ArticlePDF Available

Evaluating the Effects of Gamma-Irradiation for Decontamination of Medicinal Cannabis

  • Hazekamp Herbal Consulting

Abstract and Figures

In several countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment by gamma irradiation currently seems the only method available to meet these requirements. We evaluated the effects of irradiation treatment of four different cannabis varieties covering different chemical compositions. Samples were compared before and after standard gamma-irradiation treatment by performing quantitative HPLC analysis of major cannabinoids, as well as qualitative GC analysis of full cannabinoid and terpene profiles. In addition, water content and microscopic appearance of the cannabis flowers was evaluated. This study found that treatment did not cause changes in the content of THC and CBD, generally considered as the most important therapeutically active components of medicinal cannabis. Likewise, the water content and the microscopic structure of the dried cannabis flowers were not altered by standard irradiation protocol in the cannabis varieties studied. The effect of gamma-irradiation was limited to a reduction of some terpenes present in the cannabis, but keeping the terpene profile qualitatively the same. Based on the results presented in this report, gamma irradiation of herbal cannabis remains the recommended method of decontamination, at least until other more generally accepted methods have been developed and validated.
Content may be subject to copyright.
published: 27 April 2016
doi: 10.3389/fphar.2016.00108
Frontiers in Pharmacology | 1April 2016 | Volume 7 | Article 108
Edited by:
Adolfo Andrade-Cetto,
Universidad Nacional Autónoma de
México, Mexico
Reviewed by:
Jürg Gertsch,
University of Bern, Switzerland
Ashwell Rungano Ndhlala,
Agricultural Research Council,
South Africa
Ildikó Rácz,
University of Bonn, Germany
Arno Hazekamp
Specialty section:
This article was submitted to
a section of the journal
Frontiers in Pharmacology
Received: 25 January 2016
Accepted: 11 April 2016
Published: 27 April 2016
Hazekamp A (2016) Evaluating the
Effects of Gamma-Irradiation for
Decontamination of Medicinal
Cannabis. Front. Pharmacol. 7:108.
doi: 10.3389/fphar.2016.00108
Evaluating the Effects of
Gamma-Irradiation for
Decontamination of Medicinal
Arno Hazekamp *
Head of Research and Education, Bedrocan International BV, Veendam, Netherlands
In several countries with a National medicinal cannabis program, pharmaceutical
regulations specify that herbal cannabis products must adhere to strict safety standards
regarding microbial contamination. Treatment by gamma irradiation currently seems the
only method available to meet these requirements. We evaluated the effects of irradiation
treatment of four different cannabis varieties covering different chemical compositions.
Samples were compared before and after standard gamma-irradiation treatment by
performing quantitative UPLC analysis of major cannabinoids, as well as qualitative
GC analysis of full cannabinoid and terpene profiles. In addition, water content and
microscopic appearance of the cannabis flowers was evaluated. This study found that
treatment did not cause changes in the content of THC and CBD, generally considered as
the most important therapeutically active components of medicinal cannabis. Likewise,
the water content and the microscopic structure of the dried cannabis flowers were not
altered by standard irradiation protocol in the cannabis varieties studied. The effect of
gamma-irradiation was limited to a reduction of some terpenes present in the cannabis,
but keeping the terpene profile qualitatively the same. Based on the results presented
in this report, gamma irradiation of herbal cannabis remains the recommended method
of decontamination, at least until other more generally accepted methods have been
developed and validated.
Keywords: medicinal cannabis, cannabinoids, terpenes, gamma-irradiation, quality control
Because medicinal cannabis is often used by chronically ill patients affected by a weakened immune
system, pharmaceutical regulations in countries such as The Netherlands and Canada specify that
these products must adhere to strict safety standards regarding microbial contamination. When
harmful microbes or fungal spores are inhaled during e.g., vaporizing or smoking, they may directly
enter the bloodstream and cause opportunistic infections. Such contamination risks are not merely
hypothetical: cases of chronic pulmonary aspergillosis associated with smoking unsafe cannabis are
well established in the scientific literature (Llamas et al., 1978; Sutton et al., 1986; Marks et al., 1996;
Szyper-Kravitz et al., 2001; Kouevidjin et al., 2003; Cescon et al., 2008; Bal et al., 2010; Ruchlemer
et al., 2015). For those with compromised immune systems, such lung diseases could be even fatal
(Hamadeh et al., 1988).
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
To minimize contamination risks to patients, Dutch
regulations demand that medicinal cannabis contains no more
than 100 colony-forming units (CFUs) per gram of final product,
which is close to sterility1. Under the Canadian program, limits
are somewhat higher with a maximum of 1.000 CFUs per gram2.
Following European or US Pharmacopoeia standards for inhaled
preparations, certain specific pathogens must be completely
absent, i.e., Staphylococcus aureus,Pseudomonas aeruginosa,
and any bile-tolerant Gram-negative bacteria such as E. coli
(EP, 2015; USP, 2015). Furthermore, the absence of fungal
mycotoxins must be confirmed by additional quality control
Decontamination of medicinal (herbal) cannabis is a
necessity, as it has yet not been possible to grow cannabis plants
under sufficiently sterile conditions to keep contamination
levels below the required safety limits. Even if this were feasible,
the multiple steps involved in harvesting, drying, processing
and packaging cannabis buds would make it extremely hard
to maintain near-sterile conditions throughout the entire
production procedure. As a result, medicinal cannabis in The
Netherlands as well as in Canada is treated by gamma irradiation
before it becomes available to patients1,2.
Methods of Decontamination
Reduction of microbes can be achieved by various treatments, as
listed in Table 1. The optimal choice of decontamination depends
on the nature of the product to be treated. For herbal materials
such as cannabis, the only currently viable option for treatment is
the use of ionizing radiation. Any of the other decontamination
treatments would either affect chemical content or texture (i.e.,
heat, chemicals, pressure, steam; Ruchlemer et al., 2015) or would
not penetrate beyond the surface of the dense cannabis flowers
(i.e., UV-light).
Gamma irradiation involves exposing the target material to
packets of light (photons) that are so highly energetic (gamma
rays) that they damage the DNA strands present in microbes. As
a result, the affected microbes cannot multiply, and consequently
they will perish3. Because medicinal cannabis is a harvested and
dried (i.e., non-living) product, this effect is not relevant for the
condition of the cannabis plant cells.
Irradiation Safety and Concerns
Most commonly, the radioactive element cobalt-60 (60Co) is
used as the source for gamma irradiation. If administered at
appropriate levels, irradiation can be used for the removal of
decay-causing bacteria from many foods and herbs, and can
prevent sprouting of fruit and vegetables to maintain freshness
and flavor (EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011; Arvanitoyannis et al.,
2009). Decontamination or sterilization by gamma irradiation
is also widely applied to medical instruments and medicines
(Hasanain et al., 2014).
2 mps/marihuana/info/techni-eng.php
TABLE 1 | List of current main methods available for decontamination or
sterilization of (food) products.
Type of decontamination Main treatments
Heat: Dry heat
Steam (autoclave)
Chemicals: Gas (ethylene oxide, ozone, nitrogen dioxide)
Liquid (hydrogen peroxide, formaldehyde)
High pressure: Pascalization
Filtration: Micropore filter (NB: for liquids only)
Radiation: Non-ionizing (UV-light)
Ionizing (gamma-irradiation, X-rays, electron beam)
Over the years, the safety of irradiated foods has been
confirmed in various animal as well as human studies. These
include animal feeding studies lasting for several generations
in several different species, including mice, rats and dogs
(WHO, 1999; EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011). NASA astronauts have
been eating irradiated foods when they fly in space since the
1970s (Perchonok and Bourland, 2002). Irradiation-induced
changes in food components are generally small and not
significantly different from those reported in other conventional
preservation processes, especially those based on thermal
treatment (EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011; Shahbaz et al., 2015).
The changes in some components that are sensitive to irradiation,
like some vitamins or micronutrients (Caulfield et al., 2008) may
be minimized by using proper treatment conditions (Kilcast,
1994; WHO, 1999).
The safety of irradiated foods has been endorsed by the
World Health Organization (WHO), the Food and Agriculture
Organization of the United Nations (FAO), the U.S. Department
of Agriculture (USDA), Health Canada (HC), the European
Union (EU), and the Food and Drug Administration (FDA).
Gamma irradiation is now permitted by over 60 countries with
at least 400,000 metric tons of foodstuffs annually processed
worldwide (EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011). The regulations that
dictate how food is to be irradiated, as well as which foods
are allowed to be treated, may vary greatly from country to
Despite these developments, irradiation remains a somewhat
controversial decontamination technique that can spark
emotional debates among the general public. One specific
concern with irradiation treatment is the formation of radiolytic
compounds, in particular 2-alkylcyclobutanones (2-ACBs).
These chemicals are formed in minute quantities when high
fat containing foods (such as sesame seeds, pork meat, cheese,
eggs, fish) are subjected to gamma irradiation, and their content
increases with irradiation dose (Zanardi et al., 2007; Lee et al.,
2008). Although some contradictory in vitro findings exist on
the safety of these compounds, overall scientific consensus is that
2-ACBs are not an immediate cause for concern (EFSA Panel
Frontiers in Pharmacology | 2April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
on Food Contact Materials Enzymes Flavourings Processing
Aids-CEF, 2011).
Of course, consumers may also be concerned about the
indirect effects of irradiation, such as the way it changes
the way we relate to food or herbal medicine, or how the
use of radioactive materials affect the environment during
their mining, shipping and use. Furthermore, irradiation,
like any form of treatment, adds to the final cost of a
food product or medicine. All these concerns should be
taken into consideration when determining whether gamma
irradiation is the proper choice for decontamination of a
Evaluating the Effects of Gamma
Irradiation on Medicinal Cannabis
Patients have occasionally expressed their concerns about the
effects of irradiation treatment on medicinal cannabis. Some
have claimed a change of taste or effect, while others worry
about changes in the chemical composition or the quality of
their medicine5. In response to such concerns, some Canadian
licensed producers of medicinal cannabis initially pledged not
to apply irradiation, but were forced to reconsider when their
products could not meet microbial safety requirements. To
cushion the impact on their customers, the obscuring term “cold
pasteurization” was introduced when in fact gamma irradiation
treatment was applied6.
In fresh Cilantro leaves, gamma irradiation was shown to
reduce the content of terpenes such as myrcene and linalool (Fan
and Sokorai, 2002). Likewise, irradiation may perhaps have an
effect on cannabis terpenes, which seem to play an important
role in the synergistic effect and bioavailability of cannabinoids
(Russo, 2011). Although an early study by our group on
the effect of cannabis irradiation did not indicate changes in
the cannabinoid profile (unpublished data), chromatographic
analysis of cannabinoids has significantly improved over the
years meaning that more detailed changes in the cannabinoid
profile may now be visualized. The occurrence of 2-ACBs
seems of limited relevance in the case of cannabis, because
average daily cannabis consumption is very small compared to
other irradiated products such as meats, fruits of vegetables.
Also, cannabis flowers do not contain significant amounts
of fat needed to form these radiolytic compounds in the
first place.
To address the concerns that may exist around gamma
irradiation of medicinal cannabis, we evaluated the effects of
irradiation treatment of four different cannabis varieties covering
different compositions (THC vs. CBD dominant types, Sativa
vs. Indica types). Samples were compared before and right
after standard gamma-irradiation treatment, by performing
quantitative analysis of major cannabinoids, as well as qualitative
analysis of full cannabinoid and terpene profiles. In addition,
water content and microscopic appearance of the cannabis
flowers was evaluated.
5 an/securit/irridation/cyclobutanone-eng.php
6 marijuana-orders-
Solvents and Chemicals
All organic solvents were HPLC or analytical grade. Acetonitrile
was obtained from Boom labs BV (Meppel, The Netherlands).
Ethanol and phosphorus pentoxide (P4O10) was purchased from
VWR (Amsterdam, The Netherlands).
Cannabis Samples
Pharmaceutical-grade cannabis was obtained from the licensed
Dutch cultivator, Bedrocan BV (Veendam, the Netherlands).
Plants were grown from genetically identical clones under
standardized indoor conditions. Flower tops were harvested
and air-dried for 1 week under controlled temperature and
humidity. Four different standardized varieties available in
Dutch pharmacies were used for this study i.e., Bedrocan R
Bediol R
,Bedica R
, and Bedrolite R
. Batch information
and chemical composition of these products is listed in
Table 2.
All cannabis batches used for this study were harvested in the
period of late 2014–early 2015. Following standard procedure,
each batch was packaged in portions of 250 grams in triple
laminate foil bags with zip-lock closure (type Lamizip aluminum;
Daklapack, The Netherlands) for gamma irradiation treatment
at Synergy Health (Etten-Leur, The Netherlands). Each batch
received an irradiation dose of (minimum) 10 kGy produced with
a Cobalt-60 radiation source.
Of each cannabis variety a 10 gram sample was collected
before (non-irradiated control) as well as after (irradiated
sample) gamma irradiation, resulting in a total of 8 samples for
this study [4 varieties ×2 treatments (before/after irradiation)].
Samples were homogenized by grinding in a blender until the
material was about 5 mm in diameter. Ground samples were
finally used for determination of water content, and for sample
extraction for GC/UPLC analysis. Of variety Bedrocan, the
most popular variety used by Dutch patients (Hazekamp and
Heerdink, 2013), some non-homogenized samples were kept for
microscopic analysis.
All samples were handled and stored under equivalent
conditions. For each variety, irradiated and control samples
were extracted and analyzed on the same day, so that any
changes in chemical composition could only be attributed
to the irradiation treatment. This study was carried out
under a cannabis research license issued by the Dutch Health
TABLE 2 | Cannabis type and batch information of the cannabis varieties
used in this study.
Variety name Batch # THC/CBD
Harvest date
Bedrocan A1.01.45 THC Sativa 11-12-2014
Bediol A2.05.15 THC +
Sativa 25-12-2014
Bedrolite A2.08.13 CBD Sativa 08-01-2015
Bedica A2.07.20 THC Indica 22-01-2015
Frontiers in Pharmacology | 3April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 1 | Structures of the cannabinoids quantitatively analyzed by UPLC.
Water Content Determination
Water content of each homogenized sample was determined
by using the Loss on Drying (LOD) method according
to EP monograph 2.3.32 (method C). In short, 500 mg of
each sample (in duplicate) was accurately weighed in small
plastic containers, and dried for 24 h at 40C under vacuum
inside a desiccator containing the potent desiccant phosphorus
pentoxide. Subsequently, all samples were weighed again. Water
content (in percentage of initial weight) was determined by
comparing weight before and after the procedure.
Sample Extraction
Ground cannabis samples were extracted for Gas
Chromatography (GC) and Ultra-Performance Liquid
Chromatography (UPLC) analysis as described in the
Dutch Analvtical Monograph for release testing of Cannabis
Flos, version 7.1 (OMC, 2015)7. In short, 1000 mg of each
specificaties-en- analysevoorschriften
homogenized sample (in duplicate) was extracted with 40 mL
of absolute ethanol in plastic serum tubes (maximum content
50 mL) while mechanically shaking for 15 min at 300 rpm.
Tubes were then centrifuged at 3000 rpm and clear supernatant
was transferred to a 100 mL volumetric flask. For exhaustive
extraction, the procedure was repeated twice more with 25 mL
of ethanol, and supernatants were combined. Volumes were
adjusted to 100 mL with ethanol, mixed well, and filtered through
a 0.45 µm PTFE syringe filter to remove small particles. Filtrated
extracts were used directly for GC analysis, or further diluted
with acetonitrile/water (70:30, v/v) for analysis by UPLC.
Quantitative UPLC Analysis of Major
The UPLC profiles were acquired on a Waters (Milford, MA)
Acquity UPLC system consisting of a gradient pump, an
autosampler, a column oven and a diode array detector (DAD).
The device was controlled by Waters Empower software. Full
spectra were recorded in the range of 200–400 nm. The analytical
Frontiers in Pharmacology | 4April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 2 | Total THC and total CBD content (in % of dry weight) as determined by UPLC analysis, as well as water content (in % of total weight) as
determined by Loss on Drying method (LOD) in all studied varieties before (gray bars) and after (black bars) irradiation treatment.
column was a Waters Aquity C18 (1.7 µm, 2.1 ×150 mm)
equipped with a matching guard column. The mobile phase
consisted of a gradient of acetonitrile (A) and water (B), both
containing 0.1% formic acid. The gradient was programmed as
follows: 0–6 min (hold at 70% A); 6–10.5 min (linear increase to
100% A); 10.5–11 min (hold at 100% A). The column was then
re-equilibrated under initial conditions for 1.5 min, resulting in a
total runtime was 12.5 min. Flow-rate was 0.4 mL/min. Injection
volume was 10 µL. Chromatographic peaks were recorded at
228 nm. All determinations were carried out at 30C. All samples
were analyzed in duplicate.
Applying the standard protocol for release testing of medicinal
cannabis (OMC, 2015)7, the following cannabinoids were
quantitatively determined: THC, THCA, CBD, CBDA, delta-8-
THC, CBN. The structures of these compounds, including their
full chemical names, are shown in Figure 1.
Qualitative GC Analysis of Cannabinoid
and Terpene Profiles
Gas chromatography was used for the simultaneous qualitative
analysis of monoterpenes, sesquiterpenes, and cannabinoids
as previously reported (Hazekamp and Fischedick, 2012). An
Agilent GC 6890 series (Agilent Technologies Inc., Santa Clara,
CA, USA) equipped with a 7683 autosampler and a flame
ionization detector (FID) was used. The instrument was equipped
with a DB5 capillary column (30 m length, 0.25 mm internal
diameter, film thickness 0.25 µm; J&W Scientific Inc., Folsom,
CA, USA). The injector temperature was 230C, with an injection
volume of 1 µl, a split ratio of 1:20 and a carrier gas (N2) flow
rate of 1.2 ml/min. The temperature gradient started at 60C and
linearly increased at a rate of 3C/min until the final temperature
of 240C which was held for 5 min resulting in a total run time of
65 min/sample. The FID detector temperature was set to 250C.
The device was controlled by Agilent GC Chemstation software
version B.04.01.
Microscopic Visualization of Glandular
In order to visualize potential morphological changes in
the glandular hairs (where cannabinoids and terpenes are
produced) present in the cannabis flowers, microscopic
analysis of cannabis variety Bedrocan was performed before
and after gamma-irradiation treatment. Whole cannabis
flowers were used, without homogenizing. A Leica (type
MZ16FA) stereo-microscope was used. Images were captured
at a magnification factor ranging from 20 to 120 times
with a Leica (type DFC420C) camera, controlled by LAS
Frontiers in Pharmacology | 5April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | Continued
Loss on Drying
Inhalation, either by smoking or vaporizing, is currently the main
mode of administration used by patients (Hazekamp et al., 2013).
Water content (humidity) seems to have significant impact on
how consumers appreciate medicinal cannabis products during
inhalation (Ware et al., 2006). Although gamma irradiation does
not significantly heat up the treated product, water may be lost
during the procedure either as a result of the irradiation itself
(Yu and Wang, 2007) or because of shipping and handling
of the product during the treatment. Release specifications for
Bedrocan products require the water content to be no more
than 10%. As shown in Figure 2, the actual water content of the
analyzed varieties ranged between 5 and 8%, with no differences
between treated and control samples.
UPLC Analysis
Six major cannabinoids were quantitatively analyzed by applying
a validated UPLC methodology that is used as standard
procedure for release testing of medicinal cannabis in The
Netherlands. As customary, the sum of THC and its acidic
precursor THCA is reported as “total THC content.” Similarly,
the sum of CBD and CBDA is reported as “total CBD content.”
It should be noted that delta-8-THC and CBN are not originally
Frontiers in Pharmacology | 6April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | Continued
produced by the cannabis plant, but are formed as degradation
products of THC by exposure to heat or light, or by prolonged
storage (Hazekamp et al., 2010).
Results of cannabinoid testing are shown in Figure 2,
indicating that levels of total THC and/or CBD were not altered
by irradiation treatment in any of the varieties studied. No delta-
8-THC or CBN was detected in any of the samples (before or
after irradiation) at levels over 0.1% (which equals 1 mg/gram of
cannabis flower).
GC Analysis
Components visualized by GC analysis were not individually
quantified because of the multitude of chromatographic peaks
of interest (>50). Instead, the entire profiles of all visible
peaks are presented in Figure 3. Because of the complexity of
these profiles, the sections of the profile where monoterpenes,
sesquiterpenes, and cannabinoids elute are displayed separately.
For each variety, control (non-irradiated) samples, and treated
(irradiated) samples are shown side by side, using the same
vertical scale to allow direct comparison. The main peaks in
each variety were identified based on previously published data
(Hazekamp and Fischedick, 2012).
While the overall qualitative composition of the samples
was unaltered, differences in several terpene components could
be detected after irradiation in the cannabis varieties studied.
Components that showed a clear reduction after irradiation
Frontiers in Pharmacology | 7April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | Continued
treatment are indicated in Figure 3 by showing the relative
change (in %) compared to untreated sample. Because a small
variability of terpene content between samples is to be expected,
and is also observed between replicates of non-treated samples,
changes that are smaller than +/– 5% are not indicated. The
main components affected were the monoterpenes myrcene,
cis-ocimene and terpinolene, and the sesquiterpenes gamma-
selinene, eudesma-3,7(11)-diene and gamma-selinene. No new
terpene peaks were formed as a result of treatment. No
cannabinoids were altered or formed as a result of irradiation.
Multiple microscopic images were obtained of variety
Bedrocan on flowers collected before and after treatment
with gamma-irradiation, at a magnification of about 20–120
times. The trichomes (glandular hairs) where cannabinoid and
terpenes are excreted by the cannabis plant are clearly visible, as
shown in Figure 4. No clear differences in trichome structure,
color, density, or shape could be observed between the control
(non-irradiated) samples and treated (irradiated) samples.
Gamma irradiation treatment of cannabis has become standard
practice in the government-supported medicinal cannabis
programs of The Netherlands as well as Canada. In the study
presented here such treatment, at a radiation dose (10 kGy)
sufficient to reduce microbial contamination (bioburden) to
pharmaceutically acceptable levels, did not cause any changes
in the content of THC and CBD, generally considered as the
most important therapeutically active components of medicinal
Frontiers in Pharmacology | 8April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | GC profiles of four studied varieties showing monoterpenes, sesquiterpenes, and cannabinoids in separate sections. C, control
(non-irradiated); T, treated (irradiated); *: artifact. Numbers indicate percentage of change in treated samples compared to non-treated controls.
cannabis (Grotenhermen and Müller-Vahl, 2012). Likewise, the
water content and the microscopic structure of the dried cannabis
flowers were not altered by standard irradiation protocol in four
different cannabis varieties. The study included representative
varieties of THC and CBD dominant types, as well as Sativa and
Indica types.
In our study, irradiation had a measurable effect on the
content of multiple cannabis terpenes, mainly on the more
volatile monoterpenes. Reduction of affected terpenes was in
general between 10 and 20%, but for some components this
may be as much as 38%. In a previous study evaluating
the effect of gamma irradiation on fresh Cilantro, a decrease
in terpene content was also described (Fan and Sokorai,
2002). However, the authors concluded that the observed loss
of terpenes such as myrcene and linalool was insignificant
compared to the losses that occurred by evaporation during
refrigerated storage of Cilantro. Also in orange juice the effect
of irradiation on terpenes was found to be non-significant
in comparison to changes induced by refrigerated storage
(Fan and Gates, 2001). Likewise, the slight terpene reduction
observed in the current study is comparable to the effect
that short term storage in a paper bag had on cannabis
samples, in a study performed by (Ross and ElSohly, 1996).
A likely explanation therefore seems that gamma irradiation
Frontiers in Pharmacology | 9April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 4 | Microscopic images of trichomes (glandular hairs) before and after treatment with gamma-irradiation. Cannabis variety Bedrocan was used.
Magnification ±20–120 times.
slightly accelerates the evaporation of some of the more volatile
terpenes. This idea is supported by the fact that no degradation
products or additional chromatographic peaks were found to
account for the lost terpenes, with the exception of some
beta-caryophyllene oxide formed in the irradiated sample of
variety Bedica. Interestingly, terpenes were not affected to the
Frontiers in Pharmacology | 10 April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
same degree in all varieties, e.g., myrcene content was clearly
reduced in varieties Bedica and Bedrolite but not in variety
Bediol. Perhaps this indicates a protective effect that cannabis
components may have on each other when present in specific
Some cannabis users have claimed that irradiation changes
the taste and/or smell of cannabis during smoking or vaporizing
(personal observation by the author). Unfortunately, such
opinions may be hard to substantiate because the same cannabis
is usually not available to consumers in both its irradiated and
non-irradiated form to allow direct comparison, meaning there is
no “base-line” product to quantify the magnitude of the change.
Nevertheless, the taste and smell of cannabis mainly depends
on its terpene (essential oil) content (Russo, 2011). While the
current study indicated quantitative changes in some of the
terpenes upon irradiation, a subtle change in smell or taste may
indeed be possible as a result of such treatment. Despite these
changes, the overall terpene profile of each variety remained
clearly recognizable.
Gamma irradiation remains controversial among some
consumers of medicinal cannabis. However, weighing the risks
vs. the benefits currently keeps pointing toward the use of this
decontamination procedure. After all, cannabis plants cannot
(yet) be grown and processed under conditions aseptic enough
to meet pharmaceutical standards, while infection risks are well
documented in the medical literature and can be harmful or
even fatal to seriously ill patients. Meanwhile, the main harm of
gamma-irradiation seems to be limited to a reduction of some
terpenes present in the cannabis, leading to a small quantitative
effect, but keeping the terpene profile qualitatively essentially
Based on the results presented in this report, gamma
irradiation of herbal cannabis remains the recommended method
of decontamination, at least until other more generally accepted
methods have been developed and validated. This is especially
important when cannabis is prescribed to seriously ill and
possibly immune-deprived patients, with an increased risk of
suffering from microbial infection. Meanwhile, the development
of improved hygienic standards for cultivation and processing
of medicinal cannabis may ensure that irradiation doses can be
reduced to an absolute minimum. In time, gamma-irradiation
may eventually be replaced with other, more generally accepted,
forms of reliable decontamination.
The author confirms being the sole contributor of this work and
approved it for publication.
The Dutch Office of Medicinal Cannabis (OMC) and
pharmaceutical quality control laboratory Proxy Labs (Leiden,
The Netherlands) are gratefully acknowledged for their support
in performing this study. A big thanks to Gerda Lamers (Leiden
University) for preparing the microscopic images.
Arvanitoyannis, I. S., Stratakos, A. Ch., and Tsarouhas, P. (2009). Irradiation
applications in vegetables and fruits: a review. Crit. Rev. Food Sci. Nutr. 49,
427–624. doi: 10.1080/10408390802067936
Bal, A., Agarwal, A. N., Das, A., Suri, V., and Varma, S. C. (2010). Chronic
necrotising pulmonary Aspergillosis in a marijuana addict: a new cause of
amyloidosis. Pathology 42, 197–200. doi: 10.3109/00313020903493997
Caulfield, C. D., Cassidy, J. P., and Kelly, J. P. (2008). Effects of gamma irradiation
and pasteurization on the nutritive composition of commercially available
animal diets. J. Am. Assoc. Lab. Anim. Sci. 47, 61–66.
Cescon, D. W., Page, A. V., Richardson, S., Moore, M. J., Boerner, S., and Gold,
W. L. (2008). Invasive pulmonary aspergillosis associated with marijuana
use in a man with colorectal cancer. J. Clin. Oncol. 26, 2214–2215. doi:
EFSA Panel on Food Contact Materials Enzymes Flavourings and Processing Aids-
CEF (2011). Scientific Opinion on the Chemical Safety of Food Irradiation.
EFSA J. 9:1930. doi: 10.2903/j.efsa.2011.1930
EP (2015) European Pharmacopoeia (EP), Version 7.0 – Section 5.1.4.
Microbiological Quality of Non-Sterile Pharmaceutical Preparations and
Substances for Pharmaceutical Use. Strasbourg.
Fan, X., and Gates, R. A. (2001). Degradation of monoterpenes in orange juice by
gamma radiation. J. Agric. Food Chem. 49, 2422–2426. doi: 10.1021/jf0013813
Fan, X., and Sokorai, K. J. (2002). Changes in volatile compounds of gamma-
irradiated fresh cilantro leaves during cold storage. J. Agric. Food Chem. 50,
7622–7626. doi: 10.1021/jf020584j
Grotenhermen, F., and Müller-Vahl, K. (2012). The therapeutic potential
of cannabis and cannabinoids. Dtsch. Arztebl. Int. 109, 495–501. doi:
Hamadeh, R., Ardehali, A., Locksley, R. M., and York, M. K. (1988).
Fatal aspergillosis associated with smoking contaminated marijuana, in
a marrow transplant recipient. Chest 94, 432–433. doi: 10.1378/chest.94.
Hasanain, F., Guenther, K., Mullett, W. M., and Craven, E. (2014). Gamma
sterilization of pharmaceuticals - a review of the irradiation of excipients,
active pharmaceutical ingredients, and final drug product formulations. PDA
J. Pharm. Sci. Technol. 68, 113–137. doi: 10.5731/pdajpst.2014.00955
Hazekamp, A., and Fischedick, J. T. (2012). Cannabis - from cultivar to chemovar.
Drug Test. Anal. 4, 660–667. doi: 10.1002/dta.407
Hazekamp, A., Fischedick, J. T., Llano-Diez, M., Lubbe, A., and Ruhaak, R.
L. (2010). “Chemistry of Cannabis,” in Comprehensive Natural Products II
Chemistry and Biology, Vol. 3, eds L. Mander, H.-W. Lui (Oxford, UK: Elsevier),
Hazekamp, A., and Heerdink, E. R. (2013). The prevalence and incidence of
medicinal cannabis on prescription in The Netherlands. Eur. J. Clin. Pharmacol.
69, 1575–1580. doi: 10.1007/s00228-013-1503-y
Hazekamp, A., Ware, M. A., Muller-Vahl, K. R., Abrams, D., and Grotenhermen,
F. (2013). The medicinal use of cannabis and cannabinoids - an international
cross-sectional survey on administration forms. J. Psychoactive Drugs 45,
199–210. doi: 10.1080/02791072.2013.805976
Kilcast, D. (1994). Effect of irradiation on vitamins. Food Chem. 49, 157–164. doi:
Kouevidjin, G., Mazieres, J., Fayas, S., and Didier, A. (2003). Aggrevation of
allergic bronchopulmonary aspergillosis by smoking marijuana. Revue Francias
Allergol. Immunol. Clin. 43, 192–194. doi: 10.1016/S0335-7457(03)00050-9
Lee, J., Kausar, T., and Kwon, J. H. (2008). Characteristic hydrocarbons and
2-alkylcyclobutanones for detecting gamma-irradiated sesame seeds after
steaming, roasting, and oil extraction. J. Agric. Food Chem. 56, 10391–10395.
doi: 10.1021/jf8021282
Llamas, R., Hart, D. R., and Schneider, N. S. (1978). Allergic bronchopulmonary
aspergillosis associated with smoking moldy marihuana. Chest 73, 871–872.
doi: 10.1378/chest.73.6.871
Frontiers in Pharmacology | 11 April 2016 | Volume 7 | Article 108
Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
Marks, W. H., Florence, L., Leiberman, J., Chapman, P., Howard, D.,
Roberts, P., et al. (1996). Successfully treated invasive aspergillosis
associated with smoking marijuana in a renal transplant recipient.
Transplantation 61, 1771–1774. doi: 10.1097/00007890-199606270-
Perchonok, M., and Bourland, C. (2002). NASA food systems: past, present, and
future. Nutrition 18, 913–920. doi: 10.1016/S0899-9007(02)00910-3
Ross, S. A., and ElSohly, M. A. (1996). The volatile oil composition of fresh and
air-dried buds of cannabis sativa. J. Nutr. Prod. 59, 49–51. doi: 10.1021/np9
Ruchlemer, R., Amit-Kohn, M., Raveh, D., and Hanuš, L. (2015). Inhaled medicinal
cannabis and the immunocompromised patient. Support. Care Cancer 23,
819–822. doi: 10.1007/s00520-014-2429-3
Russo, E. B. (2011). Taming THC: potential cannabis synergy and
phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol. 163,
1344–1364. doi: 10.1111/j.1476-5381.2011.01238.x
Shahbaz, H. M., Akram, K., Ahn, J. J., and Kwon, J. H. (2015). Worldwide status
of fresh fruits irradiation and concerns about quality, safety and consumer
acceptance. Crit. Rev. Food Sci. Nutr. doi: 10.1080/10408398.2013.787384.
[Epub head of print].
Sutton, S., Lum, B. L., and Torti, F. M. (1986). Possible risk of invasive aspergillosis
with marijuana use during chemotherapy for small cell lung cancer. Drug Intell.
Clinical Pharm. 20, 289–291.
Szyper-Kravitz, M., Lang, R., Manor, Y., and Lahav, M. (2001). Early
invasive pulmonary aspergillosis in a leukemia patient linked to aspergillus
contaminated marijuana smoking. Leuk. Lymphoma 42, 1433–1437. doi:
USP (2015). U.S. Pharmacopoeia (USP), section <1111>: Microbiological
Attributes of Nonsterile Pharmaceutical Products. Rockville, MD: USP.
Ware, M. A., Ducruet, T., and Robinson, A. R. (2006). Evaluation of herbal
cannabis characteristics by medical users: a randomized trial. Harm Reduct. J.
3, 32. doi: 10.1186/1477-7517-3-32
WHO (1999). World Health Organization (WHO). High-Dose Irradiation:
Wholesomeness of Food Irradiated with Doses Above 10 kGy. Report of a Joint
FAO/IAEA/WHO Expert Committee. Geneva, World Health Organization
1999 (WHO Technical Report, Series, No. 890).
Yu, Y., and Wang, J. (2007). Effect of gamma-ray irradiation on modeling
equilibrium moisture content of wheat. J. Food Sci. 72, E405–E411. doi:
Zanardi, E., Battaglia, A., Ghidini, S., Conter, M., Badiani, A., and Ianieri, A.
(2007). Evaluation of 2-alkylcyclobutanones in irradiated cured pork products
during vacuum-packed storage. J. Agric. Food Chem. 55, 4264–4270. doi:
Conflict of Interest Statement: The author is full time employed by Bedrocan BV,
the licensed company that provided the medicinal grade cannabis used for this
Copyright © 2016 Hazekamp. This is an open-access article distributed under the
terms of the Creative Commons Attribution License(CC BY). The use, distribution or
reproduction in other forums is permitted, provided the original author(s) or licensor
are credited and that the original publication in this journal is cited, in accordance
with accepted academic practice. No use, distribution or reproduction is permitted
which does not comply with these terms.
Frontiers in Pharmacology | 12 April 2016 | Volume 7 | Article 108
... Ensuring the safety of medical cannabis is imperative for critically ill patients. The Canadian and Dutch governments have allowed gamma irradiation of cannabis flowers to remove microbial contaminants [28,29]. Canada also allows X-ray irradiation and electron beam (e-beam) irradiation for ensuring microbial sterility in cannabis and cannabis products [28]. ...
... Microbial pathogens can be eliminated using many different decontamination and sterilization methods; however, the methods for decontaminating medicinal plant materials while still retaining their bioactive properties are few [30]. A good sterilization method must not significantly alter the content, composition of, and characteristics of biologically active substances, such as cannabinoids, essential oils, terpenoids, flavonoids, poly-phenol acids, saponins, and other secondary metabolites [29][30][31]. Decontamination methods involving heat and chemical reagents can reduce/alter aromatic and biologically active compounds of plants or it can leave behind toxic residues [29,30,32]. In one study, cannabis was sterilized via autoclaving, by plasma H 2 O 2 , or by ethylene oxide gas prior to administering the cannabis to an immunocompromised patient [24]. ...
... A good sterilization method must not significantly alter the content, composition of, and characteristics of biologically active substances, such as cannabinoids, essential oils, terpenoids, flavonoids, poly-phenol acids, saponins, and other secondary metabolites [29][30][31]. Decontamination methods involving heat and chemical reagents can reduce/alter aromatic and biologically active compounds of plants or it can leave behind toxic residues [29,30,32]. In one study, cannabis was sterilized via autoclaving, by plasma H 2 O 2 , or by ethylene oxide gas prior to administering the cannabis to an immunocompromised patient [24]. ...
Full-text available
California cannabis regulations require testing for four pathogenic species of Aspergillus–A . niger , A . flavus , A . fumigatus and A . terreus in cannabis flower and cannabis inhalable products. These four pathogenic species of Aspergillus are important human pathogens and their presence in cannabis flower and cannabis products may pose a threat to human health. In this study, we examined the potential of X-ray irradiation for inactivation of cannabis flower contaminated with any of the four pathogenic species of Aspergillus . We determined that X-ray irradiation at a dose of 2.5 kGy is capable of rendering Aspergillus cells non-viable at low (10 ² spores/g dried flower), medium (10 ³ spores/g dried flower) and high (10 ⁴ spores/g dried flower) levels of inoculation. We also showed that X-ray treatment of cannabis flower did not significantly alter the cannabinoid or the terpene profiles of the flower samples. Therefore, X-ray irradiation may be a feasible method for Aspergillus decontamination of cannabis flower. More work is required to determine the consumer safety of irradiated cannabis flower and cannabis products.
... Two studies evaluated cannabis available from regulated medical sources and unregulated recreational sources in the Netherlands. Hazekamp et al. [20] found that cannabis from regulated pharmacies was more reliable and safer, as coffeeshop cannabis was often underweight and contaminated with bacteria and fungi. However, no differences were found in cannabinoid or water content. ...
... However, no differences were found in cannabinoid or water content. Reference [20] found that while gamma irradiation of herbal cannabis effectively reduces microbial contamination to meet pharmaceutical standards, it does not alter the content of THC and CBD or the water content and microscopic structure of the flowers. The effects were limited to reducing some terpenes while keeping the terpene profile the same. ...
The recent surge in medicinal cannabis uses globally, largely due to changes in supply laws, has necessitated a comprehensive examination of its safety and quality. Despite its legal use in over 40 countries, there is increasing concern about microbiological contaminants, notably fungi, in cannabis. While background (or normal levels) of microbes are considered harmless with proper growing and manufacturing practices, some can pose health risks, particularly in certain applications like smoking, tinctures, or edibles. This literature review aims to explore the occurrence, identification, and health implications of fungal pollutants in medicinal cannabis. It also examines the negative effects of specific mycotoxins and the testing standards for medical cannabis, contributing significantly to current medical practices and future policy development in this rapidly evolving field. The presence of moulds and fungi on cannabis can potentially make users sick, with Botrytis cinerea, Aspergillus, Penicillium, Fusarium and Alternaria being common contaminants. However, the evidence linking exposure to fungus in cannabis with illness after consumption is limited, and the risks seem to depend on individual factors and level of exposure. The medicinal use of cannabis and cannabinoids has been shown to control various biological processes related to cancer and other illnesses. Cannabis is being used as a supplement for chronic pain, anxiety, depression, and other neurological conditions. Nevertheless, solvents, pesticides, and fungal pathogens may contaminate therapeutic cannabis. Mycotoxins from these fungi have been detected in cannabis samples, but their health effects are unknown. In growing medicinal cannabis markets like Thailand, mycotoxins might cause considerable economic losses. To reduce supply chain risks, medical cannabis products require more research on practical microbiological safety recommendations for improved public health.
... More than 80% of licensed growers of cannabis in Canada are using irradiation treatment [110]. Medical cannabis treated with a ≥10 kGy irradiation dose from Cobalt-60 as radiation source resulted in a significant decontamination of the cannabis without largely affecting the phytocannabinoids [111]. However, irradiation has a significant use for enhancing the drying rate of different foods either using gamma irradiation or electron beam irradiation. ...
... Irradiation pre-treatments resulted in a higher drying rate for potato and apple [112], carrot, potato and beetroot [113], and tofu protein [114]. A few researchers have performed irradiation as a pre-treatment for cannabis [110,111,115]. The level of irradiation, optimization, and its effect on phytocannabinoids are yet to be investigated. ...
Full-text available
In recent years, cannabis (Cannabis sativa L.) has been legalized by many countries for production, processing, and use considering its tremendous medical and industrial applications. Cannabis contains more than a hundred biomolecules (cannabinoids) which have the potentiality to cure different chronic diseases. After harvesting, cannabis undergoes different postharvest operations including drying, curing, storage, etc. Presently, the cannabis industry relies on different traditional postharvest operations, which may result in an inconsistent quality of products. In this review, we aimed to describe the biosynthesis process of major cannabinoids, postharvest operations used by the cannabis industry, and the consequences of postharvest operations on the cannabinoid profile. As drying is the most important post-harvest operation of cannabis, the attributes associated with drying (water activity, equilibrium moisture content, sorption isotherms, etc.) and the significance of novel pre-treatments (microwave heating, cold plasma, ultrasound, pulse electric, irradiation, etc.) for improvement of the process are thoroughly discussed. Additionally, other operations, such as trimming, curing, packaging and storage, are discussed, and the effect of the different postharvest operations on the cannabinoid yield is summarized. A critical investigation of the factors involved in each postharvest operation is indeed key for obtaining quality products and for the sustainable development of the cannabis industry.
... This suggests that despite potential to develop pharmacological tolerance to the effects of compounds contained within CBMPs, there were additional benefits derived from accessing a pharmaceuticalgrade product prescribed under supervision of expert clinicians. These additional benefits may be derived from the improved consistency of product characteristics and safety provided by CBMPs (Hazekamp, 2016). However, this may also represent a selection bias within the cohort as those who had previously consumed cannabis may be selfselecting as responders to therapeutic properties of cannabinoids. ...
Full-text available
Introduction : There are limited therapeutic options for individuals with fibromyalgia. The aim of this study is to analyze changes in health‐related quality of life and incidence of adverse events of those prescribed cannabis‐based medicinal products (CBMPs) for fibromyalgia. Methods : Patients treated with CBMPs for a minimum of 1 month were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in validated patient‐reported outcome measures (PROMs). A p‐value of <.050 was deemed statistically significant. Results : In total, 306 patients with fibromyalgia were included for analysis. There were improvements in global health‐related quality of life at 1, 3, 6, and 12 months (p < .0001). The most frequent adverse events were fatigue (n = 75; 24.51%), dry mouth (n = 69; 22.55%), concentration impairment (n = 66; 21.57%), and lethargy (n = 65; 21.24%). Conclusion : CBMP treatment was associated with improvements in fibromyalgia‐specific symptoms, in addition to sleep, anxiety, and health‐related quality of life. Those who reported prior cannabis use appeared to have a greater response. CBMPs were generally well‐tolerated. These results must be interpreted within the limitations of study design.
... Bahan tanaman yang digunakan dalam penelitian adalah 3 planlet G. scriptum yang mewakili dari 3 botol kultur (masing-masing botol kultur berisi lima individu) dari tiap perlakuan dosis iradiasi. Iradiasi protokorm dengan menggunakan elemen radioaktif Cobalt-60 (Hazekamp 2016) yang merupakan planlet generasi ketiga atau hasil subkultur keempat setelah perlakuan iradiasi (M1V4) (umur 8 bulan setelah perlakuan) (Gambar 2). Pada penelitian tersebut, semua planlet dengan dosis iradiasi 60 Gy mengalami kematian, sehingga selanjutnya pada penelitian ini hanya tiga dosis perlakuan yang diamati pada eksplan telah mencapai tahap M1V4 (tanaman hasil iradiasi yang telah disubkultur untuk keempat kalinya). ...
Full-text available
Grammatophyllum scriptum (L.) Blume atau dikenal sebagai anggrek macan merupakan salah satu anggrek koleksi Kebun Raya Bogor. Jenis ini memiliki perbungaan raksasa dengan ±27 kuntum bunga. Studi ini bertujuan untuk melakukan karakterisasi stomata dan akar dari planlet G. scriptum hasil iradiasi sinar gamma. Dosis iradiasi yang digunakan adalah 0, 15, dan 30 Gray (Gy). Hasil pengamatan menunjukkan iradiasi dengan dosis 15 dan 30 Gy memberikan pengaruh yang signifikan pada kerapatan dan lebar minimum bukaan stomata, namun tidak berpengaruh secara signifikan pada jaringan akar. Planlet dengan dosis 30 Gy memiliki jaringan velamen lebih tipis, stomata dengan kerapatan lebih rendah, celah stomata lebih sempit, dan jumlah stomata rusak lebih banyak, bila dibandingkan dengan planlet dosis iradiasi 15 Gy. Perubahan yang terjadi pada stomata dan akar pada dosis yang berbeda sebagai efek dari iradiasi akan memunculkan cara yang berbeda untuk dapat beradaptasi terhadap lingkungan.
... 13,43 This is of major importance since Cannabis products, and especially products for medical purposes, are held to strict microbial specifications. 43,44 However, although dried products are considered stable, certain pathogens, such as Salmonella, may still survive in low moisture environments upon sufficient rehydration. 45,46 Importantly, scaling up is necessary for MW drying to be an eligible alternative for traditional drying, and the described technology can be scaled up to allow fast drying of large batches concurrently. ...
Full-text available
Introduction: As the medical use of Cannabis is evolving there is a greater demand for high-quality products for patients. One of the main steps in the manufacturing process of medical Cannabis is drying. Most current drying methods in the Cannabis industry are relatively slow and inefficient processes. Materials and Methods: This article presents a drying method based on solid-state microwave (MW) that provides fast and uniform drying, and examines its efficiency for drying Cannabis inflorescences compared with the traditional drying method. We assessed 67 cannabinoids and 36 terpenoids in the plant in a range of drying temperatures (40°C, 50°C, 60°C, and 80°C). The identification and quantification of these secondary metabolites were done by chromatography methods. Results: This method resulted in a considerable reduction of drying time, from several days to a few hours. The multiple frequency-phase combination states of the system allowed control and prediction of moisture levels during drying, thus preventing overdrying. A drying temperature of 50°C provided the most effective results in terms of both short drying time and preservation of the composition of the secondary metabolites compared with traditional drying. At 50°C, the chemical profile of phytocannabinoids and terpenoids was best kept to that of the original plant before drying, suggesting less degradation by chemical reactions such as decarboxylation. The fast-drying time also reduced the susceptibility of the plant to microbial contamination. Conclusion: Our results support solid-state MW drying as an effective postharvest step to quickly dry the plant material for improved downstream processing with a minimal negative impact on product quality.
Full-text available
Cannabis is cultivated in different parts of the world for different purposes. Potential dangers from microbiological contamination exist for cannabis users. Opportunistic infections in immunocompromised patients can be brought on by bacteria and fungi. Allergies and asthma can be brought on by even dead germs. Shigla toxin and aflatoxins are two examples of microbial overload-related toxins that might be problematic, though it's unlikely. There is currently work being done to identify the diverse microbiome that the cannabis plant supports. Because of how readily heavy metals bioaccumulate in the tissues of cannabis, hemp crops have been employed in bioremediation. Because heavy metals are linked to a wide range of human ailments, it is important to keep them to a minimum in crops grown for human consumption. The chapter discusses interlinkage of heavy metals and pesticides associated with cannabis.
Full-text available
Introduction There are concerns about microorganisms present on cannabis materials used in clinical settings by individuals whose health status is already compromised and are likely more susceptible to opportunistic infections from microbial populations present on the materials. Most concerning is administration by inhalation where cannabis plant material is heated in a vaporizer, aerosolized, and inhaled to receive the bioactive ingredients. Heating to high temperatures is known to kill microorganisms including bacteria and fungi; however, microbial death is dependent upon exposure time and temperature. It is unknown whether the heating of cannabis at temperatures and times designated by a commercial vaporizer utilized in clinical settings will significantly decrease the microbial loads in cannabis plant material. Methods To assess this question, bulk cannabis plant material supplied by National Institute on Drug Abuse (NIDA) was used to assess the impact of heating by a commercial vaporizer. Initial method development studies using a cannabis placebo spiked with Escherichia coli were performed to optimize culture and recovery parameters. Subsequent studies were carried out using the cannabis placebo, low delta-9 tetrahydrocannabinol (THC) potency and high THC potency cannabis materials exposed to either no heat or heating for 30 or 70 seconds at 190°C. Phosphate-buffered saline was added to the samples and the samples agitated to suspend the microorganism. Microbial growth after no heat or heating was evaluated by plating on growth media and determining the total aerobic microbial counts and total yeast and mold counts. Results and discussion Overall, while there were trends of reductions in microbial counts with heating, these reductions were not statistically significant, indicating that heating using standard vaporization parameters of 70 seconds at 190°C may not eliminate the existing microbial bioburden, including any opportunistic pathogens. When cultured organisms were identified by DNA sequence analyses, several fungal and bacterial taxa were detected in the different products that have been associated with opportunistic infections or allergic reactions including Enterobacteriaceae , Staphylococcus, Pseudomonas , and Aspergillus .
Introduction There has yet to be an evaluation of medical cannabis patient preferences with respect to future research. As such, prioritisation of research agendas has been largely driven by academia and industry. The primary aim of this study was to elicit priorities for research from medical cannabis patients in the United Kingdom (UK). Methods Patients undergoing active treatment for health conditions with medical cannabis in the UK were invited to take part in focus groups from December 2021 to February 2022. An inductive thematic analysis of responses was performed. Participants also completed a ranking exercise whereby they assigned ten counters (each equivalent to £1 million GBP) to competing research priorities. Results 30 medical cannabis patients participated across 3 focus groups. The following themes were identified as research priorities: adverse events, comparison between cannabis-based medicinal products, health conditions, pharmacology of cannabis, types of study, healthcare professionals' attitudes, social environment, agriculture and manufacturing, and the cannabis plant. Participants assigned the highest proportion of research funding to ‘assessment of effect on specific symptoms’ (26 counters; 8.7%). Conclusions This study highlighted specific themes within which to focus future research on medical cannabis. Clinically, there was a directive towards ensuring that research is condition- or symptom-specific. Participants also emphasised themes on the social impact of medical cannabis, such as knowledge of medical cannabis among healthcare professionals, stigma, and effects on driving and in the workplace. These findings can guide both research funders and researchers into effectively implementing research which fits within a more patient-centric model.
Full-text available
Development of knowledge-based food preservation techniques have been a major focus of researchers in providing safe and nutritious food. Food irradiation is one of the most thoroughly investigated food preservation techniques, which has been shown to be effective and safe through extensive research. This process involves exposing food to ionizing radiations in order to destroy microorganisms or insects that might be present on and/or in the food. In addition, the effects of irradiation on the enzymatic activity and improvement of functional properties in food have also been well established. In the present review, the potential of food irradiation technology to address major problems, such as short shelf-life, high initial microbial loads, insect pest management (quarantine treatment) in supply chain, and safe consumption of fresh fruits was described. With improved hygienic quality, other uses, such as delayed ripening and enhanced physical appearance by irradiation were also discussed. Available data showed that the irradiation of fruits at the optimum dose can be a safe and cost-effective method, resulting in enhanced shelf-life and hygienic quality with the least amount of compromise on the various nutritional attributes, whereas the consumer acceptance of irradiated fruits is a matter of providing the proper scientific information.
Full-text available
Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk.
Full-text available
Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far. In general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids.
Full-text available
Consumption of salsas and dishes containing cilantro has been linked to several recent outbreaks of food-borne illness due to contamination with human pathogens. Ionizing irradiation can effectively eliminate food-borne pathogens from various vegetables including cilantro. However, the effect of irradiation on aroma of fresh cilantro is unknown. This study was conducted to investigate the effect of irradiation on volatile compounds of fresh cilantro leaves. Fresh cilantro leaves (Coriandrum sativum L) were irradiated with 0, 1, 2, or 3 kGy Á radiation and then stored at 3 °C up to 14 days. Volatile compounds were extracted using solid-phase microextraction (SPME), followed by gas chromato- graphic separation and mass spectra detection at 0, 3, 7, and 14 days after irradiation. Most of the volatile compounds identified were aldehydes. Decanal and (E)-2-decenal were the most abundant compounds, accounting for more than 80% of the total amount of identified compounds. The amounts of linalool, dodecanal, and (E)-2-dodecenal in irradiated samples were significantly lower than those in nonirradiated samples at day 14. However, the most abundant compounds (decanal and (E)-2- decenal) were not consistently affected by irradiation. During storage at 3 °C, the amount of most aldehydes peaked at 3 days and then decreased afterward. Our results suggest irradiation of fresh cilantro for safety enhancement at doses up to 3 kGy had minimal effect on volatile compounds compared with the losses that occurred during storage.
Full-text available
Background: A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients. However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor's prescription. This study describes a retrospective database study of The Netherlands. Methods: Complete dispensing histories were obtained of all patients with at least one medicinal cannabis prescription gathered at pharmacies in The Netherlands in the period 2003-2010. Data revealed prevalence and incidence of use of prescription cannabis as well as characteristics of patients using different cannabis varieties. Results: Five thousand five hundred forty patients were identified. After an initial incidence of about 6/100,000 inhabitants/year in 2003 and 2004, the incidence remained stable at 3/100,000/year in 2005-2010. The prevalence rate ranged from 5 to 8 per 100,000 inhabitants. Virtually all patients used some form of prescription medication in the 6 months preceding start of cannabis use, most particularly psycholeptics (45.5 %), analgesics (44.3 %), anti-ulcer agents (35.9 %) and NSAIDs (30.7 %). We found no significant association between use of medication of common indications for cannabis (pain, HIV/AIDS, cancer, nausea, glaucoma) and variety of cannabis used. Conclusions: This is the first nationwide study into the extent of prescription of medicinal cannabis. Although the cannabis varieties studied are believed to possess different therapeutic effects based on their different content of tetrahydrocannabinol (THC) and cannabidiol (CBD), no differences in choice of variety was found associated with indication.
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.
Unlabelled: Sterilization by gamma irradiation has shown a strong applicability for a wide range of pharmaceutical products. Due to the requirement for terminal sterilization where possible in the pharmaceutical industry, gamma sterilization has proven itself to be an effective method as indicated by its acceptance in the European Pharmacopeia and the United States Pharmacopeia ( ). Some of the advantages of gamma over competitive procedures include high penetration power, isothermal character (small temperature rise), and no residues. It also provides a better assurance of product sterility than aseptic processing, as well as lower validation demands. Gamma irradiation is capable of killing microorganisms by breaking their chemical bonds, producing free radicals that attack the nucleic acid of the microorganism. Sterility by gamma irradiation is achieved mainly by the alteration of nucleic acid and preventing the cellular division. This review focuses on the extensive application of gamma sterilization to a wide range of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices. A summary of the published literature for each class of pharmaceutical compound or product is presented. The irradiation conditions and various quality control characterization methodologies that were used to determine final product quality are included, in addition to a summary of the investigational outcomes. Based on this extensive literature review and in combination with regulatory guidelines and other published best practices, a decision tree for implementation of gamma irradiation for pharmaceutical products is established. This flow chart further facilitates the implementation of gamma irradiation in the pharmaceutical development process. The summary therefore provides a useful reference to the application and versatility of gamma irradiation for pharmaceutical sterilization. Lay abstract: Many pharmaceutical products require sterilization to ensure their safe and effective use. Sterility is therefore a critical quality attribute and is essential for direct injection products. Due to the requirement for terminal sterilization, where possible in the pharmaceutical industry sterilization by gamma irradiation has been commonly used as an effective method to sterilize pharmaceutical products as indicated by its acceptance in the European Pharmacopeia. Gamma sterilization is a very attractive terminal sterilization method in view of its ability to attain 10(-6) probability of microbial survival without excessive heating of the product or exposure to toxic chemicals. However, radiation compatibility of a product is one of the first aspects to evaluate when considering gamma sterilization. Gamma radiation consists of high-energy photons that result in the generation of free radicals and the subsequent ionization of chemical bonds, leading to cleavage of DNA in microorganisms and their subsequent inactivation. This can result in a loss of active pharmaceutical ingredient potency, the creation of radiolysis by-products, a reduction of the molecular weight of polymer excipients, and influence drug release from the final product. There are several strategies for mitigating degradation effects, including optimization of the irradiation dose and conditions. This review will serve to highlight the extensive application of gamma sterilization to a broad spectrum of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices.
The development of space food has been evolving since the Soviet cosmonaut, German Titov, became the first human to eat in space in August 1961. John Glenn was the first American to consume food, applesauce, on the third manned Mercury mission in August 1962. Before these events, there was no knowledge that humans would be able to swallow and, hence, eat in weightlessness. Space food development began with highly engineered foods that met rigid requirements imposed by spacecraft design and short mission durations. Improvements in the habitability of the spacecraft have permitted improvements in the quality of space food. As the missions became longer, the need for better nutrition, more variety, and easily consumable foods also became more important. Currently, the International Space Station astronauts have a wide variety of foods. The goal is to provide acceptable foods that taste similar to foods we eat here on Earth. Extended planetary stays will require even more variety and more technologic advances. Plants will be grown to recycle the air and water and will provide food for the crew. These harvested crops will need to be processed into safe, healthy, and acceptable food ingredients that can then be prepared into menu items.
The Cannabis plant (Cannabis sativa L.) has a long history as a recreational drug, but also as part of traditional medicine in many cultures. Based on the number of publications, it is one of the best-studied plants in the world. The relatively recent discovery of cannabinoid receptors and the human endocannabinoid system has opened up a new and exciting field of research. But despite the pharmaceutical potential of Cannabis, its classification as a narcotic drug has prevented its successful development into modern medicine. Fortunately, the chemistry of Cannabis has been studied in much detail. In particular the psychoactive cannabinoid tetrahydrocannabinol (THC) has received great scientific attention, and much is known about its biological effects and mechanisms of action. Besides an extensive description of the chemistry of the cannabinoids, this chapter also introduces the lesser-known terpenoids, flavonoids, and other constituents of the Cannabis plant. Comprehensive information on a variety of subjects is presented, including chromatographic analytical methods, pharmacokinetics, and structure-activity relationships. The known biological effects of Cannabis constituents are discussed in relationship to the development of modern cannabinoid-based medications. Finally, some practical aspects of working with Cannabis are discussed.