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Vaporization as a Smokeless Cannabis Delivery
System: A Pilot Study
DI Abrams
1,2,3
, HP Vizoso
1,3
, SB Shade
1,3
, C Jay
4,5
, ME Kelly
1,2,3
and NL Benowitz
3,6
Although cannabis may have potential therapeutic value, inhalation of a combustion product is an undesirable delivery
system. The aim of the study was to investigate vaporization using the Volcano
s
device as an alternative means
of delivery of inhaled Cannabis sativa. Eighteen healthy inpatient subjects enrolled to compare the delivery of
cannabinoids by vaporization to marijuana smoked in a standard cigarette. One strength (1.7, 3.4, or 6.8%
tetrahydrocannabinol (THC)) and delivery system was randomly assigned for each of the 6 study days. Plasma
concentrations of D-9-THC, expired carbon monoxide (CO), physiologic and neuropsychologic effects were the main
outcome measures. Peak plasma concentrations and 6-h area under the plasma concentration–time curve of THC
were similar. CO levels were reduced with vaporization. No adverse events occurred. Vaporization of cannabis is a
safe and effective mode of delivery of THC. Further trials of clinical effectiveness of cannabis could utilize vaporization
as a smokeless delivery system.
The Institute of Medicine (10 m) report on Marijuana as
Medicine published in 1999 concluded that ‘‘scientific data
indicate the potential therapeutic value of cannabinoid drugs,
primarily THC, for pain relief, control of nausea and
vomiting, appetite stimulation; smoked marijuana, however
is a crude THC delivery system that also delivers harmful
substances’’.
1
The report recommended that clinical trials of
cannabinoid drugs for symptom management should be
conducted with the goal of developing rapid onset, reliable,
and safe delivery systems. While acknowledging therapeutic
potential, the IOM report stressed that cannabis is not a
completely benign substance, but a powerful drug with a
variety of effects, but ‘‘except for the harms associated with
smoking, the adverse effects are within the range of those
tolerated for other medications.’’ The report comments that
‘‘because of the health risks associated with smoking, smoked
cannabis should generally not be recommended for long-
term medical use. Nonetheless, for certain patients, such as
the terminally ill or those with debilitating symptoms, the
long-term risks are not of great concern.’’ The Institute of
Medicine sends a clear message suggesting that smoking is
not a desirable delivery system for the potential therapeutic
effects of cannabis.
Cannabis vaporization is a technology for delivering
inhaled tetrahydrocannabinol (THC) and other cannabinoids
while reducing toxic byproducts of smoked cannabis primarily
caused by combustion.
2,3
By heating cannabis to a tempera-
ture between 180 and 2001C, it is possible to vaporize the
cannabinoids that reside on the trichomes on the surface of
cannabis flowers and leaves, while avoiding combustion
(which occurs at 2301C and above) and attendant smoke
toxins. Vaporization is a relatively new technology. Various
vaporizer designs are currently under development. The
feasibility of vaporization of THC has been demonstrated in
a series of laboratory studies involving different vaporizer
designs.
2
An electric vaporizer was shown to release substantial
amounts of the THC while producing no measurable amounts
of the benzene, toluene, and naphthalene, which are generated
when marijuana is smoked. Reductions in carbon monoxide
(CO) and tar generation were also observed under vaporiza-
tion compared to smoking. Although no measurements were
made of other smoke toxins, it is quite possible that the
vaporizer eliminated or substantially reduced the polycyclic
aromatic hydrocarbons and other combustion-generated
toxins commonly found in cannabis smoke, as they form at
the higher temperatures of pyrolysis.
nature publishing group
ARTICLES
Received 29 September 2006; accepted 25 February 2007; advance online publication 11 April 2007. doi:10.1038/sj.clpt.6100200
1
Community Consortium, Positive Health Program, San Francisco General Hospital, San Francisco, California, USA;
2
Division of Hematology-Oncology,
San Francisco General Hospital, San Francisco, California, USA;
3
Department of Medicine, University of California, San Francisco, California, USA;
4
Division of Neurology,
San Francisco General Hospital, San Francisco, California, USA;
5
Department of Neurology, University of California, San Francisco, California, USA;
6
Division of Clinical
Pharmacology and Experimental Therapeutics, University of California, San Francisco, California, USA. Correspondence: DI Abrams (dabrams@php.ucsf.edu)
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A recent evaluation of the Volcano
s
vaporizer device used
herbal cannabis or pure cannabinoid ethanolic solution
preparations to test the efficacy and reproducibility of THC
delivery into the balloon receptacle.
4
Cannabinoids were
measured in the THC-containing materials before and after
vaporization, and in the vapor that was generated by the
device and collected within the balloon. The results validated
the Volcano
s
vaporizer as an efficient and reproducible
mode of delivery of D-9-THC. On average, 54% of the
applied dose of THC was recovered in the balloon receptacle.
This study investigated vaporization using the Volcano
s
device compared to smoked cannabis. This is the first
pharmacokinetic and pharmacodynamic evaluation conducted
in humans to determine whether the Volcano
s
may be an
appropriate system for use in clinical effectiveness studies.
RESULTS
Baseline characteristics of study subjects
A total of 68 patients were screened for eligibility between
August 2004 and May 2005. Of these, 47 were not enrolled
(33 patients were unavailable to commit to a 6-day
hospitalization, 10 patients were excluded as a result of their
medical history or concurrent illness, and four patients were
excluded because of active substance abuse). Twenty-one
patients were randomly assigned; however, three patients did
not complete the intervention of the study phase (one patient
for non-adherence to the General Clinical Research Center
(GCRC) rules of comportment, one patient for acute
influenza, and one patient withdrew consent), leaving 18
total patients for analysis.
Participants were predominately men (83%), Caucasian
(72%), with some college education (94%). All of the partici-
pants were active marijuana users (median 5–6, range 3–10
marijuana cigarettes in the past 30 days). None had used the
Volcano
s
device, although one participant had previously
experienced vaporized marijuana using a similar device.
Primary outcome measure
The mean and 95% confidence intervals (CIs) for the plasma
concentrations of THC at each time point for each strength
of THC using both vaporization and smoking are presented
in Figure 1. The vaporizer resulted in higher plasma
concentrations of THC compared to smoked marijuana at
30 and 60 min at each strength (Table 1). The two modalities
were not significantly different from one another at any of the
three strengths in the 6-h area under the plasma THC
concentration–time curve (AUC), or for the peak THC
plasma concentrations measured at 2 min.
There was evidence of decreasing bioavailability and/or
titration of THC intake with increasing strength of THC. The
plasma THC AUC derived from the vaporizer normalized for
the THC strength was highest at 1.7% THC (27.1 ng h/ml/%)
and was progressively lower at higher THC strengths (3.4%
THC: 20.5 ng h/ml/% and 6.8% THC: 14.3 ng h/ml/%;
Table 1), suggesting higher bioavailability and/or more
intensive puffing at lower THC potency. This decline was
statistically significant (ratio: 0.87; 95% CI: 0.84, 0.90;
Po0.001 per 1% increase in THC strength) and did not
appear to differ between vaporization and smoking (ratio for
interaction: 0.92; 95% CI: 0.79, 1.05; P ¼ 0.25) in a mixed
model which included fixed effects for randomization, a
linear term for THC strength, and a term for the interaction
between these effects.
There was also evidence of titration of intake of THC with
increasing THC strength based on puffing behavior. The
number of puffs taken using smoked marijuana remained
stable with increasing strength THC (mean puffs, 95% CI: 6.1
(4.8, 7.3), 5.9 (4.9, 6.8), and 6.4 (5.3, 7.6) for 1.7, 3.4, and
6.8% THC, respectively; mixed model analysis ratio: 1.01;
95% CI: 0.96, 1.05; P ¼ 0.81). The number of puffs taken
Figure 1 Plasma THC using vaporizer and smoked cannabis by THC
strength (mean and 90% CI).
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using vaporized marijuana tended to decrease with increasing
strength of THC, but the trend was not significant (mean
puffs, 95% CI: 10.1 (8.8, 11.3), 9.2 (8.2, 10.1), and 8.6 (7.7,
9.4) for 1.7, 3.4, and 6.8% THC, respectively; mixed model
ratio: 0.97; 0.92, 1.01; P ¼ 0.17).
Secondary outcome measures
The levels of exhaled CO increased very little after vaporiza-
tion; mean¼À1.9p.p.m.; 95% CI: À4.4, 0.6 for 1.7% THC;
mean¼À1.8p.p.m.; 95% CI: À3.7, 0.7 for 3.4% THC; and
mean¼À0.5p.p.m.; 95% CI: À1.9, 0.9 for 6.8% THC),
whereas there was a substantial increase after smoking
marijuana (mean¼ 15.5p.p.m.; 95% CI: 11.0, 20.1 for 1.7%
THC; mean¼ 11.9p.p.m.; 95% CI: 6.8, 17.1 for 3.4% THC;
mean¼ 7.0p.p.m.; 95% CI: 4.0, 10.0 for 6.8% THC)
(Figure 2). This difference was statistically significant
(Po0.001) at each THC strength. The increase in CO (AUC
for CO) decreased during smoking (P¼ 0.003 for trend), but
not vaporization (P¼ 0.25) with increasing THC strength. The
expired CO AUC per puff is an indicator of how much smoke
is inhaled per puff for the smoked marijuana. The CO AUC
per puff decreased progressively (1.7% THC: [mean, 95% CI]:
2.8 (2.2, 3.3); 3.4% THC: 2.1 (1.1, 3.0); 6.8% THC: 1.2 (0.6,
1.9); Po0.001 for trend), consistent with taking smaller puffs
with increasing THC content in the marijuana.
Subjective and safety observations
Self-reported high did not differ during vaporization com-
pared to smoking overall (6-h AUC) or at any observation
after consumption of cannabis (Figure 3). Self-reported high
did increase significantly during both vaporization and
smoking with increasing strength of THC (Po0.001).
Table 1 THC pharmacokinetics for vaporized cannabis and ratio of vaporized vs smoked cannabis
a,b
Vaporizer
Vaporizer/smoked ratio
THC, % outcome measure
Mean
95% CI
Minimum
Maximum
Odds ratio
95% CI*
P-value
1.7%
AUC
0–6
46.00
34.89, 57.11
15.59
98.08
1.26
0.94, 1.68
0.12
C
max
(=C
2
)
68.95
46.99, 90.91
6.00
186.20
1.01
0.65, 1.58
0.97
C
30
18.94
10.57, 27.32
4.90
79.90
1.95
1.37, 2.80
0.001
C
60
7.56
6.02, 9.50
3.70
16.50
1.56
1.26, 1.93
0.001
C
180
3.05
1.99. 4.00
0.10
9.40
1.31
0.83, 2.06
0.25
C
360
1.87
0.97, 2.77
0.20
8.20
1.17
0.82, 1.66
0.38
Puffs
10.06
8.81, 11.30
7.00
17.00
1.71
1.47, 2.00
0.001
AUC/THC %
27.06
20.52, 33.60
9.17
57.69
1.26
0.94, 1.68
0.12
3.4%
AUC
0–6
69.76
52.91, 86.62
22.30
140.44
0.99
0.81, 1.21
0.95
C
max
(=C
2
)
112.45
84.55, 140.65
36.70
201.10
1.07
0.64, 1.80
0.80
C
30
23.04
17.74, 28.35
28.35
43.20
1.50
1.29, 1.73
0.001
C
60
12.58
9.46, 15.70
3.30
24.20
1.41
1.11, 1.79
0.006
C
180
4.14
3.05, 5.24
1.40
10.10
1.24
1.06, 1.46
0.008
C
360
2.94
1.55, 4.34
0.60
12.90
1.34
1.03, 1.75
0.03
Puffs
9.17
8.23, 10.10
4.00
13.00
1.58
1.36, 1.84
0.001
AUC/THC %
20.52
15.56, 25.48
6.56
41.31
0.99
0.81, 1.21
0.95
6.8%
AUC
0-6
96.79
67.51, 126.06
18.98
278.20
1.22
0.98, 1.54
0.08
C
max
(=C
2
)
187.12
100.65, 273.59
22.50
813.20
1.19
0.86, 1.65
0.30
C
30
28.80
22.19, 35.41
9.20
50.00
1.45
1.16, 1.82
0.001
C
60
15.99
12.41, 19.58
4.60
29.40
1.38
1.13, 1.69
0.002
C
180
4.81
3.65, 5.96
1.10
9.20
1.15
0.88, 1.52
0.31
C
360
2.99
0.79, 5.20
0
19.50
0.88
0.53, 1.45
0.62
Puffs
8.55
7.72, 9.40
5.00
11.00
1.43
1.11, 1.85
0.006
AUC/THC %
14.23
9.93, 18.54
2.79
40.91
1.22
0.98, 1.54
0.08
AUC, area under the curve; CI, confidence interval; THC, tetrahydrocannabinol.
a
AUCs in ng h/ml; C
max
values in ng/ml.
b
Analysis conducted using mixed models to adjust for
day of observation.
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Although blinded with regard to dose, eight participants
selected the day they received 3.4% THC (seven vaporized,
one smoked) as their most preferred treatment day; four
participants selected the day they received 6.8% THC via
vaporization, and six participants had no treatment day
preference. Overall, vaporization was the preferred method of
administration by 14 participants, smoking was preferred by
two, and two reported no preference. During the course of
the study, no adverse events were reported.
DISCUSSION
Our study provides novel data on the absorption of THC
from marijuana inhaled via the Volcano
s
vaporizer system
compared to smoking marijuana cigarettes. We found that
THC levels were generally similar over 6 h for the two types of
delivery. The vaporizer was associated with higher plasma
THC concentrations at 30 min and 1 h compared to smoking
at each THC strength, suggesting that absorption was faster
with the vaporizer.
Bioequivalence criteria developed for drugs require that
the CIs for the ratios of AUC for the test and reference
products be between 80 and 125% to be judged bioequiva-
lent.
5
Using these criteria, we were not able to establish the
bioequivalence of vaporization and smoking of marijuana. A
much larger study would be needed to establish bioequiva-
lence in this setting.
Of interest was that the systemic dose of THC, as
estimated by the plasma AUC, normalized for the THC
content of the cannabis, varied with THC strength. The dose
of THC normalized for concentration of THC in the cannabis
was greater at lower compared to higher THC strengths, both
Figure 2 Expired CO at each time point for each mode of administration
and THC strength (mean and 95% CI).
Figure 3 Self-reported ‘‘high’’ at each time point for each mode of
administration and THC concentration (mean and 95% CI).
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for vaporized and smoked cannabis. This observation
suggests either dose-dependant bioavailability or self-titra-
tion of THC intake. Self-titration of drug intake means that
smokers adapt their smoking behavior to obtain desired
levels of THC from the particular delivery system, taking
more puffs and/or inhaling more efficiently at lower
compared to higher THC strengths. Supporting the idea of
titration was the trend to take more puffs at lower THC
concentrations of vaporized marijuana and the higher CO
per puff at lower THC concentrations of smoked marijuana.
The phenomenon of self-titration of psychoactive drug intake
from an inhaled delivery system is well documented for
nicotine from cigarette smoking,
6
but to our knowledge has
not been previously reported for marijuana.
Whereas smoking marijuana increased CO levels as
expected for inhalation of a combustion product, there was
little if any increase in CO after inhalation of THC from the
vaporizer. This indicates little or no exposure to gaseous
combustion toxins. Combustion products are harmful to
health and reflect a major concern about the use of marijuana
cigarettes for medical therapy as expressed by the Institute of
Medicine. Although we did not measure other combustion
products such as polycyclic aromatic hydrocarbons and
oxidant gases, the observation of little or no CO exposure
suggests little or no exposure to these other compounds. The
vaporizer was well tolerated, with no reported adverse effects.
Most subjects preferred the vaporizer compared to marijuana
smoking, supporting its potential for medical therapy. Thus,
the Volcano
s
is an acceptable system and may provide a safer
way to deliver THC than smoking marijuana cigarettes.
In summary, we provide data indicating that the
availability of THC delivered by the Volcano
s
vaporizer is
comparable to that of marijuana cigarettes. Vaporization of
marijuana does not result in exposure to combustion gases,
and therefore is expected to be much safer than smoking
marijuana cigarettes. The vaporizer was well tolerated and
preferred by most subjects compared to marijuana cigarettes.
The Volcano
s
device is an effective and apparently safe
vehicle for THC delivery, and warrants further investigation
in clinical trials of cannabis for medicinal purposes.
METHODS
Study patients.
Participants were healthy adults between the ages of
21 and 45 years who were current cannabis users and had smoked
cannabis within the past 30 days but in an amount totaling less than
10 cannabis cigarettes or the equivalent. Subjects with active substance
abuse (e.g., recurrent or continuous drug and/or alcohol use) or
diagnosed with marijuana dependence as defined in DSM-IV code no.
304.30. were excluded. Subjects were required to abstain from
smoking cannabis for 48h before their admission into the GCRC at
San Francisco General Hospital (SFGH). The study was approved by
the Institutional Review Board at the University of California San
Francisco, the Research Advisory Panel of California, the Drug
Enforcement Administration, the Food and Drug Administration,
and the National Institute on Drug Abuse. Written informed consent
was obtained from all patients. The trial was monitored by an
independent Data Safety Monitoring Board (DSMB) established by
the University of California Center for Medicinal Cannabis Research.
Study medication.
The National Institute on Drug Abuse provided
pre-rolled cannabis cigarettes, weighing on average 0.9 g and
containing 1.7, 3.4, and 6.8% D-9-THC, respectively. The cigarettes
were kept in a locked and alarmed freezer until they were dispensed
to a locked freezer in the San Francisco General Hospital General
Clinical Research Center where the in-patient study was conducted.
The cigarettes were bisected; one half to be smoked and the contents
of the other half to be vaporized. The half cigarettes were rehydrated
in a humidifier overnight before their use. Patients were housed in a
room with a fan ventilating to the outside. Research staff monitored
patients during smoking sessions, weighed the cannabis cigarettes
immediately before and after they were administered to patients,
and returned all leftover material to the pharmacy. To maximize
standardization of inhaled doses, patients followed the Foltin
uniform puff procedure where inhalation for 5 s is followed by a
10 s breath hold, then exhalation; the entire process is repeated after
45 s.
7
Study participants smoked or vaporized cannabis once a day.
Subjects were instructed to continue puffing until they exhausted
smoke or vapor from the delivery device or until they had inhaled as
much as they could tolerate.
The vaporizer device.
The Volcano
s
vaporizer was obtained from
Storz & Bickel GmbH & Company (Tuttlingen, Germany) and was
employed according to the manual provided. The device works as a
vaporizer that evaporates the active substances or aromas from plant
material by using a hot airflow (Figure 4). Cannabis placed in the
filling chamber is heated by the device to 1901C. The vaporized
compounds are collected in the inflatable, detachable bag fitted with
a mouthpiece and a one-way valve that allows the vapor to remain in
the balloon until inhalation. It required two to three balloon
inflations to vaporize each half cigarette. Subjects also followed the
Foltin puff procedure when inhaling the vaporization product.
Study design and procedures.
The study was a 6-day ‘‘proof of
concept’’ pilot study to investigate the delivery of cannabinoids by
way of vaporization of cannabis compared to cannabis smoked in a
standard cigarette. The in-patient setting permitted us to measure
plasma THC concentration over time and to rigorously assess the
primary and secondary outcome variables in a controlled clinical
environment.
Screening visit.
Once a subject for the protocol had been identified,
details of the study were carefully discussed and the subject was
asked to read and sign a consent form. Subjects were asked questions
about their medical history including psychiatric illness and
substance abuse. Subjects were asked to abstain from smoking or
ingesting cannabis 48 h before their hospitalization based on our
prior studies which indicated that after 24 h of abstinence, plasma
THC concentrations are sufficiently low so that the concentration-
time curve could be determined after the experimental exposure.
8
GCRC in-patient hospitalization (days 1–6).
Subjects inhaled three
strengths of cannabis (1.7, 3.4, and 6.8% THC) as smoked cigarettes
and three as vaporized cannabis using the Volcano
s
device. Half of
one cigarette was inhaled via one of the two delivery systems on each
of the 6 in-patient GCRC days. The uniform puff procedure
described above was utilized to attempt to standardize inhalation.
Blood was drawn at 2, 30, 60, 180, and 360 min after smoking on
each of the 6 inhalation days to measure the concentrations of THC.
Expired CO was measured using the Ecolyzer
s
before inhalation,
and 2, 30, 60, 180, and 360min after inhalation.
Subjects rated the subjective ‘‘high’’ they experienced using a
100 mm visual analog scale anchored by ‘‘none’’ and ‘‘highest ever’’.
On day 5 before discharge, subjects were asked to choose which in-
patient day they preferred. Subjects were asked to rate their
preferences from 1 to 5 with 1 indicating very satisfied and 5
indicating very dissatisfied.
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All adverse events were spontaneously reported by the subject or
observed by the study personnel and/or GCRC nursing staff,
documented along with any medical intervention, and evaluated
according to standardized criteria in terms of severity, frequency,
duration, and relationship to study drug. Adverse events were
graded using the NIH Division of AIDS table for scoring severity of
adult adverse experiences.
9
Randomization.
The order of administration of the six combina-
tions of THC strength and delivery method for the 18 participants
was randomized in three 6 Â 6 Latin squares. This ensured balance
in the sense that each of the six combinations occurred exactly three
times on day 1, exactly three times on day 2, and so on. In addition,
the orders were restricted so that the two delivery methods for the
same strength always occurred on consecutive days. This was to
prevent patients from developing an early preference for one
delivery method if it was used with a higher strength cigarette than
the other. Randomization was computer-generated, and study drug
distribution was managed by a research pharmacist. Subjects and
study personnel were blinded to the THC strength.
Statistical analysis.
The 18-patient target sample size was based on
a standardized effect size to calculate sample size and power for the
study. With a sample of 18 subjects, we had an 80% power to detect
a true standardized effect size (E/S) of 0.70, using an a of 0.05, where
E is the effect size and S is the standard deviation of the paired
differences.
10,11
This calculation assumes use of a paired t-test using
data at a single concentration of THC.
The primary outcome was the within-person ratio for the 6-h
area under the curve (AUC
0–6
) for plasma concentration of THC,
comparing the vaporizer with smoking cannabis cigarettes. AUC
0–6
was computed using the linear trapezoidal method, assuming zero
THC concentration at baseline. This assumption was based on our
previous research that observed undetectable plasma concentration
of THC 8 h after smoking in all subjects.
8
For each mode of
administration and THC strength, we plotted the mean and 95% CIs
of the observed values at each time point. To assess the within-
person ratio comparing vaporization to smoking, each outcome
(AUC
0–6
, C
2
, C
30
, C
60
, C
180
, C
360
, number of puffs, AUC
0–6
per THC
percent, and AUC
0–6
per puff) was log transformed for analysis
using mixed effects models. The overall effect of vaporization
compared to smoking for each parameter was assessed by fitting a
fixed effect term for randomization (vaporization vs smoking),
controlling for strength of THC (indicators for 3.4% THC and 6.8%
THC cannabis, relative to 1.7% THC cannabis). Each patient was
treated as a random effect. Another model was fit to assess THC
strength-specific effects of vaporization compared to smoking. This
model included fitting additional fixed effects for the use of the
vaporizer at each strength of THC (vaporization at 1.7% THC,
vaporization at 3.4% THC, and vaporization at 6.8% THC).
We also assessed the potential presence of order effects due to the
study day of observation, as well as potential practice effects due to
additional experience using the vaporizer. To assess the presence of
order effects, additional variables were added to both the overall and
strength-specific models to assess whether day of observation
impacted the outcomes, as well as whether there was a difference
Figure 4 Volcano
s
apparatus.
6
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in measurements taken on the first day of the study compared to
other study days. In these models, day of observation was treated
as a linear variable with and without an additional indicator
variable for the first study day. Similarly, to assess the presence of
practice effects, additional variables were added to both the overall
and strength-specific models to assess whether previous use of
the vaporizer impacted the outcomes. These models included either
a linear variable for how many days the participant had used
the vaporizer or separate indicator variables for each day of
vaporizer use.
To explore possible evidence of titration of THC intake and dose-
dependent changes in bioavailability, we created additional mixed
models for number of puffs and AUC
0–6
per THC percent, which
included fixed effects, as above, for randomization (vaporization vs
smoking), as well as linear terms for strength of THC, and the
interaction between randomization and strength of THC. As above,
these models included a random effect for each patient. These
models assess not only whether the ratio of the number of puffs or
the AUC per THC percent differs during vaporization and smoking
but also whether the ratio increases or decreases with increasing
strength of cannabis, and whether this increase or decrease differs
during vaporization compared to smoking.
We compared the observed values for expired CO and self-
reported high using similar methods. We plotted the mean and
95% CIs of response measures at each time point for each mode of
administration and THC strength. We also fit mixed models for the
6-h AUC for expired CO and self-reported high, as described above,
to compare within-person effects using vaporization and smoking.
For 6-h AUC for CO, we fit models for the within-person arithmetic
difference in effects, because we were unable to fit models for the
ratio of effects for 6-h AUC for CO due to the presence of many
negative values (and therefore non-valid log transformation of these
values) during vaporization. For 6-h AUC for self-reported high, we
fit models for the within-person ratios in effects, as above.
All analyses were conducted using SAS 8.2.
ACKNOWLEDGMENTS
We are grateful to our study participants; the General Clinical Research
Center nursing staff for their meticulous adherence to protocol; Sheila
Huang, PharmD; Peter Bacchetti, PhD, at the UCSF Department of
Biostatistics and Epidemiology for his assistance in creating the
randomization scheme; and Heather Bentley at the University of California
Center for Medicinal Cannabis Research for her invaluable assistance with
regulatory affairs, data quality management, and interaction with the Data
Safety Monitoring Board. This work was supported by the University
of California Center for Medicinal Cannabis Research and NIH Grant
5-MO1-RR00083.
CONFLICT OF INTEREST
The authors declared no conflict of interest.
& 2007 American Society for Clinical Pharmacology and Therapeutics
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