Page 1

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)

CLINICAL PHARMACOLOGY & THERAPEUTICS

1

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).

2

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ARTICLES

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.

CLINICAL PHARMACOLOGY & THERAPEUTICS

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ARTICLES

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).

4

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ARTICLES

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.

CLINICAL PHARMACOLOGY & THERAPEUTICS

5

ARTICLES

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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ARTICLES

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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