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An evaluation of medicinal grade cannabis in the Netherlands

Authors:
  • Hazekamp Herbal Consulting

Abstract and Figures

Since 2003 medicinal grade cannabis is provided in the Netherlands on prescription through phar- macies. Growing, processing and packaging of the plant material are performed according to pharmaceutical standards and are supervised by the official Office of Medicinal Cannabis (OMC). The quality is guaranteed through regular testing by certified laboratories. However, in the Nether- lands a tolerated illicit cannabis market exists in the form of so-called 'coffeeshops', which offers a wide variety of cannabis to the general public as well as to medicinal users of cannabis. Since cannabis has been available in the pharmacies, many patients have started to compare the price and quality of OMC and coffeeshop cannabis. As a result, the public debate on the success and neces- sity of the OMC program has been based more on personal experiences, rather than scientific data. The general opinion of consumers is that OMC cannabis is more expensive, without any clear dif- ference in the quality. This study was performed in order to show any differences in quality that might exist between the official and illicit sources of cannabis for medicinal use. Cannabis samples obtained from ran- domly selected coffeeshops were compared to medicinal grade cannabis obtained from the OMC in a variety of validated tests. Many coffeeshop samples were found to contain less weight than expected, and all were contaminated with bacteria and fungi. No obvious differences were found in either cannabinoid- or water-content of the samples. The obtained results show that medicinal cannabis offered through the pharmacies is more reliable and safer for the health of medical users of cannabis.
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Cannabinoids 2006;1(1):1-9
© International Association for Cannabis as Medicine 1
Original Article
An evaluation of the quality of medicinal grade
cannabis in the Netherlands
Arno Hazekamp
Leiden University, Department of Pharmacognosy, Gorlaeus Laboratories, Einsteinweg 55, 2333CC Leiden, The Netherlands
Abstract
Since 2003 medicinal grade cannabis is provided in the Netherlands on prescription through phar-
macies. Growing, processing and packaging of the plant material are performed according to
pharmaceutical standards and are supervised by the official Office of Medicinal Cannabis (OMC).
The quality is guaranteed through regular testing by certified laboratories. However, in the Nether-
lands a tolerated illicit cannabis market exists in the form of so-called ‘coffeeshops’, which offers
a wide variety of cannabis to the general public as well as to medicinal users of cannabis. Since
cannabis has been available in the pharmacies, many patients have started to compare the price and
quality of OMC and coffeeshop cannabis. As a result, the public debate on the success and neces-
sity of the OMC program has been based more on personal experiences, rather than scientific data.
The general opinion of consumers is that OMC cannabis is more expensive, without any clear dif-
ference in the quality.
This study was performed in order to show any differences in quality that might exist between the
official and illicit sources of cannabis for medicinal use. Cannabis samples obtained from ran-
domly selected coffeeshops were compared to medicinal grade cannabis obtained from the OMC
in a variety of validated tests. Many coffeeshop samples were found to contain less weight than
expected, and all were contaminated with bacteria and fungi. No obvious differences were found
in either cannabinoid- or water-content of the samples. The obtained results show that medicinal
cannabis offered through the pharmacies is more reliable and safer for the health of medical users
of cannabis.
Keywords: medicinal grade cannabis, quality control, comparison, the Netherlands, Office of Me-
dicinal Cannabis, coffeeshops.
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 www.cannabis-med.org
Author's address: Arno Hazekamp, ahazekamp@rocketmail.com
Introduction
The use of cannabis as a medicine is increasingly be-
coming a topic of public discussion in a growing num-
ber of countries around the world. As a result of the
United Nations Single Convention on Narcotic Drugs
(1961), which was followed by a range of complemen-
tary treaties, international legislation has been a major
obstacle for developments in this field for the last sev-
eral decades. However, in recent years there have been
some serious efforts to bring cannabis back into scien-
tific and clinical research and to permit its use by
medical patients. Initiatives that have been taken range
from the decriminalization of medicinal cannabis use in
the United Kingdom and Switzerland, to serious efforts
to give patients direct access to high quality cannabis,
or derivatives such as standardized extracts, like in
Spain and Canada.
The Netherlands have become the world's first country
to make herbal cannabis available as a prescription
drug in pharmacies to treat a variety of patients. Since
September 2003, pharmacies dispense medicinal can-
nabis to patients on prescription. Doctors practicing in
the Netherlands are allowed to prescribe cannabis to
treat a variety of indications (see below). As a general
guideline, cannabis should be prescribed only after
conventional treatments have been tried and found to
Original Article
2 Cannabinoids Vol 1, No 1 August 13, 2006
be ineffective. As such, cannabis is effectively treated
as a last-resort medication.
Because of the unique, liberal situation in the Nether-
lands with respect to drug laws, an illicit cannabis
market can essentially openly compete with pharma-
cies, and experienced users of medicinal cannabis natu-
rally compare both sources in terms of quality, medici-
nal effect, and price. It is therefore not surprising that
opinions about the quality and efficacy of the state-
grown cannabis emerged in the public media. Because
of the popularity of cannabis as a theme in the media,
opinions about the pharmacy product quickly found
their way to the general public and it became clear that
a group of medical cannabis users were not satisfied
with the offered type of cannabis. A group of cof-
feeshop (see below) owners even started a campaign to
promote the quality of their own material at the ex-
pense of the pharmacy cannabis. However, such opin-
ions and initiatives were generally based on subjective
measures and judgements by a group of authoritative
and experienced users. Obviously, the opinion-based
nature of this debate makes it complicated to evaluate
the introduction of medicinal grade cannabis in the
Netherlands and it clearly shows the need to address
this matter in a scientific way.
The research presented here challenges the messages in
the media about the dissatisfaction of some users with
the medicinal grade cannabis offered by the Office for
Medicinal Cannabis. This cannabis has been variously
claimed to be too weak, too potent or too dry. Accord-
ing to some patients the ‘official’ cannabis doesn’t
work, or it does so in a very different manner from
what they are used to. Other users are wary of the
treatment of medicinal grade cannabis by means of
gamma-irradiation, which is routinely done in order to
sterilize the material. The most common complaint,
however, concerns the higher price. To address these
complaints, we tested samples obtained from randomly
selected coffeeshops according to the validated quanti-
tative and microbiological analyses that are routinely
used for quality control of medicinal grade cannabis in
the Netherlands. The obtained data was compared with
that of the simultaneously obtained pharmacy product.
The tests for analysis of medicinal grade cannabis used
in this study have been described in the official Dutch
monography for medicinal cannabis.
The results presented in this study are intended as a
contribution to the discussion about the necessity or
advantage of having a policy of centrally regulated
production and distribution of medicinal grade canna-
bis. We hope it can also help the users of medicinal
cannabis to make a well-informed choice in the selec-
tion of their medicine.
The Dutch drug policy
In the current situation in the Netherlands, medicinal
users of cannabis can obtain their cannabis material
from two distinct sources: informally through the street
market and formally through the pharmacy. To under-
stand the choices that medicinal users in the Nether-
lands have to make in order to decide between these
two sources, it is important to have some understanding
about the Dutch drug policy concerning cannabis.
The basic principles of the Dutch drug policy were
largely formulated in the mid-seventies. This policy
does not moralise, but is based on the assumption that
drug use is an undeniable fact and must be dealt with as
practically as possible. The most important objective of
this drug policy is therefore to prevent or to limit the
risks and the harm associated with drug use, both to the
user himself and to society. As a results of this, the
Ministry of Health is responsible for co-ordinating drug
policy.
The cornerstone of this policy is the law known as the
Opium Act, which is based on two key principles.
Firstly, it distinguishes between different types of
drugs on the basis of their harmfulness (cannabis prod-
ucts on the one hand, and drugs that represent an "un-
acceptable" risk on the other). The terms ‘soft-drugs’
and ‘hard-drugs’ refer to this distinction. Secondly, the
law differentiates on the basis of the nature of the of-
fence, such as the distinction between possession of
small quantities of drugs intended for personal use, and
possession intended for dealing purposes. Possession of
up to 30 grams of cannabis is a minor offence, while
possession of more than 30 grams is a criminal offence.
Drug use itself is not an offence. This approach offers
the scope to pursue a balanced policy through the se-
lective application of criminal law.
Dealing in small quantities of cannabis, through the out-
lets known as “coffeeshops”, is tolerated (condoned)
under strict conditions. There are currently about 700
such coffeeshops in the Netherlands, with the majority
located in the bigger cities. Tolerance is a typically Dutch
policy instrument which is based on the power of the
Public Prosecutor to refrain from prosecuting offences.
This principle is formulated in the law and is called the
“expediency principle”. The small-scale dealing carried
out in the coffee shops is thus an offence from a legal
viewpoint, but under certain conditions it is not prose-
cuted. These conditions are: no advertising, no sales of
hard-drugs, no nuisance must be caused in the
neighbourhood, no admittance of and sales to minors
(under the age of 18), and no sales exceeding 5 grams of
cannabis per transaction. The stock of the coffeeshop
should not exceed 500 grams of cannabis. If these rules
are violated, the coffeeshop can be closed down by the
municipal authorities.
The idea behind the Netherlands' policy towards the
coffee shops is that of harm reduction. This is based on
the argument that if small-scale cannabis dealing and
use is not prosecuted under certain conditions, the users
– who are mainly young people experimenting with the
drug – are not criminalised (they do not get a criminal
record) and they are not forced to move in criminal
circles, where the risk that they will be pressed to try
more dangerous drugs such as heroin is much greater.
It is widely believed that drugs are legally available in
the Netherlands, and that no effort is made to combat
the supply side of the drug market. Nothing could be
Hazekamp
Cannabinoids Vol 1, No 1 August 13, 2006 3
further from the truth. There is continual, intensive co-
operation between the drug dependence care system,
the judicial authorities and the public administrators.
With the exception of small-scale cannabis dealing in
coffeeshops, tackling all other forms of drug dealing
and production has high priority. The police and cus-
toms officials regularly seize large hauls of drugs and
collaborate closely with other countries in the fight
against organized crime. In 2000 alone, about 40,000
kg of cannabis and about 660,000 marihuana plants
were seized and 1372 nursery gardens dismantled.
Tolerance does not mean that cannabis smokers can
just light up a smoke anywhere they like outside a
coffeeshop. Although no formal rules prohibit cannabis
smoking in public places, such as bars, restaurants or
concert halls, very few people do so. If they do, no
sanctions are applied; but the person is likely to be
asked by the personnel to put out the cigarette. The
absence of formal regulations for the use of cannabis
has opened the way for these informal norms, and their
existence and effectiveness is an aspect of Dutch drug
policy that is often underestimated and difficult to
grasp by foreigners. For example, tourists who visit
Amsterdam commonly make the mistake of thinking
they can smoke cannabis 'everywhere'. It must be noted
that the majority of the Dutch population, especially
senior citizens, has never consumed cannabis and does
not know much about cannabis regulations or habits.
It’s in this complex situation of written and unwritten
rules that consumers of medicinal cannabis in the
Netherlands have to make choices about obtaining their
medicine.
Medicinal cannabis in the Netherlands
Health Minister Els Borst (1994-2002) acknowledged
the fact that a considerable group of people was using
cannabis obtained through coffeeshops for medicinal
purposes. However, its unofficial status makes it im-
possible to make any guarantees on the quality, consis-
tency, or origin of the cannabis found in coffeeshops.
In order to supply these patients with a safe and reli-
able source of high quality cannabis, the Office of
Medicinal Cannabis (OMC) was established in March
2000 and started acting as a national agency on 1
January 2001. The OMC is the organisation of the
Dutch Government which is responsible for the pro-
duction of cannabis for medical and scientifical pur-
poses. It holds the monopoly in the Netherlands for the
import, export, and wholesale of this cannabis and its
preparations on behalf of the Minister of Health,
Welfare and Sport, and is notified to the International
Narcotics Control Board (INCB) in Vienna. The previ-
ously mentioned United Nations Single Convention on
Narcotic Drugs obliges the Netherlands to organize its
Office in this way.
After an initial preparation period, medical grade can-
nabis became available in Dutch pharmacies in Sep-
tember 2003 on prescription only. Potential users must
visit a medical professional (usually their own General
Practitioner), who can grant approval for using canna-
bis for treatment in the form of a prescription.
Based on the availability and quality of clinical data
and scientific literature, a selection of indications was
made by the OMC for treatment with its medicinal
grade cannabis. These are: nausea and loss of appetite
resulting from chemotherapy, radiotherapy or HIV-
combination therapy; palliative treatment for cancer
and HIV patients; spasticity and pain associated with
multiple sclerosis or spinal cord injury; chronic neuro-
genic pain; and physical or verbal tics caused by
Tourette's syndrome. However, if they find it necessary
in selected cases, medical professionals are allowed to
prescribe cannabis for other indications as well.
The medicinal grade cannabis comes in the form of
dried and manicured flowertops of female plants and is
produced by an authorized grower (Bedrocan BV,
Veendam, the Netherlands). Plants are cultivated in-
doors according to guidelines that have been derived
from the general rules for Good Agricultural Practise
of the Working Group on Herbal Medicinal Products of
the European Medicines Evaluation Agency (EMEA)
[3]. The detailed specifications for medicinal grade
cannabis can be found on the website of the OMC [15].
Materials and methods
Medicinal cannabis of the OMC
Currently, two different cannabis varieties are available
in Dutch pharmacies: Bedrocan, mean THC content
18% (specifications: 15.5-21.0%) and Bedrobinol,
mean THC content 13% (specifications: 11.0-14.8%).
The product is finally packaged in sealed plastic con-
tainers in quantities of 5 grams for distribution (figure
1). For this study, two original pharmacy packages
(total 10 grams) of each variety were obtained through
the OMC.
Figure 1: The 5 gram package of medicinal grade cannabis
as currently available in Dutch pharmacies. There are
currently 2 varieties available; the variety shown is
‘Bedrocan’ which has a mean THC content of 18%. (Not
shown is the variety ‘Bedrobinol’, with a mean THC content
of 13%).
Original Article
4 Cannabinoids Vol 1, No 1 August 13, 2006
Cannabis sampling
In order to conduct a statistically acceptable experi-
ment on the quality of cannabis obtained from cof-
feeshops, 10 different coffeeshops were visited. These
were randomly and independently selected by Intraval
(Groningen/Rotterdam, The Netherlands). Further-
more, an unofficial Dutch foundation specialized in
providing cannabis to medical patients was included in
the study, resulting in a total of 11 locations where
samples were collected. In order to guarantee that these
locations remain anonymous, locations are identified
by letters only (A-K). In order to limit traveling time,
only coffeeshops in the West and middle of the Nether-
lands (the provinces of Zuid-Holland, Noord-Holland
and Utrecht) were visited. About 70% of all Dutch
coffeeshops are located in this most densely populated
region of the Netherlands [18].
The person that visited the coffeeshops for collection
of the samples pretended to be a family member of a
patient suffering from multiple sclerosis, and asked
what type of cannabis was recommended for this indi-
cation. The recommended cannabis was then purchased
(10 grams) for performing the study.
Determination of cannabinoid composition and water
content
In order to compare the potency of the samples, con-
tents of delta-9-tetrahydrocannabinol (THC) and its
acidic precursor tetrahydrocannabinolic acid (THCA)
were determined by HPLC analysis. For the analysis,
we used the validated HPLC-method as described in
the official Dutch monography for medicinal cannabis
[3]. In order to confirm the results obtained by HPLC,
quantification of THC and THCA was repeated by
using a recently developed quantitative 1H-NMR
method [6].
Although THC is known to be the major active com-
pound in the cannabis plant, it is widely believed by
researchers, as well as patients, that other components
(predominantly the cannabinoids) also could play a role
in the medicinal properties of cannabis [22]. The bioac-
tivity of such compounds has been shown in a large
variety of scientific studies. Examples are the cannabi-
noid cannabidiol (CBD) that was shown to be active in
the reduction of neuropathic pain [14] and cannabinol
(CBN) that acts on the immune system [8]. To include
non-THC type cannabinoids in our evaluation, the total
profile of cannabinoids present in each sample was
measured by HPLC, as described above, and by gas
chromatography (GC) [7].
Water content of the samples was determined accord-
ing to the method of Karl-Fischer and was expressed as
% of sample weight. Obtained values were confirmed
by determining loss on drying after 24 hours heating at
40ºC under vacuum.
Microbiology
Policy of the OMC prescribes that microbiological
analysis of the medicinal cannabis must be performed
after the plants are harvested and again after the final
product is packaged. Packaged material must conform
with the European Pharmacopoeia (EP), chapter 5.1.4,
category 2: “microbiological quality of pharmaceutical
preparations”, which deals with the requirements for
medicinal preparations for inhalation. To prevent the
formation of microbial toxins, the product is sterilized
shortly after harvest by gamma-irradiation (dose <10
kGy) and subsequently packaged under aseptic condi-
tions. If the packaged product does not conform to the
microbiological specifications of the EP, the entire
batch is rejected for further medical use.
In order to determine the level of microbiological con-
tamination of the obtained samples, microbiological
analysis for the presence of potentially harmful bacteria
and fungi was performed by Bactimm BV (Nijmegen,
The Netherlands), the company that also performs the
routine analyses of medicinal cannabis for the OMC.
Price
The most relevant way to compare prices of medicinal
preparations is by expressing the price relative to the
amount of active ingredient present (price per dosage).
In the case of medicinal use of cannabis, it is widely
assumed that the major active constituent is THC, al-
though other cannabinoids are believed to play a role as
well. Therefore, prices were corrected for the obtained
weight of the samples as well as their content of THC.
Corrected prices were expressed per 100 mg of THC.
Results and discussion
For completion of all the analytical tests, 10 grams of
cannabis was needed, but the Dutch policy concerning
the toleration of coffeeshops prohibits selling more
than 5 grams per client per transaction. Therefore in
most cases the sample collector had to return at a later
time to obtain another 5 grams of the same cannabis.
However, in 4 out of 11 visits the collector was al-
lowed by the coffeeshop to obtain 10 grams at once.
The workers in most coffeeshops were found to have
experience answering questions concerning the me-
dicinal use of cannabis and were willing to offer advice
on matters such as method and frequency of use, as
well as on expected results. Although the cannabis was
explicitly purchased for medical use, none of the vis-
ited locations asked to see a doctor’s prescription be-
fore selling the cannabis.
Obtained samples were weighed in order to divide
them up in portions for performing the different tests. It
was found that less than 9.50 grams were present in the
obtained package(s) in 5 out of 11 cases, meaning a
deficit of more than 5%. A variation of 5% in content
is the tolerance that is usually accepted in trade in the
EU. In one case (coffeeshop A) only 7.49 grams (-
25%) were delivered. Although it was not an objective
of our study, these results indicate that falsification of
weight (whether intentionally or not) is not merely an
incidental problem. In contrast, both samples obtained
from the OMC contained almost exactly the expected
Hazekamp
Cannabinoids Vol 1, No 1 August 13, 2006 5
Table 1: Prices paid for each sample when ’10 grams’
was demanded, and amount of sample (in grams) actually
obtained in the purchase. For Bedrocan and Bedrobinol,
‘10 grams’ was obtained by combining 2 standard phar-
macy packages of 5 grams each.
Cannabis
sample
Price (euro) Obtained weight
(gram)
Bedrocan € 93.92 9.97
Bedrobinol € 81.94 9.90
A € 48.00 7.49
B € 50.00 9.83
C € 60.00 8.37
D € 60.00 10.79
E € 48.00 9.30
F € 60.00 9.63
G € 60.00 9.77
H € 70.00 9.61
I € 50.00 8.81
J € 60.00 9.49
K € 60.00 9.61
amount of 10 grams (± 0.1 gram). The prices and ob-
tained weights of the samples are listed in table 1.
In fresh cannabis plant material, THC is predominantly
present in the form of its acidic precursor THC-acid
(THCA). Under the influence of heat or storage, THCA
can be converted into free THC. For the recreational as
well as the medicinal user, THC is the most important
bio-active component, and therefore it is common
practise in analytical laboratories to determine the total
THC content of cannabis (THCA + THC) after heating
of the plant material. However, this method is not
completely reliable because a full conversion of THCA
to THC is difficult to achieve. Furthermore, during the
heating process degradation products of THC (such as
cannabinol or delta-8-THC) can form or evaporation of
THC can occur [19]. During this study these problems
were prevented by determining the amount of THCA
and THC individually. From these results the total
THC content was then calculated. This method has
only recently become available, through the develop-
ment of a reliable THCA reference standard for quanti-
fication [5,16].
The THC-content of samples is shown in figure 2. For
all coffeeshop samples, the THC content was found to
be in the relatively narrow range of 11.7-19.1% (as
percentage of dry weight plant material). The THC
content of the pharmacy varieties fell also within this
range: variety ‘Bedrocan’ (16.5% THC) was found in
the middle of the range, while variety ‘Bedrobinol’
(12.2% THC) was at the lower end of the range.
Besides THC and THCA, other cannabinoids were
taken into account as well during analysis of the can-
nabinoid composition of the samples. However, no
major differences were observed among the coffeeshop
samples when comparing the obtained GC- or HPLC-
chromatograms. Likely, this is the result of decades of
cross-breeding and selection for high-THC producing
strains of cannabis. This process has minimized the
variability between the cannabis strains, with some
exception for their content of THC. Some representa-
tive HPLC chromatograms are shown in figure 3.
0
5
10
15
20
25
b
Bedrobinol
f
e
c
i
Bedrocan
a
h
g
d
j
k
THC percentage
Figure 2: Content of total THC for each sample in % of sample weight. Results are shown in increasing order. Values are the mean
of 2 determinations. Errorbars indicate standard error.
Original Article
6 Cannabinoids Vol 1, No 1 August 13, 2006
0
0
0
2
0
30
10.00 12.00 14.00 16.00 18.00 20.00 22.00
Sample A
Sample D
Sample K
Bedrocan
THCA
THVA
THC
CBGA
CBG
Sample H
*
UV absorb ance @ 228 nm
0
0
0
2
0
30
10.00 12.00 14.00 16.00 18.00 20.00 22.00
Sample A
Sample D
Sample K
Bedrocan
THCA
THVA
THC
CBGA
CBG
Sample H
*
UV absorb ance @ 228 nm
Figure 3: HPLC chromatograms (228 nm) of selected sam-
ples. No cannabinoids were observed outside the shown
region of the chromatograms. Pharmacy cannabis contains a
larger proportion of free THC (*). CBG: cannabigerol;
CBGA: cannabigerolic acid; THVA: tetrahydrocan-
nabivarinic acid.
When coffeeshop samples were compared to the OMC
samples, only one noticeable difference was observed:
the latter contains a larger proportion of free THC, and
therefore a lower proportion of its carboxylic acid
precursor THCA. We expect this to be the result of
handling and packaging, which is likely to convert
some THCA into free THC. A higher content of free
THC can be beneficial when a patient consumes the
cannabis in a form that has not been heated strongly or
long enough, like in the case of an infusion (for canna-
bis tea). Under such conditions THCA will not be
completely transformed into THC so a smaller amount
of the active component THC will be consumed. How-
ever, when the cannabis is consumed by smoking or in
the form of strongly heated products (e.g. baked prod-
ucts such as cookies), the transformation of THCA into
THC will be virtually complete and the observed dif-
ferences in initial free THC content will become irrele-
vant.
When water content of the samples was compared, it
was found that the OMC-variety ‘Bedrocan’ (water
content 4.7%) was not significantly different compared
to the coffeeshop samples, where water contents
ranged from 3.9-5.5%. For the variety ‘Bedrobinol’
however, a significantly higher water content of 8.0%
was found. According to the OMC, this value was
intentionally higher, after comments from users, in
order to make the inhalation of this variety more pleas-
urable. According to OMC specifications the water
content of the cannabis at the time of quality control
(directly after packaging) must be between 5-10%.
The EP requirements with regard to microbiological
purity for inhalation preparations set the following
limits for sample contamination: total molds and aero-
bic bacteria: 10 colony forming units (CFU) per
gram; total enterobacteria and gram-negative bacteria:
100 CFU per gram. The infectious bacteria Pseudo-
monas aeruginosa and Staphylococcus aureus must be
completely absent. As shown in table 2, all samples
obtained from coffeeshops carried contamination levels
of bacteria and/or fungi above these limits. In contrast,
both cannabis varieties from the OMC were found to
be clear of such contaminations. According to the
OMC, rejection of its medicinal cannabis based on
microbiological contamination has never occurred to
date.
The mycological laboratory of Centraal Bureau voor
Schimmelcultures (CBS, Utrecht, the Netherlands)
further analyzed the contaminants present in one of the
samples (sample K), and identified several known
pathogens, including the intestinal bacterium Es-
cherichia coli, and fungi of the Penicillium,
Cladosporum and Aspergillus types. Some of these
microbes are capable of producing hazardous mycotox-
ins, such as aflatoxin B, ochratoxin A and B, and
sterigmatocystine.
Aflatoxins, in particular, are known to be extremely
potent carcinogens [17]. They are not completely de-
stroyed by heat during smoking, and thus may be in-
haled [2,10]. The presence of potentially hazardous
fungi on recreationally-used cannabis has been de-
scribed routinely and increasingly these fungi are being
acknowledged as an underestimated source of neuro-
logical toxicity [1] or infections such as aspergillosis
[4,11,20]. There are some indications that the use of
anti-inflammatory steroids can increase the susceptibil-
ity to fungal infections [12] and it should be noted that
a significant fraction of the population of patients that
uses medicinal cannabis also uses such drugs. More-
over, medicinal cannabis is relatively commonly used
by HIV/Aids patients and other types of patients that,
because of their compromised immune systems, are
specifically vulnerable to infections. Opportunistic
lung infections with Aspergillus have already been
suggested as a serious contribution to morbidity in this
subgroup of patients [9,20].
Even for consumers who are not immuno-
compromised, neurological toxicity of contaminated
cannabis samples is pointed out as a health risk [1].
Therefore, these combined data indicate that medicinal
use of cannabis that has been purchased from uncon-
trolled sources could be considered as a potential
health risk for the population of medicinal users, par-
ticularly for those who consume larger amounts of
cannabis on a daily basis.
Hazekamp
Cannabinoids Vol 1, No 1 August 13, 2006 7
Table 2: Presence of bacteria and fungi (in cfu per gram)
in the studied samples.
1) CFU per gram = colony forming units present in one
gram of the sample. 2) The contaminants on sample K
were further identified to be the bacterium E. coli, and
fungi of the types Penicillium, Cladosporum and Asper-
gillus.
Sample
Enterobacteria
and Gram-
negative bacteria
(cfu/gram) 1)
Molds and aero-
bic bacteria
(cfu/gram) 1)
OMC samples
Bedrocan <10 < 100
Bedrobinol <10 < 100
Coffeeshop sam-
ples
A <10 480000
B 4500 900
C <10 1000
D 70 120
E 13000 6500
F 80000 4800
G 180 350
H 27000 1300
I 350 4200
J 23000 91000
K 2) 5900 3600
The higher price of medicinal cannabis has proven to
be a major drawback for medical patients in the Neth-
erlands to obtain their cannabis from pharmacies. By
expressing the price of the samples relative to the level
of THC present, a fair comparison between the ob-
tained samples is possible. Results are shown in figure
4. It is shown that the price of the pharmacy variety
‘Bedrocan’ (€ 5.72) is somewhat above the range of
prices that were paid for coffeeshop samples (€ 3.11–
5.16). The relative price of the ‘Bedrobinol’ variety,
however, is significantly higher (€ 6.80). According to
OMC, the higher costs of medicinal grade cannabis are
the result of maintaining a high quality standard for the
product. Included are: production according to pharma-
ceutical standards, aseptic packaging, distribution and
costs made by pharmacies. Moreover, costs accrue as a
result of constant quality controls and microbiological
analyses. Finally, pharmacy cannabis includes a 6%
VAT charge, while the EU VAT system does not allow
that VAT is charged on the illicit (although tolerated)
cannabis from coffeeshops.
Conclusion
The simple rules of supply and demand usually result
in the consumer buying the product with the best qual-
ity-to-price ratio. Because of such forces, the unique
situation in the Netherlands has led to a confusing
situation for medicinal users of cannabis. Price com-
parisons and superficial inspection easily leads to fa-
vouring the cheaper material from the coffeeshops over
the more expensive, but seemingly equal, pharmacy
grade. The fact that only the quality of the latter is
guaranteed through regular controls does not seem to
impress most consumers. However, it is obvious that
the standards for any medicinal preparation are high
and that these can be enforced only by appropriate
analytical testing. According to the OMC, another
reason why the price of Cannabis available in pharma-
cies is currently somewhat higher than expected, is
because sales are relatively low. If the number of pa-
tients would increase, this could influence the price
because the fixed costs per sold unit would drop.
Because the number of coffeeshop samples that were
used for this study was limited, conclusions must be
drawn with some precaution and results presented here
should be reported as incidental findings. Still, based
on the obtained results we concluded that the price paid
for medicinal cannabis distributed through the Dutch
pharmacies must be considered reasonable. The can-
nabinoid strength and composition of the pharmacy
products and the water content are not significantly
different from other types of cannabis. In contrast, the
pharmacy product is guaranteed to have a consistent
potency, and potentially dangerous contaminations are
absent. These results indicate that routine analysis of
the cannabis results in a significantly safer product of
high and reproducible quality. Delivery of medicinal
cannabis to patients through the OMC and pharmacies
results in a reliable product without the health risks
commonly associated with coffeeshop cannabis.
Some patients have claimed that the official cannabis
simply is not as good as their personal choice of ‘medi-
weed’. Certainly, the possibility remains that cannabis
varieties with a similar cannabinoid profile can have
different strengths or effectiveness, based on the pres-
ence of other components such as terpenoids or flavon-
oids. Nevertheless, the current scientific consensus is
that it is mainly the cannabinoids that are responsible
for the bioactivity of cannabis, and testing of the sam-
ples by two different methods did not show obvious
differences in cannabinoid composition. In conclusion,
it seems that there remains some room for discussion
on this point.
When patients choose to obtain cannabis from an un-
controlled source, they must realize that they do so
with a certain risk to their health. In this test, we did
not check for the presence of pesticides, fungicides or
heavy metals, but there are plenty of indications that
these are frequently present in cannabis samples from
uncontrolled sources [13,21]. The same lack of quality
control makes it impossible to determine whether
products that are claimed to be grown organically, like
in some coffeeshops, are really that much more trust-
worthy. Ultimately, it is the consumer that makes the
choice. We hope that the research presented in this
article may help the consumer to make an informed and
safe choice.
Original Article
8 Cannabinoids Vol 1, No 1 August 13, 2006
3.11 3.27
3.84 3.90
4.31 4.34
4.85 5.16
6.80
3.53 3.53
3.74
5.72
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
D
K
J
G
E
A
I
H
B
F
C
Bedrocan
Bedrobinol
Euro / 100 milligram THC
Figure 4: Price of each sample, expressed as price (in euros) paid per equivalent of 100 mg THC. Results are shown in increasing
order.
Tests for the presence of heavy metals and pesticides
are routinely performed for the OMC cannabis. There-
fore the medicinal grade cannabis in Dutch pharmacies
is guaranteed to be free (below official standard limits)
of such contaminants. Unfortunately, because such
tests are very costly, they could not be carried out as
part of this study. Future studies should therefore in-
clude a larger number of sampled locations, and could
include analysis for the presence of heavy metals, pes-
ticides or fungicides.
Acknowledgements
Pieter Seijrier is gratefully acknowledged for his help
in performing this study.
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Those immunocompromised by AIDS or cancer chemotherapy use marijuana to allay symptoms of their disease or treatment. Some researchers believe that marijuana may further suppress the immune system. A list of immunological hazards that may be present in marijuana was collated and assessed, and clinical recommendations regarding the use of marijuana by immunocompromised individuals were made. Databases and other sources from 1964 to 1996 were searched using keywords (e.g., cannabinoids, cannabis, hemp, marijuana). This was supplemented by a manual search of bibliographies, nonindexed books, and journals, and by consultation with experts. All reports were analyzed for antecedent sources. Data validity was assessed by source, identification methodology, and frequency of independent observations. Substances implicated as potential immunological hazards in marijuana include endogenous constituents (cannabinoids, pyrolyzed gases, and particulates) and a longer list of exogenous contaminants, both natural (fungi and their metabolites) and synthetic (pesticides and adulterants). Burning of marijuana creates toxins of combustion. Particulate toxins (tars) are reduced by the use of vaporizer apparati. Gas-phase toxins are filtered by water pipes, but water pipes also filter some tetrahydrocannabinol, making this strategy counterproductive. Viable fungal spores in marijuana pose the greatest hazard to immunocompromised patients, though they can be sterilized by several methods. Pesticide residues and other adulterants may be present in black-market marijuana, but are absent in sources of marijuana that are approved by the Food and Drug Administration.
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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.
Article
Under favorable growth conditions, Aspergillus flavus and A. parasiticus produced aflatoxins on marihuana. Cultures of A. flavus ATCC 15548 produced both aflatoxin B1 (AFB1) and G1 (AFG1). The production of AFG1 was substantially greater than that of AFB1. Cultures of A. flavus NRRL 3251 and A. parasiticus NRRL 2999 produced only AFB1. All natural flora cultures tested negative for aflatoxins. No Aspergilli sporulations were observed in these cultures. In the cultures inoculated with known toxigenic fungi, the highest mean level for total aflatoxins was 8.7 microgram/g of medium. Marihuana appears not to yield large quantities of these mycotoxins but sufficient levels are present to be a potential health hazard for both the user and the forensic analyst who is in daily contact with such plant material. Careful processing, storage, and sanitation procedures should be maintained with marihuana. If these conditions are disregarded due to the illicit status of marihuana, the potential for mycotoxin contamination must be considered.
Article
A 34-year-old man presented with pulmonary aspergillosis on the 75th day after marrow transplant for chronic myelogenous leukemia. The patient had smoked marijuana heavily for several weeks prior to admission. Cultures of the marijuana revealed Aspergillus fumigatus with morphology and growth characteristics identical to the organism grown from open lung biopsy specimen. Despite aggressive antifungal therapy, the patient died with disseminated disease. Physicians should be aware of this potentially lethal complication of marijuana use in compromised hosts.
Article
The possible role of marijuana (MJ) in inducing sensitization to Aspergillus organisms was studied in 28 MJ smokers by evaluating their clinical status and immune responses to microorganisms isolated from MJ. The spectrum of illnesses included one patient with systemic aspergillosis and seven patients with a history of bronchospasm after the smoking of MJ. Twenty-one smokers were asymptomatic. Fungi were identified in 13 of 14 MJ samples and included Aspergillus fumigatus, A. flavus, A. niger, Mucor, Penicillium, and thermophilic actinomycetes. Precipitins to Aspergillus antigens were found in 13 of 23 smokers and in one of 10 controls, while significant blastogenesis to Aspergillus was demonstrated in only three of 23 MJ smokers. When samples were smoked into an Andersen air sampler, A. fumigatus passed easily through contaminated MJ cigarettes. Thus the use of MJ assumes the risks of both fungal exposure and infection, as well as the possible induction of a variety of immunologic lung disorders.
Article
Invasive pulmonary aspergillosis (IPA) is often a lethal entity in transplant recipients (up to 90%). We report the successful treatment of a case of IPA in a renal transplant recipient whose only risk for exposure was habitual marijuana smoking. Although marijuana smoking has been linked to the development of IPA in patients immunosuppressed for a variety of reasons, this case is the first report involving a solid organ transplant recipient. The patient's clinical course and treatment are described and the literature is reviewed with respect to environmental and patient risk factors. In this case, IPA was associated with the patient's heavy usage of marijuana during the immediate posttransplant period. Treatment was successful and included the experimental amphotericin product amphotericin B colloidal dispersion. Contemporaneous exposure to a large amount of inocula of Aspergillus within 30 days of receiving high doses of steroids appeared to be the most important factor that predisposed this patient to IPA. Transplant recipients should be specifically proscribed from marijuana use during periods of high steroid administration.
Article
To examine the significance of previously suggested risk factors and assess outcomes associated with Aspergillus identification in respiratory specimens from HIV-seropositive individuals. This was a nested case-control study. Patients who had Aspergillus species identified in respiratory specimens were matched at the time of study entry 1:2 with control subjects according to study center, age, gender, race, HIV transmission category, and CD4 count. The multicenter Pulmonary Complications of HIV Infection Study. HIV-seropositive study participants. Between November 1988 and March 1994, Aspergillus species were detected in respiratory specimens from 19 (1.6%) participants. The rate of Aspergillus identification among participants with CD4 counts <200 cells per cubic millimeter during years 2 through 5 after study entry ranged from 1.2 to 1.9%. Neutropenia, a CD4 count <30 cells per cubic millimeter, corticosteroid use, and Pneumocystis carinii infection were associated with subsequent identification of Aspergillus in respiratory specimens. Cigarette and marijuana use, previously suggested risk factors, were not associated with Aspergillus respiratory infection. A substantially greater proportion of patients with Aspergillus compared with control subjects died during the study (90% vs 21%). Excluding four cases first diagnosed at autopsy, 67% died within 60 days after Aspergillus was detected. Although Aspergillus is infrequently isolated from HIV-infected persons, the associated high mortality would support serious consideration of its clinical significance in those with advanced disease and risk factors.
Article
To describe the clinical features, causes, imaging characteristics, treatment, and outcome of patients with the acquired immunodeficiency syndrome (AIDS) and sino-orbital aspergillosis. Records of 5 patients were reviewed. Results of imaging and histopathologic examinations and clinical courses of the patients were studied. There were 3 women and 2 men (mean age, 34.0 years). All had received a diagnosis of AIDS, and mean CD4+ cell count was 0.014 x 10(9)/L (14 cells/mm3). Computed tomographic scanning exhibited heterogeneous, enhancing sino-orbital soft tissue lesions with bony erosion, and magnetic resonance imaging disclosed soft tissue masses hypointense on T1- and T2-weighted images. The infection involved 1 or more paranasal sinuses, with extension into the right orbit in 3 patients and into the left orbit in 2. Patients were treated with aggressive surgical debridement and intravenous antifungal agents. In addition, local irrigation of amphotericin B was performed in 3 patients. Aspergillus fumigatus was found to be the cause in all 5 patients. Intracranial extension developed in 4 patients, and all subsequently died. The 2 longest surviving patients were the only ones being treated with protease inhibitors. Three patients had a history of frequent marijuana smoking. Sino-orbital aspergillosis is a progressive, relentless, and usually fatal opportunistic infection of advanced AIDS. Patients are first seen with long-standing headache and proptosis with minimal external inflammatory signs. Marijuana smoking may increase the risk for development of sino-orbital aspergillosis in these patients. Aggressive surgical and medical treatment, combined with newer combination therapies using protease inhibitors, may improve the longevity of these patients.