J.

of Supercritical Fluids 161 (2020) 104850

Contents lists available at ScienceDirect

The Journal of Supercritical Fluids

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

Extraction of cannabinoids from hemp (Cannabis sativa L.) using high

pressure solvents: An overview of different processing options
Teresa Moreno a,∗ , Fernando Montanes a , Stephen J. Tallon a , Tina Fenton a , Jerry W. King b
a
Callaghan Innovation, 69 Gracefield Road, Lower Hutt, 5010, New Zealand
b
CFS, 1965 E Spinel Link#7, Fayetteville, AR 72701, USA

h i g h l i g h t s g r a p h i c a l a b s t r a c t

• Efficient cannabinoid extraction from

raw and decarboxylated hemp with
CO2 and propane.
• High CBD extracts (up to 449 mg/g)
obtained from hemp by means of
supercritical CO2 .
• Addition of 5 % ethanol co-solvent
enhances the extraction of cannabi-
noid acid forms.
• Propane more effective than CO2 for
extraction of cannabinoid acid forms.
• Apparent solubility at 300 bar was 11
g/kg CO2 for raw hemp (dry basis).

a r t i c l e i n f o a b s t r a c t

Article history: Hemp varieties of Cannabis Sativa L. contain low levels of 9 -tetrahydrocannabinol (THC) and can be
Received 17 October 2019 used to produce therapeutic extracts rich in cannabidiol (CBD). In this work, extracts containing up
Received in revised form 25 March 2020 to 449 mg/g CBD were obtained from New Zealand industrial hemp varieties by extraction of flower
Accepted 26 March 2020
buds with supercritical CO2 . The composition of the extracts and the influence of different processing
Available online 2 April 2020
parameters (extraction pressure up to 1300 bar, use of ethanol co-solvent, decarboxylation of feed) were
determined. The apparent solubility of the extract in CO2 at different pressures was measured. Extractions
Keywords:
using near-critical propane and dimethyl-ether were also performed. Total extraction yields reached 12.0
Hemp
CBD
wt% with CO2 and 8.2 wt% with propane, whereas total cannabinoid yield ranged from 51 to 100 % with
Decarboxylation CO2 and from 74 to 99 wt% with propane. Addition of 5 % ethanol co-solvent enhances the extraction of
Propane extraction cannabinoid acid forms, as does an increase in extraction pressure.
Dimethyl-ether extraction © 2020 Elsevier B.V. All rights reserved.
CO2 extraction

1. Introduction June 2018. CBD is the dominant cannabinoid found in industrial

The potential therapeutic uses of cannabidiol (CBD), one of the
cannabinoids present in Cannabis sativa L., have recently gained
considerable attraction, particularly after approval of the anti-
convulsant drug Epidiolex containing 98 % CBD by the FDA in
∗ Corresponding author.
E-mail address: teresa.moreno@callaghaninnovation.govt.nz (T. Moreno).
hemp, a term that is used for cannabis varieties that have been
traditionally used for fibre and seed oil production and that con-
tain low concentrations of the main psychoactive cannabinoid
(–)-trans-9 -tetrahydrocannabinol (9 -THC or THC). A number
of isomers of THC such as (+)-cis-9 -THC and 8 -THC can be
found in the cannabis plant, but they are generally present in
minuscule amounts and are not considered in this work. In con-
trast to THC, CBD has no psychoactive effects but it does exhibit
anti-inflammatory, analgesic, antioxidant, antimicrobial, neuro-

https://doi.org/10.1016/j.supflu.2020.104850
0896-8446/© 2020 Elsevier B.V. All rights reserved.
2 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850
Fig. 1. Simplified cannabinoid synthetic pathway: decarboxylation, biosynthesis,
and oxidation reactions.
protective and anticonvulsant properties [1,2]. In addition to
CBD and THC, other cannabinoids commonly found in hemp are
cannabigerol (CBG), a relatively unknown non-psychoactive phy-
tocannabinoid with analgesic, anti-proliferative and antibacterial
activity [3], and cannabinol (CBN), a minor constituent in fresh
plant material that results of the oxidation of THC [2] and that is
normally considered a chemical marker for poor or lengthy storage
conditions [4,5].
These compounds are produced in the stems, leaves and
flowers of growing plants in their carboxylated form, i.e. 9 -
tetrahydrocannabinol acid (THCA), cannabidiol acid (CBDA) and
cannabigerol acid (CBGA), as indicated in the simplified synthetic
pathway shown in Fig. 1 [6] (note that this figure only shows
the main compounds that are relevant to this work). Cannabinoid
acids are thought to have certain interesting properties, particu-
larly CBDA [5]; however, they have not been as extensively studied
as their neutral counterparts and are generally considered as non-
active cannabinoid forms that require a decarboxylation process
[7] to be converted into the more desirable and stable neutral ana-
logues. These neutral forms of the cannabinoids are believed to offer
better bioactivity since the molecular structure of the acid forms
(i.e. the presence of the carboxylic acid group) limits access to the
central nervous system through the blood-brain barrier [3,8]. Neu-
tral forms are also expected to have higher solubility in supercritical
CO2 given their lower polarity.
Decarboxylation is a slow process that occurs naturally in the
plant over time, but it can be accelerated by exposure to heat, light
and oxygen [7,9–11]. One of the main drawbacks of the decarboxy-
lation process is the loss of terpenes or terpenoids, i.e. volatile
components of the cannabis plant having repeating units of the
isoprene structure and that are responsible for the specific aroma
and flavour profile associated with the different strains. These
compounds are not unique to cannabis; however, their synergis-
tic interaction with cannabinoids, often called the entourage effect,
enhances the effectiveness of the cannabinoids found in hemp and
is a promising new research field [12].
The non-polar nature of neutral cannabinoids makes them
amenable to CO2 extraction [13], hence CO2 has been used exten-
sively by the cannabis industry over the last twenty years [14,15],
and is now a well-established process with a number of dedi-
cated equipment suppliers in the industry [16]. However, despite
the popularity and widespread acceptance of supercritical CO2
extraction among manufacturers and aficionados alike, scientific
publications on the subject are still scarce. Due to governmen-
tal regulations, some of the published extraction studies were
performed using either threshing residues collected after harvest-
ing and/or cleaning of industrial hemp seeds [17] or hemp waste
obtained from the hemp fibre industry [18]. These materials, how-
ever, have very low cannabinoid concentrations and are not good
candidates for medicinal cannabis extraction.
Early studies with cannabis flowers include a study of the effect
of particle size on supercritical CO2 extraction of THC [19]. Perrotin-
Brunel et al. performed the first comprehensive study on the topic,
analysing the solubility of different cannabinoids in supercritical
CO2 [20–23]. Omar et al. studied the effect of ethanol co-solvent
(0–40 %), pressure (100−250 bar), temperature (35−55 ◦ C) and flow
rate (1−2 mL/min) when extracting 100 mg of non-decarboxylated
cannabis buds using a 1 mL extraction vessel; they concluded that
only the ethanol content and its quadratic effect were significant
in the extraction of neutral cannabinoids; acid forms however
were not quantified [24]. Rovetto and Aieta analysed the effect
of pressure (170−340 bar) and ethanol co-solvent (0–10 %) in the
extraction of 500 g of different samples of non-decarboxylated, high
THC/THCA cannabis leaves and buds using a 5 L extraction vessel
with three separator stages [25]. They obtained apparent solubili-
ties at three different pressures and studied the cannabinoid profile
in the different extract fractions. The use of ethanol was found to
improve the overall extraction rate, but the results are hard to inter-
pret since the ethanol extracts were not evaporated nor analysed
for cannabinoid concentration. Brighenti et al. compared sev-
eral techniques, such as solvent maceration, ultrasound-assisted,
microwave-assisted and supercritical CO2 extraction (at 100 bar,
35 ◦ C and with the addition of 20 % ethanol co-solvent) for the
extraction of non-decarboxylated hemp buds from different cul-
tivars [26]. Ethanol extraction at room temperature was found to
be superior to other extraction techniques in terms of giving the
highest extraction yield of non-psychoactive cannabinoids. More
recently, Ribeiro Grijó et al. compared two different strategies in
the extraction of neutral cannabinoids: (1) decarboxylation of the
buds followed by supercritical CO2 extraction (without co-solvent),
and (2) addition of 6 % ethanol co-solvent for extraction of non-
decarboxylated cannabis buds [27]. Although the overall extraction
yield was increased with the addition of ethanol, the highest con-
tent of THC and CBD were obtained using the CO2 -based method
on decarboxylated flower. Acid forms of the cannabinoids were not
quantified in this study, but higher yield levels were expected in
the second strategy extracts due in part to the use of ethanol as
co-solvent.
In this work, both decarboxylated and non-decarboxylated
hemp was extracted using supercritical CO2 at different pressures,
with and without the use of ethanol co-solvent. Liquefied propane
and dimethyl-ether (DME) extractions were also carried out on the
same hemp material for comparison. Light hydrocarbon extrac-
tion has traditionally been carried out in the recreational cannabis
industry to produce the well-known butane hash oil (BHO) extract.
Light hydrocarbon extraction is traditionally performed with these
liquid state solvents at very low temperatures (−20 to −30 ◦ C) and
very short extraction times, which preserves the delicate terpene
profile associated with the specific hemp or cannabis cultivar in the
final product [28,29]. However, to the best of our knowledge there
are no published works on light hydrocarbon extraction of cannabis.
Although terpenes are outside the scope of this work, the extrac-
tion data obtained using propane can provide valuable information
in this field.
2. Experimental
2.1. Materials
Hemp plant material, predominantly flower buds but containing
some additional hemp leaf and trimmings, of two different culti-
vars was supplied by three different New Zealand hemp growers.
The plant material was milled using a PM-3 pin mill from Mill Pow-
der Tech Solutions (Taiwan) with a 2 mm mesh attached and then
 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850
stored in a sealed bag at room temperature before its use. Since
the composition of the plant material can change during storage,
it was characterized before each experiment. THC, THCA, deuter-
ated THC, and CBD standards were obtained from Cerilliant (United
States). CBDA, CBG and CBN standards were obtained from Lipomed
(Switzerland). CBGA standard was obtained from SPEX (United
States).
CO2 (>99.8 % purity) was purchased from BOC (New Zealand).
Ethanol (>99.7 % purity) was purchased from Pacific Sphere (New
Zealand). Dimethyl-ether and unodorized propane (89.9 % purity)
were purchased from Aerosol Supplies (Australia).
2.2. Decarboxylation
In some experiments, the milled plant material was decarboxy-
lated immediately prior to extraction by placing it on a tray in a
convection oven at 150 ◦ C for specific periods of time.
2.3. Supercritical CO2 extraction
Supercritical CO2 extractions were carried out at either 0.5, 1, 2
or 10 L scale. In all cases, the milled material was first loaded into
a basket with porous sintered steel end plates, and the basket was
then loaded into the extraction vessel. The detailed procedure for
the individual extractions is given below.
2.3.1. 0.5 L scale extractions: ultra high pressure extractions
The 0.5 L scale extraction plant consists of two Teledyne ISCO
syringe pumps (United States) operating in tandem to provide
a continuous supply of high pressure CO2 , and a temperature-
controlled 0.505 L vessel (High Pressure Equipment Company,
United States) where the sample is placed in a basket (working
volume 0.37 L). An Emerson (United States) MicroMotion Coriolis
flow meter was used to measure CO2 flow rate. The CO2 containing
the dissolved extract after passing through the bed was depressur-
ized through a micro metering valve and passed into a separation
vessel where the extract was accumulated. Gas phase CO2 exiting
from the separator was condensed and recirculated. Extract accu-
mulating in the separation vessel was recovered through a valve
periodically during the run to determine the progress of the extrac-
tion. Temperature in the extraction and separation vessel was set
at 50 ◦ C by means of heating jackets.
2.3.2. 1 L and 2 L scale: CO2 and CO2 +ethanol extractions and
apparent solubility measurements
1 L extraction trials were carried out by initially filling and
then circulating CO2 using a Newport Scientific Ltd (United States)
diaphragm pump. An Emerson (United States) MicroMotion Cori-
olis flow meter was used to measure CO2 flow rate. Temperature
in the extraction vessel was set at 50 ◦ C by means of a heating
jacket, whereas the separator was submerged in a controlled tem-
perature water bath. After passing through the bed, CO2 containing
the dissolved extract was depressurized through a Badger Meter
(United States) Research Control valve and passed into a separa-
tion vessel where the extract was accumulated and gas phase CO2
from the separator was condensed and recirculated. Extract accu-
mulating in the separation vessel was recovered through a valve
periodically during the run to determine the progress of the extrac-
tion. When used, ethanol co-solvent was introduced by a Williams
(United States) V-Series metering piston pump and its flow rate was
determined by mass loss of the supply tank via gravimetry. Upon
completion of the extraction, the extractor was depressurized and
the residual marc was allowed to degas before being unloaded.
Apparent solubility measurements were performed in the same
plant described above except for use of a 2 L volume extraction ves-
sel. The extraction pressure was sequentially increased (100, 200
3
and 300 bar) and a constant temperature of 40 ◦ C was maintained
during the extraction. Each extraction step was run until a constant
extraction rate was observed and enough data points had been col-
lected to allow for calculation of apparent solubility, at which point
the pressure was increased. The apparent solubility, i.e. g extract
per kg of CO2 , was then calculated as the slope of the extraction
curve in the stationary period, i.e. yield (g extract per kg of feed) vs
CO2 usage (kg CO2 per kg of feed). The starting feed material had a
moisture content of 10.3 %, measured at 120 ◦ C in a Computrac Max
5000 XL moisture analyser (AMETEK Arizona Instrument, United
States). Some of this moisture was co-extracted and the extracts
were dried under vacuum using a Büchi (Germany) rotary evapo-
rator to determine their moisture content. The apparent solubilities
were then also calculated on a dry basis, i.e. g extract solids per kg
of CO2 .
2.3.3. 10 L scale: pilot plant extractions
10 L extraction trials were carried out in a plant using a Haskel
(United States) DSF-72 air driven pump to circulate CO2 . A Rheonik
(Germany) Coriolis flow meter was used to measure CO2 flow rate.
Two separation vessels (10 L) in series were used for fractionation
of the extract. Temperature in the extraction and separation ves-
sels was set at 50 ◦ C by means of heating jackets. After passing
through the bed, CO2 containing the dissolved extract was depres-
surized through a FlowServe Kämmer (United States) control valve
and passed into the first separation vessel where the first (least
volatile) extract fraction was accumulated. Following this, the CO2
phase was further depressurized through a second valve into the
second separator where the second (more volatile) extract frac-
tion was accumulated. Gas phase CO2 was then condensed and
recirculated. Extract accumulating in the separation vessels was
manually recovered through a valve periodically during the run to
determine the progress of the extraction. After extraction, the plant
was depressurized, and the residual marc was allowed to degas
overnight before being unloaded.
2.4. Pressurised propane and dimethyl-ether (DME) extraction
The feed material to be extracted was contained in a basket
and placed in a 2 L extraction vessel and either propane or DME
was then passed through the vessel in upflow direction using a
Haskel (United States) pump. An Emerson (United States) Micro-
Motion Coriolis flow meter was used to measure solvent flow rate.
Both the extraction and separator vessels were submerged in a con-
trolled temperature water bath held at 55 ◦ C. The extraction was
performed at 40 bar. After passing through the bed, the solvent
containing the dissolved extract was depressurized through a Bad-
ger Meter (United States) Research Control valve and passed into
a separation vessel where the extract was accumulated. Gas phase
solvent from the separator was condensed and recirculated. Extract
accumulating in the separation vessel was recovered through a
valve periodically during the run to determine the progress of
the extraction. After extraction, the plant was depressurized and
the residual marc was allowed to degas overnight before being
unloaded.
2.5. Cannabinoid analysis by LCMSMS
Duplicate samples (either plant material or extracted resin), of
about 0.5 g, were accurately weighed into hexane-rinsed silanised
glass test tube. Five millilitres of methanol (analytical grade from
Fisher Scientific) were added to the samples, which were then vor-
texed for 10 min and stored refrigerated overnight. The samples
were removed from refrigeration and allowed to come to room
temperature, then vortexed for 10 min and then centrifuged for
5 min. Each sample was further diluted with methanol, depending
4 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850

Table 1
Cannabinoid composition and moisture content of different feed materials used in this work (mg/g DB).

THC THCA CBD CBDA CBG CBGA CBN Moisture

Raw 0.74 1.62 3.62 35.9 0.21 0.78 0.01 16.1 %

Cultivar A
Decarboxylated 1.65 0.23 25.2 13.4 0.63 0.29 0.03 4.2 %
Raw 0.50 0.53 2.88 13.7 0.13 0.49 0.00 11.7 %
Cultivar B-1
Decarboxylated 1.07 0.00 15.8 0.54 0.47 0.02 0.05 2.7 %
Raw 0.20 0.00 4.40 0.56 0.14 0.02 0.01 10.3 %
Cultivar B-2
Decarboxylated 0.10 0.00 3.50 0.02 0.11 0.00 0.02 0.84 %

on type of sample (i.e. plant material or extracted resin), to ensure

all the major cannabinoids present in the extract fell within the
calibration curve.
Analysis was carried out in a Sciex (United States) 5500
Q-TrapTM quadrupole mass spectrometer operating in multiple
reaction monitoring (MRM) mode with an electrospray ion-
ization (ESI) source in positive ionization mode. A KinetexTM
Biphenyl (2.1 mm × 50 mm, 2.6 ␮m particle size) column with
SecurityGuardTM ULTRA Biphenyl guard holder-cartridge assembly
from Phenomenex (United States) was used. The column temper-
ature was maintained at 40 ◦ C. Chromatographic separation was
achieved using a multistep gradient consisting of mobile phase A
(0.1 % formic acid in water) and mobile phase B (0.1 % formic acid in
methanol). The gradient program was as follows: 0−0.5 min 30 % A,
0.5–7.5 min 30−22% A, 7.5−8 min 22−5% A, 8–9.4 min 5% A, 9.4–9.5
min 5–30 % A, 9.5−10 min 30 % A. Total analysis time was 10 min
Fig. 2. Cannabis extraction curves at different pressures:  100 bar, 䊉 200 bar, 䊏
with a flow rate of 0.5 mL/min. A calibration curve using certified
300 bar [empty symbols indicate decarboxylated feeds]. Results for each sequential
reference standards for THC, THCA, CBD, CBDA, CBG, CBGA and CBN pressure increase are calculated using an adjusted feed mass allowing for previously
was established, and deuterated THC was used as internal standard. extracted feed mass.

3. Results
3.1. Feed material: cultivars and decarboxylation
Three different feed materials were used throughout this work:
a sample of Cultivar A (undisclosed variety due to commercial
sensitivity) and two different samples of Cultivar B (Ferimon12);
their cannabinoid composition is shown in Table 1. There is a wide
variation in cannabinoid composition between the two cultivars,
with Cultivar A showing the highest total cannabinoid concentra-
tion. There are also clear differences between the two samples of
the same cultivar, Cultivar B. The cannabinoids in the raw (pre-
decarboxylation) samples are predominantly in the acid form; CBD
and CBDA are the dominant cannabinoids in all cases.
The total cannabinoid concentration in Cultivar A raw material
was 42.9 mg/gDB (i.e. mg per g on a dry basis); of which 8.4 % was
CBD, and 83.7 % CBDA. After decarboxylation at 150 ◦ C for 20 min, 63
% of the CBDA was converted to CBD, which then represented 60.8
% of total cannabinoids in the decarboxylated feed. Conversion of
THCA and CBGA into their neutral forms was 86 % and 63 %, respec-
tively. In both cases, the total CBD (CBD + CBDA) represents over 90
% of the total cannabinoids present in the hemp cultivar. The total
cannabinoid concentration remained relatively constant before and
after decarboxylation, indicating no major losses. The level of CBN
found was very low and in most cases below the lowest calibration
point of the analysis, which suggests that the material had been
freshly harvested. The decarboxylation conditions used were based
on information available online for recreational cannabis grow-
ers as well as existing data [7]. These results suggested that the
decarboxylation process was not complete and therefore the decar-
boxylation time was increased for the samples of cultivars B-1 and
B-2.
The Cultivar B-1 sample contained a total concentration of
cannabinoids of 18.2 mg/gDB , with CBD and CBDA representing 16
and 75 % of the total, respectively. Decarboxylation for this sample
was carried out at 150 ◦ C for 60 min. Conversion of THCA, CBDA
and CBGA was 100, 96 and 96 % respectively, with no loss of total
cannabinoids observed after decarboxylation.
The Cultivar B-2 sample contained a significantly lower level of
cannabinoids (5.3 mg/gDB ), comprised mostly of CBD and contain-
ing no detectable THCA. This sample was decarboxylated at 150
◦ C for 50 min, which led to a 96 and 100 % conversion of CBDA
and CBGA, respectively. A loss of 30 % of total cannabinoids was
observed in the decarboxylated material.
3.2. CO2 extraction: apparent solubility and extract composition
at different pressures
The apparent solubility of the cannabis extract in supercritical
CO2 was studied at 40 ◦ C and increasing pressures using both raw
and decarboxylated Cultivar B-2 plant material. By sequentially
increasing the pressure, the compositional changes occurring dur-
ing the previous steps might have an impact on the extraction at
the higher pressure end. To minimise this, the extraction in each
step was limited to low CO2 :feed ratios that allowed collection of
sufficient data points while keeping the remaining feed material
as representative as possible. It is therefore important to note that
the apparent solubility reported in this work is a measure of the
initial extraction rate, which could be indicative of the solubility
value under certain conditions.
Fig. 2 shows the extraction curves obtained in the constant
extraction period of each step, i.e. yield (g extract per kg of feed)
vs CO2 usage (kg CO2 per kg of feed). The curves are shown on
a dry basis for comparison purposes, since the raw material had
a high moisture content (10.3 %) compared to the decarboxylated
material (0.84 %). The influence of extraction pressure and therefore
CO2 density on the apparent solubility is shown in Fig. 3. Solubility
increases linearly with CO2 density for all sets of extraction data,
i.e. raw material on a dry and wet basis, as well as decarboxylated
material. The solubility data obtained by Rovetto and Aieta [25] is
also shown for comparison.
 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850 5

Table 2
Apparent solubilities obtained at 40 ◦ C and different pressures.

P (bar) CO2 density (kg/m3 )a Solubility (g extract/kg CO2 ) R2

100 628.6 1.3 0.997

Decarboxylated material
200 839.8 6.8 0.999
(dry basis)
300 909.9 9.9 0.998
100 628.6 2.2 0.996
Raw material (wet basis) 200 839.8 9.2 0.997
300 909.9 12.6 0.984
100 628.6 1.7 0.996
Raw material (dry basis) 200 839.8 8.6 0.997
300 909.9 11.0 0.984
170 705.0 2.4 0.988
Rovetto and Aieta [25] b 240 801.9 4.6 0.973
340 876.0 6.7 0.988
a
NIST Chemistry Webbook.
b
Data obtained at 55◦ C.

Table 3
Composition of different fractions obtained in the solubility measurements (mg/g). THCA was not detected in any of the samples.

THC CBD CBDA CBG CBGA CBN

Marc 0.02 0.3 0.43 0.02 0.02 0.001

Extract 1 (100 bar) 1.50 84 0.65 0.95 n/d 0.044
Raw
Extract 2 (200 bar) 1.20 40 1.06 0.88 0.01 0.041
Extract 3 (300 bar) 1.20 17 1.68 0.96 0.02 0.062
Marc 0.02 0.3 0.01 0.04 0.001 0.005
Extract 1 (100 bar) 1.20 95 0.03 0.8 n/d 0.075
Decarboxylated
Extract 2 (200 bar) 1.10 75 0.01 0.76 n/d 0.073
Extract 3 (300 bar) 1.40 36 0.01 1.11 n/d 0.110

decarboxylated marc (9.2 %). This indicates that extraction of

Fig. 3. Apparent solubility as a function of CO2 density for different samples: 䊉 raw
material, wet basis, 䊏 raw material, dry basis,  decarboxylated material,  Rovetto
and Aieta [25] (raw material, wet basis).
The extraction yields and the apparent solubilities obtained
with decarboxylated plant material were slightly lower than those
obtained with raw material for all the pressures tested (Table 2).
This is contradictory to an expected increase in solubility when
cannabinoids are decarboxylated; however, in this case the raw
material had a relatively low level of cannabinoids in the acid
form even before decarboxylation, and the majority of the dis-
solved compounds in the extract are non-cannabinoids, i.e. lipid
matter, waxes, etc. The differences in solubility may be related to
the co-solvent effect of the higher water content in the raw (non-
carboxylated) material improving the extraction of higher polarity
components from the matrix. The presence of extractable volatile
components such as terpenes in the non-decarboxylated material
could also contribute to a higher extraction solubility and yield.
Nonetheless, the composition of the extracts (Table 3) shows
that the cannabinoid concentration and therefore cannabinoid
recovery was significantly higher in the extracts obtained from
the decarboxylated material; and the proportion of non-extracted
cannabinoids was higher in the raw marc (12.9 %) than in the
the decarboxylated plant material was more selective towards
cannabinoids, gave a higher total cannabinoid recovery, and
extracted a smaller quantity of non-cannabinoid compounds. The
relative composition of the different fractions in Fig. 4 shows that
CBDA was the main cannabinoid left in the raw marc (54.3 % of
total cannabinoids). Acidic cannabinoids were mostly absent from
the decarboxylated feed, and the decarboxylated marc was com-
prised mostly of CBD (79.8 % of total cannabinoids) followed by CBG
(10.6 % of total cannabinoids). As expected, neither CBDA nor CBGA
were readily extracted by CO2 , particularly at the lower extraction
pressures. THC and CBG extraction was also favoured at the higher
pressure end, while CBD can be extracted at 100 bar. This agrees
with the findings of Perrotin-Brunel et al., who reported that the
solubility order of individual cannabinoids in supercritical CO2 was
THC < CBG < CBD across the pressure and temperature range they
studied, and that the solubility of all components increased with
extraction pressure [21]. This also agrees with the lower solubility
obtained by Rovetto and Aieta [25] (Fig. 3) when they used a starting
plant material (of the HashBerry cultivar) containing the less solu-
ble THCA (12.95 %) and THC (5.28 %) as the major cannabinoids. The
cannabinoids in the extracts obtained in the present study at 100
bar are comprised almost entirely of CBD (97.8 % of total cannabi-
noids for decarboxylated flower, 96.4 % for raw material). At 300
bar, the presence of non-CBD cannabinoids rises to 6.8 % in the
decarboxylated extract (mainly CBG and THC) and 18.7 % in the
raw extract (mainly CBDA, CBG and THC).
The extraction pressure not only affects the composition of the
extract but also its colour and visual appearance. At low pressure
(100 bar), the extract is a thin oil, rich in CBD and with a light
golden colour. As the pressure increases, the viscosity of the extract
thickens, and its colour becomes brown and increasingly darker,
particularly for the raw plant material extract (Fig. 5).
3.3. CO2 extraction: cannabinoid fractionation
The differential solubility of each cannabinoid in CO2 can be
used to attempt a partial fractionation of these compounds during
6 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850
Fig. 4. Relative composition of different fractions in the CO2 extraction of raw (left) and decarboxylated (right) cannabis.
Fig. 5. Visual comparison of the extracts obtained at different pressures from raw
(left) and decarboxylated (right) cannabis.
Fig. 6. Cannabinoid fractionation −CO2 extraction at 300 bar and two separation
stages.
extraction. One way to achieve this is by using a two-step extraction
process where the pressure is initially low in order to favour extrac-
tion of CBD, and is subsequently increased to obtain the less soluble
components [21]. An alternative approach is a staged depressuri-
sation process, where two or more separators are used in series at
decreasing pressures (i.e. decreasing solvent density) [25] to sepa-
rate the different components. This was studied in the present work
using decarboxylated Cultivar B-1 plant material and two separa-
tion stages, with varying pressure of the first stage, (90-130 bar) to
study its effect on cannabinoid fractionation (Fig. 6), while the sec-
ond stage remained constant at 50 bar. Less soluble cannabinoids
such as THC and CBG along with heavier compounds such as waxes
and lipids are preferentially collected in the first separator (S1),
whereas CBD and other more volatile compounds are collected in
the second separator (S2).
When a lower pressure was used in S1 (90 bar), the extract from
the first separator contained 159 mg/g CBD (89.5 % of the total
cannabinoid concentration) and 18.7 mg/g non-CBD cannabinoids
(THC, CBG and CBN; 10.5 % of the total cannabinoid concentration).
When the first stage separation pressure was increased to 130 bar,
the ratio of non-CBD cannabinoids in S1 increased to 16.9 %. Under
these conditions, the fractionation of THC and CBG between S1 and
S2 was slightly more pronounced (Table 4).
Fig. 7. Cannabis extraction curves for 䊏 raw and 䊉 decarboxylated material [empty
symbols indicate ethanol co-solvent period].
3.4. CO2 extraction: effect of ethanol co-solvent
The addition of a polar entrainer such as ethanol to supercritical
CO2 has been shown to increase extraction of cannabinoids [24,27],
particularly for the acidic cannabinoids due to their higher polarity.
To study the effect of ethanol, several experiments with Cultivar A
raw and decarboxylated material were carried out.
The first set of experiments was performed in a 1 L extraction
vessel and the plant material was extracted with CO2 at 300 bar
and 50 ◦ C until a S/F = 25 (solvent to feed, wet basis) ratio had
been reached. At this point, 5% ethanol was added to the CO2 (1:1
ethanol:feed) and the extraction continued with the extract col-
lected separately to the extract obtained with CO2 only. Following
this stage, CO2 without co-solvent was circulated in order to flush
residual ethanol and extract from the system. The extraction curves
for the raw and decarboxylated material (Fig. 7) show an identical
initial extraction rate followed by a slowdown after approximately
S/F = 5 (dry basis); this decrease in extraction rate was more acute
for the decarboxylated material, leading to a lower extract yield
in the initial CO2 period. The raw material extract obtained in
this period contained 17.6 % free water by weight. As discussed in
Section 3.2, it is possible that the presence of water and other com-
ponents (e.g. terpenes) in the raw material could lead to a higher
extraction yield.
The yield obtained in the ethanol co-solvent extraction stage
was also slightly higher for the raw material (2.6 % vs 2.2 %, dry
basis), which is likely caused by the higher concentration of CBDA
present in the feed. The cannabinoid composition of the extracts
(mg/g) in the CO2 period (extract A) and the CO2 + ethanol period
(extract B) is displayed in Table 5. Fig. 8 shows this data expressed as
g per 100 g of feed (dry basis) to allow better comparison between
the fractions as well as to illustrate the recovery of each cannabi-
noid. The concentration of neutral cannabinoids (THC, CBD, CBG and
CBN) in both extracts obtained from the raw material was almost
identical, whereas the addition of ethanol co-solvent led to con-
 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850 7

Table 4
Composition of S1 and S2 under different pressure conditions (CO2 extraction at 300 bar).

Concentration in S1 (mg/g) Concentration in S2 (mg/g)

First separator pressure
CBD THC CBG CBN CBD THC CBG CBN

90 bar 159.1 12.1 5.9 0.7 340.7 16.2 6.7 0.8

110 bar 187.1 15.4 7.8 0.6 309.2 17.4 8.3 0.6
130 bar 94.2 13.4 5.1 0.7 296.1 21.3 8.3 1.1

Fig. 8. CO2 (extract A) followed by CO2 + ethanol (extract B) extraction of cannabis: composition (left) and relative cannabinoid content (right) of the different fractions for
raw (top) and decarboxylated (bottom) plant material.

Table 5
Composition of different fractions obtained in the CO2 + ethanol extraction of cannabis (mg/g DB).

THC THCA CBD CBDA CBG CBGA CBN

Marc 0.01 0.11 0.05 2.37 0.00 0.14 0.00

Raw Extract A 5.49 11.4 24.7 278 1.85 3.01 0.04
Extract B 5.64 24.0 25.3 442 1.79 15.3 0.04
Marc 0.01 0.02 0.13 0.71 0.01 0.05 0.00
Decarboxylated Extract A 23.0 1.78 342 144 8.91 1.10 0.30
Extract B 8.84 5.72 100 260 4.36 8.42 0.16

centrations of THCA, CBDA and CBGA in extract B that were 2.1,
1.6 and 5.1 times higher than those in extract A, respectively. In
the decarboxylated material, the available concentration of neutral
cannabinoids in the feed was much higher, and these were concen-
trated in extract A, while the acidic forms were again concentrated
in extract B. The positive effect of ethanol addition on extraction
yield for acid cannabinoids was most pronounced for CBGA, fol-
lowed by THCA and CBDA. Based on the non-extracted material
remaining in the marc, cannabinoid recovery was slightly higher
for the decarboxylated plant material (98 % vs 94 %). The highest
CBD concentration was obtained in the decarboxylated extract A
(over 34 % by weight), representing 65.7 % of the total cannabinoid
concentration in this fraction (Table 5).
3.5. CO2 extraction: effect of extraction pressure
Extractions performed at pressures above about 700 bar may
be referred to as ultra-high pressure supercritical fluid extraction
(UHPSFE) [30]. The main advantage of the higher pressure is the
increased solubility of certain lipids, leading to shorter extraction
times and/or the extraction of compounds that otherwise have lim-
ited solubility in CO2 [30,31]. Several experiments were performed
on Cultivar A raw and decarboxylated plant material with extrac-
tion pressures up to 1300 bar. It is important to note that these
extractions were not performed to completion but rather for a fixed
extraction duration of S/F = 20. Separate experiments were carried
out, using fresh feed material, for each pressure condition studied.
Cannabinoid concentration in the CO2 extracts for both raw
and decarboxylated material is shown in Fig. 9 (left). In the raw
extracts, all key cannabinoids follow a generally increasing trend,
with higher pressures favouring the extraction. In the decarboxy-
lated extracts, CBD extraction was favoured at low to mid pressures
(200−500 bar) whereas the extraction of the other three key
cannabinoids (CBDA, THCA and THC) benefitted from higher extrac-
tion pressures (1000 bar). This agrees with previous results by
Perrotin-Brunel et al. [21]
The extraction yields obtained when using the raw material
consistently increase with pressure, reaching 9.8 % at 1300 bar.
However, cannabinoid extraction is not complete in these runs, and
ranges between 51 (at 200 bar) and 79 % (at 1300 bar), caused by
8 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850

Fig. 9. Ultrahigh pressure CO2 extraction of cannabis: composition (left) and relative cannabinoid content (right) of the different fractions for raw (top) and decarboxylated
(bottom) plant material. Lines in the extraction yield (left) added to guide the eye.

poor extraction of the predominant acidic forms (i.e. CBDA) in CO2 .

These results are consistent with what was obtained in the CO2
extraction period as described in Section 3.4. With the decarboxy-
lated material, where water had been mostly removed during the
decarboxylation step, the overall extraction yield peaked at 8.6 % at
500 bar, and then decreased with pressure. A large proportion of the
acidic forms had been transformed into the more easily extractable
neutral forms, and thus the overall cannabinoid yield in these runs
was improved, ranging from 78 (at 1300 bar) to 97 % (at 500 bar),
but there was still a small amount of non-extracted acidic forms.
In terms of CBD concentration in the extract, the highest concen-
tration was achieved with decarboxylated material at the lowest
tested pressure (200 bar), with 45 g CBD per 100 g of extract
(Table 6); however, the overall extraction yield under these con-
ditions was low (6.2 %), so the CBD extract concentration in terms
of CBD g per 100 g of dry feed (as seen in Fig. 9 bottom left) was actu- Fig. 10. Effect of ethanol co-solvent addition in extract composition at different
ally lower at 200 bar than at 500 bar. Some of the extracts in Fig. 9 pressures.
show higher amounts of CBD than what was originally available in
the feed material (expressed in g per 100 g of feed DB), leading to
CO2 while offering excellent solubility for lipophillic compounds
>100 % recoveries for this compound. This indicates that the CBDA
[29,32]. Increased solubilities normally lead to shortened extrac-
present in the feed is likely being partially decarboxylated during
tion times. Fig. 11 shows a comparison of extractions performed
the extraction, generating additional CBD in the process.
using different solvents and materials. Plant material from Culti-
Two additional experiments were performed in this plant
var A was extracted with propane in raw and decarboxylated form.
with addition of 5 % ethanol co-solvent. A comparison between
Unlike what was observed with CO2 , the corresponding extraction
extractions carried out on decarboxylated material in equivalent
curves (dry basis) and yields were identical for raw and decar-
conditions with and without ethanol addition can be seen in Fig. 10,
boxylated material. The solubility of water in propane is low and
showing the composition of the extracts in terms of the four major
very little water is co-extracted in the propane extraction of raw
cannabinoids (CBD, CBDA, THC, THCA). Addition of ethanol signif-
material, supporting the co-solvent effect of water observed in CO2
icantly increased the extraction of CBDA and THCA. Regardless of
extractions that led to higher overall extraction yields.
the presence of co-solvent, increasing the pressure from 200 to 500
Raw plant material from a different cultivar (Cultivar B-1) was
bar led to improved extraction of all major cannabinoids.
also extracted using liquefied propane. This cultivar had a signif-
icantly lower cannabinoid concentration (18.2 mg/g feedDB ) than
3.6. Other pressurised solvents: propane and dimethyl-ether Cultivar A (40.3 mg/g feedDB ) and resulted in a much lower total
extraction extraction yield (4.8 % vs 8.2 %). For comparison, the extraction
curve obtained with CO2 at 300 bar in the 10 L plant using decar-
Near-critical propane or dimethyl-ether (DME) are alternative boxylated Cultivar B-1 material as described in Section 3.3 is also
extraction solvents that require lower operating pressures than shown in Fig. 11 (extraction yield is a combination of extracts S1 and
 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850 9

Table 6
Composition of different extracts obtained from Cultivar A with different CO2 extraction pressures (mg/g DB).

Extraction pressure THC THCA CBD CBDA CBG CBGA CBN

200 bar 6.36 51.7 234 2.09 1.03 0.12 0.00

500 bar 10.1 51.6 263 1.69 2.09 0.11 0.00
Raw 700 bar 12.3 52.5 269 1.66 1.97 0.13 0.00
1000 bar 12.1 51.5 254 1.96 2.23 0.12 0.00
1300 bar 10.4 55.3 265 2.04 2.29 0.10 0.00
200 bar 24.3 0.80 450 67.4 7.97 0.50 0.33
500 bar 20.6 0.67 367 69.9 9.11 0.45 0.36
Decarboxylated
1000 bar 24.0 1.09 338 108 10.7 0.68 0.33
1300 bar 19.6 0.72 353 74.3 7.20 0.57 0.37

Table 7
Composition of different cannabis extracts obtained with near-critical propane and DME (mg/g DB).

THC THCA CBD CBDA CBG CBGA CBN

Raw 6.58 15.5 37.9 419 2.45 6.41 0.06

Cultivar A Propane
Decarboxylated 18.1 1.18 315 86.6 5.76 0.71 0.36
Propane Raw 11.3 12.1 46.1 204 2.27 3.39 0.04
Cultivar B-1
DME Decarboxylated 18.0 0.03 229 5.03 6.94 0.17 0.82

Supercritical CO2 and liquefied propane allow efficient and flexi-

Fig. 11. Cannabis extraction curves for different cultivars and solvents (× propane,
Cultivar A, decarboxylated;  propane, Cultivar A, raw; ♦ propane, Cultivar B-1, raw;
䊐 DME, Cultivar B-1, decarboxylated;  CO2 , Cultivar B-1, decarboxylated).
S2). The CO2 extraction reached a similar final yield to the propane
extraction of the same material, albeit taking considerably longer.
Finally, this material (decarboxylated Cultivar B-1) was also
extracted using liquefied DME. The yield obtained in this case
is increased with respect to CO2 and propane due to the higher
polarity of DME, which leads to extraction of a broader range of
compounds. DME is very efficient at extracting cannabinoids, but it
is also able to extract larger amounts of waxes and pigments, which
produces heavily coloured, thick extracts that will require further
purification to obtain a higher concentration of cannabinoids.
When the propane extraction of raw Cultivar A plant material
was compared to the equivalent CO2 extraction of the same mate-
rial (as described in Section 3.4), the extraction yield obtained with
propane (8.2 %) was slightly lower than with CO2 (9.3 %), and the
propane extract was more concentrated in the key cannabinoids,
particularly CBD and CBDA (Table 7). Propane appears to be more
efficient than CO2 at extracting the acidic cannabinoids. For decar-
boxylated Cultivar A plant material the extraction yield obtained
with propane (8.2 %) was higher than the equivalent yield obtained
with CO2 (5.9 %), and the individual cannabinoid concentrations in
the extract were slightly lower.
4. Conclusions
Cannabinoids, and in particular CBD, offer an exciting new
opportunity in the supercritical extraction business in light of
the ongoing regulatory changes and market trends worldwide.
ble extraction of cannabinoids from raw and decarboxylated plant
material. Total gross extract yields ranged from 5.8 to 12.0 wt% with
CO2 and from 4.8 to 8.2 wt% with propane, whereas total cannabi-
noid yield (i.e. the proportion of total cannabinoids available in the
feed material that are extracted) ranged from 51 to 100 % with CO2
and from 74 to 99 wt% with propane. CBD concentration reached
449 mg/g in a CO2 extract obtained at 200 bar. Decarboxylating
the plant material prior to extraction led to a slightly lower total
extraction yield, but it had a positive effect on the cannabinoid yield,
since the decarboxylated form is more soluble in non-polar sol-
vents than the acid form, and on the concentration of cannabinoids
in the extract. Addition of 5 % ethanol co-solvent to supercritical
CO2 enhances the extraction of acid forms, as does an increase in
extraction pressure. Propane is also more effective than CO2 for the
extraction of the acid forms, and it offers a similar extract compo-
sition (in terms of cannabinoids extracted) to the extracts obtained
with CO2 + ethanol for non-decarboxylated material. For decar-
boxylated material, the propane extract was richer in CBD, with
CBD representing 73.6 % of total cannabinoids present in the extract
vs 57.2 % in the CO2 + ethanol extract. A partial fractionation of the
extracted cannabinoids can be achieved by using two separation
stages.
Declaration of Competing Interest
The authors declare no conflict of interest for this work.
Acknowledgements
The authors wish to acknowledge the New Zealand Institute of
Environmental Science and Research for their analytical services,
and Rua Bioscience and Kanapu Holdings for supplying some of the
raw material.
References
[1] D.C. Hao, X.-J. Gu, P.G. Xiao, 11 - phytochemical and biological research of
Cannabis pharmaceutical resources, in: D.C. Hao, X.-J. Gu, P.G. Xiao (Eds.),
Medicinal Plants, Woodhead Publishing, 2015, pp. 431–464, ISBN
978-0-08-100085-4.
[2] A.A. Izzo, F. Borrelli, R. Capasso, V. Di Marzo, R. Mechoulam, Non-psychotropic
plant cannabinoids: new therapeutic opportunities from an ancient herb,
Trends Pharmacol. Sci. 30 (2009) 515–527, http://dx.doi.org/10.1016/j.tips.
2009.07.006.
[3] E.B. Russo, J. Marcu, Chapter Three - Cannabis pharmacology: the usual
suspects and a few promising leads, in: D. Kendall, S.P.H. Alexander (Eds.),
10 T. Moreno, F. Montanes, S.J. Tallon et al. / J. of Supercritical Fluids 161 (2020) 104850
Advances in Pharmacology, Academic Press, 2017, pp. 67–134, ISBN
1054-3589.
[4] J.M. McPartland, E.B. Russo, Cannabis and Cannabis extracts: greater than the
sum of their parts? J. Cannabis Ther. 1 (2001) 103–132, http://dx.doi.org/10.
1300/J175v01n03 08.
[5] J.A. Hartsel, J. Eades, B. Hickory, A. Makriyannis, Chapter 53 - Cannabis sativa
and hemp, in: R.C. Gupta (Ed.), Nutraceuticals, Academic Press, Boston, 2016,
pp. 735–754, ISBN 978-0-12-802147-7.
[6] A. Hazekamp, J.T. Fischedick, M.L. Díez, A. Lubbe, R.L. Ruhaak, 3.24 - chemistry
of Cannabis, in: H.-W. Liu, L. Mander (Eds.), Comprehensive Natural Products
II, Elsevier, Oxford, 2010, pp. 1033–1084, ISBN 978-0-08-045382-8.
[7] M. Wang, Y.-H. Wang, B. Avula, M.M. Radwan, A.S. Wanas, J. van Antwerp, J.F.
Parcher, M.A. ElSohly, I.A. Khan, Decarboxylation study of acidic
cannabinoids: a novel approach using ultra-high-performance supercritical
fluid chromatography/photodiode array-mass spectrometry, Cannabis
Cannabinoid Res. 1 (2016) 262–271, http://dx.doi.org/10.1089/can.2016.0020.
[8] E. Rosenthal, G. Zeman, Terpenes and cannabinoids, in: Beyond Buds, Next
Generation: Marijuana Concentrates and Cannabis Infusions, Quick American
Archives, 2018, pp. 14–41, ISBN 9781936807383.
[9] C. Citti, B. Pacchetti, M.A. Vandelli, F. Forni, G. Cannazza, Analysis of
cannabinoids in commercial hemp seed oil and decarboxylation kinetics
studies of cannabidiolic acid (CBDA), J. Pharm. Biomed. Anal. 149 (2018)
532–540, http://dx.doi.org/10.1016/j.jpba.2017.11.044.
[10] H. Perrotin-Brunel, W. Buijs, J.V. Spronsen, M.J.E.V. Roosmalen, C.J. Peters, R.
Verpoorte, G.J. Witkamp, Decarboxylation of 9-tetrahydrocannabinol:
kinetics and molecular modeling, J. Mol. Struct. 987 (2011) 67–73, http://dx.
doi.org/10.1016/j.molstruc.2010.11.061.
[11] T. Veress, J.I. Szanto, L. Leisztner, Determination of cannabinoid acids by
high-performance liquid chromatography of their neutral derivatives formed
by thermal decarboxylation: I. Study of the decarboxylation process in open
reactors, J. Chromatogr. A 520 (1990) 339–347, http://dx.doi.org/10.1016/
0021-9673(90)85118-F.
[12] E.B. Russo, Taming THC: potential cannabis synergy and
phytocannabinoid-terpenoid entourage effects, Br. J. Pharmacol. 163 (2011)
1344–1364, http://dx.doi.org/10.1111/j.1476-5381.2011.01238.x.
[13] E. Rosenthal, G. Zeman, CO2 extracts, in: Beyond Buds, Next Generation:
Marijuana Concentrates and Cannabis Infusions, Quick American Archives,
2018, pp. 149–168, ISBN 9781936807383.
[14] I.R. Flockhart, G.W. Wheatley, S. Dring, L. Archer, Method of preparing
cannabidiol from plant material, 2004, WIPO Patent 2004026802A1.
[15] B. Whittle, C.A. Hill, I.R. Flockhart, D.V. Downs, P. Gibson, G.W. Wheatley,
Extraction of pharmaceutically active components from plant materials, 2008,
US Patent 7344736B2.
[16] K. Hawthorne, Leading the Way: Eden Labs Brings Precision and Safety to the
New Cannabis Era, Cannabis Brightline Focus Media Group, 2019, pp. 14–17.
[17] V. Kitrytė, D. Bagdonaitė, P. Rimantas Venskutonis, Biorefining of industrial
hemp (Cannabis sativa L.) threshing residues into cannabinoid and
antioxidant fractions by supercritical carbon dioxide, pressurized liquid and
enzyme-assisted extractions, Food Chem. (2017), http://dx.doi.org/10.1016/j.
foodchem.2017.09.080.
[18] T.M. Attard, C. Bainier, M. Reinaud, A. Lanot, S.J. McQueen-Mason, A.J. Hunt,
Utilisation of supercritical fluids for the effective extraction of waxes and
Cannabidiol (CBD) from hemp wastes, Ind. Crops Prod. 112 (2018) 38–46,
http://dx.doi.org/10.1016/j.indcrop.2017.10.045.
[19] L. Eöry, B. Dános, T. Veress, Supercritical fluid extraction of
tetrahydrocannabinol from marihuana - study of the effect of particle size,
Problems of Forensic Sciences 47 (2001) 322–327.
[20] H. Perrotin-Brunel, Sustainable production of cannabinoids with supercritical
carbon dioxide technologies, in: Mechanical, Maritime and Materials
Engineering, TU Delft, 2011.
[21] H. Perrotin-Brunel, M.C. Kroon, M.J.E. Van Roosmalen, J. Van Spronsen, C.J.
Peters, G.J. Witkamp, Solubility of non-psychoactive cannabinoids in
supercritical carbon dioxide and comparison with psychoactive cannabinoids,
J. Supercrit. Fluids 55 (2010) 603–608, http://dx.doi.org/10.1016/j.supflu.
2010.09.011.
[22] H. Perrotin-Brunel, P.C. Perez, M.J.E. van Roosmalen, J. van Spronsen, G.J.
Witkamp, C.J. Peters, Solubility of 9-tetrahydrocannabinol in supercritical
carbon dioxide: experiments and modeling, J. Supercrit. Fluids 52 (2010)
6–10, http://dx.doi.org/10.1016/j.supflu.2009.12.001.
[23] H. Perrotin-Brunel, M.J.E. Van Roosmalen, M.C. Kroon, J. Van Spronsen, G.J.
Witkamp, C.J. Peters, Solubility of cannabinol in supercritical carbon dioxide, J.
Chem. Eng. Data 55 (2010) 3704–3707, http://dx.doi.org/10.1021/je100245n.
[24] J. Omar, M. Olivares, M. Alzaga, N. Etxebarria, Optimisation and
characterisation of marihuana extracts obtained by supercritical fluid
extraction and focused ultrasound extraction and retention time locking
GC-MS, J. Sep. Sci. 36 (2013) 1397–1404, http://dx.doi.org/10.1002/jssc.
201201103.
[25] L.J. Rovetto, N.V. Aieta, Supercritical carbon dioxide extraction of
cannabinoids from Cannabis sativa L, J. Supercrit. Fluids 129 (2017) 16–27,
http://dx.doi.org/10.1016/j.supflu.2017.03.014.
[26] V. Brighenti, F. Pellati, M. Steinbach, D. Maran, S. Benvenuti, Development of a
new extraction technique and HPLC method for the analysis of
non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp), J.
Pharm. Biomed. Anal. 143 (2017) 228–236, http://dx.doi.org/10.1016/j.jpba.
2017.05.049.
[27] D. Ribeiro Grijó, I.A. Vieitez Osorio, L. Cardozo-Filho, Supercritical extraction
strategies using CO2 and ethanol to obtain cannabinoid compounds from
Cannabis hybrid flowers, J. Co2 Util. 30 (2019) 241–248, http://dx.doi.org/10.
1016/j.jcou.2018.12.014.
[28] E. Rosenthal, G. Zeman, BHO: Butane Hash Oil - Shatter, Wax, Sauce and
Beyond, in: Beyond Buds, Next Generation: Marijuana Concentrates and
Cannabis infusions, Quick American Archives, 2018, pp. 87–116, ISBN
9781936807383.
[29] J.W. King, The relationship between cannabis/hemp use in foods and
processing methodology, Curr. Opin. Food Sci. (2019), http://dx.doi.org/10.
1016/j.cofs.2019.04.007.
[30] J.W. King, Supercritical fluid extraction at high pressures (& 700 bar):
theoretical considerations and practical applications, in: III Iberoamerican
Conference on Supercritical Fluids, Cartagena de Indias (Colombia), 2013.
[31] F. Montañés, O.J. Catchpole, S. Tallon, K.A. Mitchell, D. Scott, R.F. Webby,
Extraction of apple seed oil by supercritical carbon dioxide at pressures up to
1300 bar, J. Supercrit. Fluids 141 (2018) 128–136, http://dx.doi.org/10.1016/j.
supflu.2018.02.002.
[32] O. Catchpole, T. Moreno, F. Montañes, S. Tallon, Perspectives on processing of
high value lipids using supercritical fluids, J. Supercrit. Fluids 134 (2018)
260–268, http://dx.doi.org/10.1016/j.supflu.2017.12.001.