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Cannabis oil: Chemical evaluation of an upcoming cannabis- based medicine

  • Hazekamp Herbal Consulting
Cannabinoids 2013;1(1):1-11
© International Association for Cannabinoid Medicines 1
Original article
Cannabis Oil: chemical evaluation of an upcoming
cannabis-based medicine
Luigi L Romano, Arno Hazekamp
Department of Pharmacy, University of Siena, Italy
Plant Metabolomics group, Institute of Biology, Leiden University, The Netherlands
Concentrated cannabis extracts, also known as Cannabis oils because of their sticky and viscous
appearance, are becoming increasingly popular among self-medicating patients as a claimed cure
for cancer. In general, preparation methods for Cannabis oils are relatively simple and do not re-
quire particular instruments. The most well-known example of such a product is called ‘Simpson
oil’. The purpose of the extraction, often followed by a solvent evaporation step, is to make canna-
binoids and other beneficial components such as terpenes available in a highly concentrated form.
Although various preparation methods have been recommended for Cannabis oils, so far no stud-
ies have reported on the chemical composition of such products.
Recognizing the need for more information on quality and safety issues regarding Cannabis oils,
an analytical study was performed to compare several generally used preparation methods on the
basis of content of cannabinoids, terpenes, and residual solvent components. Solvents used include
ethanol, naphtha, petroleum ether, and olive oil. The obtained results are not intended to support or
deny the therapeutic properties of these products, but may be useful for better understanding the
experiences of self-medicating patients through chemical analysis of this popular medicine.
Keywords: cannabis oil, Rick Simpson oil, cancer, cannabinoids, terpenes
This article can be downloaded, printed and distributed freely for any non-commercial purposes, provided the original work is prop-
erly cited (see copyright info below). Available online at
Author's address: Arno Hazekamp,
Cannabinoids exert palliative effects in cancer patients
by reducing nausea, vomiting and pain, and by stimu-
lating appetite [1]. In addition, preclinical evidence has
shown cannabinoids to be capable, under some condi-
tions, of inhibiting the development of cancer cells by
various mechanisms of action, including apoptosis,
inhibition of angiogenesis, and arresting the cell cycle
[2,3]. As a result of such exciting findings, a growing
number of videos and reports have appeared on the
internet arguing that cannabis can cure cancer. But
although research is on-going around the world, there
is currently no solid clinical evidence to prove that
cannabinoids - whether natural or synthetic - can effec-
tively treat cancer in humans. It is therefore important
to be cautious when extrapolating preclinical results to
Anecdotal reports on cannabis use have been historical-
ly helpful to provide hints on the biological processes
controlled by the endocannabinoid system, and on the
potential therapeutic benefits of cannabinoids. The
antiemetic [4], appetite-enhancing [5], analgesic [6],
and muscle-relaxant effects [7] and the therapeutic use
of cannabinoids in Tourette’s syndrome [8] were all
discovered or rediscovered in this manner. But alt-
hough it is possible - and even desirable - that cannabis
preparations exert an antineoplastic activity in, at least
some, cancer patients, the current anecdotal evidence
reported on this issue is still poor, and, unfortunately,
remains far from supporting that cannabinoids are
efficacious anticancer drugs for large patient popula-
Original Article
2 Cannabinoids Vol 7, Issue 1 May 5, 2013
tions [9]. It should be noted, however, that the potential
effects of terpenes on cancer, either alone or in combi-
nation with cannabinoids, have not yet been addressed
in laboratory studies. Indeed, the synergistic effect
between cannabinoids and terpenes is often claimed to
be the major difference between ‘holistic’ herbal prepa-
rations of cannabis, and products based on single can-
nabinoids [10]. Moreover, self-medicating patients
often use extraction methods and/or administration
forms that are quite different from conditions used in
(pre)clinical studies, possibly resulting in different
serum profiles of cannabinoids and their metabolites
[11] and, consequently, in different therapeutic effects.
Because of this gap between clinical research and real
experiences, the curative potential of whole cannabis
preparations for the treatment of different cancer types
remains unclear.
In recent years an increasing number of patients have
been using concentrated extracts of herbal cannabis,
which, because of its sticky and viscous appearance,
has become known as “Cannabis oil”. Among the self-
medicating population, it is firmly believed that these
products are capable of curing cancer, a claim that is
backed up by numerous anecdotal patient stories. Can-
nabis oil is a concentrated extract obtained by solvent
extraction of the buds or leaves of the cannabis plant.
Various non-polar solvents have been recommended
for this purpose, including petroleumether, naphtha,
alcohol and olive oil. The purpose of the extraction,
often followed by a solvent evaporation step, is to
make cannabinoids and other beneficial components
such as terpenes available in a highly concentrated
form. In general, preparation methods for Cannabis oil
are relatively simple and do not require particular in-
struments. For this reason, people who have access to
cannabis, either home grown or obtained from licensed
pharmacies, dispensaries, coffee shops or the black
market, may prepare it at home by themselves.
In particular, the captivating story of a former patient
called Rick Simpson, a Canadian who claims to have
cured his skin cancer through repeated topical applica-
tion of Cannabis oil produced according to his own
recipe, has received increasing attention. His detailed
story is described on his website [12] and in a docu-
mentary film called “run from the cure” [13] where
various cancer patients describe the therapeutic effects
of ‘Simpson’ oil on their medical condition. In both the
website and documentary, it is explained in detail how
to prepare and administer the product. The method
suggests the use of naphtha or petroleum ether as a
solvent for the extraction, without specifying a particu-
lar quality or source. Both solvents are a mixture of
petroleum hydrocarbons (PHCs), often available in a
wide range of qualities. In general, petroleum ether and
naphtha refer to very similar products, even though
different names may be used around the world; e.g. in
some countries naphtha is equivalent to diesel or kero-
sene fuel. As a result, extensive discussions on solvent
choice can be found on web-forums. Following the
success of Simpson oil, a number of related recipes
have sprung up, emphasizing small but significant
changes to the original recipe. Examples include focus-
ing on extraction with safer solvents such as ethanol
[14], or preventing exposure to organic solvents alto-
gether, by using olive oil [15].
Since cancer is a devastating disease that affects a large
proportion of the world population, it causes some
patients to seek alternative treatments outside the realm
of modern medicine. With a growing interest in Can-
nabis oils for self-medication it is important not to
overlook the importance of quality control and stand-
ardization. In this regard it should be noted that none of
the production methods for Cannabis oil have been
validated in published literature, and no reports have
been made on the chemical composition of these prod-
ucts either. As a result, although many believe Canna-
bis oil may cure cancer, no one seems to know what is
actually in it. Instead, the positive effects of Cannabis
oil are based almost exclusively on case-reports by
people who have used it. This paper evaluates the ef-
fects of preparation methods, and particularly the sol-
vents used, on the final composition of the different
Cannabis oils. The obtained results are not intended to
support or deny the therapeutic properties of these
products, but may be useful for better understanding
the experiences of self-medicating patients through
chemical analysis of this popular medicine.
Materials and Methods
Plant material
Cannabis plant material used in this study was of the
variety ‘Bedrocan’ (19% THC w/w) and was obtained
from Bedrocan BV (Veendam, The Netherlands) where
it was cultivated under standardized conditions accord-
ing to the requirements of Good Agricultural Practice
(GAP). Only female flower tops were used (‘Cannabis
Flos’). After harvest, the plant material was air-dried in
the dark under constant temperature and humidity for 1
week. Dried flowers were manicured to remove leaves
and stems, and finally cut in smaller pieces. The same
cannabis material is officially dispensed through Dutch
pharmacies under the medicinal cannabis program of
the Netherlands, supervised by the Office of Medicinal
Cannabis (OMC). The plant material was homogenized
by grinding, and stored at -20°C until used.
Chemicals and solvents
Ethanol (HPLC grade), methanol (HPLC grade), acetic
acid (analytical grade) and activated charcoal (analyti-
cal grade) were purchased from Sigma-Aldrich (Stein-
heim, Germany). Petroleum ether (boiling point 40-
65°C; analytical grade) was purchased from Boom BV
(Meppel, The Netherlands). Naphtha (light hydrotreat-
ed petroleum distillate; Coleman® fuel) was purchased
from the Coleman Company (Wichita, USA). Olive oil
(extra virgin quality) was purchased from a local gro-
cery store. Deuterated chloroform (CDCl3) was from
Eurisotop (Gif-sur-Yvette, France). Pure ethanolic
standards for delta-9-tetrahydrocannabinol (THC) and
Cannabinoids Vol 5, No 1 January 23, 2010 3
delta-9-tetrahydrocannabinolic acid (THCA) were
produced as previously described [16,17]. Cellulose filter paper for filtration of extracts was from Whatman
Ltd. (Maidstone, UK).
Table 1: Detailed description of the five different protocols used for preparation of Cannabis oils.
Preparation step
(200 mL)
Petroleum ether
(200 mL)
(200 mL)
Olive oil (20 mL) +
water (70 mL)
Olive oil
(100 mL)
Extraction #1:
5 g cannabis + 100 mL
naphtha, agitate 20
min. (a)
Filtration with filter
Extraction #2:
Same cannabis + 100
mL naphtha, agitate 20
min. (a)
Filtration with filter
Combine extracts
Extraction #1:
5 g cannabis + 100 mL
petr. ether, agitate 20
min. (a)
Filtration with filter
Extraction #2:
Same cannabis + 100
mlLpetr. ether, agitate
20 min. (a)
Filtration with filter
Combine extracts
Extraction #1:
5 g cannabis + 100 mL
ethanol, agitate 20
min. (a)
Filtration with filter
Extraction #2:
Same cannabis + 100
mL ethanol, agitate 20
min. (a)
Filtration with filter
Combine extracts
5g cannabis + 20 mL
olive oil + 50 mL water.
Heat in water bath
~98°C for 60 min.
Before filtration, let it
stand to cool off.
Filtrate by pressing (b)
Rinse the plant
material with 20 mL of
hot water
Filtrate by pressing (b)
Combine extracts
10 g cannabis + 100
mL olive oil. Heat in
water bath ~98°C for
120 min.
Before filtration, let it
stand to cool off.
Filtrate by pressing (b)
(optional): Filter
extract over a column
filled with activated
Evaporate solvent in
water bath ~98°C
under stream of
nitrogen gas
Evaporate solvent in
water bath ~98°C
under stream of
nitrogen gas
Evaporate solvent in
water bath ~98°C
under stream of
nitrogen gas
Let the solution stand
to separate water and
oil. Put it in the freezer
(-20°C) overnight
Reconstitute residue
with EtOH to 100 mL
Reconstitute residue
with EtOH to 100 mL
Reconstitute residue
with EtOH to 100 mL
Collect upper layer
(oil) by pouring it off
the frozen water layer
Collect the oil
5 g/100 mL
5 g/100 mL
5 g/100 mL
5 g/20 mL
10 g/100 mL
2.5 mg/mL
2.5 mg/mL
2.5 mg/mL
2.5 mg/mL
2.5 mg/mL
a): agitate by using a shaking platform @ 120 rpm
b): separate oil from plant material by using a French coffee press
Effects of preheating
Preheating of cannabis samples has been recommended
as a way to potentiate the final extract, i.e. to decar-
boxylate the acidic cannabinoids naturally present in
cannabis plant material, such as THCA and CBDA,
and turn them into their more potent counterparts such
as THC and CBD [18,19]. Therefore, we tested two
decarboxylation methods by heating cannabis plant
material (1 g in an open glass vial) under two condi-
tions: I) in a water bath at a low boil (temp. 98-100°C)
for 5 min, and II) in an oven heated at 145°C for 30
min. Unheated samples were used as a control for these
experiments. All experiments were done in duplicate.
Subsequently, samples were extracted as previously
described [20,21] and analyzed by HPLC and GC.
Preparation of concentrated extracts
Five different extraction protocols for the preparation
of concentrates were assessed. Details are described in
table 1. These included a naphtha (1) and a petroleum
ether extraction (2) according to the procedure of Rick
Simpson [12,13]; an ethanol extraction based on an
Original Article
4 Cannabinoids Vol 7, Issue 1 May 5, 2013
authoritative Dutch website on Cannabis oil [14]; and
two olive oil extractions using different heating dura-
tions (4, 5) based on popular Youtube videos [15].
Chemically, naphtha and petroleum ether are very
similar solvents, and sometimes hard to distinguish
because of the many different qualities available. In the
context of this study we selected an industrial quality
naphtha that was sold as camping fuel (Coleman®) and
contains added chemicals for improving stability, while
the petroleum ether used was of laboratory quality, and
represents a more pure and better characterized prod-
uct. Both solvents may be purchased by inexperienced
patients under the name naphtha or petroleum ether.
All preparation methods consisted of only a few simple
steps, typically involving one or two extraction steps,
separating plant material from solvent, and finally (in
case of organic solvents) an evaporation step to pro-
duce a concentrate. For the ethanol extraction (3) we
also tested the effect of filtration over activated char-
coal, intended to remove chlorophyll which is strongly
extracted by ethanol and may add an unpleasant
‘green’ flavour to the extract. Because the different
extraction methods used different solvent-to-plant
ratios, all extracts were finally diluted in ethanol to
obtain a solvent-to-plant ratio of 2.5 mg/mL in order to
allow direct chromatographic comparison of canna-
binoid and terpene contents by high performance liquid
chromatography (HPLC) and gas chromatography
GC/FID analysis
Because of the heat applied during injection and sepa-
ration, GC is not able to show the presence of acidic
cannabinoids without sample derivatization. As a re-
sult, GC reveals the total cannabinoid content (acidic +
neutral cannabinoids) after decarboxylation, only.
However, terpenes can be efficiently analyzed by GC.
Therefore, an Agilent GC 6890 series (Agilent Tech-
nologies Inc., Santa Clara, CA, USA) equipped with a
7683 autosampler and flame ionization detector (FID)
was used for the analysis of cannabis terpenes as previ-
ously described [20,21]. The instrument was equipped
with a DB5 capillary column (30 m length, 0.25 mm
internal diameter, film thickness 0.25 μm; J&W Scien-
tific Inc., Folsom, CA, USA). The injector temperature
was 230°C, with an injection volume of 4 μL, a split
ratio of 1:120 and a carrier gas (N2) flow rate of 1.2
mL/min. The temperature gradient started at 60°C and
increased at a rate of C/min until 240°C which was
held for 5 min resulting in a total run time of 65 min.
The FID temperature was set to 250°C. The GC was
controlled by Agilent GC Chemstation software ver-
sion B.04.01
HPLC analysis
Cannabinoid profiles were studied in more detail by
HPLC, which enables the differentiationof acidic can-
nabinoids (THCA, CBDA etc.) and their neutral ana-
logues (THC, CBD etc.). Analyses were carried out
using an Agilent (Agilent Technologies Inc., Santa
Clara, CA, USA) 1200 series HPLC system, consisting
of a G1310A pump, an G1322A solvent degasser, and
a G1329A autosampler. Full spectra were recorded in
the range of 200-400 nm using a G1315D photodiode-
array (PDA) detector. Chromatographic separation was
achieved using a Phenomenex C18 column (type
Kinetex, 2.6 μm, 3 x 100 mm). Equipment control, data
acquisition and integration were performed with Ag-
ilent Chemstation software. The mobile phase consist-
ed of methanol and water, acidified with 25 mM formic
acid. Initial setting was 75% methanol (v/v), which was
linearly increased to 100% methanol over 10 min.
After maintaining this condition for 1 min, the column
was re-equilibrated under initial conditions for 4 min,
resulting in a total runtime of 15 min. The flow-rate
was set to 0.5 mL/min, the injection volume was 2 μL,
and the detection wavelength was 228 nm. All experi-
ments were carried out at a column temperature of 40
NMR analysis
Proton Nuclear Magnetic Resonance (1H-NMR) analy-
sis for detection of solvent residues was performed by
dissolving sample aliquots in deuterated chloroform.
Spectra were recorded on a Bruker DPX 300MHz
spectrometer, as previously described [17].
Results and Discussion
Effects of preheating
In the cannabis plant, cannabinoids are biosynthesized
as their acidic forms, characterized by the presence of a
carboxyl group attached to the phenolic ring. Acidic
cannabinoids can be rapidly converted into their ‘neu-
tral’ analogues under the influence of heat or extended
storage [18], which causes loss of the relatively unsta-
ble carboxyl group in the form of carbon dioxide (de-
carboxylation). Preparation of cannabis oil, mainly
intended for oral use, usually involves temperatures
that are relatively low compared to other forms of ad-
ministration where heating of the material is typically
performed at much higher temperatures (e.g. smoking,
vaporizing or baking). For a more thorough decarboxy-
lation, preheating of herbal cannabis before preparation
of cannabis oil has been suggested, for example by
placing the cannabis in an oven.
Besides cannabinoids, the cannabis plant contains a
range of terpenes, which are the volatile compounds
that give cannabis its distinct smell and may act syner-
gistically with cannabinoids [10]. Although preheating
the plant material may release more of the known ac-
tive (neutral) cannabinoids, it may simultaneously also
cause loss by degradation or evaporation of compo-
nents such as terpenes. Our tests were intended to bet-
ter clarify the balance between desired decarboxylation
and unwanted degradation. Unheated cannabis material
was analyzed as a control.
Figure 1A shows the cannabinoid profile of the decar-
boxylated samples, obtained by HPLC analysis. The
Romano & Hazekamp
Cannabinoids Vol 7, Issue 1 May 5, 2013 5
mild water bath treatment did not lead to significant
changes in the acidic-to-neutral cannabinoid ratio. In
contrast, the oven treatment resulted in a complete
decarboxylation of the major cannabinoids detected.
THCA, cannabigerolic acid (CBGA) and canna-
bichromenic acid (CBCA) had all fully converted into
THC, cannabigerol (CBG) and cannabichromene
(CBC), respectively. Further conversion of THC into
its’ main degradation product cannabinol (CBN) only
took place to a small degree during the oven treatment.
Figures 1B and 1C show the terpene profile acquired in
our decarboxylated samples using GC. Compared to
the untreated control, monoterpenes (the most volatile
class of terpenes) were reduced to about half of their
original levels even after exposing the plant material to
boiling water for just 5 min. After the more intense
oven treatment, only small traces of the monoterpenes
terpineol, myrcene and terpinolene could still be de-
tected. As may be expected, the less volatile sesquiter-
penes were more resistant to the mild treatment with
the water bath. However, most of them were lost in the
oven treatment, and only traces of gamma-cadinene
and eudesma-3,7(11)-diene remained.
These data indicate that significant decarboxylation of
the major cannabinoid acids occurs only by exposure to
higher temperatures for extended time (oven at 145°C
for 30 min), which is in agreement with previous stud-
ies [18,22]. However, under these conditions all major
terpenes present were affected by significant evapora-
tion. Although milder decarboxylation using a boiling
water bath may be efficient when applied for longer
time [22], the terpene profile already changes signifi-
cantly after only 5 min of treatment. For this reason, all
further experiments were carried out without applica-
tion of a preheating step.
Analysis of the extracts: cannabinoid and terpene con-
Analysis by HPLC to reveal the ratio between acidic
and neutral cannabinoids in the different extracts was
limited to the main cannabinoids THCA and THC.
Results are shown in Figure 2A. Most extracts con-
tained only a small proportion of THC (5-10% of total
THCA + THC content), as a result of the relatively low
heat of max. 100°C applied during the evaporation
(protocol 1-3) or extraction (protocol 4-5) step. A nota-
ble exception was the naphtha extract, which was
found to contain 33% of total THCA + THC content
present in the form of THC. This is remarkable because
the extract prepared with petroleum ether did not show
the same composition, even though both solvents are
chemically quite similar. Perhaps added chemicals (e.g.
for stability) in the naphtha used in this study may be
responsible for the observed difference.
Analysis of the extracts by GC indicated that the major
components present in the cannabis material used were
the monoterpenes beta-pinene, myrcene, beta-
phellandrene, cis-ocimene, terpinolene and terpineol,
and the sesquiterpenes beta-caryophyllene, humulene,
delta-guaiene, gamma-cadinene, eudesma-3,7(11)-
diene and elemene. This is in agreement with previous
reports on cannabis variety ‘Bedrocan’ [20,21].
The extraction solvents showed comparable efficiency
for extracting terpenes, with the notable exception of
naphtha (Figure 2B and 2C). While this solvent gener-
ally extracted terpenes less efficiently than the other
solvents, several terpenes could not be detected at all in
the naphtha extract. It is not known whether (i) these
components were not extracted from the plant material,
(ii) were degraded or evaporated during the extraction
protocol, or (iii) GC retention times for these compo-
nents were changed as a result of interaction with sol-
vent components. Interestingly, the use of petroleum
ether (chemically very similar to naphtha) did not show
the same absence of components.
The use of olive oil as extraction solvent was found to
be most beneficial based on the fact that it extracted
higher amounts of terpenes than the other sol-
vents/methods, especially when using an extended
heating time (120 min; protocol 5). This may be ex-
plained by the highly non-polar but also non-volatile
character of olive oil, resulting in a good solubilization
of terpenes while limiting their loss by evaporation.
Treatment of the ethanolic extract with activated char-
coal, intended to remove chlorophyll, resulted in a
considerable reduction of cannabinoid content (~50%)
as well as all other sample components (data not
shown). For this reason, the use of charcoal should not
be recommended and was not further evaluated in our
Residual solvent testing
Naphtha and petroleum ether are mixtures of various
hydrocarbon solvents with a range of boiling points,
typically between 30 - 200°C. All the solvent compo-
nents should be considered harmful and flammable,
and some of them, such as hexane and benzene, may be
neurotoxic. Both naphtha and petroleum ether are con-
sidered potential cancer hazards according to their
respective Material Safety Data Sheets (MSDS) pro-
vided by manufacturers. Moreover, products sold as
naphtha may contain added impurities (e.g. to increase
stability) which may have harmful properties of their
own [23]. For these reasons, the naphtha and petroleum
ether extracts were analyzed for residual solvent con-
Analysis by GC as well as NMR revealed significant
residues of petroleum hydrocarbons (PHCs) in the
naphtha and petroleum ether extracts. As may be ex-
pected, mainly PHCs with a higher boiling point (as
indicated by longer GC retention times) were detected,
as they are more resistant to the evaporation procedure
used (Figure 3A). In the naphtha extract, based on GC
peak areas, the content of naphtha residue was roughly
similar to the total content of terpenes remaining in the
extract (Figure 3B).
Reconfirmation using an actual patient sample
In order to confirm our experimental results, we also
analyzed a sample provided by a patient in the Nether-
lands who produced his own cannabis oil using
Original Article
6 Cannabinoids Vol 7, Issue 1 May 5, 2013
Figure 1: (A) Effect of (pre-)heating on the cannabinoid (HPLC analysis), (B) monoterpene and (C) sesquiterpene
composition (GC analysis) of herbal cannabis material. (THCA: tetrahydrocannabinolic acid; THC: tetrahydrocannabinol;
CBN: cannabinol; CBGA: cannabigerolic acid; CBG: cannabigerol; CBCA: cannabichromenic acid; CBC: cannabichromene)
Romano & Hazekamp
Cannabinoids Vol 7, Issue 1 May 5, 2013 7
Figure 2: (A) Effect of five different preparation methods on the cannabinoid (HPLC analysis), monoterpene and
sesquiterpene composition (GC analysis) of concentrated cannabis extracts.
Original Article
8 Cannabinoids Vol 7, Issue 1 May 5, 2013
Figure 3a: Residual naphtha solvent components present in the naphtha extract as indicated by GC analysis. Dotted lines are
added for easier comparison. All chromatograms are shown at the same vertical scaling.
Romano & Hazekamp
Cannabinoids Vol 7, Issue 1 May 5, 2013 9
Figure 3b: GC analysis showing the same ethanol and naphtha extracts as above (Fig. 3a), but now using a larger time scale
to compare total peak area of naphtha components to the sesquiterpenes present in these samples.
Bedrocan® cannabis and following the Simpson meth-
od as described in the internet. The patient was a 50
year old male suffering from cancer of the (left) tonsil
and the tongue. The analytical results (data not shown)
were equivalent to our lab experiments described
above, confirming the residual presence of PHCs at
significant concentrations in a product that is intended
for self-medication of cancer.
Concentrated cannabis extracts, also known as Canna-
bis oils, are increasingly mentioned by self-medicating
patients as a cure for cancer. Despite this growing
popularity, so far no studies have been reported on the
chemical composition or on the different preparation
methods of such products. Recognizing the need for
more information on quality and safety issues regard-
Original Article
10 Cannabinoids Vol 7, Issue 1 May 5, 2013
ing Cannabis oils, the small study presented here com-
pared on the basis of cannabinoid, terpene, and residual
solvent content a few generally used recipes for prepa-
ration of Cannabis oils,.
Based on the results of our preheating experiments,
comparing a mild water bath treatment to more intense
heating in an oven, it can be concluded that it is not
feasible to perform decarboxylation of cannabinoids,
without significant loss of terpene components. This is
particularly important because of the fact that users of
Cannabis oils often claim the holistic nature of canna-
bis components to be responsible for its therapeutic
effects. Retaining the full spectrum of terpenes present
in fresh cannabis material should therefore be a major
focus during optimal Cannabis oil production.
When comparing five methods of Cannabis oil prepara-
tion, some interesting differences were observed be-
tween the resulting extracts. Specifically the prepara-
tion method described by Rick Simpson has attracted
quite a following of self-medicating patients. This
method favours the use of naphtha as solvent for can-
nabinoid extraction, without specifying issues regard-
ing quality or safety. According to the Simpson web-
site: “All these solvents […] are poisonous in nature,
but if you follow these instructions solvent residue in
the finished oil is not a concern. […] Even if there was
a trace amount of solvent residue remaining, the oil
itself would act upon it to neutralize any harmful poi-
sonous effect.” [13]. In other words, the curative prop-
erties are considered to be strong enough to counteract
any and all potential negative effects caused by residu-
al solvents. Chemical analysis of our laboratory sam-
ples, as well as a sample obtained from a patient,
showed that the heavy fraction (components with high
boiling point) of naphtha indeed remains in the extract
despite the recommended evaporation step. Based on
GC-FID peak areas, the total content of PCHs roughly
equalled the total content of terpenes present in the
extract. The potential harmful effects of these solvent
residues have been discussed above.
It should be noted that as a result of sample viscosity,
the more concentrated an extract becomes, the more
difficult it will be to remove the residual solvent from
it. In such a case, applying more heat will increase
evaporation, but simultaneously more terpene compo-
nents will be lost as well. Especially under conditions
where Cannabis oil is prepared by simple household
methods, there will always be a trade-off between re-
sidual solvents and terpene content. For this reason, the
use of non-toxic solvents should always be advised, so
that potential residues are not harmful to health.
As extraction solvents for the production of Cannabis
oils, ethanol and olive oil were shown to perform much
better, extracting all terpenes and cannabinoids tested
very efficiently. Additionally, these solvents are not
harmful. Unfortunately, pure ethanol efficiently ex-
tracts chlorophyll from cannabis, which will give the
final extract a distinct green colour, and often unpleas-
ant taste. Removing chlorophyll by filtering the ethanol
extract over activated charcoal was found to be very
effective, but it also removed a large proportion of
cannabinoids and terpenes, and is therefore not ad-
vised. Additionally, in most countries consumption-
grade ethanol is an expensive solvent, as a result of
added tax on alcohol products.
Of the solvents tested, this leaves olive oil as the most
optimal choice for preparation of Cannabis oils for
self-medication. Olive oil is cheap, not flammable or
toxic, and the oil needs to be heated up only to the
boiling point of water (by placing a glass container
with the product in a pan of boiling water) so no over-
heating of the oil may occur. After cooling down and
filtering the oil, e.g. by using a French coffee press, the
product is immediately ready for consumption. As a
trade-off, however, olive oil extract cannot be concen-
trated by evaporation, which means patients will need
to consume a larger volume of it in order to get the
same therapeutic effects. In a follow-up study on the
use of Cannabis oils, there should be more focus on the
characteristics and motivations of those who use it for
LR was funded for this research by the Puglia (Italy)
regional government with a “Ritorno al futuro grant.
AH is the head of Research and Development at Bed-
rocan BV, the Netherlands.
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... Maceration is a technique that involves the infusion of the dried parts of the plant, properly minced to expose a larger surface area in an appropriate liquid medium-in this case, fat oils-for the extraction of the plant's active components. To prepare these oils, the Italian jurisdiction allows different methods proposed by Società Italiana Farmacisti Preperatori (SIFAP), Romano Hazekamp, Cannazza and Calvi [10][11][12][13]. Pharmacies manufacture these preparations as fit-to-patient drugs, known as galenic formulas. ...
... Samples (n. 28) were gathered and analyzed, distributed as follows: n. [11], B-Citti/Cannazza [12], C-SIFAP [10] and D-Calvi [13]). The two MCT preparations were made using the SIFAP method (C). ...
... The preparation methods for the cannabis medicinal oils are mainly based on the maceration of vegetable materials in olive oil at high temperature, at about 100 • C or over (Methods A-Hazekamp et al. [11] and B-Citti/Cannazza et al. [12]). Both of them do not require a preliminary decarboxylation of the vegetal matrix. ...
The therapeutic use of Cannabis oil extracts is constantly increasing. However, in Italy, they are allowed to be prepared with only a few methods and matrices. With this work, we aimed to assess how the different processes might affect the chemical composition of two different matrices (olive oils and medium chain triglycerides oils - MCT), accounting as variables for both the presence of Cannabis dried apices of the female flower and the adding of tocopherol acetate as an antioxidant. The macerated oils were prepared with four of the methods allowed according to the Italian legislation (Romano-Hazekamp, Cannazza-Citti, SIFAP and Calvi) and analyzed for normal and oxidized tocopherols, oxidized and conjugated fatty acids and volatile carbonyl compounds (VCCs), all using liquid chromatography coupled to UV or PDA detectors. According to our results, neither normal nor oxidized tocopherols are affected by the addition of antioxidants or Cannabis, while the oxidation state (according to the levels of oxidized and conjugated fatty acids) is often altered in either case. The VCCs concentrations, on the other hand, are never notably altered. These results suggest a worthless use of antioxidants in Cannabis macerated oils preparations, while the dried apices of female flowers might have a protective role in maintaining the oil oxidation state.
... Medicinal cannabis extracts and other processed forms may thus contain residual solvents. This is especially relevant to extracts which have a sticky and viscous nature that make it difficult to remove solvents (Romano & Hazekamp, 2013). The most common examples of such cannabis extracts are termed "Rick Simpson oils" or "FECO's" (full extract cannabis oil). ...
... Cannabinoids as well as terpenoids and flavonoids are extracted by a solvent, followed by an evaporation step in order to increase the concentration of these compounds in the extract (Romano & Hazekamp, 2013;Hazekamp, 2006). These types of cannabis oils or extracts are becoming increasingly popular amongst self-medicating patients because of the simplicity and low cost involved in producing the oils (Romano & Hazekamp, 2013). ...
... Cannabinoids as well as terpenoids and flavonoids are extracted by a solvent, followed by an evaporation step in order to increase the concentration of these compounds in the extract (Romano & Hazekamp, 2013;Hazekamp, 2006). These types of cannabis oils or extracts are becoming increasingly popular amongst self-medicating patients because of the simplicity and low cost involved in producing the oils (Romano & Hazekamp, 2013). After solvent evaporation, residues are still present in the extract and the concentrations of the solvent residues should be controlled through good manufacturing practice (GMP) and quality control of the final products (International Community of Harmonization (ICH), 2011). ...
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Organic solvents are used for manufacturing herbal medicines and can be detected as residues of such processing in the final products. It is important for the safety of consumers to control these solvent residues. South African cannabis-based product samples were analysed for solvent residue contaminants as classified by the United States Pharmacopeia (USP), chapter 467. The origin of these samples ranged anywhere from crude extract, product development samples, and market ready final products. Samples were submitted to a contract laboratory over a period of 2 years from 2019 to 2021. To date, no data of this kind exist in South Africa specifically relating to cannabis-based medicinal, recreational, or complementary products. A total of 279 samples were analysed in duplicate by full evaporation headspace gas-chromatography mass-spectrometry and the results are reported in an anonymised format. The results showed an alarming 37% sample solvent residue failure rate with respect to adherence to USP 467 specification. It is important to ensure regulation is enforced to control product quality. The South African public need to be educated about the risks associated with cannabis-based products.
... In general, the predominant cannabinoid in all extracts was THCA (190-617 mg/g), while the least present was THCV which was found only in Chocolope EtOH extract. The lower content of cannabinoids in EtOH extracts can probably be attributed to the higher polarity of the solvent and thus lower extraction ability of these compounds into the resulting extract (Politi et al., 2008;Romano and Hazekamp, 2013). ...
... Both EtOH extracts compared to BUT and DME ones lacked most of the identified monoterpenes (i.e., thujene, α-pinene, ß-myrcene, and (+)-limonene). These terpenes were probably lost during the evaporation of the solvent under vacuum and increased temperature (Romano and Hazekamp, 2013). In conclusion, the gas extraction was Results are expressed as mean ± standard deviation. ...
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Cannabis preparations are gaining popularity among patients with various skin diseases. Due to the lack of scientific evidence, dermatologists remain cautious about their prescriptions. So far, only a few studies have been published about the effects of high-potency cannabis extracts on microorganisms (especially dermatophytes) causing skin problems that affect more than 25% of the worldwide population. Even though, the high-potency cannabis extracts prepared by cold extraction are mostly composed of non-psychoactive tetrahydrocannabinolic acid (THCA) and only low amount of THC, their use in topical treatment can be stigmatized. The in vitro antimicrobial and antifungal activity of two high potent cannabis strains extracted by three solvents traditionally or currently used by cannabis users (ethanol; EtOH, butane; BUT, dimethyl ether; DME) was investigated by broth dilution method. The chemical profile of cannabis was determined by high-performance liquid chromatography with ultraviolet detection and gas chromatography with mass spectrometer and flame ionization detector. The extraction methods significantly influenced chemical profile of extracts. The yield of EtOH extracts contained less cannabinoids and terpenes compared to BUT and DME ones. Most of the extracts was predominantly (>60%) composed of various cannabinoids, especially THCA. All of them demonstrated activity against 18 of the 19 microorganisms tested. The minimal inhibitory concentrations (MICs) of the extracts ranged from 4 to 256 μg/mL. In general, the bacteria were more susceptible to the extracts than dermatophytes. Due to the lower content of biologically active substances, the EtOH extracts were less effective against microorganisms. Cannabis extracts may be of value to treat dermatophytosis and other skin diseases caused by various microorganisms. Therefore, they could serve as an alternative or supportive treatment to commonly used antibiotics.
... The most common ways to administer Cannabis orally for medical purposes, that are permitted by certain legislations, include decoctions and oil extracts (Baratta et al., 2019). There are three common methods to prepare cannabis oils: the so-called RH method described by Romano and Hazekamp (2013); the CC method described by Citti et al. (2016); and the SF method instructed by Societa Italiana Farmacisti Preparatori (2016) (Baratta et al., 2019;Citti et al., 2016;Romano & Hazekamp, 2013;Societa Italiana Farmacisti Preparatori, 2016). All of these methods are designed for a weight-to-solvent volume ratio of 100:1. ...
... The most common ways to administer Cannabis orally for medical purposes, that are permitted by certain legislations, include decoctions and oil extracts (Baratta et al., 2019). There are three common methods to prepare cannabis oils: the so-called RH method described by Romano and Hazekamp (2013); the CC method described by Citti et al. (2016); and the SF method instructed by Societa Italiana Farmacisti Preparatori (2016) (Baratta et al., 2019;Citti et al., 2016;Romano & Hazekamp, 2013;Societa Italiana Farmacisti Preparatori, 2016). All of these methods are designed for a weight-to-solvent volume ratio of 100:1. ...
Due to the multiple health benefits associated with the consumption of cannabinoids, there is a current trend on continuing to explore their biological properties. Cannabidiol (CBD) is likely to be the most investigated endocannabinoid from the cannabis plant. Unfortunately, the purification of CBD from its natural source and psychotropic analogue (tetrahydrocannabinol, THC) is timely challenging for the research community based on the similar physiochemical properties of both molecules. This latter fact becomes relevant for the final application of CBD in edibles as a bioactive compound. Therefore, this paper comprehensively reviews the latest development works (over the last 2–3 years) aiming at the extraction of cannabinoids and purification of CBD using traditional, emerging, and synergistic extraction techniques and strategies. Particular emphasis and discussion have been focused on the innovative extraction techniques and the relevant outcomes with detailed strategies to meet such high extraction rates. Biological properties (at lab-scale and clinical case studies), current practices, progress in legislation and commercialization of CBD are also overviewed. Finally, according to the findings of this review, the future trends and research gaps are also given.
... MPa 1/2 ) and olive oil (16.8-17.7 MPa 1/2 ) (King, 2019). In addition, ethanol has been reported as a suitable solvent for extraction of cannabinoids due to it exhibited high extraction capacity and safety than other organic solvents, including petroleum ether, naphtha, hexane, acetone, and methanol (Romano and Hazekamp, 2013;Brighenti et al., 2017;Ubeed et al., 2022). ...
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Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase in-hibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of −7.5 and −6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in vitro assay on α-glucosidase revealed that THC and CBD exhibited good inhibitory activity, with the IC 50 values of 3.0 ± 0.37 and 5.5 ± 0.28 μg/ml, respectively. These were better than the standard drug, acarbose (IC 50 of 488.6 ± 10.23 μg/ml). Furthermore, two standardized cannabinoid extracts, SCE-I (C. sativa leaf extract) and SCE-II (C. sativa inflorescence extract) exhibited stronger inhibitory activity than THC and CBD, with the IC 50 values of 1.2 ± 0.62 and 0.16 ± 0.01 μg/ml, respectively. The present study provides the first evidence that the standardized cannabinoid extracts containing THC and CBD have greater potential than CBD and THC in application as an α-glucosidase inhibitor.
... El aceite de "cannabis" se prepara a partir de un extracto vegetal concentrado, obtenido por extracción de las flores secas y en algunos casos, también de las hojas superiores de la planta de "cannabis", que luego es vehiculizado en un aceite fijo para su posterior utilización. El propósito de la extracción es disponer de los cannabinoides en altas concentraciones y en su forma activa (18) . Sin embargo, la composición química (cualitativa y cuantitativa) del extracto y del aceite preparado a partir de éste, está vinculada a muchos factores tales como: morfotipo/quimiotipo de "cannabis" utilizado; condiciones de cultivo; forma de recolección y desecación de la planta; partes de la planta utilizada y método de extracción empleado. ...
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Introduction: The therapeutic use of the “cannabis” oil is a social problem that puts legal, health, scientific and cultural aspects under stress. Difficulty in access generates an emptiness exploited by the illegal market, to which patients and relatives resort to improve their health and quality of life. These oils, with unknown chemical composition, are used without therapeutic follow-up. An interdisciplinary team from the Universidad Nacional de Córdoba (UNC) started the study of this problem with the aim of characterizing the socio-therapeutic use of “cannabis" oil in Córdoba and establishing a relationship with the real content of cannabinoids. Methodology: Observational-descriptive and cross-sectional study approved by the Comité Institucional de Ética de las Investigaciones en Salud, Hospital Nacional de Clínicas from UNC (CIEIS-HNC-UNC): interviews with patients/caregivers of legal age who used the “cannabis” oil (year 2019). Experimental study: analysis of oil samples obtained from interviewees to determine their cannabinoid content, specifically delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), by High Performance Liquid Chromatography analysis (HPLC). Results: thirty-seven interviews were conducted, and 48 samples were analysed. The 73% were adults and older adults. The 92% started using the oil without prescription or medical suggestion, mainly due to the lack of effectiveness of other therapies (54%) and in the search for therapeutic alternatives (33%). The 84% perceived it to be effective (moderate to highly effective), and 78% reported no adverse events. Main uses: refractory epilepsy 27% and arthritis/arthrosis 24%. Fifteen percent of the samples showed no quantifiable content of CBD and THC, and 67% had only THC. The quantifiable content of cannabinoids was very low. Conclusions: This work allowed carrying out a preliminary information-gathering on several aspects (social and therapeutic) about the use of “cannabis” oil in Córdoba, and to analyze the chemical quality of the oils consumed. An important finding was the discrepancy between the effectiveness perceived by users and the low cannabinoid content detected.
Background: The presence of contaminants in cannabis presents a potential health hazard to recreational users and susceptible patients with medical conditions. Because of the federally illegal status of cannabis, there are no unified regulatory guidelines mitigating the public health risk of cannabis contaminants. Objective: To inform further research and provide solutions to the public health risk of cannabis contaminants at a national level, we examined the current landscape of state-level contaminant regulations, and cannabis contaminants of concern, as well as patient populations susceptible to contaminants. Methods: We examined the regulatory documents for medical and recreational cannabis in all legalized U.S. jurisdictions and compiled a complete list of regulated contaminants, namely, pesticides, inorganics, solvents, microbes, and mycotoxins. We data mined the compliance testing records of 5,654 cured flower and 3,760 extract samples that accounted for ∼6% of California's legal cannabis production in 2020-2021. We also reviewed the publicly available medical cannabis use reports to tabulate the susceptible patient populations. Results: As of 18 May 2022, 36 states and the District of Columbia listed a total of 679 cannabis contaminants as regulated in medical or recreational cannabis, including 551 pesticides, 74 solvents, 12 inorganics, 21 microbes, 5 mycotoxins, and 16 other contaminants. Different jurisdictions showed significant variations in regulated contaminants and action levels ranging up to four orders of magnitude. A failure rate of 2.3% was identified for flowers and 9.2% for extracts in the California samples. Insecticides and fungicides were the most prevalent categories of detected contaminants, with boscalid and chlorpyrifos being the most common. The contaminant concentrations fell below the regulatory action levels in many legalized jurisdictions, indicating a higher risk of contaminant exposure. Cannabis use reports indicated usage in several patient populations susceptible to contamination toxicity, including cancer (44,318) and seizure (21,195) patients. Discussion: Although individual jurisdictions can implement their policies and regulations for legalized cannabis, this study demonstrates the urgent need to mitigate the public health risk of cannabis contamination by introducing national-level guidelines based on conventional risk assessment methodologies and knowledge of patients' susceptibility in medical use.
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Kenevirin tıpta yeri
Carbon dioxide (CO2) is a major greenhouse gas. Therefore, its alternative utilization is beneficial from sustainability perspectives. CO2 at a temperature and pressure above its critical points (i.e., 31.1°C and 7.38 MPa) is known as supercritical CO2 (SCCO2). SCCO2 exhibits some unique features such as a gas-like viscosity and liquid-like density. These properties promote its utilization for several industrial applications. This chapter provides an overview of the unique properties of SCCO2 and its applications in several industrial applications such as hydrotreating of biofuels, extraction of bioactive compounds, including cannabinoids, biomass pretreatment, sterilization of medical equipment, and conversion of waste heat into power. Moreover, its solvent properties can be fine-tuned through density adjustments to meet specific operating conditions for different chemical processes. In addition, the chapter also provides challenges and future perspectives of SCCO2 utilization in several industries.
Background Cannabis oils from FM2®, Bedica®, Bediol®, Bedrocan®, Bedrolite® and Pedanios 22/1® are largely used for medical purposes such as spasticity, chronic pain and appetite stimulating. Several studies showed cannabinoids action on CB1 and CB2 receptors reduces the hyperalgesic phase in inflammatory pain, leading to an improvement of conditions. The active compounds of these galenic preparations show a high variability making titration mandatory. For this reason, the exact oil composition knowledge is fundamental for personalizing therapy. This amis at adapting the correct dose to the patient, improving safety and efficacy of the galenic formulation, choosing the best preparation for each patient. Purpose The aim of this study was to investigate oil preparations variability among different galenic laboratories in order to highlight the importance of titration activity. Methods Cannabis pharmacological active compounds titration has been performed in a large cohort of galenic laboratories in Italy. CBD, CBN, THC, THCA and CBDA quantification was carried out by a previous validated method in UHPLC-MS/MS. Results A number of 4318 samples of Cannabis oil from 83 pharmacies between January 2021 and February 2022 were evaluated. All galenic preparation specialities showed statistically significant differences among galenic laboratories (p-value < 0.001). THCA and CBDA concentrations were investigated as percentage of the extration yelds for total THC and CBD: these compounds had different values in the same specialities among distinct galenic laboratories. Moreover, seasonal variability in analytes concentrations was observed. Conclusion This study described a wide range of oily samples from a large number of galenic laboratories, compared to published papers. In conclusion, knowledge of the exact oil composition is fundamental in the perspective of personalized therapy. Further studies aiming at the correlation between galenic composition and cannabinoids pharmacokinetics, clinical outcomes and toxic effects could be useful to improve our knowledge.
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A simple method is presented for the preparative isolation of seven major cannabinoids from Cannabis sativa plant material. Separation was performed by centrifugal partition chromatography (CPC), a technique that permits large‐scale preparative isolations. Using only two different solvent systems, it was possible to obtain pure samples of the cannabinoids; (−)‐Δ‐(trans)‐tetrahydrocannabinol (Δ‐THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), (−)‐Δ‐(trans)‐tetrahydrocannabinolic acid‐A (THCA), cannabigerolic acid (CBGA), and cannabidiolic acid (CBDA). A drug‐type and a fiber‐type cannabis cultivar were used for the isolation. All isolates were shown to be more than 90% pure by gas chromatography. This method makes acidic cannabinoids available on a large scale for biological testing. The method described in this report can also be used to isolate additional cannabinoids from cannabis plant material.
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In recent years, cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to findings that they can affect the viability and invasiveness of a variety of different cancer cells. Moreover, in addition to their inhibitory effects on tumor growth and migration, angiogenesis and metastasis, the ability of these compounds to induce different pathways of cell death has been highlighted. Here, we review the most recent results generating interest in the field of death mechanisms induced by cannabinoids in cancer cells. In particular, we analyze the pathways triggered by cannabinoids to induce apoptosis or autophagy and investigate the interplay between the two processes. Overall, the results reported here suggest that the exploration of molecular mechanisms induced by cannabinoids in cancer cells can contribute to the development of safe and effective treatments in cancer therapy.
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Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL -1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endo- genous substances - the endocannabinoids - that activate specific cell surface receptors. Cannabi- noids exert palliative effects in cancer patients. For example, they inhibit chemotherapy-induced nausea and vomiting, stimulate appetite and inhibit pain. In addition, cannabinoids inhibit tumor growth in laboratory animals. They do so by modulating key cell signaling pathways, thereby in- ducing antitumoral actions such as the apoptotic death of tumor cells as well as the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds as they can kill tumor cells without significantly affecting the viability of their non-transformed counter- parts. On the basis of these preclinical findings a pilot clinical study of ∆ 9 -tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has recently been run. The fair safety profile of THC, together with its possible growth-inhibiting action on tumor cells, may set the ba- sis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
Our knowledge of the pharmacodynamics of cannabinoids, that is, “the study of the biochemical and physiologic effects of drugs and their mechanisms of action” (The Merck Manual), has considerably increased within the past decade due to the detection of an endogenous cannabinoid system with specific receptors and their endogenous ligands. THC (δ⁹-tetrahydrocannabinol), the main source of the pharmacological effects caused by the use of cannabis including the medicinal benefits of the plant, is an agonist to both the CB1 and the CB2 subtype of these receptors. Its acid metabolite THC-COOH (11-nor-9-carboxy-THC), the non-psychotropic cannabidiol (CBD), analogues of these natural compounds, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues (spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart, etc.). Additionally, there is evidence for non-receptor dependent mechanisms of cannabinoids. Five endogenous cannabinoids, anandamide, 2-arachidonylglycerol, noladine ether, virodhamine, and NADA, have been detected. There is evidence that besides the two cannabinoid receptor subtypes cloned so far, additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of endocannabinoids that include, for example, motor coordination, memory procession, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of re-uptake into cells and inhibition of their degradation to increase concentration and duration of action. At doses exceeding the psychotropic threshold, ingestion of exogenous CB1 receptor agonists or cannabis, respectively, usually causes an enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important potential adverse acute effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects, increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term damages on psyche and cognition, immune system, fertility and on pregnancy remain controversial. They are reported to be low in humans and do not preclude a legitimate therapeutic use of cannabis based drugs. Properties of cannabinoids that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, anti-inflammation, anti-allergic effects, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects.
Decarboxylation of cannabidiolic and tetrahydrocannabinolic acids was studied in open reactors in order to investigate the accuracy and reliability of the decarboxylation sample preparation process applied prior to indirect methods, which has been widely used for the determination of cannabinoid acids. The rate of the decarboxylation reaction was followed by the high-performance liquid chromatographic determination of the neutral cannabinoids formed. The effects of different parameters (temperature, solvents, sorbent phases, salts) on decarboxylation were investigated. Reliable results could only be obtained by the mathematical correction of data obtained from experiments in an open reactor.
Various reports have shown that cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms. This Opinion article discusses our current understanding of cannabinoids as antitumour agents, focusing on recent insights into the molecular mechanisms of action, including emerging resistance mechanisms and opportunities for combination therapy approaches. Such knowledge is required for the optimization of preclinical cannabinoid-based therapies and for the preliminary clinical testing that is currently underway.