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Evaluation of a vaporizing device (Volcano®) for the pulmonary delivery of tetrahydrocannabinol

  • Hazekamp Herbal Consulting

Abstract and Figures

What is currently needed for optimal use of medicinal cannabinoids is a feasible, nonsmoked, rapid-onset delivery system. Cannabis "vaporization" is a technique aimed at suppressing irritating respiratory toxins by heating cannabis to a temperature where active cannabinoid vapors form, but below the point of combustion where smoke and associated toxins are produced. The goal of this study was to evaluate the performance of the Volcano vaporizer in terms of reproducible delivery of the bioactive cannabinoid tetrahydrocannabinol (THC) by using pure cannabinoid preparations, so that it could be used in a clinical trial. By changing parameters such as temperature setting, type of evaporation sample and balloon volume, the vaporization of THC was systematically improved to its maximum, while preventing the formation of breakdown products of THC, such as cannabinol or delta-8-THC. Inter- and intra-device variability was tested as well as relationship between loaded- and delivered dose. It was found that an average of about 54% of loaded THC was delivered into the balloon of the vaporizer, in a reproducible manner. When the vaporizer was used for clinical administration of inhaled THC, it was found that on average 35% of inhaled THC was directly exhaled again. Our results show that with the Volcano a safe and effective cannabinoid delivery system seems to be available to patients. The final pulmonal uptake of THC is comparable to the smoking of cannabis, while avoiding the respiratory disadvantages of smoking.
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Evaluation of a Vaporizing Device (Volcano
) for the
Pulmonary Administration of Tetrahydrocannabinol
Division of Pharmacognosy, Institute of Biology, Leiden University, Leiden, The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
Division of Pharmacognosy, Section Metabolomics, Institute of Biology, Leiden University, Leiden, The Netherlands
Received 1 January 2005; revised 15 April 2005; accepted 25 October 2005
Published online ? ???inWiley InterScience ( DOI 10.1002/jps.20574
xx. ß2005 Wiley-Liss, Inc. and the American Pharmacists Association J
Pharm Sci 9999:1– 10, 2005
Keywords: delta-9-tetrahydrocannabinol; cannabis; vaporizer; aerosol; pulmonary
drug delivery; formulation vehicle; controlled delivery
Cannabis (Cannabis sativa L.) has a long history
as a recreational drug and as part of traditional
medicine in many cultures of the world. Nowa-
days, cannabis is used medically by patients
suffering from diseases varying from cancer and
HIV/AIDS to multiple sclerosis, frequently
in the form of unprescribed self-medication.
, an oral form of the main psychoactive
constituent of cannabis, delta-9-tetrahydro-
cannabinol (THC), has been developed for some
indications. However, oral THC is notoriously
unreliable in its effects.
Drawbacks of Marinol
include its slow onset of action, large varia-
bility in bioavailability, and extensive first
pass metabolism. Moreover, there is the incon-
venience of taking oral medication in case of
nausea or vomiting. Therefore, for many patients
the demand for more effective cannabinoid-based
medications persists. For this group of pati-
ents cannabis smoking is a more convenient
method of administration, allowing self-titration
of the desired effects. However, inhalation of toxic
compounds during cannabis smoking poses a
serious hazard. This risk is not thought to be due
to cannabinoids, but rather to noxious pyrolytic
Consequently, the shortcomings of
smoked cannabis have been widely viewed as a
major obstacle for approval of crude cannabis as a
medicine by public health authorities.
Cannabis ‘‘vaporization’’ or ‘‘volatilization’’ is a
technique aimed at suppressing irritating respira-
tory toxins by heating cannabis to a temperature
where active cannabinoid vapors are formed, but
below the point of combustion where pyrolytic
toxic compounds are made. Vaporization offers
patients who use medicinal cannabis the advan-
tages of the pulmonary routes of administration,
that is: rapid delivery into the bloodstream, ease of
self-titration, and concomitant minimizing the
risk of over- and under-dosing, while avoiding
the respiratory disadvantages of smoking.
In a series of studies the vaporizing of can-
nabis samples was systematically tested to show
its advantage over smoking. When a variety of
smoking devices (including water pipes) were
compared, specifically examining THC and solid
smoke tars, it was found that only vaporizers were
capable of achieving reductions in tar relative to
THC when compared to direct smoking of canna-
A follow-up study tested a vaporizer that
was found to deliver THC while completely elimi-
Correspondence to: Arno Hazekamp (Telephone: 31-71-527-
4519; Fax: 31-71-527-4511;
Journal of Pharmaceutical Sciences, Vol. 9999, 1 –10 (2005)
ß2005 Wiley-Liss, Inc. and the American Pharmacists Association
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nating three specic toxins (naphthalene, benzene,
and toluene) in the solid phase of the vapor.
The study also detected a 56% reduction in tars
and a qualitative reduction in carbon monoxide,
but did not test for any other chemicals.
In a more
recent study,
GC-mass-spectrometry was used to
analyze the gas phase of vaporized cannabis for
a wide range of toxins, particularly concentrating
on the highly carcinogenic polynuclear aromatic
hydrocarbons (PAHs). The vaporizer that was
used was the Volcano
It consists of a heater,
a ventilator, a lling chamber, a valve, and a
balloon. During operation the balloon is inated
with hot air and cannabinoid vapors. Using
cannabis plant material as the sample, vapors
were found to consist overwhelmingly of cannabi-
noids, while the combusted control contained over
one hundred additional chemicals, including sev-
eral known PAHs.
Although a large variety of vaporizing devices is
available on the market, the Volcano is one of the
few devices that have been tested scientically to
some extent. It is a herbal vaporizer, intended for
the vaporization of whole cannabis plant materials
(i.e., owertops), but numerous unexplored vari-
ables could affect the efciency and output of
vaporization. These parameters are variations in
temperature; differences in specimen density,
weight, content of water and essential oils, and
consistency of material in the lling chamber;
differences in the variety and potency of cannabis
used; and use of different preparations such as
crude owertops, hashish, hash oil, etc. Because of
the paucity of data it has so far been difcult to
show that the Volcano vaporizer can be used as a
reliable tool for the reproducible administration of
THC or other cannabinoids. A solution to this
would be in the use of pure cannabinoid prepara-
tions of known concentration to guarantee an
exact and reproducible loading of cannabinoids.
In this study the Volcano vaporizer was eval-
uated as a novel method for the administration of
THC. Pure cannabinoid preparations were used in
order to obtain quantitative results in terms of
efciency and reproducibility of THC delivery into
the balloon of the Volcano. By changing para-
meters such as temperature setting, type of
evaporation sample, and balloon volume, the
vaporization of THC was systematically improved
to its maximum yield, while preventing the
formation of degradation products. Factors that
resulted in loss of THC by condensation, that is,
storage time of the balloon and use of the lling
chamber, were evaluated. The inter-device repro-
ducibility of THC vaporization under optimized
conditions was determined. Finally, the results of
this study were used for the clinical administra-
tion of THC by vaporizing. The amount of exhaled
THC was determined and compared to the dose,
which was inhaled through the Volcano.
Our results indicate that the Volcano is a
convenient device for the administration of THC
by inhalation.
All organic solvents were HPLC or analytical
grade, and were purchased from J.T. Baker
(Deventer, The Netherlands). Anthracene (min.
99% purity) was purchased from Aldrich (St.
Louis, MO). Deuteriated chloroform (CDCl
) was
from Eurisotop, Gif-sur-Yvette, France. Glass
ber lters (Cambridge type, borosilicate glass,
92 mm diameter) and tightly tting lter holders
for vapor extraction were obtained from Borg-
waldt Technik GmbH (Hamburg, Germany).
Cannabis plant material (female owertops)
was medical grade and obtained from Bedro-
BV (The Netherlands). It had a water
content of about 8%, a THCA content of about
12%, and virtually no free THC.
Puried THC and THCA (purity 98%) were
produced and quantied as reported earlier.
THC was of pharmaceutical grade. The cannabi-
noids were stored as ethanolic solutions at 208C
at a concentration of 50 mg/mL.
The Volcano Device
The Volcano
was obtained from Storz & Bickel
GmbH & Co. (Tuttlingen, Germany) and was
used according to the manual as provided by the
manufacturer. It is a vaporizer or evaporator
that can evaporate the active substances or
aromas from plant material by using a hot air
ow (Fig. 1). Depending on the type of lling
chamber used, whole plant material or liquid
samples (e.g., aromatic oil, extract, or pure
compounds in solution) can be used. Evaporated
compounds are collected in a detachable plastic
balloon, which can be removed and tted with
a mouthpiece for inhalation. Volume of the
balloon can be varied. Unless otherwise stated, a
balloon length of 55 cm (around 8 L) was used, as
recommended by the manufacturer. The tempera-
Author Proof
ture control ranges from setting 1 9, correspond-
ing to temperatures of 1302268C (see Tab. 1).
Before each new set of experiments the whole
device was thoroughly cleaned with ethanol.
At the start of each evaporation the Volcano
was preheated until the indicator light showed
that the target temperature was reached. The
balloon, connected to the lling chamber, was
then immediately placed onto the Volcano and the
ventilation was started. When the balloon was
completely inated, ventilation was stopped and
the content of the balloon was processed for
analysis within 5 min, unless stated otherwise.
All laboratory experiments were carried out in a
standard laboratory fume hood under constant
ventilation with an ambient room temperature of
about 228C and a humidity of 40 60%. The air was
not conditioned (e.g., by HEPA lters).
Use of the Liquid Pad
The pure cannabinoids THC or THCA were used
as ethanolic solutions. For these liquid samples an
adapted lling chamber was used, containing a
removable disc made of tightly packed stainless
steel wire mesh (liquid pad), obtained from the
manufacturer of the Volcano. For each experi-
ment the appropriate amount of the cannabinoid
was dissolved in a nal volume of 200 ml of ethanol
for application onto the liquid pad and ethanol
was allowed to evaporate for 10 min under
ambient conditions. A new liquid pad was used
for each experiment.
Extraction of THC from the Vapor and the Liquid Pad
Cannabinoids were recovered from the vapor
phase inside the balloon by condensation onto
glass ber lters, designed to capture particles
>0.1 microns. Vapor was slowly aspired through
the glass-ber lter which was then extracted
twice with 15 mL of methanol/chloroform (9:1, v/v)
under ultrasonication. After evaporating the
extraction solvent, samples were reconstituted
in 5 mL of ethanol for analysis by HPLC or NMR.
These ethanolic samples will be further referred
to as vapor extracts.
Residual THC on the liquid pad was recovered
by extracting the liquid pad twice using methanol/
chloroform (9:1, v/v) under ultrasonication. Extra-
cts were further handled as described above for the
vapor extracts. Recovery was determined by spik-
ing lters or liquid pads with THC (2 mg) and
performing the described extraction procedure.
To assess the efciency of condensation of
cannabinoids onto the glass ber lter, a wash
bottle lled with ethanol was placed after the lter.
The escaping gases were bubbled through this
liquid which was thereafter analyzed by HPLC to
measure untrapped cannabinoids.
H-Nuclear Magnetic
Resonance Spectroscopy (NMR)
Quantication of THC in the extracts was done by
H-NMR using a Bruker 300 MHz
NMR apparatus as described by Hazekamp et al.
Table 1. Temperature (8C) of the Heating Unit of the
Volcano Corresponding to the Different Temperature
Temperature Setting Temperature in 8C
1 130
3 154
5 178
7 202
9 226
Figure 1. The Volcano vaporizer.
Author Proof
In short, an exact volume of the sample was mixed
with 1.0 mg of anthracene as internal standard
for quantication. The sample was then evapo-
rated to dryness under vacuum and reconstituted
in chloroform (deuteriated) for
H-NMR analysis.
High Pressure Liquid Chromatography (HPLC)
HPLC was used for both qualitative and quanti-
tative analysis of the obtained extracts. The
HPLC proles were acquired on a Waters (Mil-
ford, MA) HPLC system consisting of a 626 pump,
a 717 plus autosampler, and a 2996 diode array
detector (DAD), controlled by Waters Millennium
3.2 software. Full spectra were recorded in the
range of 200400 nm. The analytical column was
a Vydac (Hesperia, CA) C
, type 218MS54
(4.6 250 mm, 5 mm), with a Waters Bondapak
(2 20 mm, 50 mm) guard column. The mobile
phase consisted of a mixture of methanol-water
containing 25 mM of formic acid in gradient mode;
methanol:water in ratios from 65:35 to 100:0 over
25 min, then isocratic to 28 min. The column was
reequilibrated under initial conditions for 4 min.
Flow-rate was 1.5 mL/min and total runtime was
32 min. All determinations were carried out
at ambient temperature. The main neutral and
acidic cannabinoids were well separated with
this method.
Analyzed concentrations were
well above the limit of quantication of the used
Evaluation of Temperature Control
Temperature control was evaluated at setting 1,
3, 5, 7, and 9 (see Tab. 1). Time needed to reach
target temperature, and accuracy and stability of
target temperature were determined using an
electronic thermometer (response time; 250 ms).
Temperature was measured in the middle of the
lling chamber, on top of the liquid pad, and each
measurement was started directly after the
indicator light of the heater had switched off.
Inter-device variability for the same parameters
was tested for four different Volcano devices. All
experiments were repeated three times.
Optimization of Vaporizing Parameters
(a) Temperature: Cannabis plant material, and
pure cannabinoids THCA and THC were
vaporized at temperature settings 1, 3, 5, 7,
and 9 in order to determine the delivery
into the balloon as well as the formation of
degradation products. Vapor extracts were
qualitatively analyzed by HPLC for detec-
tion of degradation products, while quanti-
tative analysis by NMR was used for
determination of delivery.
(b) Heating time: In order to determine the
minimal time that is needed to reach
maximal evaporation of THC, the following
experiment was performed: THC (2 mg)
was applied onto the liquid pad and the
ventilation was activated for a duration
ranging from 10 to 300 s, without balloon
attached to the device so THC could
evaporate freely. Subsequently, residual
THC was extracted from the liquid pads
and extracts were quantitatively analyzed
by NMR.
Relationship Between Loaded Dose and Delivery
The relationship between quantity of THC loaded
onto the lling chamber and delivery into the
balloon was determined in the range of 28mgof
THC. Vapor extracts were analyzed by NMR and
HPLC, and each experiment was performed
Inter-Device Variability
Using the optimized parameters as determined in
this study, four Volcano devices were nally
evaluated for inter-device variability in THC
delivery. Samples of 4 mg of THC were used for
vaporizing and each Volcano was tested on ve
occasions. Vapor extracts were analyzed by NMR.
Condensation of THC onto the
Balloon and Filling Chamber
The effect of storage time of the balloons on
condensation of THC was determined by storage
of the balloon at room temperature for a duration
of up to 180 min after vaporizing (2 mg THC). The
vapor extract was then collected for analysis.
Each experiment was performed threefold.
Throughout this study balloons were always
processed within 5 min after vaporizing. There-
fore, it was determined more exactly how much
THC was lost due to condensation onto the walls
of the balloon after 5 min of storage by carefully
Author Proof
cutting the balloon (n¼5) into pieces and extract-
ing twice with ethanol under ultrasonication.
In order to determine the amount of THC that
condensated onto the lling chamber (excluding
liquid pad) and valve, after some experiments
these parts were extracted twice with ethanol
under ultrasonication. Finally, extracts were con-
centrated and THC was quantied by NMR.
Clinical Application of the Volcano
At the Centre for Human Drug Research (CHDR,
Leiden, The Netherlands) a methodology study
was performed to study the effects of THC
administration using the Volcano vaporizer. The
study was approved by the Medical Ethical
Committee of Leiden University, The Nether-
lands. Preliminary results of this study were
published recently,
and full results will be
published in the near future. In short, during
two separate occasions subjects received a rising
dose of 2, 4, 6, and 8 mg THC (loading dose in
lling chamber) or placebo (ethanol only) admi-
nistered via the Volcano, using the optimized
parameters as determined in this study. Admin-
istrations were given with 1.5 h intervals. The
balloon (8 L) had to be inhaled through the mouth
within 3 min and breath was held for 10 s after
each inhalation. Following each inhalation, sub-
jects were asked to exhale through a lter of the
same type as used for vapor extraction. Filters
were subsequently extracted as mentioned before
and the quantity of exhaled THC was determined
by NMR. Because of time restraints, no further
evaluation of lung function (e.g., FEV1) could be
Trapping and Recovery of THC for Analysis
Since no trace of THC could be found in the ethanol
fraction of the wash bottle inserted after the lter,
it was concluded that THC was completely trapped
onto the used type of lter. Recovery of THC was
found to be 99.3 (1.1)% from the lter and 83.0
(2.5)% from the liquid pad. All measurements
were corrected for these values.
Accuracy of the Temperature Setting
At all tested temperature settings it was found
that temperature reached a rst plateau after
about 30 s. After that temperatures remained
relatively stable for some time, but kept below
accepted limits (target temperature 48C, as
claimed by the manufacturer) for all tested
settings. Results can be seen in Figure 2a. How-
ever, after about 4560 s, depending on the
setting, the heating element was activated again
by the temperature sensor, and about 20 s later
temperatures increased by a few degrees bringing
the temperature within specied limits. It must
be concluded that the liquid pad and the lling
chamber need some time to heat up to the target
Reproducibility of the Vaporizer
When four different Volcano devices were eval-
uated under equal conditions to evaluate inter-
device variability (Fig. 2b), some small differences
Figure 2. (a): Temperature prole over time of the
Volcano at different settings. Dotted lines indicate
target temperatures at settings 1, 3, 5, and 7. (b):
Comparison of temperature prole of four different
Volcano devices at setting 9. Dotted lines indicate
allowed target temperature range (48C). Data is shown
as mean values of three experiments, and errorbars
indicate standard deviation.
Author Proof
in heating prole were found. Only temperature
setting 9 was evaluated here after it had been
shown to be the optimal temperature for THC
delivery. Although two devices reached target
temperature (accepted variation 48C) already
after 30 s, the two others needed 60 s or more to do
so. For two devices the temperature increased
above the maximum limit of target temperature
in the 90 s duration of our experiment. In
conclusion each individual Volcano device shows
little variability during sequential uses (intra-
device variability), although small differences do
exist between different devices (inter-device
Optimizing of Vaporizing Parameters
with Different Substrates
THCA: Under the inuence of heat THCA can be
converted into THC by decarboxylation. Indeed,
when THCA was used it was observed that this
conversion increased with temperature and max-
imum delivery of THC was about 33% at the
highest temperature setting (Fig. 3). However,
conversion was not complete and THCA was
present in the vapor extracts at a level of about
5.5 (1.3)% relative to THC.
Crude ower tops: The use of plant material
(200 mg at 12% THCA) resulted in a maximum
THC delivery of only 29% (Fig. 3). In fresh
cannabis plant materials THC is present in the
form of its acidic precursor THCA and the use of
plant material resulted in an incomplete decar-
boxylation with about 3.8% residual THCA pre-
sent in the vapor. Besides THC, several other
cannabinoids as well as a range of other plant
components were detected. Therefore, the use of
cannabis plant material in the Volcano should not
be recommended for the administration and study
of THC alone.
Pure THC: Evaporation of THC was shown to
increase with temperature with a maximal deliv-
ery of about 53% at setting 9 (Fig. 3), while no
degradation products (delta-8-THC (D
cannabinol (CBN), or other unknown peaks in
the HPLC-chromatogram) were observed at any
setting. Therefore, using the Volcano device, it was
concluded that the highest delivery yield was
achieved with an ethanolic of pure THC. When
liquid pads were extracted after vaporizing it
showed a very low amount of residual THC,
indicating a very high yield of evaporation, at the
highest temperature setting. This strongly sug-
gests that nondelivered THC does not remain on
the liquid pad, but is probably lost by condensation
after initial evaporation.
Minimum time was determined for the maximal
evaporation of THC from the liquid pad by
measuring residual THC after vaporizing.
Figure 4 shows that the amount of residual THC
rapidly decreases between 20 and 40 s after
starting of the vaporizing. This corresponds with
the observation that in the same time-period the
(near) target temperature of the Volcano is
reached (Fig. 2a and b). After 45 s most of the
Figure 3. Amount of delta-9-tetrahydrocannabinol
(THC) delivered into the balloon after using different
sample types in the lling chamber: THC (~, 8 mg);
THCA (&, 9 mg); plant material (^, 200 mg) at different
temperature settings. Delivery is expressed as %
relative to the loaded dose of THC. For THCA and plant
material, the theoretical loaded dose of THC was
calculated based on a 100% conversion of THCA into
THC. Data is shown as mean values. Error bars indicate
standard deviation.
Figure 4. Residual THC on liquid pad after varying
vaporizing time at setting 9. Datais shown as mean values
of three experiments, and error bars indicate standard
deviation. Values were corrected for the maximum
recovery of 83% for extraction of the liquid pads.
Author Proof
THC is evaporated and just a small fraction of THC
can be found in the liquid pad extract, indicating
that vaporizing time should be at least 45 s. When
using a temperature setting of 9 with a balloon
volume of 4 L (lling time around 30 s), a low THC
delivery (only 30% for 8 mg of THC) with a high
dose variability (relative SD 22%) was observed
indicating that the maximum delivery yield was
not yet reached.
It was observed that the maximal evaporation of
THC is reached after 120 s, (Fig. 4). Since the
Volcano is blowing air at a constant rate of about 9
L per min, this corresponds to a balloon volume of
about 18 L. However, by empirical testing in our
laboratory (data not shown) it was found that a
maximum volume of about 8 L could be inhaled
within 3 min when following the protocol of the
clinical trial. Therefore, a balloon volume of 8 L
(lling time of about 55 s) was selected for further
Relationship between Loaded Dose and
Delivery under Optimal Conditions
With a Volcano operating under the aforemen-
tioned optimized conditions (temperature setting
9, balloon volume 8 L) the delivery was deter-
mined with an increasing amount of THC ranging
from 2 to 8 mg. It is shown in Figure 5 that the
delivery was proportional to the loaded dose of
THC; a linear curve was obtained with a regres-
sion coefcient (R
-value) of 0.99. From the slope
of the line, a mean delivery yield of 57.8 (6.9)%
could be calculated.
Four available devices were then tested under
conditions as mentioned above using a sample of
4 mg of THC. Differences in delivery between the
Volcano devices were relatively small. Average
delivery of all four Volcanos was 53.9 (8.1)%, and
this value was taken as the average delivery for
further considerations.
Condensation onto Balloon and Filling Chambers
Loss of THC during experiments could partially
be accounted for by incomplete evaporation and
condensation onto parts of the Volcano vaporizer.
Prolonged storage of the balloon at room tem-
perature after vaporizing led to a steadily increas-
ing loss of THC by condensation up to the point
that after 180 min almost no THC could be
detected anymore in vapor extracts (Fig. 6).
However, if the balloon was extracted within
5 min after vaporizing, less than 2% of the total
dose was recovered from the inner surface of the
balloon. Condensation of THC onto the other
parts of the Volcano setup was found to be of
signicant importance. Visual inspection of the
lling chamber shows the presence of a conden-
sate mostly on the inside of the lling chamber
just above the liquid pad. Extraction of the lling
chamber together with the valve, but excluding
the liquid pad, showed that an average of 23.6
(14.1)% of the loaded THC had condensated onto
Figure 5. Relationship between delivery of THC
under optimized setting conditions with four different
THC loading doses ranging from 2 to 8 mg. Data are
shown as mean values of three experiments and error
bars indicate standard deviation. Linearity (r
was 0.99, as determined by linear regression.
Figure 6. Relationship between storage time and
percentage of initial THC that could be recovered from
the balloon. Data are shown as mean values of three
experiments, expressed as % of initially recovered THC.
Error bars indicate standard deviation. During this
study all balloons were processed within 5 min after
evaporation, which is indicated by the dotted line.
Author Proof
these parts of the Volcano, and could therefore
account for a large part of the nondelivered THC.
Clinical Study and Loss by Exhalation
The clinical trial was nished without any serious
complaints by the test subjects. Some mild
complaints included irritation of the throat and
lungs, and coughing. However, these effects were
also observed during inhalation of placebo and
therefore could be an effect of residual ethanol.
The development of signicant physiologic chan-
ges after inhalation of vaporized THC indicates
that THC can be effectively administered by this
Interestingly, it was shown that a large propor-
tion of inhaled THC was not absorbed by the lungs.
The total amount of THC used for evaporation was
20 mg of THC for each subject (Rising dose of 2, 4, 6,
and 8 mg resulting in a total dose of 20 mg). Taking
into account the average delivery yield of 53.9% as
found in this study, only an average of 10.8 mg of
THC was totally inhaled from the balloon. The
amount of THC recovered from exhaled breath
ranged from 2.5 to 4.4 mg, which means that up to
30%40% of inhaled THC was not absorbed by the
lungs. The variability of THC in exhaled breath
(relative SD 5.4%) is comparable to the varia-
bility in delivery of THC by the Volcano. Taking
this into account it could be concluded that
absorption of THC by the lungs is probably very
similar between different subjects.
The Volcano
vaporizer was validated for the
efcient and reproducible delivery of delta-9-THC,
and was found to be able to deliver an average
amount of about 54% of applied dose of THC into
the balloon for inhalation. THC recoveries from
smoke was found to range from 34% to 69% in a
variety of studies using different types of smoking
Because the plant material is not
burned in the Volcano, no signicant harmful
cancer causing combustion products are expected
and the noxious intake, when compared to smok-
ing, is greatly reduced.
Using the Volcano
device for pulmonary administration of THC, a
delivery is reached that is comparable to smoking,
but without the presence of degradation products
or harmful byproducts in signicant amounts.
Loading the Volcano with Cannabis plant
material or pure THCA resulted in a residual
amount of THCA in the vapor in the order of 5%
relative to THC. Not much is known about
biological effects or metabolism of THCA, and
therefore the use of THCA as sample for intended
clinical administration of pure THC should be
avoided. Older studies at least indicate that
THCA is not psychoactive in monkeys.
ugh in our study cannabis plant material was used
only for comparative reasons, it is clear that a
variety of cannabinoids and other compounds such
as terpenoids are present in the vapor.
With pure THC as the loading sample, tem-
perature setting and balloon volume were opti-
mized for a maximal, reproducible delivery of THC
without formation of detectable amounts of degra-
dation products. Using the highest temperature
setting together with a balloon volume of 8 L was
found to yield optimal results. Balloon volumes
over 8 L were not tested because of restraints in the
clinical trial protocol. The target temperature of
the Volcano was found to be not completely
accurate and stable. Possibly this is a contributing
factor to the relative variability in the delivery of
THC, which was about 15% at setting 9. However,
this is reasonable when compared to the varia-
bility that has been previously found in smoking
studies of cannabis plant material.
Accuracy of
temperature control therefore does not seem to be
of crucial importance under these conditions,
although a more accurate temperature control
might result in an even lower variability in THC
In the range of 28 mg of THC, the delivery was
found to be linear with the amount of THC used.
Prolonged storage of the balloon before inhalation
resulted in an increasing loss of THC by condensa-
tion inside the balloon and after 3 h almost no THC
could be recovered from the vapor in the balloon.
However, if the content was extracted within 5 min
after vaporization not more than 2% of THC
present was lost. Vaporized THC was visible inside
the balloon as a thin gray mist which was absent in
placebo balloons, so during the clinical trial
balloons had to be blinded with a black plastic
During the clinical administration, it was found
that about 35% of total THC was exhaled directly
after inhalation and was therefore not absorbed by
the lungs. When the efciency of delivery during
vaporizing and incomplete absorption by the lungs
is considered, the nal administered dose equaled
about 68 mg of THC of the total amount of 20 mg
loaded. The subjective effect upon the subjects
seemed to be in accordance with such a dose as
Author Proof
described in other papers.
So it seems that a
nal uptake of 3040% was reached (relative to
loaded amount of THC), which is comparable to the
efciency reached by smoking of cannabis.
It has been shown that the administration of
THC by aerosol is capable of producing the full
constellation of cannabinoid effects in mice. These
effects were CB1-receptor mediated, as shown by
the use of selective CB1 antagonists,
conrms that the pulmonary administration
of cannabinoids certainly has a clinical potential.
Several studies have been performed using an
aerosol for the administration of THC.
because cannabinoids are almost completely inso-
luble in water this requires the use of solubilizers
that are to be inhaled together with THC, which
frequently results in irritation of the lungs and
coughing. Moreover, part of an administered
aerosol can be swallowed and thereby adminis-
tered orally, complicating the effect, kinetics, and
metabolism of the administered compound. This
has already been shown for aerosol administration
of radiolabeled isoproterenol.
Using the Volcano vaporizer seems to eliminate
at least part of the problems associated with the
use of an aerosol for the delivery of THC or other
cannabinoids. It is likely that the Volcano also
produces an aerosol, that is, droplets of various
sizes in a gas phase made up of vapor and air.
However, in an articial lung model the majority of
vaporized THC could reach the deepest compart-
ment (personal communication with Volcano
manufacturer) indicating that the exhaust blown
from the Volcano consists for a large part of very
ne droplets and vapor. Nonetheless, the composi-
tion of an aerosol is partially dependent on the
ambient conditions such as humidity and presence
of nuclei for condensation. So although our results
were found to be reproducible with a relatively low
variability, these factors must be taken into
consideration for further development of the
What is currently needed for optimal use of
medicinal cannabinoids is a feasible, nonsmoked,
rapid-onset delivery system. With the Volcano a
safe and effective cannabinoid delivery system
seems to be available to patients. Although our
current study has concentrated on the delivery of
THC, it should be noted that other cannabinoids
might also have a role to play for some indications.
In several medical studies, the effect of THC or
dronabinol alone could not match the effect of a
total cannabis preparation, indicating there might
be other active cannabinoids needed for a full
range of effects.
As an example, a combination of
THC with CBD is now under clinical investigation
for the treatment of chronic pain conditions.
next step in the evaluation of the Volcano vapor-
izer should therefore include the study of mixtures
of pure cannabinoids.
The authors thank the manufacturer of the
Volcano vaporizer, Storz & Bickel GmbH & Co.,
for providing the department of Pharmacognosy
with the Volcano devices for our study. Bedrocan
BV (The Netherlands) is acknowledged for pro-
viding us with medical grade cannabis plant
materials. Farmalyse BV (Zaandam, The Nether-
lands) was involved in the development of the
procedure to produce clinical grade cannabinoid
samples of THC and THCA.
1. Page SA, Verhoef MJ, Stebbins RA, Metz LM, Levy
JC. 2003. Cannabis use as described by people with
multiple sclerosis. Can J Neurol Sci 30:201205.
2. Furler MD, Einarson TR, Millson M, Walmsley S,
Bendayan R. 2004. Medicinal and recreational
marijuana use by patients infected with HIV. AIDS
Patient Care STDS 18:215228.
3. Grinspoon L. 1997. Marijuana, the forbidden
medicine. Revised edition. New Haven, CT: Yale
University Press.
4. Hiller FC, Wilson FJJ, Mazumder MK, Wilson JD,
Bone RC. 1984. Concentration and particle size
distribution in smoke from marijuana cigarettes
with different D9-tetrahydrocannabinol content.
Fundam Appl Toxicol 4:451454.
5. Matthias P, Tashkin DP, Marques-Magallanes JA,
Wilkins JN, Simmons MS. 1997. Effects of varying
marijuana potency on deposition of tar and delta9-
THC in the lung during smoking. Pharmacol
Biochem Behav 58:11451150.
6. Institute of Medicine. 1999. Marijuana and medi-
cine: Assessing the scientic base. Washington DC,
MD: National Academy Press.
7. Gieringer D. 1996. Marijuana research: Waterpipe
study. MAPS (Multidisciplinary Association for
Psychedelic Studies) Bull 6:5966.
8. McPartland JM, Pruitt PL. 1997. Medical mar-
ijuana and its use by the immunocompromised.
Altern Ther Health Med 3:3945.
9. Chemic Laboratories. 2000. Proof of concept:
Release of chemical constituents in cannabis sativa
at 1701858C versus combustion. Unpublished
report to California NORML and MAPS, Nov
17th, 2000.
Author Proof
10. Gieringer D. 2001. Cannabis vaporization: A
promising strategy for smoke harm reduction.
J Cannabis Ther 1:153170.
11. Gieringer D, StLaurent J, Goodrich S. 2004.
Cannabis vaporizer combines efcient delivery of
THC with effective suppression of pyrolytic com-
pounds. J Cannabis Ther 4:727.
12., website visited 10 January
13. Hazekamp A, Simons R, Peltenburg-Looman A,
Sengers M, van Zweden R, Verpoorte R. 2004a.
Preparative isolation of cannabinoids from Canna-
bis sativa by centrifugal partition chromatography.
J Liq Chrom Rel Technol 27:24212439.
14. Hazekamp A, Choi YH, Verpoorte R. 2004b.
Quantitative analysis of cannabinoids from Canna-
bis sative using
H-NMR. Chem Pharm Bull 52:
15. Hazekamp A, Giroud C, Peltenburg A, Verpoorte R.
2005. Spectroscopic and chromatographic data of
cannabinoids from Cannabis sativa. J Liq Chrom
Rel Technol 28:23612382.
16. Zuurman L, Roy C, Hazekamp A, Schoemaker R,
den Hartigh J, Bender JCME, Pinquier JL, Cohen
AF, van Gerven JMA. 2005. Effect of THC admin-
istration in humans: Methodology study for further
pharmacodynamic studies with cannabinoid
agonist or antagonist. Br J Clin Pharmacol 59:
17. Leweke FM. 2002. Acute effects of cannabis and the
cannabinoids. In: Grotenhermen F, Russo E,
editors. Cannabis and cannabinoids. New York,
NY: Haworth Press. pp 249256.
18. Abood ME, Martin BR. 1992. Neurobiology of
marijuana abuse. Trends Pharmacol Sci 13:201
19. Fehr KO, Kalant H. 1972. Analysis of cannabis
smoke obtained under different combustion condi-
tions. Can J Physiol Pharmacol 50:761767.
20. Manno JE, Kiplinger GF, Haine SE, Bennett IF,
Forney RB. 1970. Comparative effects of smoking
marihuana or placebo on human motor perfor-
mance. Clin Pharmacol Ther 11:808815.
21. Davis KH. 1984. Some smoking characteristics of
marijuana cigarettes. In: Agurell S, Dewey WL,
Willette RE, editors. The cannabinoids: Chemical,
pharmacologic and therapeutic aspects. New York,
NY: Academic Press.
22. Edery H, Grunfeld Y, Porath G, Ben-Zvi Z, Shani A,
Mechoulam R. 1972. Structure-activity relation-
ships in the tetrahydrocannabinol series. Modica-
tions on the aromatic ring and it the side-chain.
Arzneimittelforschung 22:19952003.
23. Wilson DM, Peart J, Martin BR, Bridgen DT, Byron
PR, Lichtman AH. 2002. Physiochemical and
pharmacological characterization of a D
aerosol generated by a metered dose inhaler. Drug
Alcohol Depend 67:259267.
24. Naef M, Russmann S, Petersen-Felix S, Brenneisen
R. 2004. Development and pharmacokinetic char-
acterization of pulmonal and intravenous delta-9-
tetrahydrocannabinol (THC) in humans. J Pharm
Sci 93:11761184.
25. Lichtman AH, Peart J, Poklis JL, Bridgen DT,
Razdan RK, Wilson DM, Poklis A, Meng Y, Byron
PR, Martin BR. 2000. Pharmacological evaluation
of aerosolized cannabinoids in mice. Eur J Phar-
macol 399:141149.
26. Hartley JP, Nogrady SG, Seaton A. 1978. Bronch-
odilator effect of delta1-tetrahydrocannabinol. Br J
Clin Pharmacol 5:523525.
27. Lyons HA, Ayres SM, Dworetzky M, Failliers CS,
Harris MC, Dollery CT, Gandevia B. 1973. Sympo-
sium on isoproterenol therapy in asthma. Ann
Allergy 31:144.
28. Williamson EM, Evans FJ. 2000. Cannabinoids in
clinical practice. Drugs 60:13031314.
29. Notcutt W, Price M, Miller R, Newport S, Phillips
C, Simmons S, Sansom C. 2004. Initial experiences
with medicinal extracts of cannabis for chronic
pain: Results from 34 Nof1studies. Anaesthesia
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... Similarly, for vaping flower, we used the mean efficiency (50%) reported across four laboratory studies. [27][28][29][30] For vaping concentrates, the approximate mean efficiency (50%) across three studies was used. 25,29,30 However, we emphasize that these studies were not designed to develop MAECs and hence should not be perceived as valid or prematurely used without additional scrutiny and empirical study. ...
... [27][28][29][30] For vaping concentrates, the approximate mean efficiency (50%) across three studies was used. 25,29,30 However, we emphasize that these studies were not designed to develop MAECs and hence should not be perceived as valid or prematurely used without additional scrutiny and empirical study. To test for differences in sociodemographic and use variables among those who chose to report their quantity in hits versus grams, we used Wilcoxon rank sum and chi-squared tests (Tables 1 and 2). ...
Introduction: Quantification of consumption patterns of the primary psychoactive compounds in cannabis, which cause euphoria or intoxication, is sorely needed to identify potential risks and benefits of use and to provide meaningful safety information to the public. The diversity of products available, multiple methods of administration, and lack of labeling of products have made such quantification challenging. Our group is developing a survey instrument for estimating the quantity of delta 9-tetrahydrocannabinol (THC) consumed in population samples, which is flexible and incorporates individualized reports of patterns of consumption. This study provides an illustration of a procedure for translating self-reported consumption into milligrams of THC (mgTHC), which may serve as a working model for future quantification efforts. Methods: Social media advertising was leveraged to enroll 5627 adults who use cannabis into an online, anonymous survey study. Only those who used cannabis in the past 7 days, used flower or concentrate products, and who chose to report their quantity of use in hits per day or grams per week (n=3211) were included in this report. Formulas were used to estimate mgTHC used per day, in hits per day or grams per week; potency (%THC); constants for estimating the amount of material consumed for each hit; and a method of administration efficiency constant to account for THC loss due to the administration method. Results: The estimate for mgTHC used per day was M=92.8 mg/day (SD=97.2 mg; 1st-3rd quartile range=25-132 mg). The estimated quantity of use was much lower for those reporting in hits (M=43.7 mg, SD=43.8) than for those reporting in grams (M=115.1 mg, SD=107.0). The estimated rate of binge use in the past week, arbitrarily defined as more than 50 mgTHC within any one daily time quadrant, was 6.8%, which increased to 29.3% if 25 mgTHC was used. Conclusions: The approach illustrated in this study goes beyond existing cannabis measures by asking participants to provide highly detailed estimates of their past 7-day use patterns and then applying a logical formula to translate this information into mgTHC. This initial procedure has limitations and lacks generalization; however, we hope this demonstration stimulates testing of similar approaches and relevant laboratory experiments that will enhance the validity of cannabis consumption estimation procedures.
... Study treatment GH001 (GH Research, Dublin, Ireland) is an investigational drug product based on a proprietary formulation of synthetic, high purity, GMP pharmaceutical grade 5-MeO-DMT for administration via inhalation. GH001 was administered after a standardized vaporization procedure using the Volcano Medic Vaporization System (Storz and Bickel, Germany), approved in Europe, Australia, and Canada for medical use with cannabinoids (27)(28)(29). The device consists of a hot air generator, which facilitates formation of an aerosol from GH001, and a detachable valve balloon from which the aerosol is inhaled by the participant with a single breath. ...
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Background Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD. Methods The Phase 1 part ( n = 8) of the trial investigated two single dose levels of GH001 (12 mg, 18 mg) with a primary endpoint of safety, and the Phase 2 part ( n = 8) investigated an individualized dosing regimen (IDR) with up to three increasing doses of GH001 (6 mg, 12 mg, and 18 mg) within a single day, with a primary endpoint of efficacy, as assessed by the proportion of patients in remission (MADRS ≤ 10) on day 7. Results Administration of GH001 via inhalation was well tolerated. The proportion of patients in remission (MADRS ≤ 10) at day 7 was 2/4 (50%) and 1/4 (25%) in the 12 mg and 18 mg groups of Phase 1, respectively, and 7/8 (87.5%) in the IDR group of Phase 2, meeting its primary endpoint ( p < 0.0001). All remissions were observed from day 1, with 6/10 remissions observed from 2 h. The mean MADRS change from baseline to day 7 was −21.0 (−65%) and − 12.5 (−40%) for the 12 and 18 mg groups, respectively, and − 24.4 (−76%) for the IDR. Conclusion Administration of GH001 to a cohort of 16 patients with TRD was well tolerated and provided potent and ultra-rapid antidepressant effects. Individualized dosing with up to three doses of GH001 on a single day was superior to single dose administration. Clinical Trial registration : Identifier NCT04698603.
... The % recovery after vaporization was selected from [39]. For the 40 mg/mL solution, this value would be 0.6 mg/L. ...
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Background: Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. Objective: We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration. Methods: Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis. Results: Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment. Conclusion: This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.
... The balloon was covered in an opaque bag so the contents were not visible. This method has been shown to be safe Morgan et al., 2018) and produce similar pulmonary and plasma cannabinoid levels to smoked cannabis, but with lower expired carbon monoxide levels (Abrams et al., 2007;Hazekamp et al., 2006;Lanz et al., 2016). The minimum washout period between drug sessions was 72 hours, the mode was 7 days, and the maximum was 51 days (Heuberger et al., 2015;Taylor et al., 2018). ...
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Cannabis is the third most commonly used controlled substance worldwide, after alcohol and nicotine. With its changing legal profile, a deeper understanding of how cannabis affects the brain and cognition is in urgent need. Cannabis use has historically been linked with the ‘amotivational syndrome’, implying that reward or motivational processes are dysfunctional in cannabis users. Maladapted reward processing, such as anhedonia and apathy, is a cross-diagnostic symptom in psychiatric disorders, including substance use disorders. Finally, adolescents may be particularly vulnerable to adverse effects of cannabis, due to the important socio-emotional, cognitive, and neuromaturation that takes place during this time. The aims of this thesis were twofold. First, to investigate whether acute and chronic cannabis exposure was associated with disrupted reward processing across psychological, behavioural, and neuroimaging outcomes. Second, to assess whether adolescents showed stronger reward processing disruption after acute or chronic cannabis exposure compared with adults. Firstly, a systematic review of the human literature examining the association between cannabis exposure and reward processing was conducted. Results were mixed, with the strongest evidence for a positive relationship between anhedonia and cannabis use in adolescents. A number of caveats prevented the distillation of clear conclusions, including highly variable operationalisation of cannabis use, lack of or only partial control of important confounders, and small, chiefly adult samples, with consequently low power. The subsequent empirical work expanded on previous research by directly comparing large samples of adult and adolescent cannabis users (1-7 days/week) and gender- and age-matched controls on several measures of reward processing, with rigorous assessment of cannabis use and control of important confounders. The primary source of data for this thesis was the CannTeen study, which is a large study of the effects of cannabis in adults and adolescents. The CannTeen study has an acute arm and a non-acute longitudinal arm, and includes both behavioural measures and neuroimaging. First, data from the CannTeen acute study was used to examine whether cannabis exposure was associated with altered neural responses to reward anticipation on the Monetary Incentive Delay task in adults and adolescents. Acute active cannabis attenuated neural reward anticipation responses in key reward regions, including the ventral striatum and insula, relative to placebo. No previous study has shown this effect in healthy participants or adolescents. Subsequently, adult and adolescent cannabis users and controls from the CannTeen non-acute study were compared on neural reward anticipation and feedback, using the same task. There were no significant differences between cannabis users and controls during reward anticipation or in pre-defined regions during feedback. However, cannabis users showed unhypothesised greater feedback activity in the frontopolar and inferior parietal cortex in an exploratory whole-brain analysis. Neither study found differential effects of cannabis exposure in adolescents and adults. Adult and adolescent cannabis users and controls from the CannTeen non-acute study were then compared on two novel, non-neuroimaging reward processing tasks. The Physical Effort task assessed effort-based decision-making for reward and the Real Reward Pleasure task assessed subjective reward wanting and liking. There were no significant differences between cannabis users and controls on any outcomes, and no interactions between user-group and age-group. Finally, two samples of adult and adolescent cannabis users and controls from the CannTeen non-acute study and a separate online survey study, respectively, were compared on anhedonia and apathy. There was tentative evidence of elevated anhedonia in adolescent cannabis users, but not adult users, and no overall differences between users and controls in levels of apathy. This work suggests that cannabis affects the brain’s reward system acutely, but is not associated with lasting disruptions to reward or motivation non-acutely. Adolescents may show greater vulnerability to cannabis-related anhedonia, but not other reward processing outcomes. Thus, reward processes appear to be largely spared in adolescents and adults with moderate cannabis use, and the cannabis-related ‘amotivational syndrome’ is not supported by scientific evidence.
... Each subject inhaled 100 mg of the grinded flower material after it was vapourised using a vapouriser (Volcano Medic 2; Storz & Bickel GmbH & Co., Tuttlingen, Germany). 30 In the vapouriser, cannabis flower 100 mg was heated to 210 C, allowing the THC acid to be converted into the active THC. The vapour was collected in an 8 L bag, and the subject inhaled the complete content of the bag through a mouthpiece in 3e7 min; after each inhalation, the subject was instructed to hold the breath for 5 s. ...
Full-text available
Background: In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ9-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined. Methods: In this randomised controlled crossover trial, healthy volunteers were administered inhaled Bedrocan® 100 mg (Bedrocan International B.V., Veendam, The Netherlands), a pharmaceutical-grade high-THC cannabis variant (21.8% THC; 0.1% cannabidiol), after placebo or oral oxycodone 20 mg pretreatment; THC was inhaled 1.5 and 4.5 h after placebo or oxycodone intake. The primary endpoint was isohypercapnic ventilation at an end-tidal Pco2 of 55 mm Hg or 7.3 kPa (VE55), measured at 1-h intervals for 7 h after placebo/oxycodone intake. Results: In 18 volunteers (age 22 yr [3]; 9 [50%] female), oxycodone produced a 30% decrease in VE55, whereas placebo was without effect on VE55. The first cannabis inhalation resulted in VE55 changing from 20.3 (3.1) to 23.8 (2.4) L min-1 (P=0.06) after placebo, and from 11.8 (2.8) to 13.0 (3.9) L min-1 (P=0.83) after oxycodone. The second cannabis inhalation also had no effect on VE55, but slightly increased sedation. Conclusions: In humans, THC has no effect on ventilatory control after placebo or oxycodone pretreatment. Clinical trial registration: 2021-000083-29 (EU Clinical Trials Register.).
... GH001 (GH Research, Dublin, Ireland) is an investigational drug product based on a proprietary formulation of highly pure, GMP pharmaceutical grade 5-MeO-DMT for administration via inhalation. Liquid GH001 was administered after a standardized vaporization procedure using the Volcano Medic Vaporization System (Storz and Bickel, Germany), approved in Europe, Australia, and Canada for medical use with cannabinoids (Gieringer et al., 2004;Hazekamp et al., 2006;Abrams et al., 2007). The device consists of a hot air generator, which allows formation of an aerosol from GH001, and a detachable valve balloon (3 L) from which the aerosol is inhaled by the participant with a single breath. ...
... Each preparation was vaporised at 210°C into a transparent polythene bag. This temperature has been found to maximise cannabinoid delivery [17]. Once filled, the transparent bag was encased with an opaque bag to ensure blinding (a higher CBD:THC ratio produces a denser vapour). ...
Full-text available
As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change in delayed verbal recall on the Hopkins Verbal Learning Task. Secondary outcomes included change in severity of psychotic symptoms (e.g., Positive and Negative Syndrome Scale [PANSS] positive subscale), plus further cognitive, subjective, pleasurable, pharmacological and physiological effects. Serial plasma concentrations of THC and CBD were measured. THC (0:1) was associated with impaired delayed verbal recall (t(45) = 3.399, d = 0.50, p = 0.001) and induced positive psychotic symptoms on the PANSS (t(45) = −4.709, d = 0.69, p = 2.41 × 10–5). These effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures. There was a dose-response relationship between CBD dose and plasma CBD concentration, with no effect on plasma THC concentrations. At CBD:THC ratios most common in medicinal and recreational cannabis products, we found no evidence that CBD protects against the acute adverse effects of cannabis. This should be considered in health policy and safety decisions about medicinal and recreational cannabis.
Background Adolescents may respond differently to cannabis than adults, yet no functional magnetic resonance imaging (fMRI) study has examined acute cannabis effects in this age-group. We investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. Methods This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n=24, 12 females, 16-17 years) and adults (n=23, 11 females, 26-29 years), matched on cannabis use frequency (0.5-3 days/week), completed the Monetary Incentive Delay task during fMRI after inhaled cannabis with 0.107 mg/kg THC (‘THC’) (8 mg THC for a 75 kg person) or THC plus 0.320 mg/kg CBD (‘THC+CBD’) (24 mg CBD for a 75 kg person), or placebo cannabis (‘PLA’). We investigated reward anticipation activity with whole-brain analyses and region of interest (ROI) analyses in right and left ventral striatum, right and left anterior cingulate cortex, and right insula. Results THC reduced anticipation activity compared to placebo in the right (P=.005, d=0.49) and left (P=.003, d=0.50) ventral striatum, and right insula (P=.01, d=0.42). THC+CBD reduced activity compared to placebo in the right ventral striatum (P=.01, d=0.41) and right insula (P=.002, d=0.49). There were no differences between ‘THC’ and ‘THC+CBD’ and no significant Drug*Age-Group effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. Conclusions In weekly cannabis users, cannabis suppresses the brain’s anticipatory reward response to money and CBD does not moderate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.
In 2019 an estimated 200 million people aged 15-64 used cannabis, making cannabis the most prevalent illicit substance worldwide. The last decade has seen a significant expansion in the cannabis vaporiser market, introducing cannabis vaporisation as a common administration method alongside smoking and ingestion. Despite reports of increased prevalence of cannabis vaporisation there has been little research into the use of these devices. To remedy the current dearth of data in this area this study utilised an anonymous online survey of individuals who self-reported past cannabis vaporisation. The respondents (N=557) were predominantly young (<35 years) and male. Most (91.4%) stated they had ever vaped dry herb cannabis, 59.1% reported vaporisation of cannabis oil or liquids, and 34.0% reported vaporisation of cannabis concentrates. This study identifies the types of vaporisation devices (including brands and models) employed by cannabis vapers, as well as the vaporisation temperatures and puff durations commonly used for dry herb, cannabis liquids and cannabis concentrates. To the best of our knowledge, this is the first time the usual operating temperatures of these vaporisation devices and user specific consumption patterns such as puff duration have been reported for cannabis vaping. This information will allow for a more realistic understanding of patterns of recreational use and improve experimental conditions in research settings to reflect the user’s context.
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This randomised, double-blind, placebo-controlled, cross-over study was designed to identify which pharmacodynamic parameters most accurately quantify the effects of delta-9-Tetrahydrocannabinol (THC), the predominantly psychoactive component of cannabis. In addition, we investigated the acceptability and usefulness of a novel mode of intrapulmonary THC administration using a Volcano® vaporizer and pure THC instead of cannabis. Rising doses of THC (2, 4, 6 and 8 mg) or vehicle were administered with 90 minutes intervals to twelve healthy males using a Volcano® vaporizer. Very low between-subject variability was observed in THC plasma concentrations, characterising the Volcano® vaporizer as a suitable method for the administration of THC. Heart rate showed a sharp increase and rapid decline after each THC administration (8 mg: 19.4 bpm: 95% CI 13.2, 25.5). By contrast, dose dependent effects of body sway (8 mg: 108.5%: 95% CI 72.2%, 152.4%) and different subjective parameters did not return to baseline between doses (Visual Analogue Scales of 'alertness' (8 mg:-33.6 mm: 95% CI-41.6,-25.7), 'feeling high' (8 mg: 1.09 U: 95% CI 0.85, 1.33), 'external perception' (8 mg: 0.62 U: 95% CI 0.37, 0.86)). PK/PD-modeling of heart rate displayed a relatively short equilibration half-life of 7.68 min. CNS parameters showed equilibration half-lives ranging between 39.4-84.2 min. Some EEG-frequency bands, and pupil size showed small changes following the highest dose of THC. No changes were seen in saccadic eye movements, smooth pursuit and adaptive tracking performance. These results may be applicable in the development of novel cannabinoid agonists and antagonists, and in studies of the pharmacology and physiology of cannabinoid systems in humans.
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Cannabis vaporization is a technology designed to deliver inhaled cannabinoids while avoiding the respiratory hazards of smoking by heating cannabis to a temperature where therapeutically active cannabinoid vapors are produced, but below the point of combustion where noxious pyrolytic byproducts are formed.This study was designed to evaluate the efficacy of an herbal vaporizer known as the Volcano®, produced by Storz & Bickel GmbH&Co. KG, Tuttlingen, Germany ( Three 200 mg samples of standard NIDA cannabis were vaporized at temperatures of 155°–218°C. For comparison, smoke from combusted samples was also tested.The study consisted of two phases: (1) a quantitative analysis of the solid phase of the vapor using HPLC-DAD-MS (High Performance Liquid Chromatograph-Diode Array-Mass Spectrometry) to determine the amount of cannabinoids delivered; (2) a GC/MS (Gas Chromatograph/ Mass Spectrometer) analysis of the gas phase to analyze the vapor for a wide range of toxins, focusing on pyrene and other polynuculear aromatic hydrocarbons (PAHs).The HPLC analysis of the vapor found that the Volcano delivered 36%–61% of the THC in the sample, a delivery efficiency that compares favorably to that of marijuana cigarettes.The GC/MS analysis showed that the gas phase of the vapor consisted overwhelmingly of cannabinoids, with trace amounts of three other compounds. In contrast, over 111 compounds were identified in the combusted smoke, including several known PAHs.The results indicate that vaporization can deliver therapeutic doses of cannabinoids with a drastic reduction in pyrolytic smoke compounds. Vaporization therefore appears to be an attractive alternative to smoked marijuana for future medical cannabis studies.
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Chromatographic and spectroscopic data was determined for 16 different major cannabinoids from Cannabis sativa plant material as well as 2 human metabolites of Δ‐tetrahydrocannabinol. Spectroscopic analysis included UV absorbance, infrared‐spectral analysis, (GC‐) mass spectrometry, and spectrophotometric analysis. Also, the fluorescent properties of the cannabinoids are presented. Most of this data is available from literature but scattered over a large amount of scientific papers. In this case, analyses were carried out under standardised conditions for each tested cannabinoid so spectroscopic data can be directly compared. Different methods for the analysis of cannabis preparations were used and are discussed for their usefulness in the identification and determination of separate cannabinoids. Data on the retention of the cannabinoids in HPLC, GC, and TLC are presented.
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A simple method is presented for the preparative isolation of seven major cannabinoids from Cannabis sativa plant material. Separation was performed by centrifugal partition chromatography (CPC), a technique that permits large‐scale preparative isolations. Using only two different solvent systems, it was possible to obtain pure samples of the cannabinoids; (−)‐Δ‐(trans)‐tetrahydrocannabinol (Δ‐THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), (−)‐Δ‐(trans)‐tetrahydrocannabinolic acid‐A (THCA), cannabigerolic acid (CBGA), and cannabidiolic acid (CBDA). A drug‐type and a fiber‐type cannabis cultivar were used for the isolation. All isolates were shown to be more than 90% pure by gas chromatography. This method makes acidic cannabinoids available on a large scale for biological testing. The method described in this report can also be used to isolate additional cannabinoids from cannabis plant material.
Particle size and mass concentration are important determinants of site and quantity of respiratory tract deposition of aerosols. Particle concentrations and size distributions of smoke from marijuana cigarettes with different concentrations (as measured in the marijuana leaf) of Δ9-tetrahydrocannabinol (Δ9-THC) were measured using a single particle aerodynamic relaxation time (SPART) analyzer. The SPART analyzer measures aerodynamic diameter of single suspended particles at a rate of 3000/min. Cigarettes were smoked using a 35-cc, 2-sec puffing device attached to a diluter; dilution and analysis were completed within 4 sec of puff generation. The size distribution of smoke from all marijuana cigarettes was similar to that for tobacco cigarettes, ranging from 0.35 to 0.43 μm (count median aerodynamic diameter). The particle number and mass concentration increased as Δ9-THC concentration increased, being, respectively, 2.2- and 3.8-fold higher in the marijuana cigarette leaf with highest Δ9-THC concentration compared to the placebo marijuana cigarette. These data indicate the need for quantitative comparisons of other potentially toxic constituents in marijuana cigarettes of different Δ9-THC concentrations.
Particle size and mass concentration are important determinants of site and quantity of respiratory tract deposition of aerosols. Particle concentrations and size distributions of smoke from marijuana cigarettes with different concentrations (as measured in the marijuana leaf) of Δ9-tetrahydrocannabinol (Δ9-THC) were measured using a single particle aerodynamic relaxation time (SPART) analyzer. The SPART analyzer measures aerodynamic diameter of single suspended particles at a rate of 3000/min. Cigarettes were smoked using a 35-cc, 2-sec puffing device attached to a diluter; dilution and analysis were completed within 4 sec of puff generation. The size distribution of smoke from all marijuana cigarettes was similar to that for tobacco cigarettes, ranging from 0.35 to 0.43 μm (count median aerodynamic diameter). The particle number and mass concentration increased as Δ9-THC concentration increased, being, respectively, 2.2- and 3.8-fold higher in the marijuana cigarette leaf with highest Δ9-THC concentration compared to the placebo marijuana cigarette. These data indicate the need for quantitative comparisons of other potentially toxic constituents in marijuana cigarettes of different Δ9-THC concentrations.