvents and reagents through methods like solid-phase
can differ greatly based on the subspecies, cultivars, and growing con­ microextraction (SPME) and dispersive liquid-liquid microextraction
ditions. For instance, hemp cultivars contain CBD concentrations (DLLME), which significantly lower solvent consumption [31]. When
ranging from 5 to 20 %, and about 2 % of THC, whereas marijuana solvent use is necessary, recovery and reuse through closed-loop sys­
strains may have CBD concentrations below 1 % [9]. tems, such as vacuum distillation and membrane filtration, enhance
Hemp (Cannabis sativa) is a fast-growing, herbaceous annual plant sustainability. Additionally, replacing petroleum-based solvents with
that can reach heights ranging from 3 to 18 feet, depending on envi­ green alternatives such as ionic liquids (ILs), superheated water, and
ronmental factors such as soil composition, climate, and cultivation supercritical fluids (SCFs), particularly sCO₂ improves selectivity and
practices [10]. During the flowering stage, “resin” which is the main efficiency while reducing toxicity. These advancements not only pro­
intoxicant (the primary source of cannabinoids) accumulates on the mote environmental responsibility but also optimize analytical pro­
surface of the leaves and branches. This resin is rich in bioactive com­ cesses, reduce costs, and align with global sustainability goals, making
pounds, including cannabinoids, terpenes, and flavonoids, which green analytical methodologies increasingly vital in modern research
contribute to the plant’s pharmacological and industrial value. Among and industry [32,33].
these, CBD and THC are the most studied cannabinoids [11]. The pro­ Within the hemp industry, the term "extraction" designates two
duction of resin is largely influenced by environmental conditions, diverse procedures and classifications: a) the trichome category, which
which not only affect the plant’s cannabinoid profile, but also its overall includes the extraction of terpenes and cannabinoids from trichomes to
morphology. Resin secretion continues throughout the flowering phase create supplements fit for either medicinal or recreational purposes; and
until the plant reaches full maturity, making optimal growing conditions b) the seed category, which includes the extraction of lipids or fatty acids
essential for maximizing cannabinoid yield and quality [12]. from hemp seeds [29].
The therapeutic potential of CBD has attracted considerable interest The CBD can be extracted through both traditional and modern
from researchers and healthcare professionals due to its purported techniques and research has explored these methods to optimize the
health benefits. CBD has demonstrated analgesic, anti-inflammatory, phytochemical extraction process from Cannabis. The efficiency of both
anxiolytic, neuroprotective, and antipsychotic properties in preclinical conventional and advanced extraction technologies is primarily deter­
and clinical studies [1,13]. Moreover, it is believed that CBD can miti­ mined by important input parameters, making it essential to understand
gate long-term injury from excitotoxicity and inflammation, as well as the chemistry of bioactive substances, how they interact with various
minimize mood and pain-related symptoms of traumatic brain injury solvents and the characteristics of the plant matrix [34,35]. Common
(TBI). This is due to its impacts on different neurotransmitter systems extraction techniques, including solvent extraction and sCO2, are
and the equilibrium between excitatory and inhibitory neurons being employed to isolate CBD from Cannabis biomass [36]. Every extraction
restored [14]. Consequently, CBD-based pharmaceuticals have emerged technique has benefits and drawbacks related to effectiveness, expense,
as promising treatments for various medical conditions, including epi­ expandability, and safety. Additional investigations are required to
lepsy, chronic pain, anxiety disorders, multiple sclerosis, and schizo­ create novel extraction methods and quality assurance procedures to
phrenia [15–17]. The FDA-approved CBD-based medication Epidiolex satisfy the increasing market for high-quality CBD products in the
has been shown to effectively reduce seizures in patients with rare forms medical and pharmaceutical sectors.
of epilepsy, such as Dravet syndrome and Lennox-Gastaut syndrome [18, CBD extraction techniques vary in environmental impact, toxicity,
19]. Moreover, ongoing research suggests that CBD may hold thera­ and industrial applicability (Table 1). The sCO₂ extraction is widely
peutic potential for addressing other health issues. For example, the five recognized as the most sustainable approach due to its low toxicity
major cannabinoids: CBD, CBN, cannabichromene, cannabigerol and, (ChlorTox), high greenness (ComplexGAPI/AGREEprep), and excellent
THC show strong activity against Methicillin-resistant Staphylococcus applicability (BAGI index), as it eliminates the need for organic solvents
aureus (MRSA), a type of bacteria that is resistant to many antibiotics and ensures high product purity [37]. For example, UAE, when com­
and is significant in modern healthcare [15]. bined with bio-based solvents like ethanol or DES, enhances mass

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S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

Fig. 1. Common steps involved in processing hemp to obtain cannabidiols (CBD).

Table 1
Green Characterization of CBD Extraction Methods.
Extraction Method Toxicity (ChlorTox Scale) Greenness (ComplexGAPI/AGREEprep) Applicability (BAGI Index) References

Supercritical carbon dioxide Very Low (Non-toxic) High (Solvent-free, recyclable) Excellent (Highly scalable) [39]
Ultrasound-assisted Low (Depends on solvent) High (Eco-friendly with green solvents) High (Efficient, cost-effective) [38]
extraction
Microwave-assisted Low to Moderate (Solvent- Moderate to High (Energy-efficient, solvent- Good (Lab-scale, needs optimization) [40]
extraction dependent) reducing)
Deep eutectic solvent Low (Biodegradable, non-toxic) High (Sustainable, emerging technology) Promising (Needs industrial [41]
extraction optimization)
Pressurized liquid extraction Moderate (Depends on solvent) Moderate to High (Efficient, but energy-intensive) Very Good (Widely used in industries) [42]

ColorTox scale, The color-coded toxicity scale is a system that uses colors to indicate the level of toxicity of a substance; ComplexGAPI, Complementary green analytical
procedure index; AGREEprep, Analytical greenness metric for sample preparation; BAGI Index, Blue applicability grade index.

transfer efficiency while reducing solvent consumption, making it an treatment [46]. The methods of grinding, milling, or chopping are
eco-friendly alternative [38]. Meanwhile, future advancements should frequently employed to reduce the particle size of CBD extracts [47,48].
focus on integrating hybrid extraction techniques and optimizing green Particle size has a significant impact on the yield of CBD extraction, as
solvent recovery to enhance CBD extraction sustainability. Thus, this several studies have shown. A recent study examined the effects of
review article examines emerging CBD extraction techniques, their particle size, categorizing them as coarse (2–4 mm), medium (0.5–2
benefits and drawbacks, and the most current developments in this field. mm), and fine (0.25–0.5 mm). The findings concluded that higher yields
are achieved with finer particles due to their greater surface area
2. General pre-extraction treatments exposure to the extraction solvent [49].
Drying of Cannabis plant material is essential to reduce moisture
The versatile nature of hemp, characterized by its abundant content, which can impact the derived CBD’s stability and quality. High
ecological, agronomic, and pharmaceutical benefits, makes it a valuable moisture content can lead to microbial growth and enzymatic degra­
raw material for a wide range of applications, including traditional uses dation, impacting the overall extraction process and product quality.
such as fiber, food, oil, and medicine, as well as advanced industrial Research indicates that, drying at 4 ◦ C is optimal for preserving the
products [1,43]. The food, medicinal, textile, and materials sectors integrity of CBD and enhancing extraction efficiency [49]. However,
extensively utilize hemp’s fibers, leaves, seeds, and other byproducts. process optimization is an essential factor as excessive drying temper­
Since some hemp varieties can be used as raw material sources for atures or prolonged drying times can degrade the heat-sensitive can­
extracting CBD, which can also be used as a narcotic, hemp cultivation is nabinoids [35]. Cannabinoids and their acidic precursors are highly
prohibited in many counties and areas. Additionally, the selection of heat-sensitive and undergo decarboxylation at elevated temperatures
specific hemp cultivars optimized for CBD yield enhances the efficiency [50]. Specifically, THCA transforms into THC at temperatures ranging
and sustainability of extraction processes, making them an essential from 105 ◦ C to 110 ◦ C, and CBDA converts into CBD between 110 ◦ C and
component of the growing cannabinoid-based industry [44]. >30 % of 120 ◦ C. While CBD can produce oxidized derivatives like cannabielsoin
hemp seed weight is composed of triglycerides, the ideal type of fat for (CBE), excessive heat and exposure to oxygen can further break down
trans-esterification into fatty-acid methyl esters (FAME) which can be THC into CBN. Prolonged heating may also lead to oxidative changes in
used in food and cosmetics sectors or as biodiesel [45]. cannabinoids, including CBC and CBG [51]. Additionally, the break­
The extraction of CBD from Cannabis plants involves several pre- down of cannabinoids may accelerate due to the volatilization of ter­
extraction treatments aimed at optimizing the yield, purity, and qual­ penes at temperatures above approximately 50 ◦ C. Therefore, drying
ity of the final products. This includes (a) size reduction, (b) drying, (c) temperatures should be maintained below 60 ◦ C to prevent undesirable
decarboxylation, (d) solvent selection, (e) defatting, and (f) acid/base thermal degradation, preserve bioactive components, and maintain the

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phytochemical integrity of the cannabis plant [52]. heating, and steam distillation, have been investigated for their effi­
Decarboxylation of CBD extraction is crucial to obtain CBD in its ciency in converting CBDA to CBD [62].
active form. Decarboxylation of neutral cannabinoids occurs more The choice of solvent plays another significant role in CBD extrac­
quickly at high temperatures and with prolonged reaction times; how­ tion, with various solvents exhibiting different extraction efficiencies
ever, minimizing exposure to oxygen can help mitigate this effect [53]. and selectivity. Commonly used solvents include ethanol, sCO2, iso­
Several environmental factors affect the rate of the reaction, including propanol and hydrocarbons such as butane or propane [2]. Solvents
temperature, light, and oxygen levels. While decarboxylation can such as butane, propane, hexane, and methanol are not commonly used
naturally take place at room temperature, it happens at a much slower in CBD extraction because they can create an uncontrolled and haz­
rate [54]. Consequently, the conditions under which cannabinoids are ardous environment. Methanol, in particular, poses significant toxicity
stored, and the duration of storage significantly influence their compo­ risks to human health and environmental safety [63], further limiting its
sition [55]. Cannabinoids such as cannabidiolic acid (CBDA) found in suitability for extraction. Additionally, using these solvents raises con­
raw Cannabis undergo decarboxylation to form CBD through heating for cerns about safety and ecological impact [64,65].
15–120 min at 100–150 ◦ C to transform into neutral counterparts Ethanol-based extraction is preferred for its ability to extract a wide
(Fig. 2). This process releases CO₂ and transforms the molecular struc­ range of cannabinoids and terpenes while being relatively safe and cost-
ture of CBDA into CBD. The resulting CBD molecule is more stable and effective [3]. Alcohol is used as a solvent in a variety of medical Cannabis
has a different set of psychotropic pharmacological properties compared extraction processes due to its superior effectiveness and purity for food.
to its acidic precursor [56,57]. Heat and time are the two primary cat­ The solvents such as butane, propane, and hexane have limited use in
alysts that facilitate decarboxylation. Decarboxylation can be partially CBD extraction as they have the potential to create an uncontrolled
achieved from curing and drying over time; however, it is not effective dangerous environment for human safety [2]. Butane, propane, hexane,
as heating the plant at specific time and temperature combinations. and methanol are not commonly used in CBD extraction because they
The use of extremely high temperatures in smoking and vaping, pose safety risks and can lead to an unregulated processing environment
rapidly decarboxylate Cannabis, making it instantly available for ab­ [64,65].
sorption through inhalation [59]. To conserve terpenes, many users The choice of solvent has an impact on the final color of the extract.
decarboxylate the Cannabis materials for a significantly longer amount Depending on the temperature and particle size, the use of different
of time at somewhat lower temperatures. Since many mono- and solvents produced varying extract colors; yellow with hexane, green
sesqui-terpenes are volatile, they may evaporate at higher temperatures, with butanol, and dark green with ethanol [49]. The most commonly
leaving behind odors and fragrances that may not be desired. It has been used extraction technique is sCO2 extraction, which accounts for 45 % of
observed that maximum THC formation occurs in <10 min at 145 ◦ C, the methods employed, followed by solvent-based methods at 11 % [3].
however, prolonged exposure leads to a significant loss, likely due to The selection of solvent depends on factors such as safety, regulatory
THC evaporation beginning at 157 ◦ C [60]. This conversion process also compliance, cost, desired product characteristics, and the plant’s
enhances the potency and bioavailability of CBD in extracted products. cannabinoid profile. As non-decarboxylated raw materials contain can­
The complete conversion of THCA to THC at 150 ◦ C for 15 min with a nabinoids in their acidic forms, they are more soluble in polar solvents
yield of 70 %, contributed to the formation of CBD [61].Various compared to neutral cannabinoids. In addition to solvent selection,
decarboxylation methods, including oven drying, microwave-assisted factors such as extraction temperature, pressure, duration, and agitation

Fig. 2. Chemical conversion (decarboxylation) of CBDA to CBD [58] (adapated figure); Distributed under the terms and conditions of the Creative Commons
Attribution (CC BY) license).

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also influence CBD extraction efficiency and product quality. For simplicity, ease of optimization, and high extraction yields [29]..
instance, higher temperatures and pressures may enhance CBD solubil­ However, it has limitations such as extended extraction times, sub­
ity and extraction rates but can also increase the risk of thermal stantial solvent consumption increasing operational costs and environ­
degradation and solvent contamination [66]. mental impact and potential thermal degradation of analytes due to
The potential interaction between CBD and solvent molecules, as prolonged high-temperature exposure [82,83]. While the method is
well as other plant constituents, must be considered to avoid unwanted capable of achieving yields between 10 and 15 % of the plant’s dry
chemical reactions or impurities in the final extract. To separate the weight, is highly dependent on prior feed treatment, such as milling, and
required cannabinoids from other molecules, such as nitrogenous to maintain efficiency, this method requires significant energy to sustain
chemicals, amino acids, sugars, aldehydes, alcohols, ketones, flavo­ the distillation-evaporation cycles, posing substantial challenges for
noids, glycosides, vitamins, pigments, and terpenes, and avoid co- scalability due to energy waste, prolonged extraction times, and fire
extraction of such substances, it is imperative to choose a solvent with hazards [83] Meanwhile, maceration yields 5–10 % CBD extraction,
the proper polarity [67,68]. Meanwhile, high levels of non-polar com­ however, after decarboxylation, a 24-hour maceration can yield up to 40
pounds such as lipids, waxes, and other non-target compounds can % CBD extracts with solvent recovery [47]. Both methods require
interfere with CBD extraction and purity; hence defatting or lipid extensive employment of organic solvents such as ethanol, methanol,
removal treatments are employed to minimize these contaminants and and hexane [84]. which are potentially environmentally toxic and pose
improve the overall quality of the extracted CBD [69]. While some polar health risks due to their flammability and toxicity.
solvents dissolve polar components found in Cannabis plants, including The HRE on the other hand, is also a method for extracting CBD by
terpenes, alkaloids, and chlorophyll, these impurities might impair the continuously evaporating and condensing a solvent, which washes over
final product’s aroma, flavor, and consistency if post-processing actions the hemp plant material, enhancing CBD yield by prolonged solvent
are not taken to remove them. Various defatting techniques, including contact. However, it requires careful solvent selection and condition
winterization, liquid-liquid extraction, and membrane filtration, have control to avoid excessive solvent usage, energy consumption, and
been investigated for their effectiveness in removing lipids from CBD thermal degradation of heat-sensitive compounds like CBD [85]. The
extracts [70]. Optimizing defatting factors such as solvent-to-feed ratio, method utilizes different solvents at 95 ◦ C under reflux to achieve higher
temperature, and time is essential to achieve efficient lipid removal extraction efficiencies [86]. However, this method is energy-intensive
without compromising CBD yield or quality, furthermore, limited and not always scalable.
extraction selectivity results in lower final product proportional Ensuring the removal of solvents from the final CBD product can be
amounts of the targeted cannabinoids [71]. difficult, leading to potential contamination, energy-intensive, and less
Acid or base treatment of Cannabis plant material can alter the pH sustainable for large-scale operations [85]. Additionally, it often re­
and enhance the solubility of cannabinoids, including CBD. Acidic quires specialized equipment and meticulous monitoring, increasing
conditions promote the conversion of cannabinoid acids to their neutral operational costs and complexity. Given these challenges, there is a
forms, facilitating extraction and improving product purity. A recent in critical need to explore more sustainable and efficient extraction
vitro study to assess the solubility of CBD, CBDA, and cannabichromene methods for CBD. Potential alternative green extraction methods
(CBC) in different media ranging from pH 1.2, 6.8, fasting, and fed state include sCO₂ extraction, which offers high efficiency, selectivity, scal­
intestinal fluid simulation dissolution tests anticipated that the minimal ability, and solvent-free final products. However, it requires specialized
amount of cannabis release in acidic conditions could be caused by the equipment and operating conditions [87]. Some emerging advanced
breakdown of CBD, CBDA, or CBC in addition to their poor solubility in extraction techniques such as Ultrasonic-Assisted Extraction (UAE)
the stomach environment [72]. Conversely, basic conditions may aid in which enhances solvent penetration and extraction efficiency, and MAE
the breakdown of plant cell walls, releasing intracellular cannabinoids which increases the yield and reduces extraction time can also be
for extraction. However, the use of acid or base treatment requires employed for efficient CBD extraction [88].
careful control to avoid undesirable chemical reactions or degradation Nevertheless, the choice of a suitable extraction technique is influ­
of sensitive compounds [66]. enced by such as purity requirements, equipment availability, cost, and
environmental considerations. These methods often require substantial
3. Conventional extraction methods of CBD amounts of solvents, which are costly and pose environmental hazards.
The inefficiencies and environmental impacts associated with these
Various traditional extractions have been employed to obtain CBD traditional techniques underscore the need for developing innovative,
from plant material, each characterized by distinct processes and out­ green extraction methods [89].
comes. Solvent extraction is a significant conventional method, using
solvents such as ethanol or other hydrocarbons, dissolves cannabinoids 4. Ionic solvents for CBD extraction
for subsequent evaporation, offering high efficiency but risking residual
solvents and terpene loss [25]. Traditional solvent-based CBD extraction Ionic solvents are an emerging alternative to common organic sol­
methods include percolation, maceration, Soxhlet, and Heat Reflux vents. These solvents are classified as molten salts composed entirely of
Extraction (HRE) (Table 2). Percolation, involving the passage of sol­ ions, including small amounts of an organic or inorganic anion and a
vents through plant material, enables faster extraction however, it re­ large organic cation. Ionic liquids have a different structure and set of
quires precise control of solvent flow; the method uses 95 % ethanol characteristics that cause them to remain liquid at or close to room
passed through plant material, achieves rapid extraction and high CBD temperature, unlike ordinary salts, which usually have high melting
recovery while preserving cannabinoids [73]. In contrast, maceration, temperatures [90]. Furthermore, such solvents consist of several distinct
which includes immersing plant material in a solvent, thoroughly ex­ chemical and physical characteristics, including high thermal stability,
tracts cannabinoids and is time-consuming and solvent intensive. The and low volatility, which is significant, especially during energy storage
method involves soaking plant material in 95 % ethanol at a material: to chemical synthesis [91]. Numerous types of ionic solvents are
solvent ratio of 1:5 over an extended period at controlled temperatures, currently utilized in the extraction of cannabinoids, each exhibiting
ensuring thorough extraction. However, it also is a slower and more distinct advantages and limitations (Table 3). This diversity underscores
solvent-intensive method [58,74]. the need for careful consideration of solvent properties to optimize
Soxhlet extraction of CBD allows for efficient extraction by a extraction efficiency and selectivity in cannabinoid recovery processes.
continuous solvent cycle, providing a strong extraction driving force by Meanwhile, the efficiency and selectivity of the extraction process
exposing Cannabis plants to fresh n-hexane or methanol throughout the for CBD are mainly based on the composition of the ionic compounds. To
process, ensuring thorough extraction, offering methodological maximize the solvation properties of ionic liquids and extract desired

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Table 2
Summary of non-conventional solvents applied for CBD extraction.
Solvent type Solvent characteristics Sample (and Extraction technique Extraction conditions Yield CBD Ref.
pretreatment) quantification
method

Ionic liquid 1-hexyl-3-methylimidazoliumbis Industrial hemp Maceration Temperature = 60 ◦ C 7.23 mg/ HPLC–IC [75]
(trifluromethylsulfonyl)imide leaves dried at 50 ◦ C Time = 50 min g of DW
1-ethyl-3-methylimidazolium bis and powdered Solid-liquid ratio= 5.6 mg/g
(trifluoromethylsulfonyl)imide 25:1 of DW
1-butyl-3-methylimidazolium bis 5.5 mg/g
(trifluoromethylsulfonyl)imide of DW
1-butyl-3-methylimidazolium 3.5 mg/g
hexafluorophosphate of DW
1-hexyl-3-methylimidazolium 3.5 mg/g
hexafluorophosphate of DW
1-ethyl-3-methylimidazolium N/D
chloride
1-butyl-3-methylimidazolium N/D
chloride
1-hexyl-3-methylimidazolium N/D
chloride
1-butyl-3-methylimidazolium N/D
acetate
1-hexyl-3-methylimidazolium N/D
acetate
Ionic liquid 1‑hydroxy‑2-ethyl-imidazol-3- CBD cream Solid-liquid microextraction Temperature = 4.61 mg/ HPLC-UV [76]
oxid [HEtIMO] controlled ultrasonic g of DW
1-Butoxy-2-ethyl-imidazol-3- bath (<40 ◦ C) or on a 1.44 mg/
oxide [BuEtIMO] ThermoMixer (1800 g of DW
1-butoxy-3-ethoxy-2-ethyl- rpm, 25 ◦ C) 0.95 mg/
imidazolium ethyl sulfate Time = 60 min g of DW
[BuEtEtIMO] [EtOSO3] Solid-liquid ratio =
1-butoxy-3-ethoxy-2-ethyl- 20:1 N/D
imidazolium bis
(trifluoromethane)sulfonimide
[BuEtEtIMO] [Tf2N]
Deep eutectic Betaine: Lactic Acid (1:2) Hemp dried leaves Solid-liquid extraction Temperature = 60 ◦ C 3.9 mg/g HPLC-UV [77]
solvent were powdered. Pressure = under of DW
Glucose: Lactic Acid (1:5) atmospheric pressure 3.8 mg/g
Sonication time = 90 of DW
Proline: Lactic Acid (1:1) min 6.1 mg/g
Ultrasonic power = of DW
Menthol: Lactic Acid (2:1) 100 W 6.4 mg/g
Solid-liquid ratio = of DW
Menthol: Lauric Acid (2:1) 1:10 (w/w) 11.1 mg/
g of DW
Menthol: Myristic Acid (4:1) 6.1 mg/g
of DW
Menthol: Steric Acid (8:1) 6.3 mg/g
of DW
Choline chloride: Urea (1:2) Industrial hemp Solid-liquid extraction coupled Temperature = 48 ◦ C 4.0 mg/g HPLC-UV [78]
leaves were dried at with resin enrichment Time = 55 min of DW
Choline chloride: D- Sorbitol (1:1) 40 ◦ C for 12 h and Solid-liquid ratio = 0.5 mg/g
powdered 1:24 of DW
Choline chloride: Oxalic acid 1.4 mg/g
(1:1) of DW
Choline chloride: Benzoic acid 1.5 mg/g
(1:1) of DW
Choline chloride: Citric acid (1:1) N/D
Choline chloride: Diethyl L- 12.2 mg/
tartrate (1:1) g of DW
Choline chloride: Zinc chloride 1.0 mg/g
(1:1) of DW
Choline chloride: (+)-Lactic acid 6.0 mg/g
(1:1) of DW
Choline chloride: Glycerol (1:2) 1.0 mg/g
of DW
Choline chloride: Salicylic acid 3.0 mg/g
(1:1) of DW
Choline chloride: Succinic acid 1.2 mg/g
(1:1) of DW
Choline chloride: Mannitol (1:2) 3.0 mg/g
of DW
Choline chloride: Acetamide 1.5 mg/g
(1:2) of DW
Betaine: Glycerol (1:2) 1.6 mg/g
of DW
(continued on next page)

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Table 2 (continued )
Solvent type Solvent characteristics Sample (and Extraction technique Extraction conditions Yield CBD Ref.
pretreatment) quantification
method

Betaine: Citric acid (1:1) 0.2 mg/g

of DW
Betaine: Urea (1:2) 8.0 mg/g
of DW
Supercritical Supercritical CO2 Crude hemp nut Supercritical fluid extraction Temperature = 50 ◦ C 1.08 mg/ HPLC-EC [79]
CO2 Pressure = 5000 psi g of DW
Time = 120 min; 30-
min static extraction,
90-min dynamic
extraction
Air flow rate = 2.5 L/
min
Supercritical CO2 at 50 ◦ C and Milled dried hemp Supercritical fluid extraction Sieved pore sizes =450 1.5 mg/g GC–MS [80]
100 bar flowers with samples of varying particle μm of DW
size + extraction with different Sieved pore sizes =630 2.0 mg/g
durations μm of DW
Sieved pore sizes = 2.8 mg/g
1000 μm of DW
Time = 15 min 0.252
mg/g of
DW
Time = 30 min 0.562
mg/g of
DW
Time = 45 min 0.903
mg/g of
DW
Time = 60 min 1.255
mg/g of
DW
Time = 75 min 1.610
mg/g of
DW
Time = 90 min 1.962
mg/g of
DW
Time = 105 min 2.273
mg/g of
DW
Time = 120 min 2.566
mg/g of
DW
Time = 135 min 2.791
mg/g of
DW
Supercritical CO2 Aerial parts of Supercritical fluid extraction at Temperature and 99.74 GC–MS [81]
industrial hemp are different temperatures and pressure = 40 ◦ C and mg/g of
air-dried at ambient pressures, but constant 100 bar DW
temperature separator conditions = 15 bar Temperature and 65.55
and 23 ◦ C; and flow rate = 1 pressure = 50 ◦ C and mg/g of
mL/min 100 bar DW
Temperature and 56.56
pressure = 60 ◦ C and mg/g of
100 bar DW
Temperature and 84.60
pressure = 40 ◦ C and mg/g of
200 bar DW
Temperature and 47.83
pressure = 50 ◦ C and mg/g of
200 bar DW
Temperature and 47.72
pressure = 60 ◦ C and mg/g of
200 bar DW
Temperature and 61.11
pressure = 40 ◦ C and mg/g of
300 bar DW
Temperature and 56.83
pressure = 50 ◦ C and mg/g of
300 bar DW
Temperature and 65.54
pressure = 60 ◦ C and mg/g of
300 bar DW
(continued on next page)

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Table 2 (continued )
Solvent type Solvent characteristics Sample (and Extraction technique Extraction conditions Yield CBD Ref.
pretreatment) quantification
method

Supercritical Subcritical water extraction Aerial parts of Subcritical water extraction at 120 ◦ C 0.0145 GC–MS [81]
solvent industrial hemp are different temperatures, with mg/ml of
air-dried at ambient constant: DW
temperature Pressure = 30 bar (obtained by 140 ◦ C 0.0183
introduction of nitrogen) mg/ml of
Time = 10 min DW
Solid-liquid ratio = 1 g/10 mL 160 ◦ C 0.0156
mg /ml
of DW
180 ◦ C 0.0138
mg/ml of
DW
200 ◦ C 0.0063
mg/ml of
DW
220 ◦ C 0.0039
mg/ml of
DW

ND- Not Detectable, CBD- Cannabidiol, RTIL- Room Temperature Ionic Liquid, LOQ- limit of quantification, LPME- Liquid-Phase Microextraction Experiments,
HPLC–IC system- High-Performance Liquid Chromatography Ion Chromatography, HPLC–UV system High-Performance Liquid Chromatography Ultraviolet Detection,
sCO2- Supercritical CO2, SWE- Subcritical water extraction, GC–MS- Gas Chromatography-Mass Spectrometry.

composition to enhance the extraction yield, purity, and overall effi­

Table 3
ciency of CBD extraction processes. Additionally, certain ionic liquids
Overview of commonly used ionic solvents1 in cannabinoid extraction: advan­
have the capacity to dissolve both polar and non-polar substances,
tages and limitations.
which can facilitate the extraction of a variety of cannabinoids and other
Ionic solvent/Abbreviation Advantages Limitations
desirable compounds from Cannabis plants[89].
1-hexyl-3-methylimidazolium bis High solubility for High cost, may Furthermore, CBD stability can be a concern due to its susceptibility
(trifluoromethylsulfonyl)imide cannabinoids, tunable require post- to degradation when becomes accessible to certain environmental fac­
[C6mim][NTf2] properties, non-volatile, extraction
tors such as light, heat, oxygen, and moisture. Degradation of CBD can
low toxicity purification
1-butyl-3-methylimidazolium Moderate solubility for Cost, potential for lead to a loss of potency and efficacy, affecting the functionality of CBD
hexafluorophosphate [C4mim] cannabinoids, stability deposition of products. Common degradation pathways for CBD include oxidation,
[PF6] over various conditions, residuals in final isomerization, and degradation into smaller compounds [95]. Ionic
relatively low toxicity product
liquids can offer a solution to some of the stability issues associated with
1-Ethyl-3-methylimidazolium Moderate solubility for Cost, may require
acetate [EMIM][OAc] cannabinoids, relatively post-extraction
CBD. Because of their distinctive characteristics, such as low volatility
low viscosity, non-toxic purification and high thermal stability, ionic liquids can provide a protective envi­
1-Butyl-3-methylimidazolium Moderate solubility for Cost, potential ronment for CBD, shielding it from factors that might cause degradation.
Tetrafluoroborate [C4mim] cannabinoids, stability toxicity, may Additionally, the choice of specific ions in the ionic liquid formulation
[BF4] over various conditions, require post-
can be tailored to minimize interactions that could lead to the degra­
non-volatile extraction
purification dation of CBD molecules [96]. While some ionic liquids such as
1-octyl-3-methylimidazolium Moderate solubility for Cost, potential 1‑butyl‑3-methylimidazolium hexafluorophosphate (BMIM-PF6) and
chloride [C8mim][Cl] cannabinoids, relatively toxicity, may 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM BF4) have been
low viscosity, stability require post-
found to enhance the stability of CBD through mechanisms such as
over various conditions extraction
purification
encapsulation or complexation [97,98]. Improved CBD bio-accessibility
1-butyl-3-methylimidazolium Moderate solubility for Cost, potential was seen in all three food-grade CBD nano-emulsions when the physi­
chloride[C4mim][Cl] cannabinoids, relatively toxicity, may cochemical stability and bioaccessibility of CBD were compared using
low viscosity, stability require post- medium-chain triacyclglycerols, canola oil, or hemp seed oil as the
over various conditions extraction
carrier oil. These interactions between CBD molecules and the ions
purification
Trihexyl(tetradecyl) Moderate solubility for Cost, potential present in the ionic liquid can stabilize the CBD structure and protect it
phosphonium bis cannabinoids, stability toxicity, may from degradation processes. As a result, CBD dissolved in certain ionic
(trifluoromethylsulfonyl)imide over various conditions, require post- liquids may exhibit improved stability over time compared to traditional
[P14,6,6,6][Tf2N] non-volatile extraction solvents or extraction methods [99]. However, it’s crucial to remember
purification
that the stability of CBD in ionic liquids can still be impacted by elements
The ionic solvents are versatile solvents that exist as molten salts at room tem­ like the specific formulation of the ionic liquid, concentration of CBD,
perature, exhibiting unique physiochemical properties such as negligible vapor temperature, and duration of exposure. Therefore, thorough research
pressure, non-flammability, high stability and excellent transportation charac­ and optimization of the ionic liquid system are necessary to maximize
teristics. These traits make ionic solvents suitable as green media for extracting
the stability of CBD and ensure the quality of CBD products [100].
bioactive compounds from and enhancing the activity and stability of these
The bioactive chemical profile of the extracts resulting from the
compounds in solution. This table includes some commonly used ionic solvents
and their advantages and limitations [75,92,93].
various protocols showed significant variation, indicating the need for
additional research on the impact of processing on therapeutic efficacy
and the significance of labelling in the marketing of multi-component
chemicals, such as CBD particular combinations of cations and anions
Cannabis products [101].
can be chosen [94]. Hence the choice of solvent significantly affects the
The ionic liquids could also be utilized as extractants, stabilizers, and
interaction between the solvent and the desired compounds in the plant
accelerants for the conversion of CBDA to CBD by decarboxylation and
matrix, making it essential to select the appropriate ionic liquid

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based on the density functional theory calculations, it has been proved secondary metabolites of plant materials. These include compounds
that ionic liquids can prevent CBD from being degraded and enhance its such as phenolics, flavonoids, isoflavonoids, terpenoids, alkaloids, an­
stability by the weak interactions between CBD and its constituents [75]. thocyanins, anthraquinones, and polysaccharides, such substances that
In this study, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl) provide biodegradable and low-toxicity solutions [106]. Certain NADES
imide, which is more polar than methanol was used as the extractant, can dissolve manufactured or natural substances with varying polarity,
resulting in nearly double the extraction yield compared to methanol. depending on the composition. They are also potentially entirely
Similarly, a novel solvent composed of 1-butoxy-3-ethoxy-2-ethyl-imi­ biocompatible due to their composition of natural metabolites, making
dazolium bis(trifluoromethane)sulfonimide, a room temperature ionic them a more environmentally friendly option for concepts and appli­
liquid demonstrated 80 % recovery of CBD and its stability at room cations requiring some organic solvents and ionic liquids [78,111].
temperature for three days and at 4 and − 20 ◦ C for fourteen days [76]. Additional factors influencing the extraction efficiency of DES can be
Further, as CBD is a lipophilic molecule, the lipophilicity of ionic liquid the viscosity, temperature, and water content. The viscosity of DES af­
cations increases with the number of side chains, making the extraction fects mass transfer rates and mixing efficiency during the extraction
of CBD easier [102]. process [106]. Higher viscosity DES can hinder the diffusion of CBD
Despite the growing interest in ionic liquids as green solvents for CBD molecules, leading to slower extraction kinetics, thus the solvent’s
extraction, several critical limitations hinder their widespread applica­ ability to penetrate the hemp material and dissolve CBD is reduced,
tion. Experimental studies in past have revealed that many conven­ resulting in lower extraction efficiency. Conversely, lower viscosity DES
tionally used ILs exhibit varying degrees of toxicity to aquatic improves mass transfer, facilitating quicker and more efficient extrac­
ecosystems and human health, raising significant safety concerns [103]. tion of CBD from the plant material [112]. Temperature on the other
Furthermore, some ILs are derived from petroleum-based precursors, hand influences the physical properties and phase behavior of DES,
which conflicts with sustainability goals and restricts their approval in affecting the solvation capacity and extraction efficiency. Higher tem­
food-related and pharmaceutical applications by regulatory bodies such peratures can enhance the solvation capacity of DES by aggregating the
as the FDA [104]. Another major drawback is the high cost of ILs, which solubility of CBD and reducing the viscosity of the solvent. This leads to
currently limits their feasibility for large-scale industrial applications. improved extraction efficiency as the DES can more effectively solubilize
The combination of toxicity, non-renewable origins, regulatory chal­ and transport CBD from the hemp material [113]. DES can contain
lenges, and high production costs underscores the urgent need for varying amounts of water, which can impact their solvation properties
further research to develop truly sustainable and cost-effective “green” and extraction efficiency, nevertheless, water can alter the hydrogen
alternatives[105]. bonding network and polarity of DES, affecting their ability to dissolve
While the use of ionic solvents holds promise for CBD extraction, CBD [114].
researchers must consider various factors, including formulation opti­ The differences in the hydrogen bond acceptor (HBA) component of
mization, stability assessment, solvent recovery, regulatory compliance, DES can significantly affect the solvation properties and extraction ef­
and further exploration of extraction parameters. By addressing these ficiency. HBAs with different chemical structures and functionalities can
considerations, researchers can effectively harness the benefits of ionic exhibit varying affinities for specific solutes and influence the selectivity
solvents for CBD extraction while advancing the field with innovative of the extraction process. For example, in a study conducted with
approaches and insights. choline (a) chloride/ethylene glycol, (b) citric acid/ethylene glycol, (c)
menthol/lauric acid, (d) choline chloride/urea, and (e) choline chlo­
5. Deep eutectic solvents for CBD extraction ride/glycerol, expressed the highest amount of CBD was extracted using
choline chloride/ethylene glycol (0.87 %), then choline chloride/urea
Deep eutectic solvents (DES) are environmentally friendly solvents (0.78 %) because of the high solubility, while menthol/lauric acid being
formed by mixing hydrogen bond donors (HBDs) such as quaternary less viscous and hydrophobic, yet the extraction efficiency of CBD was
ammonium salts, urea, or organic acids, with hydrogen bond acceptors very low due to temperature at 60 ◦ C ultrasonic bath based extraction
(HBAs). The HBDs are generally can be urea, carboxylic acid, sugar, and method being used [115]. Further, DES containing metal chlorides as
amide; whereas HBAs can either be quaternary salt with metal halides or HBAs have different solvation capacities and extraction efficiencies
hydrophobic natural compounds[106,107]. The ingredients are com­ compared to DES with metal acetates or other HBAs. Hence, under­
bined, heated to a predetermined temperature, and then stirred standing the effects of HBA differences on DES properties is essential for
magnetically until a translucent liquid is formed. The most crucial factor tailoring DES formulations to specific extraction applications and opti­
in the development of these systems is the strong link between HBA and mizing extraction processes for maximum efficiency and selectivity
HBD [108]. The system’s melting point is lowered concerning its con­ [116].
stituent parts because of this interaction. Industrial-scale production is Another research based on the DES solution media was formed by
made possible by this straightforward manufacturing technique, which mixing two components that can interact with HBA/HBD molar ratios.
eliminates the need for sophisticated facilities and skilled labor. It also By altering the HBA molar ratios of the components DES, such as using
generates no waste or byproducts and does not require solvents [78]. (a) choline chloride (ChCl) and (b) betaine with several HBDs as D-
These solvents exhibit unique properties which mimic the ionic liq­ sorbitol, urea, oxalic acid, lactic acid, L (+)‑diethyl L-tartrate (DT), citric
uids and are simpler in composition and easier to prepare. With the acid, salicylic acid, succinic acid, mannitol, acetamide and glycerol;
capacity to dissolve a wide range of compounds and low melting points, investigated the resulting DES extraction of CBD molecules. It was
high viscosity, increased efficiency, shorter extraction times, reduced evident that, among the DESs, the maximum extraction yield was
costs, lack of toxicity, biodegradability, and improved product purity, attained with ChCl-DT; the extractant provided a yield of 11 mg/g DW.
DES are a promising replacement for conventional organic solvents in a Nevertheless, the ChCl-DT exhibited lower extractability than methanol
variety of applications, including extraction processes [109,110]. (a control), however superior extractability in contrast to organic sol­
The efficiency of DES in extraction can be affected by several factors, vents like ethanol and ethyl acetate used in the study. The primary
including the content, selection, and ratio of HBD and HBA components benefit of using DESs above all other frequently used organic solvents is
in DES. Optimizing the composition of DES can enhance its ability to the extreme environmental friendliness. This variation was used for the
solubilize target compounds and improve extraction yields. Most of the potential hydrogen bonding, hydrophobic interactions, electrostatic
DESs that have been developed thus far are based on renewable re­ interactions, and van der Waals forces that influenced DES extraction
sources, such as sugars, amines, carboxylic and amino acids, and car­ capacity influencing CBD solubility and extraction efficiency [77].
bohydrates [102]. Natural deep eutectic solvents (NADES) are a class of Eventually, the best combination depends on factors like extraction ef­
deep eutectic solvents derived from natural sources, specifically ficiency, cost, environmental impact, and regulatory considerations.

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S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

The effect of differences in HBDs directly affects the acidity, efficiency and product quality [119].
hydrogen bonding capability, and polarity of the DES, all of which Pressure and temperature adjustments made throughout the extrac­
significantly influence CBD extraction efficiency. For example, lactic tion process can affect the fluids’ discernment for chemically highly
acid, as a weak acid, contributes to the pH and proton concentration of sensitive phytochemicals [29,120]. The pressure determines the solva­
the solvent system. Different ratios of lactic acid led to different levels of tion power and density of the sCO2, which in turn influences the
acidity in the DES, influencing CBD solubility and the stability of the extraction of CBD and other compounds from the plant material. Higher
solvent. Moreover, changes in the HBD alter the hydrogen bonding pressures generally result in increased solubility of CBD in sCO2, leading
capability of the DES. Hydrogen bonds play a crucial part in solvation, to higher extraction efficiency. This occurs because higher pressure
affecting the interactions between the solvent and CBD molecules. enhances the density of the sCO2, allowing it to penetrate the plant
Different HBD ratios result in varied hydrogen bond strengths, impact­ material more effectively and dissolve a greater amount of CBD.
ing the ability of the DES to dissolve CBD efficiently. Furthermore, Consequently, higher pressure can yield higher CBD concentrations in
variations in the HBD influence the polarity of the DES. Lactic acid, the extracted oil. However, excessively high pressures can also have
being a polar molecule, contributes to the overall polarity of the solvent negative effects, such as increased viscosity of the sCO2 and the potential
system. Different ratios of lactic acid cause modifications to the DES’s for co-extraction of impurities compounds. Conversely, lower pressures
polarity, resulting in an impact on CBD solubility and extraction effi­ may lead to reduced solubility of CBD and lower extraction efficiency. At
ciency. By understanding these differences, researchers can optimize the lower pressures, the sCO2 may not be able to effectively penetrate the
choice of HBD to achieve the desired extraction outcomes, balancing plant material or dissolve CBD molecules as efficiently. This can result in
factors such as yield, purity, and environmental impact [78]. lower CBD concentrations in the extracted oil and reduced overall yield
Citric acid, on the other hand, is a stronger acid with the ability to [80].
form multiple hydrogen bonds, potentially improving extraction effi­ Similar results were reported with a study explored the impact of
ciency for specific compounds, particularly those with higher acidity or pressure on CBD extraction. A pressure of 250 bar, 47 ◦ C, and a high
polarity; its strong hydrogen-bonding capability can enhance the inter­ operational sCO2 density (818 kg/m3) produced the best yield; yet the
action between the solvent and CBD molecules, facilitating better sol­ maximum density tested (911 kg/m3) did not increase the extraction
vation and extraction [115]. Malic acid, with its unique solvation yield any further [36]. Based on these studies, a recommended pressure
properties stemming from its dicarboxylic nature, offers a balance be­ range for CBD extraction using sCO2 would be between 2000 and 4000
tween acidity and selectivity. The strong solvation capabilities of malic psi. This range has been found to yield efficient extraction of CBD while
acid can facilitate better interaction between the solvent and CBD maintaining the purity of the extract. However, the specific pressure
molecules, leading to higher extraction yields as extended [117]. used may change based on several circumstances such as the composi­
Therefore, the selection of HBD is contingent upon the intended results tion of the plant material and the desired properties of the final extract.
of the extraction procedure, considering factors like target compounds, The SFCs are beneficial for extraction because of their special qual­
extraction efficiency, selectivity, and environmental impact. ities, including high diffusivity, low viscosity, and tunable solvation
Despite the promising applications of DES shown in cosmetic and power [121]. In this process, CO2 is pressurized above its critical point
pharmaceutical fields, their cytotoxicity remains underexplored. In a and passed through the plant material, where it acts as a solvent to
study conducted by Macário et al., [Chol]Cl- and [N1111]Cl-based DES extract the desired compounds, such as essential oils, without solvent
exhibited low cytotoxicity and enhanced HaCaT cell viability, suggest­ residues. Co-solvents, like ethanol, are sometimes added to sCO2
ing potential for skin regeneration. Conversely, [N4444]Cl-based DES extraction to increase the solubility of some compounds that are less
demonstrated cytotoxic effects, likely due to the toxic nature of [N4444] soluble in pure CO2, thereby improving extraction efficiency [122,123].
Cl, regardless of the hydrogen bond donor used. These findings suggest Ethanol can also modify the polarity of the supercritical fluid (SCF),
the need for further research on DES safety and biomedical applications allowing for the extraction of a broader range of compounds. Overall,
[118]. SFE, such as sCO2 extraction with co-solvents such as ethanol offers a
Overall, variations in HBDs influence the acidity, hydrogen bonding clean, efficient, and selective method for extracting various compounds
capability, and polarity of the DES, ultimately affecting its efficiency in from natural sources, especially CBD extraction due to its strong solu­
extracting bioactive compounds from Cannabis, hence DES not only bility [124].
improves the solubility and recovery of CBD but also aligns with sus­ Nevertheless, sCO2 extraction offers distinct benefits over conven­
tainable practices by minimizing environmental impact. This innovative tional methods in terms of efficiency, purity, and environmental impact.
approach highlights the potential of DES in developing eco-friendly and A recent study highlights the green extraction and purification processes
efficient extraction methods for high-purity CBD. involved in sCO2 extraction, emphasizes its ability to produce high-
quality CBD extracts with minimal solvent residues. The extraction
6. sCO2 for CBD extraction yield reaches a plateau at around 14 %. This indicates that the yield
obtained with sCO2 is lower compared to traditional methanolic
The sCO2 extraction is highlighted as a possibly advantageous extraction, which is consistent with findings from previous literature
method for producing high quality CBD extracts from Cannabis plants [125]. However, sCO2 extraction is a more selective procedure than
with less or no environmentally harmful by-products suggesting being traditional solvent methods. While it may result in lower yields, it often
one of the “clean technologies”. Although many substances have been produces extracts of higher purity. The sCO2 selectively dissolves can­
studied as possible supercritical fluid extraction (SFE) solvents, sCO2 is nabinoids, terpenes, and other target compounds, leaving behind un­
by far the most utilized because of its high availability, easily accessible desirable components [22]. Occasionally 5 % v/v ethanol is added to
supercritical states at 31.0 ◦ C and 73.8 bar, and "generally recognized as CO2 to enhance Cannabis extraction; nevertheless, it has been shown
safe" designation making it an efficient solvent for extracting CBD from that the use of CO2 alone results in extracts with higher CBD purity [25].
plant material [67]. The sCO2 extraction can be performed using This method allows for precise control over extraction parameters,
different setups, each with its unique characteristics that can influence resulting in extracts for the recovery of 75 % w/w of the total fat from
CBD extraction efficiency. The setup designed for sCO2 extraction in­ hemp oil, indicating that CO2 has a significant affinity for lipophilic
cludes a CO2 cylinder connected to a high-pressure pump, an extraction compounds with consistent quality and potency; making it suitable for
vessel, a separator, and a collection vessel. Furthermore, it was discov­ use in various applications, including food products [126].
ered that increasing the extract’s yields through repeated washings with While both conventional and SCF extraction methods can yield CBD
new sCO2 [36]. It is essential to control the parameters including pres­ extracts, the latter is favored for its higher purity, lower environmental
sure, temperature, and flow rate of sCO2 to optimize the extraction impact, and potential for producing premium-quality CBD products.

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S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

Additionally, sCO2 extraction offers scalability and can be easily tailored the hemp seeds. An experimental setup involves a CO2 pump connected
to meet specific extraction requirements, making it a preferred choice to a stainless-steel extraction vessel, equipped with a coiled cooling
for industrial-scale CBD extraction. A study focused on isolating the system to maintain the desired temperature, sCO2 is circulated within
bioactive compounds, mainly the CBD from the aerial parts of industrial the extraction vessel under controlled pressure and temperature condi­
hemp assortment Helena, demonstrated the highest extraction yield of tions to pursue the above objective Further, the recommended setup for
72 to 163 mg/g DW with the use of sCO2 extraction, 65 mg/g DW with CBD extraction would involve moderate pressure (around 3000 to 4000
Soxhlet extraction and lowest levels ranging from 0.004 to 0.018 mg/mL psi) and temperature (around 40 to 60 ◦ C) to balance extraction effi­
with the subcritical water extraction [81]. After a comparative analysis ciency and extract quality. A moderate flow rate that ensures sufficient
of all the applied extraction procedures, the most valuable method for contact time without causing channeling or bypassing is also recom­
isolating hemp’s bioactive compounds was determined to be sCO2 fol­ mended. The setup should include an extraction vessel intended to
lowed by conventional extraction. When combined, these two methods facilitate uniform distribution of sCO2 and maximize contact with the
produced acceptable results for the extraction of polar molecules like plant material. In conclusion, the choice of sCO2 extraction setup
polyphenols and low-polar molecules like terpenes and cannabinoids. significantly influences CBD extraction efficiency and extract quality
Specifically, sCO2 extraction resulted in the highest CBD content in the [36].
extract, along with a variety of other valuable hemp sesquiterpenes. These settings are aimed at achieving a balance between extraction
Additionally, the residue left after sCO2 extraction yielded extracts rich productivity and the quality of the extract, ensuring high yields of CBD
in hemp phenolic bioactives. Both sCO2 extraction and conventional while minimizing degradation or contamination. The sCO2 processing
extraction are widely used on an industrial scale, which makes this might have displayed technological and physicochemical traits that are
combined process highly suitable for commercial application in utilizing comparable to raw materials that have not been processed. Conse­
a cultivated variety of hemp [81]. quently, the non-thermal processing of Cannabis biomass offers several
The industrial hemp waste presents a significant environmental prospects for the commercialization of hemp, with a particular emphasis
challenge, and there’s an increasing need to reduce waste and utilize it on its biorefinery, which can concurrently create food-grade bioproducts
efficiently. With the growing interest in sustainability and environ­ and CBD. In the manufacturing process, thermal treatments play a
mental conservation, finding ways to minimize waste and utilize crucial role in maintaining food and beverage safety as well as
byproducts is crucial. Hemp waste contains valuable compounds, increasing their shelf life [131]. One such example includes the hemp
including CBD and waxes, making it a valuable resource that shouldn’t seed flour that was added to rice-based yogurt to create a new beverage
be overlooked. The two main components of hemp stems are the woody with the right nutrition, functionality, and taste. Adding hemp seed flour
core (65 %), also known as shiv, which has a higher lignin concentration aided in the fermentation process by certain lactic acid bacteria,
(21–24 %) and lower quantities of cellulose (40–48 %). The bast fibers lowering the anticipated glycemic index, and contributing to the ex­
(35 %) have a high cellulose content (57–77 %) and low lignin content pected high protein, fiber, and mineral contents of the yogurt-like
(5–8 %) [127]. High-quality hemp fibers have long been recognized for product [132]; other examples include plant-based alternative milk
their applications in a variety of industries, including the production of [133], an alternative to meat made from hemp seed protein [134], and
paper, textiles, automobiles, and bio-building. It has also been utilized as hemp seed flour incorporated into wheat bread [135]. Hence, a viable
biofuel in some nations, including Sweden [128]. Extracting these non-thermal solution, high-pressure CO2-based manufacturing pro­
compounds from hemp waste not only reduces environmental pollution cesses can be integrated into biorefineries serving the food industry. This
but also allows to produce high-value products. approach preserves the bioactivity of sensitive compounds, which can be
Therefore, the use of hemp waste to extract bioactives including CBD degraded by heat in traditional extraction methods, thereby maintaining
and waxes using SCFs, particularly SCO2 is investigated [129]. The re­ therapeutic and nutritional properties. Additionally, it opens new op­
sults indicate that the highest oil yield (around 34.9 % w/w) is obtained portunities in the food industry for creating plant-based ingredients and
at a pressure of 600 bar, a temperature of 40 ◦ C, and a CO2 flow rate of functional additives, catering to the rising consumer demand for
20 g/min. These conditions also lead to the highest content of unsatu­ high-quality, clean-label products. This non-thermal processing method
rated fatty acids, particularly linoleic acid (around 54.4 % w/w) and provides a competitive market advantage, aligning with regulatory and
α-linolenic acid (around 16.3 % w/w), in the extracted oil. Furthermore, consumer preferences for natural and sustainable products [131].
the study finds that increasing the pressure from 400 to 600 bar leads to Moreover, SFE’s can be fully automated that is a key notable
a significant increase in oil yield, from approximately 24.8 to 34.9 % advantage for enhancing efficiency, reproducibility, and process control
w/w. However, further increasing the pressure to 800 bar does not result [136]. Automation in SFE allows for precise regulation of temperature,
in a substantial increase in yield. Similarly, increasing the temperature pressure, and flow rates, ensuring optimal extraction conditions while
from 30 to 50 ◦ C leads to an increase in oil yield, from around 23.7 to minimizing human intervention [137]. This not only improves extrac­
33.8 % w/w. However, a further increase in temperature to 60 ◦ C results tion yield and selectivity but also reduces solvent consumption and
in a slight decrease in yield. Moreover, the CO2 flow rate also affects the operational costs. Furthermore, automated SFE systems integrate
oil yield, with higher flow rates generally resulting in higher yields. At a real-time monitoring and data collection, enabling researchers and in­
pressure of 600 bar and a temperature of 40 ◦ C, increasing the flow rate dustries to maintain high standards in pharmaceutical, cosmetic, and
from 10 to 20 g/min leads to an increase in oil yield from approximately food applications [138].
27 to 35 % w/w. Overall, the study demonstrates that sCO2 extraction is However, further research is needed to optimize and refine the sCO2
an effective method for obtaining hemp seed oil, with optimal condi­ extraction method. Further investigations are required to investigate (1)
tions yielding a high oil content and a favorable fatty acid composition. exploring different plant materials and cannabinoids that influence
These findings contribute to the development of efficient extraction extraction efficiency, (2) optimizing extraction parameters to meet
processes for hemp seed oil, with potential applications in the food, precise application requirements and achieve preferred product fea­
cosmetic, and pharmaceutical industries [129]. tures, (3) investigating the scalability and economic viability of sCO2
The use of SCF in CBD extraction is effective as SCF can only target extraction on an industrial scale, and (4) exploring innovative designs
the required material from the sample matrix because of its adjustable for extraction vessels and packing materials to enhance extraction effi­
nature [130]. However, the design of the vessel is also an important ciency. Hence sCO2 extraction is a key technology for producing high-
factor in SCF extraction. The vessel should be designed to accommodate quality CBD extracts with diverse applications in the pharmaceutical,
the hemp seeds evenly and provide optimal flow of sCO2 throughout the nutraceutical, food, and cosmetic industries.
material which maximizes contact with the plant material avoiding
channeling or bypassing to facilitate the uniform extraction of oil from

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S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

7. Pressurized liquid extraction of CBD values for PLE using ethanol include a pressure range of 1500–2000 psi,
a temperature range of 50–60 ◦ C, an extraction time of 30–60 min, and
Pressurized liquid extraction (PLE) is a modern extraction technique an ethanol concentration of 70–90 %. These conditions optimize CBD
that utilizes solvents under high pressure to extract compounds from yield while ensuring efficient extraction [151]. Overall, using ethanol
solid samples. Pressurized fluid extraction (PFE), pressurized solvent for pressurized liquid extraction is preferred over water due to its higher
extraction (PSE), enhanced solvent extraction (ESE), and accelerated solubility and versatility, leading to higher CBD yields and better
solvent extraction (ASE) are some of the terms used to refer to PLE extraction efficiency.
[139]. PLE is distinguished by its efficiency and ease of use, making use Additionally, another experiment compares conventional macera­
of high temperatures and moderate to high pressures rising to 200 bar to tion (CM) with rapid solid-liquid dynamic extraction (RSLDE) for
20 MPa [140]. Because it enables quick extraction and lower solvent extracting hemp inflorescence extracts using ethanol. The study exam­
use, PLE is a desirable substitute for bioactive extraction [141]. This ined the kinetics of the extraction process to determine the optimal
approach is unique in that it can be easily automated, which lowers costs conditions for ethanol-based extraction. Pressure and temperature play
and has a positive environmental impact due to the low solvent usage significant roles in determining the solubility of CBD in ethanol. Higher
[142].By using elevated pressure, PLE can increase the solubility of pressure and temperature generally increase the solubility of cannabi­
target compounds, leading to higher extraction efficiency and shorter noids, leading to higher extraction yields. Extraction time influences the
extraction times compared to traditional methods. The water being the contact time between the solvent and the hemp material, affecting the
primary solvent, additional terminology like high-temperature water extraction efficiency. Additionally, the concentration of ethanol used as
extraction, superheated water extraction, hot liquid water extraction, the solvent affects the extraction yield, with higher ethanol concentra­
pressurized hot water extraction, and hot water extraction are tions typically resulting in greater yields because of the cannabinoid’s
commonly employed [143]. A study on supercritical water extraction enhanced solubility. Comparing water and ethanol as solvents for
(SWE) suggests that SWE is effective in extracting a wide range of pressurized liquid extraction, ethanol generally offers higher CBD yields
bioactive compounds from hemp, including cannabinoids like CBD [81, [152]. These outcomes highlight the promise of this method for the
144]. To extract the solid sample, it must be inserted into a pressure extraction of cannabinoids, particularly cannabidiol, in addition to
vessel or extraction cell, water must be added, and the system must be providing further prospects for the economic viability of hemp plant
heated to the required temperature below the critical point of water leftovers and other components [153].
(usually between 100 and 374 ◦ C). Water is an effective solvent for
removing organic molecules from the sample matrix because of its 8. Microwave-assisted extraction of CBD
ability to modify its characteristics under subcritical circumstances. The
extract can be collected for additional examination or purification after Microwave Assisted Extraction (MAE) is an emerging method for
extraction. Additionally, PLE allows for the use of a wide range of sol­ isolating bioactive compounds. MAE utilizes microwave radiation to
vents, not limited to water, which enhances its versatility for extracting heat and evaporate water, thereby disrupting cell structures and aiding
various compounds, including CBD, from botanical materials. A study the release of bioactives [3]. Compared to conventional methods such as
investigating the efficiency of PLE in extracting CBD, compared to other HRE or Soxhlet Extraction (SE), SFE, and UAE, MAE offers advantages
methods indicates that PLE is a promising method for extracting CBD such as higher yields, lower energy and solvent usage, and shorter
from Cannabis biomass, providing high extraction yields. Several vari­ extraction times, with less thermal degradation of sensitive compounds
ables influence pressurized water extraction of CBD, including pressure, [154]. The above advantages of MAE are well demonstrated in a
temperature, extraction time, and water-to-sample ratio. Higher pres­ quantitative study by Chang and colleagues, MAE demonstrated supe­
sure and temperature generally enhance the solubility of CBD in water, rior efficacy in CBD extraction, yielding approximately 2.56 µg/g DW
leading to higher extraction yields. Further, PLE is also highly efficient with optimized conditions with methanol as the extraction solvent, a
in decarboxylation of cannabidiolic acid to CBD [145]. microwave power of 375 W, a temperature of 109 ◦ C, and an extraction
Pressurized water extraction methods which include subcritical time of 30 min. as the MAE has the least solvent consumption and
water extraction (SWE), and pressurized hot water extraction (PHWE) shortest operation time [79]. Moreover, the morphological observations
offer efficient and selective extraction of CBD and other cannabinoids also revealed significant cell ruptures in the hemp nut microstructure
from Cannabis biomass. These methods provide advantages such as post-MAE; contributing to highly effective and practical methods for
environmentally friendly operation, high extraction yields, and selec­ industrial applications. The success of MAE is highly dependent on
tivity for target compounds. Pressurized hot water extraction (PHWE) is optimizing operative conditions such as solvent-to-feed ratio, extraction
thought to be a quick, effective, and environmentally friendly method of temperature, time, and microwave irradiation power [79]. The lower or
extracting polar to least polar chemicals from plant materials [146]. The moderate power with a longer exposure time is chosen to prevent the
use of Cannabis sativa seeds for cannabinoid extraction via the PHWE "bumping" phenomenon, which can occur when using a high-power
process has proven to be effective [147]. A study explores the effects of output. Another factor was the temperature when increased, the
various extraction parameters, including pressure, temperature, and desorption of analytes from the sample into the matrix also increased.
extraction time, on the extraction of cannabinoids from Cannabis seeds. Additionally, higher temperatures improved the lowering of solvent
Results show that PHWE can selectively extract cannabinoid compounds viscosity and surface tension to improve matrix penetration and sample
from Cannabis seeds, with optimal conditions achieving high extraction viscosity [155]. Among various solvents tested, methanol emerged as
yields [148]. Despite the advantages of using PLE in bioactive com­ the most effective due to its strong solvating power and efficient mi­
pound extraction, the extraction yield of sCO2 can reach levels that are crowave absorption, while water was the least effective because of poor
even tenfold greater than those produced with PLE [149]. cannabinoid solubility and high electric constant leading to sample
Apart from water, ethanol can also be used as a solvent for PLE to burning. Acetonitrile also showed high efficiency, followed by 95 %
extract cannabinoids from hemp or hemp processing residues. A study ethanol, isopropanol, and ethyl acetate, the latter being the least effec­
which evaluates various influencing variables indicates that extraction tive among organic solvents due to weaker solvation and lower micro­
yields of 19.8 mg of CBD/g DW, and a 99.3 % extraction efficiency were wave absorption capacity. Another factor interconnected with MAE is
obtained by utilizing modest pressures, 100 ◦ C, and 60 min of time. the extraction time, which extends from 10 to 30 min and improved
Ethanol has better solubility for cannabinoids compared to water, yields due to increased solvent contact time, enhancing cannabinoid
resulting in higher extraction efficiency [29]. Additionally, ethanol is a diffusion and solubility [155]. However, durations beyond 30 min
more versatile solvent that can dissolve a wider range of compounds reduced yields, likely due to cannabinoid degradation, re-adsorption, or
from hemp, including cannabinoids and terpenes [150]. Recommended volatile compound loss. Prolonged high-temperature exposure resulted

12
S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

in thermal degradation, negatively impacting yields [79]. effectiveness, which led to greater CBD yields for use in topical appli­
Moreover, it is understandable that the recommended optimal con­ cations. Further research should consider additional variables, including
ditions for CBD extraction were methanol as the extraction solvent, a ultrasound power, intensity, time, and the solid-to-solvent ratio, to
microwave power of 375 W, a temperature of 109 ◦ C, and an extraction enhance the extraction process efficiency and consistency. This opti­
time of 30 min. However, the risk associated with the toxicity of mization is crucial for developing a reliable, scalable method for CBD
methanol residues of CBD extracts makes the need to identify safer extraction using UAE.
solvents to be used in MAE. By addressing various critical factors, MAE
can be further refined to achieve higher yields, improved cannabinoid
integrity, and broader applicability in commercial CBD extraction pro­
cesses. Key areas for improvement include exploring alternative solvents
like ethanol or water-based systems to enhance efficiency and reduce
Table 4
toxicity; studying the thermal stability of cannabinoids to optimize Advantages and disadvantages of CBD extraction techniques.
conditions and minimize degradation; and investigating the effects of
Method Advantages Disadvantages References
varying microwave power on different plant matrices to ensure uniform
heating and efficient extraction [156]. Additionally, optimizing extrac­ Percolation • efficient • low efficiency [163,164]
solvent • high solvent
tion times for different hemp varieties, evaluating the synergy of MAE
utilization consumption
with other techniques such as sCO2 extraction, and assessing the feasi­ • high yield • selective extraction
bility of scaling up for industrial applications is essential. Finally, • mild • degradation risk
analyzing the environmental footprint of MAE, including energy con­ processing • filtration issues
sumption and solvent waste, can lead to more sustainable practices, conditions • post-processing
requirements
making MAE a cutting-edge method for efficient and eco-friendly “green
Soxhlet • high efficiency • risking residual solvents [165–168]
method” for cannabinoid extraction [157]. Extraction • simplicity and terpene loss
• ease of • extended extraction
9. Ultrasonic-assisted extraction of CBD optimization times
• high extraction • increasing operational
yields costs
UAE is an emerging process for isolating bioactive ingredients from • environmental impact
plant materials. The method uses ultrasonic waves that assist with the Heat Reflux • higher • energy-intensive [169,170]
extraction process, which allows for larger yields and faster extraction Extraction extraction • less sustainable for
times than traditional methods. The advantages of UAE include the efficiencies large-scale operations
• contamination in the
preservation of thermolabile chemicals decreased solvent usage, and CBD extracts
enhanced extraction efficiency [158]. Ethanol, a prominent and “green” • high operational costs
solvent in the Cannabis industry, is used for extraction due to its Maceration • simple method • time-consuming [169]
renewability, biodegradability, low toxicity, reduced greenhouse gas • solvent intensive
Ionic Solvents • wide solubility • high cost of synthesis [171–173]
emissions, water miscibility, and regulatory approvals. Compared to
range • toxicity and
conventional methods, ultrasound-, and microwave-assisted extraction • non- environmental concerns
are considered to be improved extraction procedures because of several flammability
benefits, including lesser removal times, lesser solvent volumes, and • tunable nature
greater extract yields [159]. A study investigated the extraction of • reduce
chemical waste
cannabinoids from C. sativa using UAE; amplified the produce and • higher
effectiveness of cannabinoid extraction, and optimized many variables, extraction
including solvent type (ethanol, methanol, and hexane), extraction time yield
(20–40 min), and ultrasonic power (20–40 kHz) to maximize the yield in Deep eutectic • low vapor • high viscosity [174]
solvents pressure • limited solubility for
which it was discovered that longer extraction durations and higher
• low cost non-polar compounds
ultrasound power led to enhanced extraction efficiency by 20–30 % Supercritical • higher • requires high pressure [175–178]
compared to traditional methods. Traditional extraction methods yiel­ carbon dioxide extraction • releases of carbon
ded 50–60 % cannabinoids, while UAE achieved 70–85 % yields and extraction efficiency dioxide has an
90–95 % purity, underscoring its efficacy and superior quality. It was • high diffusivity environmental impact
• higher purity • expensive,
also observed that the UAE was more active at extracting cannabinoids of extracts decarboxylation needs
when associated with other extraction techniques [158]. In CBD to be done and large
extraction, the UAE might be more selective than maceration. The pre­ capital costs
cise extraction of particular bioactive is made possible by the carefully • thermal degradation of
volatile terpenes
calibrated use of ultrasonic waves, which may also lessen the extraction
• reduction in overall
of undesirable components. UAE often requires specific equipment, such efficiency
as an ultrasonic bath or probe, which may come with greater initial Microwave- • higher • caution of using proper [179,180]
expenditures. On the other hand, these expenses might eventually be assisted extraction conditions to avoid
offset by the UAE’s improved yields and efficiency [160,161]. extraction control thermal degradation
• higher product
In another recent study, researchers aimed to develop a more effi­ yield
cient extraction and quantification of CBD for use in topical products • shorter
through UAE integrated with gas chromatography-mass spectrometry extraction
(GC–MS). The extraction of cannabinoids using MAE and UAE at a period
• lower energy
sample-to-solvent ratio of 1:15 and 1:14.4, respectively, and for 30 min
usage
at 60 ◦ C. The highest desirability for MAE and UAE was 0.75 % and 0.83 Ultrasound- • enhances • scaling the process [181,182]
%, respectively. Compared to MAE, UAE enhanced the amount of assisted solvent
extracted crude oil, cannabinoid concentration, and total terpene by extraction penetration
14.4 %, 13.2–39.2 %, and 14.7 %, respectively. Hence, understanding • extraction
efficiency
UAE greatly shortened the extraction process and improved extraction

13
S. Selvaraj et al. Green Analytical Chemistry 13 (2025) 100270

10. Current challenges and future perspectives Acknowledgement

The current pitfalls and challenges in CBD extraction (Table 4) are The authors would like to thank the University of Cambridge
poor extraction efficiency, low purity, difficulties in scalability, high ReachSci Society for their support. For the purpose of open access, au­
initial costs of equipment, and environmental impact. The major need thors have applied a ‘Creative Commons Attribution (CC BY) license to
for the Cannabis industry is to develop a CBD extraction process with any Author Accepted Manuscript version arising’.
high efficiency with the least amount of green solvent use in a shorter
manufacturing time. Conventional extraction methods such as solvent Data availability
extraction or steam distillation often require large amounts of solvents,
energy, and time, leading to higher production costs and potential No data was used for the research described in the article.
environmental concerns [162]. Another major need of the industry is
scalable CBD extraction processes to meet the rising global demand for References
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