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A recent law (DCTO-2020-883-APN-PTE - Law No. 27,350. Regulation) passed in Argentina put an end to the ban imposed for the last 60 years on cannabis cultivation within the country. The law permits restricted access to cannabis derivatives for medicinal, therapeutic and palliative use by individuals and communities, allowing self- and community-based cannabis production. This is cause for concern in view of the lack of quality controls for cannabis derivatives. The several varieties of cannabis grown in Argentina have different chemical profiles and are processed in a variety of ways ―mostly by alcohol extraction or maceration at different temperatures and for different amounts of times― making the cannabinoid content of these preparations highly variable. Determining the characteristics of home- and community-grown cannabis products will facilitate the implementation of public policies conducive to their safety and improvement. Objective. The aim of the present study was to determine the cannabinoid chemotypes used for therapeutic purposes in Argentina and evaluate whether the cannabinoids present in home-made derivatives are comparable to those in commercially available products. Methods HPLC/UV-DAD analysis of 436 samples (oils, resins and inflorescences) was carried out to determine the identity and concentration of five cannabinoids: THCA, THC, CBDA, CBD and CBN. From three different sources, the samples represent the type of medical cannabis preparations to which patients have access. Results The results indicate that the medium-to-low cannabinoid concentration in a significant number of home-made oil samples is similar to that found in commercial products. Most of the samples have a THC/CBD ratio ˃ 1 or only contain THC. Acidic cannabinoids were detected in home-made preparations but were not reported in package inserts of commercial products. Conclusions Our results indicate that despite their considerable variability, home-made preparations as a whole show cannabinoid levels and profiles equivalent to the commercially available products commonly used for medicinal, therapeutic and palliative purposes in Argentina. Keywords: Cannabis oil, inflorescences, resins, cannabinoids, home-made herbal products
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Cannabinoid Content in Cannabis Flowers
and Homemade Cannabis-Based Products Used
for Therapeutic Purposes in Argentina
Daniela Sedan,
1
Cristian Vaccarini,
1
Pablo Demetrio,
1
Marcelo Morante,
2
Romina Montiel,
3
Alvaro Saurı
´,
3
and Dario Andrinolo
1,
*
Abstract
Introduction: A recent law (DCTO-2020-883-APN-PTE—Law No. 27,350. Regulation) passed in Argentina put
an end to the ban imposed for the last 60 years on cannabis cultivation within the country. The law permits
restricted access to cannabis derivatives for medicinal, therapeutic, and palliative use by individuals and commu-
nities, allowing self- and community-based cannabis production. This is cause for concern in view of the lack of
quality controls for cannabis derivatives. The several varieties of cannabis grown in Argentina have different
chemical profiles and are processed in a variety of ways—mostly by alcohol extraction or maceration at different
temperatures and for different amounts of times—making the cannabinoid content of these preparations highly
variable. Determining the characteristics of home- and community-grown cannabis products will facilitate the
implementation of public policies conducive to their safety and improvement.
Objective: The aim of this study was to determine the cannabinoid chemotypes used for therapeutic purposes
in Argentina and evaluate whether the cannabinoids present in homemade derivatives are comparable to those
in commercially available products.
Materials and Methods: High performance liquid chromatography with ultraviolet and diode array detector
(HPLC/UV-DAD) analysis of 436 samples (oils, resins, and inflorescences) was carried out to determine the identity
and concentration of five cannabinoids: tetrahydrocannabinolic acid (THCA), tetrahydrocannabinol (THC), canna-
bidiolic acid (CBDA), cannabidiol (CBD), and cannabinol (CBN). From three different sources, the samples repre-
sent the type of medical cannabis preparations to which patients have access.
Results: The results indicate that the medium-to-low cannabinoid concentration in a significant number of
homemade oil samples is similar to that found in commercial products. Most of the samples have a THC/CBD
ratio >1 or only contain THC. Acidic cannabinoids were detected in homemade preparations, but were not
reported in package inserts of commercial products.
Conclusions: Our results indicate that despite their considerable variability, homemade preparations as a whole
show cannabinoid levels and profiles equivalent to the commercially available products commonly used for me-
dicinal, therapeutic, and palliative purposes in Argentina.
Keywords: cannabis oil; inflorescences; resins; cannabinoids; homemade herbal products
Introduction
Most of the effects of cannabis on the human organism
are exerted through phytocannabinoids, lipophilic
molecules whose therapeutic action is owed to the
fact that they interact with the endocannabinoid sys-
tem (ECS) receptors (CB1 and CB2), triggering the
same effects as endocannabinoids, such as anandamide
(AEA) and 2-arachidonoylglycerol (2-AG).
1
Phytocan-
nabinoids therefore act as modulators of many physio-
logical processes that involve the intervention of the
1
Environmental Research Center, National Council for Scientific and Technical Research CIM UNLP-CONICET, La Plata, Argentina.
2
Medicine School of La Plata National University UNLP, La Plata, Argentina.
3
Palliative Care Service of the Oncology Institute Angel H. Roffo IOAR, National University of Buenos Aires, UBA, Buenos Aires, Argentina.
*Address correspondence to: Dario Andrinolo, PhD, Environmental Research Center, National Council for Scientific and Technical Research CIM UNLP-CONICET, La Plata,
Argentina, E-mail: dandrinolo@yahoo.com
Cannabis and Cannabinoid Research
Volume X, Number X, 2021
ªMary Ann Liebert, Inc.
DOI: 10.1089/can.2020.0117
1
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ECS, whose main role is to regulate the body homeosta-
sis. New actions of ECS are being discovered, enabling
us to learn more about the beneficial effects of phyto-
cannabinoids in the treatment of the symptomatology
associated with several diseases.
2,3
Around 554 compounds have been identified in
Cannabis sativa sp. plants, among which 113 were phy-
tocannabinoids
3,4
and over 120 terpenes.
5
One of the most well-known and studied phytocan-
nabinoids is D9-tetrahydrocannabinol (THC), initially
linked to the psychoactive effects of cannabis, but
now also shown to be highly effective for treating
chronic pain in adults and nausea and vomiting in che-
motherapy treatment, and relieving the symptoms of
spasticity in multiple sclerosis.
6
Other common phyto-
cannabinoids that have been studied are cannabidiol
(CBD), a nonpsychoactive substance claimed to have
anti-inflammatory, analgesic, antianxiety, and antipsy-
chotic properties; and cannabinol (CBN), a cannabi-
noid with considerably less psychoactivity than THC
and known for its sedative effects, and anticonvulsant
and antibacterial properties. Furthermore, since CBN
derives from the oxidation of THC, it has been linked
to the aging or overheating of cannabis-based prepara-
tions.
7–9
These neutral cannabinoids are present in low
quantities in fresh plants and are biosynthesized as
prenylated aromatic carboxylic acids such as tetrahy-
drocannabinolic acid (THCA) or cannabidiolic acid
(CBDA), convertible to their neutral counterparts by
decarboxylation when exposed to light or heat.
10,11
Unlike THC, the acidic form THCA is not psychoactive
since it is unable to pass through the blood–brain bar-
rier and has low affinity for the CB1 receptor.
12,13
Acidic cannabinoids also have pharmacological prop-
erties such anti-inflammatory effects since they are
COX2-selective inhibitors.
12,14
When acidic and neu-
tral cannabinoids are administered together, they in-
teract with each other and with other substances
contained in phytopreparations (terpenes, flavonoids,
sterols, etc.), generating different effects from when
they are administered separately; this phenomenon is
known as ‘‘entourage effect.’
14,15
In recent years, the use of medicinal cannabis has be-
come more widespread in Latin America, providing a
therapeutic alternative being increasingly taken into ac-
count by patients and doctors. As in many countries,
there are no legally available medicinal cannabis prep-
arations on the market in Argentina for patients to
include in their treatment. Thus, self-cultivation and
home processing of phytopreparations based on canna-
bis are currently their main options. In many of these
cases, physicians are aware that their patients use
cannabis-based derivatives therapeutically and take
this into account when prescribing other medications,
monitoring for any improvement in symptoms as
well as possible side effects or drug-drug interactions.
In the absence of legal products for sale in pharmacies,
patients are forced to access cannabis-based oils on the
illegal market. As described above, this situation means
that the composition of these products is not checked
by quality control and can therefore vary widely. Self-
cultivation and solidarity cultivation have expanded
in recent years in Argentina, generating cannabis-
based herbal preparations with levels and chemoptypes
of cannabinoids compatible with therapeutic require-
ments of the user. This socially propelled process was
fundamental in helping to bring about the recent
changes in the law, permitting this informal cultivation
to provide access to medicinal cannabis. Due to the re-
cent law (DCTO-2020-883-APN-PTE—Law No. 27,350.
Regulation) passed in, Argentina permits the access to
cannabis-based derivatives for medicinal purposes
through self- and community-based cannabis produc-
tion; it is necessary to know the characteristics of
these kinds of products. Determining the characteristics
of home- and community-grown cannabis products
will provide information and facilitate the implementa-
tion of public policies conducive to their safety and im-
provement. Therefore, the aim of this study was to
analyze the cannabinoid composition of a variety of
cannabis-based inflorescences, resins, and oils used for
therapeutic purposes in Argentina.
Materials and Methods
Samples analyzed
The study was carried out using inflorescence (n=34),
resin (n=40), and oil (n=362) samples received
between 2018 and 2019 within the framework of the
Cannabis and Health project conducted at the Environ-
mental Research Center (CIM, Institute dependent of
National Council for Scientific and Technical Research
of Argentina [CONICET] and National University of
La Plata [UNLP], La Plata, Argentina). The samples
came from different sources, together representing a
cross-section of the type of medical cannabis prepara-
tions to which patients have access. Given the variabil-
ity of oil sources and therapeutic objectives for which
they have been used and to carry out a differential anal-
ysis of total cannabinoid content, we established three
subgroups of oils based on their origin: GENERAL
2 SEDAN ET AL.
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(n=220), oil samples corresponding to patients or
growers with no concrete affiliation with any nongov-
ernmental organization or health institution; ROFFO
(n=125), oil samples used by patients of the Palliative
Care Area of the Oncologic Institute A
´ngel H. Roffo
(IOAR, Buenos Aires, Argentina) who participated in
an observational study supervised by Dr. Saurı
´(Pallia-
tive Care Area Director); and ACUFALP (n=17),
homemade oil samples from different home-grown
strains used by the civil association ‘‘Cultivo en Familia
La Plata,’’ La Plata, Argentina.
Determination of cannabinoids
in studied samples
Sample conditioning and processing. The samples
were conditioned and processed according to the fol-
lowing cannabinoid extraction protocols:
The flowers were received in the laboratory dried.
However, to ensure this condition before sample process-
ing, the inflorescences were dried in an oven (SAN
JOR—SL 17C) for 1 h at low temperature (30C) to
avoid decarboxylation. Once dry, the flowers were ho-
mogenized with sterile scissors and in each case, 1 g
was used for cannabinoid extraction using 20 mL of eth-
anol 96(Purocol) and sonication for 10 min (Omnirup-
tor). Filtration was then performed using sterile cotton
gauzes followed by filtration with Whatman filter paper.
For resins and oils, the extraction was performed
with 96ethanol (Purocol) using 100 mL/g resin or
20 mL/g oil and shaking in vortex (10 min) to favor ef-
ficient contact and extraction. The obtained solution
was then centrifuged for 10 min at 5000 rpm (Rolco
Centrifuge) to separate the alcohol extract from insol-
uble residues. Matrix cleanup was carried out on alco-
hol extracts obtained from inflorescences, resins, or oils
using a mixture of activated carbon, C
18
, and Mg
2
SO
4
and sonication for 10 min. The supernatant was sepa-
rated by centrifugation and the salts were washed
with ethanol and sonication for 10 min to recover
any cannabinoids adsorbed on the salt surfaces. Centri-
fugation (10 min at 5000 rpm) was subsequently per-
formed and the supernatant was incorporated into
the initially treated alcoholic phase. In previous studies,
we determined cannabinoid content in oil, resin, and
alcoholic extract samples with and without carrying
out the matrix cleanup procedure. An 8% decrease in
cannabinoid content for CBD and CBD-A, 9% for
THC and THC-A, and 7% for CBN were determined
after the cleanup process. Based on these previous stud-
ies, we included a corresponding correction factor in
the cannabinoid quantification. Finally, the alcoholic
phase was filtered using Osmonics 45 lm filters, to
further analyze by high performance liquid chroma-
tography with ultraviolet and diode array detector
(HPLC/UV-DAD).
Analytical determination of cannabinoids. Cannabi-
noid profiles were studied by HPLC/UV-DAD (Shi-
madzu LC-20A), employing a Thermo Hypersil BDS
C18 column (150 ·4.6 mm, 5 lm) according to the an-
alytical technique described by De Backer et al.,
16
with
slight modifications. The mobile phase consisted in A:
methanol and B: 25 mM ammonium acetate solution.
The gradient was: 75% A: 1 min, 75% to 95% A in
15 min, 95% A: 2 min, 95% to 75% A in 2 min, and
75% A: 5 min. Total run time was 25 min, flow:
1 mL/min, and detection at 205 nm. Cannabinoid an-
alytical standards were purchased from Cerilliant
Corporation. This technique allowed us to differenti-
ate the acidic (THCA, CBDA, etc.) from the neutral
cannabinoids(THC,CBD,etc.).Basedonthecanna-
binoid concentration obtained, ratios and derived
variables were establishedaccordingtothefollowing
equations:
Total cannabi noids =CBDA½þTHC A½þCBD½
þCBN½þTHC½
THC=CBD ratio =(0:877½ [THC A] þ[THC])=
(0:877½ [CBD A]) þ[CBD]]
Acidic=neutral ratio =CBD A½þTHC A½ðÞ=
CBD½þTHC½ðÞ
A conversion factor of 0.877 was employed in the Total
THC (sum of THC and THCA) and Total CBD (sum of
CBD and CBDA) calculations to adjust for the loss of
mass of THCA and CBDA after decarboxylation.
17
Data analysis. All the results were subjected to a one-
way analysis of variance (ANOVA) with the help of
Systat (version 12.0 for Windows) from SPSS Science
(Chicago, IL) and represent the mean standard
error (nis indicated in each case). The differences
in the mean of the groups were evaluated by a two-
tailed Student’s t-test, with a statistical significance
level of p<0.05.
Results
We analyzed a total of 436 samples (362 oils, 40 resins, and
34 inflorescences) and determined the identity and con-
centration of five cannabinoids: THCA, THC, CBDA,
CANNABIS CONTENT IN HOMEMADE HERBAL PREPARATIONS 3
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CBD, and CBN. Based on these findings, the samples
were analyzed according to total cannabinoid content,
THC/CBD ratio, acidic/neutral ratio, and CBN content,
these parameters being directlyrelatedtothequalityand
therapeutic potential of cannabis and its derivatives.
Total cannabinoids in resin, inflorescence,
and oil samples
Of all the samples analyzed, resins—basically obtained
by alcohol extraction followed by alcohol evaporation—
showed the highest average concentration of total
cannabinoids (358.8 40.9 mg/g), followed by inflo-
rescences, with a 5-fold lower total cannabinoid
level (62.5 6.0 mg/g). The total mean cannabinoid
concentration in oils was 8.41.1 mg/mL (Table 1).
These groups differed significantly from one another
in total cannabinoid content, with significant variabil-
ity within each group.
In view of this wide variability and to analyze canna-
binoid distribution, relative frequencies (%) were calcu-
lated for oil, inflorescence, and resin samples based on
five total cannabinoid concentration (TCC) ranges (0–
0.1, 0.1–1, 1–10, 10–100, and over 100 mg/mL [oils] or
mg/g [resins and inflorescences]) (Fig. 1).
Most resin samples (82.5%) were within the highest
TCC range (over 100 mg/g) with a relative frequency of
7.5% for each one in the 10–100 and 1–10 mg/g ranges.
The rest of the resin samples (2.5%) presented TCCs in
Table 1. Parameters Used in the Characterization of the Samples
Samples Total cannabinoids THC/CBD Acidic/neutral CBN
Inflorescences 62.5 6.0 A (34) 43.4 14.4 A (28) 8.6 1.9 A (34) 0.8 0.7 A (34)
Resins 358.8 40.9 B (40) 38.2 22.7 A (34) 1.5 0.3 B (33) 2.7 0.8 A (40)
Oils 8.4 1.1 C (362) 26.8 3.1 A (297) 1.0 0.1 B (276) 0.25 0.04 B (362)
Total cannabinoids and CBN are expressed in mg/g for resins and inflorescences, and in mg/mL for oils.
The significant differences among results [mean SE, (n)] are indicated with different letters ( p>0.05).
CBD, cannabidiol; CBN, cannabinol; SE, standard error; THC, tetrahydrocannabinol.
FIG. 1. Relative frequency (%) of samples of oils (total) (striped bar), inflorescences (squared gray bar), and
resins (black bar) based on TCC ranges. TCC, total cannabinoid concentration.
4 SEDAN ET AL.
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one of the lowest TCC range (0.1–1 mg/g), which is rare
for a usually concentrated material such as resin (Fig. 1).
In the case of inflorescences, 82.4% of the samples were
within the 10–100 mg/g TCC range, while a smaller per-
centage of the samples (17.6%) were in the highest range
(over 100 mg/g), some samples reaching 220 mg/g (Fig. 1).
Oils had the highest number of samples distributed in
relatively low TCC ranges, with relative frequencies of
60.4% and 20.6% in 1–10 and 0.1–1mg/mL ranges, re-
spectively (Fig. 1). Moreover, 1.7% of oil samples were
within the lowest range established (0–0.1 mg/mL) and
16.2% and 1.1% corresponded to the two highest ranges,
10–100 mg/mL and over 100 mg/mL, respectively.
Analysis of oil subgroups according to their origin
Total cannabinoid levels detected in oil subgroups
differed significantly from one another. The sub-
group presenting the highest TCC was ACUFALP
(42.7 23.9mg/mL)followedbytheGENERAL
(11.1 1.8 mg/mL) and ROFFO (3.2 0.4 mg/mL)
subgroups (Table 2).
Table 3 shows the TCC reported on the labels of the
some of the more dominant brands of oils available on
the international market, often alluded to in Argentina
by the community, but not available in the country.
They cover a varied range of cannabinoid concentra-
tions in their different presentations. Compared to
these products, ROFFO oils have the lowest TCC and
those of the GENERAL subgroup were ranked fourth,
presenting concentrations close to 10 mg/mL. Oils of
the ACUFALP subgroup ranked in the middle of
Table 3, with an average of 42.7 mg/mL, seven products
having higher concentrations.
Most oil samples of the ACUFALP subgroup
were within the three highest TCC ranges: over
100, 100–10, and 1–10 mg/mL, with relative fre-
quencies of 14.3%, 42.9%, and 35.7% respectively;
7.1% of the samples were in the 0.1–1 mg/mL
rangeandtherewerenosamplesinthelowest
established TCC range.
Even though the ROFFO and GENERAL subgroups
showed the highest proportion of samples in the 1–
Table 2. Parameters Used in the Characterization of the Oil Samples by Origin (GENERAL, ROFFO, and ACUFALP)
Oils Total cannabinoids THC/CBD Acidic/neutral CBN
GENERAL 11.1 1.8 A (220) 21.7 2.1 A (186) 1.1 0.1 A (164) 0.3 0.1 A (220)
ROFFO 3.2 0.4 B (125) 22.2 4.2 A (95) 1.1 0.2 A (100) 0.1 0.1 B (125)
ACUFALP 42.7 23.9 C (17) 14.1 4.5 A (16) 0.4 0.2 A (12) 0.9 0.6 C (17)
Total cannabinoids and CBN are expressed in mg/g for resins and inflorescences; and in mg/mL for oils. The significant differences among results
[mean SE, (n)] are indicated with different letters ( p>0.05).
Table 3. Total Cannabinoids and THC/CBD Ratio in Different Cannabis-Based Products Available in the Market,
Produced by International Pharmaceutical Companies and Firms, as Well as the Subgroups of Oils Studied Here
(GENERAL, ROFFO, and ACUFALP)
Product Origin/pharmaceutical company Pharmaceutical formulation
Total
cannabinoids THC/CBD ratio
ROFFO Self-cultivation/solidarity cultivation
and undetermined
Oral solution: oil 3.2 mg/mL 22.2:1
Charlotte’s Web CBD Oil Stanley Brothers Oral solution: oil 7 mg/mL Only CBD informed
RSHO: Green, Blue and Gold Label Hemp Meds Oral solution: oil 8.5 mg/mL Only reports CBD
GENERAL Self-cultivation/solidarity cultivation
and undetermined
Oral solution: oil 11.1 mg/mL 21.7:1
Charlotte’s Web CBD Oil Stanley Brothers Oral solution: oil 17mg/mL Only reports CBD
THC 20:1—Oil (Formerly Champlain) Aphria Oral solution: oil 21.3 mg/mL 20:1
THC:CBD 10:13—Oil (Formerly Capilano) Aphria Oral solution: oil 21.5 mg/mL 10:13
CBD 25:1—Oil (Formerly Ridean) Aphria Oral solution: oil 25.2mg/mL 1:25
ACUFALP Self-cultivation/solidarity cultivation Oral solution: oil 42.7 mg/mL 14.1:1
Charlotte’s Web CBD Oil Stanley Brothers Oral solution: oil 50mg/mL Only reports CBD
Sativex GW Pharmaceutical Solution for oral spray 52 mg/mL 1:1
Charlotte’s Web CBD Oil Stanley Brothers Oral solution: oil 60mg/mL Only reports CBD
Epidiolex GW Pharmaceutical Oral solution 100 mg/mL Only reports CBD
RSHO Green Label 3G Pure CBD Oil Hemp Meds Hemp oil 120mg/g Only reports CBD
RSHO Blue Label 3G Pure CBD Oil Hemp Meds Decarboxylated hemp oil 170 mg/g Only reports CBD
RSHO Gold Label 3G Pure CBD Oil Hemp Meds Decarboxylated and filtered
hemp oil
240 mg/g Only reports CBD
CANNABIS CONTENT IN HOMEMADE HERBAL PREPARATIONS 5
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10 mg/mL TCC range (60.8% and 61.8%, respectively),
there were differences in the distribution of the relative
frequencies in the other ranges (Fig. 2). Oils of the
GENERAL subgroup showed the following relative
frequencies: 1% in the over 100 mg/mL range, 20% in
10–100 mg/mL range, and 17.2% in the 0.1–1 mg/mL
range. There were no samples with concentrations within
the lowest range. The ROFFO subgroup showed relative
frequencies of 28% in the 0.1–1 mg/mL range and 4.8%
in the 0–0.1 mg/mL range; 8.4% of this subgroup’s sam-
ples were found in the 10–100 mg/mL range, with no
sample in the maximum established range (Fig. 2).
THC/CBD ratio
There were no significant differences in the THC/CBD
ratio among inflorescence, resin, and oil samples, nor
among the oil subgroups (Tables 1 and 2). Only 0.5%
of the oil samples showed no THC content, whereas
CBD was not detected in 24.3% of inflorescences,
15% of resins, and 19.1% of oils (Fig. 3A). Inflorescen-
ces and oils presented their highest relative frequency
in the 10–100 THC/CBD range (37.8% and 40.4%, re-
spectively) and resins in the 0.1–1 range (37.5%). Our
results indicate that resins presented a higher propor-
tion of samples with balanced THC and CBD content
or enriched in CBD, with 42.5% of samples with
THC/CBD <1. Inflorescences and oils showed 16.2%
and 14.4% of samples with THC/CBD <1, respectively.
We detected THC and CBD in different propor-
tions in samples of the ACUFALP oil subgroup.
THC was not detected in 0.9% of the GENERAL sub-
group samples, and CBD was not detected in 16.8%
and 25.4% of samples of GENERAL and ROFFO sub-
groups, respectively.
FIG. 2. Relative frequency (%) of samples from
oil subgroups: GENERAL (black bars), ROFFO
(gray bars), and ACUFALP (white bars) based on
the TCC range.
AB
FIG. 3. Relative frequency (%) of samples based on THC/CBD ratio range. (A) Inflorescences (gray bars),
resins (black bars), and oils (white bars). (B) Oil subgroups: GENERAL (white bars), ROFFO (gray bars), and
ACUFALP (black bars). CBD, cannabidiol; THC, tetrahydrocannabinol.
6 SEDAN ET AL.
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The highest proportion of samples from the
ACUFALP subgroup was found in the 10–100
(46.7%) and 1–10 (33.3%) ranges and frequencies
of 6.7% and 13.3% were determined in the 0–0.1
and 0.1–1 ranges, respectively. The distribution of
relative frequencies of the THC/CBD ratio for the
GENERAL subgroup was as follows: 5% for 0–0.1,
12.3% for 0.1–1, 19.1% for 1–10, 42.7% for 10–
100, and 3.2% for over 100 (Fig. 3B). For the
ROFFO subgroup, the following relative frequency
distributions were determined: 2.4% for 0–0.1,
6.4% for 0.1–1, 26.2% for 1–10, 35.7% for 10–100,
and 4% for over 100.
Acidic/neutral ratio
Our results indicate that the highest proportion of sam-
ples rich in acid cannabinoids is among inflorescences,
with 91.2% of the samples presenting acid/neutral >1.
Resins and oils presented higher proportions of sam-
ples enriched in neutral cannabinoids, most of them
presenting acid/neutral <1 or no acidic cannabinoids
at all (57.5% resins and 78.4% oils) (Fig. 4A).
The GENERAL and ROFFO oil subgroups showed
acidic/neutral ratios close to 1 (1.1 0.1 and 1.1 0.2,
respectively), whereas the ACUFALP subgroup showed
a slightly lower ratio (0.4 0.2) (Table 2).
The relative frequency distribution was quite
homogeneous among lower acid/neutral ratio ranges,
with the highest relative frequency for each subgroup
in the 0.1–1 range (GENERAL: 32.7%, ROFFO:
36.2%, and ACUFALP: 35.3%). However, the
GENERAL subgroup presented 25% of the samples
in the 1–10 range—indicating samples enriched in
acid cannabinoids—followed by the ROFFO (16.5%)
and ACUFALP (5.9%) subgroups. All three subgroups
presented samples in which acid cannabinoids were
not detected, with relative frequencies of 25%, 17.1%,
and 29.4% for GENERAL, ROFFO, and ACUFALP,
respectively(Fig.4B).TheACUFALPsubgroupthere-
fore presented the highest proportion of samples
enriched in neutral cannabinoids and 94.1% present-
ing acid/neutral <1ornoacidiccannabinoidsatall,
followed by the ROFFO (82.9%) and GENERAL
(74.1%) subgroups.
CBN content
As expected, inflorescences and resins showed signifi-
cantly higher levels of CBN (0.8 0.7 mg/mL and
2.7 0.8 mg/mL) than oils (0.3 0.1 mg/mL), which
are usually more diluted (Table 1). However, given
the differences observed in relation to total cannabi-
noid content, these CBN levels represent 0.5% and
1% of the total cannabinoids for inflorescences and res-
ins, respectively; in the case of oils, they constitute 6%
of total cannabinoids. Moreover, most of the samples of
each group (91.2% for inflorescences, 65% for resins,
and 94.5% for oils) showed low CBN concentrations
of below 1 mg/mL.
AB
FIG. 4. Relative frequency (%) of samples based on the acidic/neutral ratio range. (A) Inflorescences (gray
bars), resins (black bars), and oils (white bars). (B) Oil subgroups: GENERAL (white bars), ROFFO (gray bars),
and ACUFALP (black bars).
CANNABIS CONTENT IN HOMEMADE HERBAL PREPARATIONS 7
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CBN levels in the oil subgroups showed significant
differences: GENERAL: 0.3 0.1 mg/mL, ROFFO:
0.1 0.1 mg/mL, and ACUFALP: 0.9 0.6 mg/mL
(Table 2), representing 6% of total cannabinoids for
GENERAL; 0.1% for ROFFO; and 1% for ACUFALP
subgroups. It is worth mentioning that 93.6%,
97.6%, and 83.4% of the samples from the GENERAL,
ROFFO, and ACUFALP subgroups, respectively, con-
tained CBN levels below 1 mg/mL.
Discussion
This work constitutes the first reported analysis of
cannabis derivatives such as inflorescences (n=34),
resins (n=40), and oils (n=362) used therapeutically
in Argentina. The analysis was based on parameters
traditionally used in scientific studies to characterize
cannabis strains or derivatives linked particularly to
therapeutic functions, such as total cannabinoid con-
tent and THC/CBD ratio.
18–20
CBN content was also
analyzed and the relationship between acid and neu-
tral cannabinoids studied.
Our results indicate that total cannabinoid levels in res-
ins were on average 5- and 43-fold higher than those
found in inflorescences and oils, respectively. This is in
line with the concentration and dilution processes associ-
ated with the elaboration of resins and oils from inflores-
cences. However, the variability in each group was
relatively high for all analyzed parameters. This could
be due to the use of different Cannabis sp. strains and
growing conditions (indoor and outdoor); different pro-
cesses carried out to obtain resins and oils, such as alcohol
extractions or macerated in oil; short or prolonged con-
tact times; different temperatures; and the use of the
whole plant or inflorescences only. Other aspects to be
taken into account are the different ways of preserving in-
florescences and their derivatives such as different tem-
perature conditions (room temperature, refrigerator,
and freezer), pressure (atmospheric and vacuum), and
light or darkness, during different periods of time.
14
Our findings show no significant difference among
resins, inflorescences, and oils in the THC/CBD ratio
traditionally used to characterize cannabis oils and de-
rivatives. It should be highlighted that virtually all the
studied resin, inflorescence, and oil samples showed
the presence of THC. Most of the samples in each
group were rich in THC, the THC/CBD ratio being
greater than 1 in 59.4%, 42.5%, and 65.9% of inflores-
cences, resins, and oil samples, respectively. In addition,
24.3% (inflorescences), 15% (resins), and 19.1% (oils) of
samples contained no measurable amount of CBD.
However, the acidic/neutral cannabinoid ratio for in-
florescences showed significant differences with respect
to resin and oil values, evidencing the changes occurring
in acidic and neutral cannabinoid content during the
processes to obtain resins and oils. Thus, 91.2% (inflo-
rescences), 42.5% (resins), and 21.3% (oils) of samples
showed an acidic/neutral ratio >l; note that acidic can-
nabinoids were not detected in 17.5% of the resins and
22.1% of the oils employed for therapeutic proposes.
CBN could occur in cannabis in low concentrations
as a degradation product of THC. High levels of CBN
might indicate poorly stored or aged cannabis with
prolonged exposure to elevated temperatures, light,
and/or oxygen.
21
The low CBN levels observed indicate
that samples were fresh and in accordance with good
practices of the homemade oil production, employing
usually from 5 to 20 g of inflorescences.
Our results indicate that oils form ACUFALP sub-
group presented the highest concentrations of total
cannabinoids, being average 4 and 13 higher than
those observed in GENERAL and ROFFO subgroups,
respectively. In this regard, it should be noted that
only in ACUFALP subgroup, although in different pro-
portions, as opposed to GENERAL and ROFFO sub-
groups, where CBD was not detectable in 16.8% and
25.4% of samples, respectively. Even though most
oils presented higher THC content than CBD, it is
noteworthy that the ACUFALP subgroup presented
the highest proportion of CBD-rich oils, with 20%
of samples showing THC/CBD <1, followed by the
GENERAL (17.3%) and ROFFO (8.8%) subgroups.
Our findings show that the oils studied in this work
presented medium-to-low concentrations of cannabi-
noids compared to a random selection of cannabis prod-
ucts available in other countries. Oils of the ROFFO
subgroup showed the lowest TCC, at approximately
half the concentration of the most diluted oil
(Table 3). Oils of the ROFFO subgroup presented an av-
erage THC/CBD ratio of 22:1, whereas most of the prod-
ucts listed in Table 3 only show the presence of CBD.
When applying cannabis-based oil treatment con-
comitantly with traditional oncological medications
and treatments, the medical team at the Palliative
Care Service (IOAR, Oncologic Institute A
´ngel H.
Roffo) observed that ROFFO subgroup oils employed
by patients in their observational study were associated
with pain reduction and a decrease in OMED (Oral
Morphine Equivalent Dose)
22,23
The presence of THC and CBD in oils of the ROFFO,
GENERAL, and ACUFALP subgroups contrasts with the
8 SEDAN ET AL.
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exclusive CBD content of many products on the interna-
tional market, including Epidiolex (approved by the U.S.
Food and Drug Administration [FDA] for Lennox-
Gastaut and Dravet syndrome treatment). In most
cases, the proportion of acidic and neutral cannabinoids
(THCA, THC, CBDA, and CBD) in studied homemade
oils was different.
Conclusions
In Argentina, as in a growing number of countries around
the world, the use of cannabis for therapeutic purposes is
becoming increasingly widespread for treating symptoms
in a number of diseases. However, access to cannabis-
based products is hindered by legal/economic issues, mak-
ing homemade preparations the norm.Inthiscontext,itis
essential to gain more detailed information on the total
cannabinoid content, the THC/CBD ratio, and the acidic
cannabinoid content of these preparations, all of which
contribute to the oils’ various properties.
23,24
Further-
more, oils containing acidic cannabinoids constitute
an alternative cannabis-based oil since most of the
currently available commercial formulations contain
neutral cannabinoids.
Approval in November 2020 of the new regulation of
medicinal cannabis law 27,350 underscores the need to
expand our knowledge of and protocolize all related
processes, from strain cultivation to material process-
ing and storage, to enhance the quality, safety, and re-
producibility of homemade products.
Our findings indicate that despite their wide vari-
ability, homemade preparations in Argentina show av-
erage levels of cannabinoids and profiles, compatible
with effective therapeutic action.
Acknowledgments
This study was conducted within the framework of the
X780 Cannabis and Health project of the National Uni-
versity of La Plata. We appreciate the contribution and
collaboration of Accio
´nMedia
´tica SRL and their support
to medical cannabis R&D. The authors thank the many
social organizations that havemadeitpossibleforthis
type of research to be conducted in the Public University,
in particular, ACUFALP, the cultural association and
grow club Jardin del Unicornio, Mama Cultiva Argentina,
and to the health workers of Palliative Care Service of the
Oncology Institute Angel H. Roffo.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
X780 Medicinal Cannabis in Argentina. Quality con-
trol of phytopreparations and obtaining phytoprepara-
tions and cannabinoids applied to basic and clinical
research. Research Project. National University of La
Plata UNLP.
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Cite this article as: Sedan D, Vaccarini C, Demetrio P, Morante M,
Montiel R, Saurı
´A, Andrinolo D (2021) Cannabinoid content in
cannabis flowers and homemade cannabis-based products used
for therapeutic purposes in Argentina, Cannabis and Cannabinoid
Research X:X, 1–10, DOI: 10.1089/can.2020.0117.
Abbreviations Used
2-AG ¼2-arachidonoylglycerol
AEA ¼anandamide
ANOVA ¼analysis of variance
CBD ¼cannabidiol
CBDA ¼cannabidiolic acid
CBN ¼cannabinol
CONICET ¼National Council for Scientific and Technical Research
of Argentina
ECS ¼endocannabinoid system
FDA ¼U.S. Food and Drug Administration
HPLC/UV-DAD ¼high performance liquid chromatography/ultraviolet
diode array detector
IOAR ¼Oncologic Institute A
´ngel H. Roffo
NGO ¼nongovernmental organization
SE ¼standard error
TCC ¼total cannabinoid concentration
THC ¼tetrahydrocannabinol
THCA ¼tetrahydrocannabinolic acid
UNLP ¼National University of La Plata
10 SEDAN ET AL.
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