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REPORT OF THE LYNN PIERSON THERAPEUTIC RESEARCH PROGRAM

NEW MEXICO STATE DEPARTMENT OF HEALTH

Oral VS. Inhaled Cannabinoids for Nausea/Vomiting from Cancer

Chemotherapy. 1. Methodology and Efficacy of Initial Dose*

Daniel A. Dansak, M.D.

Associate Professor

Department of Psychiatry

College of Medicine

University of South Alabama

1504 Springhill Avenue

Mobile, Alabama 36604

Katy Brazis, MA, RN

Research Nurse

Department of Psychiatry

School of Medicine

University of New Mexico

2400 Tucker NE

Albuquerque, New Mexico 87131

Edward B. Deaux, Ph.D.

Director, Information Management Services

Health Planning Division

State of New Mexico

Santa Fe, New Mexico 87501**

Harold D. Delaney, Ph.D.

Associate Professor

Department of Psychology

University of New Mexico

Albuquerque, New Mexico 87131

Paul R. Duncan, M.D.

Clinical Associate Professor

Department of Medicine and

Director of Medical Oncology

St. Joseph's Hospital

Albuquerque, New Mexico 87102

*This study was conducted under Contract Number 72-665.63.13-001

from the State of New Mexico, Health and Environment Department.

Correspondence regarding manuscript should be directed to Daniel

A. Dansak, M.D.

**Dr. Deaux is presently a health care consultant at P.O. Box

92379 Anchorage,AK 99509-2379.

ABSTRACT

One-hundred-sixty-nine cancer patients received oral delta-

9-tetrahydrocannabinol, or smoked marijuana, to reduce nausea and

vomiting from chemotherapy.. Both forms were effective with the

inhaled form superior for vomiting only. Chemotherapy severity

was a significant predictor of improvement. Patients on mild or

moderate nausea/emetic provoking chemotherapy improved more than

those on severe. Prior use of marijuana did not predict

improvement. Euphoria ("high") was not associated with efficacy.

Anticipatory nausea and vomiting was highest in patients

receiving oral THC and mild chemotherapy. Ninety percent of

patients chose to continue the drug after the first dose. Prior

use and mild or moderate chemotherapy were marginally associated

with continuation. Side effects were minimal for most patients;

only three required medical intervention. Oral cannabinoid was

associated with more drop outs due to side effects or

ineffectiveness. Mean cannabinoid use on the program was 735 mg

(forty-nine 15 mg doses or six two-day treatments).

Based on the study of Sallan et al(1) and anecdotal reports,

the State of New Mexico Legislature, In February, 1978, passed

the Controlled Substance Therapeutic Research Act. This document

permitted cancer chemotherapy patients to use cannabinoids as

anti-emetics subject to existing Federal regulations, and only

when conventional anti-emetics failed or were contraindicated. A

research protocol, approved by the Food and Drug Administration

(FDA), National Institute of Drug Abuse (NIDA), National Cancer

Institute (NCI), and the Drug Enforcement Administration (DEA),

was implemented In February, 1979, and completed In June, 1986.

This report will present the initial results of the study.

Since inception of this project, results appeared of

numerous other studies on delta-9-tetrahydrocannabinol (THC).

Several reviews concluded that THC seems efficacious in

alleviating nausea/vomiting provoked by anti-cancer

chemotherapy.(2-6) The reviewers' conclusions were somewhat

tentative because of many methodologic, pharmacologic, and

patient response problems. Carey et al (7) and Lover et al (8)

discussed these problems in detail. When this study was designed

and implemented, the authors were aware of many of these

difficulties, so the detailed data necessary to account for some

were gathered for later statistical analysis.

Purpose

The purpose of the study was four-fold: 1) assess the

efficacy of cannabinoids as anti-emetics; 2) compare the efficacy

of synthetic oral delta-9-tetrahydrocannabinol (oral THC) with

natural inhaled marijuana cigarettes (Inhaled THC); 3) assess the

side effects and long-term efficacy of the cannabinoids in cancer

patients; 4) ascertain psychosocial or pharmacologic predictors

of response and side effects. This report discusses the first

three only.

It was hypothesized that a) both oral and inhaled

cannabinoids would produce significant reduction in nausea and

vomiting; b) inhaled cannabinoids would be significantly better

than oral; c) repeated intermittent dosing of either cannabinoid

would not result in tolerance to the antiemetic action nor

produce significant side effects.

Basic criteria for inclusion in the study were: a) severe

nausea/vomiting from cancer chemotherapy unresponsive to one or

more conventional FDA-approved anti-emetics given in adequate

doses; or b) conventional anti-emetics contraindicated by medical

condition or history of serious or life-threatening adverse

effects from them. Relevant exclusion criteria were: a) pregnant;

b) living alone or no adults available for assistance while

taking the medication; c) must operate a motor vehicle or

complicated machinery during medication use; d) mentally disabled

by significant psychiatric or neurologic disease, or diagnosed

with a condition that may be aggravated by use of cannabinoids,

e.g., chronic schizophrenia, paranoid states and paranoid

personality; e) patient currently enrolled in a drug or alcohol

treatment program; f) liver disease manifested by total serum

bilirubin exceeding 2 mg% van den Bergh or equivalent; g) renal

disease with abnormal electrolytes and serum creatinine exceeding

3 mg%; h) cardiovascular disease that may be aggravated by the

effects of cannabinoids, e.g., angina pectoris, conduction

defects, or arrhythmias; and l) lung or gastrointestinal disease

that may impair medication absorption, e.g., severe emphysema,

gastric or intestinal obstruction.

Method

The patient and attending physician requested participation

in the study and completed several forms. A Medical History

Form assessed the medical inclusion/exclusion criteria.

Psychiatric status was screened with the Symptom Check List-90-

Revised (SCL-90-R). (9) Score Profile B (Normals) was used to plot

its twelve subscales. Patients whose T-scores exceeded 80 on

Paranoid Ideation or Psychoticism were to be excluded from the

study. The severity of baseline nausea and vomiting experienced

by patients during their most recent chemotherapy treatment

was rated retrospectively with the Target Problem Self-Rating

Scale (TPSS) .(10-14) Nausea and vomiting were scored on a five

point scale: 1 = not a problem, 2 = slight, 3 = mild, 4 =

moderate. 5 = severe. This baseline symptom data was used later

to establish difference scores for assessment of drug efficacy

during subsequent chemotherapy. Thus, patients served as their

own controls.

A ten question Drug Use and Attitude Questionnaire (DUAQ)

elicited information about the subject's past use of alcohol,

marijuana or hashish, and other non-medical drugs; expectations

about the use of marijuana for nausea/vomiting; and overall

attitude toward the use of drugs. For this report, the primary

concern was that prior use of cannabinoids might influence

efficacy and side effects.

The patients and their attending physician read and signed a

consent form approved by the University of New Mexico Human

Research Review Committee. The attending physician's

participation provided implicit confirmation of the severity of

the patient's nausea and vomiting from chemotherapy. Also, since

the oncologlst author (PRD) reviewed each Medical History, there

was additional oversight and confirmation of symptom severity.

Parents of cancer patients under 18 years old and the attending

physician signed a slightly modified consent form approved by the

same committee.

Accepted patients were randomized initially to oral or

inhaled forms, with those refusing the offered form automatically

receiving the other. (Of the first 80 patients, sixteen refused

the randomized form; thirteen refusing cigarettes). Later, this

partial randomization procedure was terminated because it

essentially permitted patient choice of their preferred drug

form. Patients were then allowed to openly self-select oral or

inhaled drug forms. However, sufficient subjects accrued (N =

59) so it was possible to statistically assess pre- and post-

randomization groups on the null hypothesis of no difference in

efficacy.

On the day of chemotherapy, patients were prepared as usual

by their attending physician for treatment, be it in the office,

clinic or hospital. The nurse administering the chemotherapy was

instructed earlier by the research nurse about the protocol and

completion of the study data sheets. When feasible, the research

nurse acquired the data or directly assisted data gathering by

the attending nurse. Direct involvement of the research nurse

occurred for 87% of the patients. Chemotherapy agents, dose,

route, and time of administration were also recorded.

Patients completed the TPSS again immediately before (Pre-

THC) and four hours after (Post-THC) cannabinoid intake. Supine,

sitting, and standing blood pressures and pulse rates were taken

pre-drug and hourly thereafter for four hours. The presence or

absence of eight side effects (Euphoria, Sleepy, Agitation,

Depression, Fearful, Anxious, Visual Hallucinations, Other) were

also recorded during this four hour observation period.

After recording baseline measures, patients ingested 15 mg

oral synthetic THC (in soft gelatin capsules with sesame oil

vehicle) with fresh tap water 30 minutes before chemotherapy.

Or, they smoked a marijuana cigarette (900 mg with 2% THC) as

tolerated in the 10 minutes preceeding chemotherapy.*

Typically, at least three fourths of the cigarette was

smoked. These time intervals were chosen to assure some near-

peak blood level of THC at the expected onset of nausea and

vomiting. Above doses were selected after reviewing previous

reported studies and consulting with investigators at NIDA.*

There were 125 different combinations of anticancer drugs,

dosages, and routes of administration that eventually appeared.

*The authors and patients gratefully acknowledge the invaluable

assistance and technical support of the FDA (especially John

Scillagno, Ph.D.) and NIDA (especially Robert Hawkes, Ph.D.)

To simplify, chemotherapy severity was classified as mild,

moderate or severe based on data from Cadman (15) and Drapkin.(16)

Verification of the classification was done by surveying four

oncology nurses and six oncology physicians. Correlation

coefficients ranged from .44 to .78, with the three highest

coefficients (.70, .71, and .78) occurring with medical

oncologlsts. (Dansak DA, Brazis K: unpublished data).

After the four hour observation period, the patient, if

agreeable, received additional marijuana cigarettes or THC

capsules to use at home or in hospital at 4-6 hour intervals.

Patients released home were cautioned not to drive or use

complicated machinery for 24 hours after the last dose of drug.

(To assure safety, all patients were driven home by a friend or

family member.) Within the next four days, patients or family

were contacted to assess their desire to continue on the program

or drop out and their reason for stopping. Patients electing to

stop for any reason were asked to return the unused portion of

medication directly to the University of New Mexico Hospital

Pharmacy. Patients electing to continue were permitted

additional doses in conjunction with each scheduled chemotherapy

session and in accord with the duration and intensity of

nausea/vomiting experienced thereafter. Any patient could

terminate participation at any time and for any reason.

A sample size of N = 180 was determined retrospectively from

Cohen's matched pair t-test tables 17-18 for a small difference

between population means at alpha = 0.05 and beta = 0.80.

Difference scores, post-THC minus baseline, for nausea and

vomiting self-ratings were used as measures of cannabinoid anti-

emetic efficacy (Baseline = chemotherapy plus conventional

antiemetics; Post-THC = chemotherapy plus cannabinoids).

Acceptance of the null hypothesis that difference scores were

greater than or equal to zero would indicate no efficacy of

cannabinoids against nausea and vomiting. The alternative is

that the differences are less than zero. A difference score of

minus 2 or less was arbitrarily deemed "clinically significant",

since this would mean, on the rating scale, a change from severe

to mild, moderate to slight, or mild to not a problem.

All data was analyzed using the General Linear Models pro-

cedure in the Statistical Analysis System (SAS) release 82.4 on

the IBM 3081 at the University of New Mexico.

Results

To July 1, 1984, one hundred ninety-six cancer patients

received oral or inhaled cannabinoid. Only 169 will be reported

because the remainder returned incomplete data (N=13), received

concurrent conventional anti-emetics (N=ll), or didn't receive

chemotherapy (N=3). These 27 patients did not differ from the

experimental group on age, group assignment, sex, cancer stage,

prior marijuana use, or baseline and pre-cannabinoid nausea and

vomiting ratings.

Tables 1-3 list frequencies and means of pertinent

variables.

Matched pair t-tests showed significant reduction in nausea

(-2.50, SD = 1.32, p < .0001) and vomiting (-2.52, SD = 1.46, p <

.0001)

Between baseline rating and ingestion of cannabinoid, 90 %

of the patients did not change category of chemotherapy severity,

2 % changed to more severe, and 8 % to less severe. The median

interval between baseline ratings and THC ingestion was 12 days

(Range 0 - 150 days).

Because of the non-uniform symptom baseline measures, an

initial multi-variate analysis of variance (MANOVA) used post-

THC nausea and vomiting scores as dependent variables with

baseline nausea and vomiting scores as covariates, and group

(oral, inhaled), chemotherapy severity (mild, moderate, severe),

and their interaction as independent variables. Chemotherapy

severity was the only predictor of nausea (p < .0018) and

vomiting (p < .0004) self-ratings four hours post THC ingestion.

Mean nausea scores were curvilinear from mild to severe

chemotherapy (1.80, 1.68, 2.44), while mean vomiting scores were

more linear (1-24, 1.37, 2.22). Pairwise comparisons (experiment-

wise) showed mean nausea scores for severe chemotherapy to be

significantly higher than the mild or moderate classes (p < .05).

For vomiting, the pairwise comparisons (experiment-wise)

indicated that mild and moderate subclasses both were

significantly different from the severe subgroup (p < .05). A

differential efficacy of cannabinoid versus chemotherapy severity

is thus suggested.

Pre-THC nausea and vomiting scores (an indicator of

anticipatory nausea and vomiting) showed no significant

predictors from group, chemotherapy severity, or their

interaction.

Post-THC minus baseline difference scores on nausea and

vomiting were dependent variables in a MANOVA with independent

variables of group, chemotherapy severity, prior use of marijuana

(at least once versus never), group by chemotherapy severity

interaction, group by prior use interaction, and chemotherapy

severity by prior use interaction. For nausea, only chemotherapy

severity and its interaction with group proved significant (p <

.038). Patients receiving mild and moderately severe

chemotherapy showed the larger improvement in nausea (-2.76 and -

2.77) respectively, compared to the severe group (-2.15), but the

latter was still significant. The inhaled treatment group showed

slightly more improvement than the oral (-2.54 vs -2.45), but the

difference is not clinically significant. Examination of the

group by chemotherapy interaction showed that the mild

chemotherapy subclass receiving oral cannabinoid had the least

reduction in nausea (-1.88) relative to the other five subclasses

(-2.14 to -3.34).

Change in vomiting was significantly predicted by group per

se and its interaction with chemotherapy severity. THC smokers

reported more improvement than those using oral THC (-2.69 versus

-2.40). Assessment of the group interaction with chemotherapy

severity showed, again, that the oral subgroup receiving mild

chemotherapy had less improvement (-1.38) than the other five

subgroups (-2.11 to -2.90).

The above analyses highlighted the oral THC-mild

chemotherapy subset, so additional analyses were done on the

baseline nausea and vomiting scores.

MANOVA of these baseline scores versus the predictor

variables of group, chemotherapy severity, and their interaction

showed no significant relation to nausea scores, but all three

were predictive of baseline vomiting scores (Group: p < .008;

Chemotherapy severity: p < .016; Interaction: p < .004)> Two-way

analysis of variance (ANOVA) of the six THC group by chemotherapy

severity subclasses indicated, again, no effect on baseline

nausea, but a significant group effect on baseline vomiting.

Pairwise comparisons (experiment-wise) demonstrated that the

oral THC-mild chemotherapy subclass alone is responsible because

its mean vomiting score (2.86) was significantly less than those

of the other five subsets (4.21 to 4.46). However, there were

only eight patients in the oral THC-mild chemotherapy class,

rendering interpretation of this result somewhat problematic. For

information purposes, Table 4 lists pertinent demographics.

As previously noted, prior use of marijuana (at least once

versus never) was not a predictor of change in nausea or vomiting

scores (post-THC minus baseline). A closer look at both target

symptom scores at baseline, pre-THC, and post-THC, showed prior

use a predictor of baseline nausea scores only (p < .03). Non-

users reported significantly higher baseline nausea scores than

prior users (4.63 versus 4.38). A similar trend appeared on the

pre-THC and post-THC nausea scores and vomiting scores at all

three times: prior users of marijuana had lower mean scores on

nausea and vomiting at all three times measured. This suggests

that prior users did not exaggerate symptoms just to receive

a cannabinoid.

The question arises as to how representative the subjects in

this study are relative to other cancer patients. Two non-

randomized control groups existed. One group.(N = 26) were cancer

patients who requested THC but never received it. A second (N =

27) were cancer patients who did not request THC even though

aware of its availability. Both groups, in similar fashion to the

experimental group, rated nausea and vomiting experienced at

their most recent chemotherapy. MANOVA of the two control groups

(independent variables) versus age, months with cancer, and

nausea and vomiting scores disclosed no significant differences.

Chi-square analysis of the two groups on sex, prior use of

marijuana, stage of cancer, and chemotherapy severity showed no

significant differences as well. Thus the two groups were

combined (N = 53) for comparison with the experimental subjects

(N= 169) using MANOVA.

There was a significant difference in mean age between the

controls (50.87 years) and the experimental subjects (43.95

years), but not in mean months with cancer (Control = 18.42 vs

18.32). Nausea and vomiting scores were higher in the

experimental group (Nausea: 4.52 vs 3.86, p < .0001; Vomiting:

4.25 vs 3.67, p < .0018), However, chemotherapy severity was also

significantly different (Experimental: mild = 11%, moderate =

45%, severe = 44%; Control: mild = 21%, moderate = 56%, severe =

23%; chi-square = 8.56, p < .014). Chi-square analysis of sex,

stage of cancer, and prior use of marijuana showed no significant

differences between the two groups. The difference between groups

in nausea and vomiting appears to be primarily due to the

different distribution of chemotherapy severity, probably

reflecting the self-selection process of the patients as well as

the study criteria.

Post-THC minus baseline nausea and vomiting difference

scores were dependent variables in MANOVA tests of the randomized

(N=59) versus nonrandomized groups (N=110). No significant

differences occurred, suggesting that a subtle bias operated in

the initial randomization procedure via the choice to refuse a

proffered form of THC.

A step-wise discriminant analysis was performed using

several variables (group, chemotherapy severity, prior use of

marijuana, age, THC dose per meters-squared body surface area,

and SCL-90-R scales) to predict nausea and vomiting responders,

i.e., those showing a difference score of two or more on the

target symptoms. The significance level chosen for cut-off was

p < 0.15. Chemotherapy severity, the Phobia sub-scale of the SCL-

90-R, and group were predictors of nausea response at p < 0.0027,

0.1029, and 0.1164 respectively. The classification table gave

true positives at 96.5% and true negatives at 13.5%. However,

there were 86.5% false negatives and 3.3% false positives. In

effect, knowledge of chemotherapy severity alone can correctly

predict 76% of nausea responders. Patients receiving mild and

moderate severity chemotherapy benefited most from cannabinoid

anti-nausea.

Chemotherapy severity and group were the only predictors of

improvement in vomiting (p < .0217 and .0753 respectively) The

classification table showed 99.2% true positives and 5.3% true

negatives. False positives were at 94.7% and false negatives at

0.8%. Again, knowledge of chemotherapy severity alone can predict

76% of responders with patients on mild and moderate chemotherapy

having the greatest likelihood of anti-emetic response.

Another approach to comparative efficacy of oral vs inhaled

THC concerns the number of patients electing to continue the drug

after the first dose. Regardless of dose form, 90% of patients

elected to continue. Chi-square analysis of dose form vs

continue-discontinue showed no association. Similar analyses, but

controlling for prior use, then chemotherapy severity, were also

not significant, but at least one expected cell frequency was

below five in each contingency table. Trends in the data showed

prior users more likely to continue, whether on oral (96%) or

inhaled (95%). Non-prior users were more likely to continue if on

inhaled (94%) than oral (82%). Restated, non-prior users using

oral THC were three times more likely to drop out than if on

inhaled (18% vs 6%). Non-prior users, irrespective of dose form,

were three times more likely to drop out after the first dose

(14%) than prior users (4%). Four patients (2%, all on oral)

dropped out because of side effects; nine patients (5%, eight on

oral) stopped because it was not effective; one quit because of

smoke irritation, and two because of increased nausea and

vomiting (both on inhaled); one drop out gave no reason.

A comparison of group vs prior use showed significant

differences in all frequencies. Sixty-nine percent of non-prior

users received oral drug compared with 28% of prior users. This

is consistent with the patients ability to choose a particular

drug form.

For patients on mild chemotherapy (N=20), 95% elected to

continue (100% of 12 inhaled and 88% of 8 oral). of those on

moderate chemotherapy (N=73), 95% continued (100% of inhaled, N-

31, and 90% of oral). In the severe group (N=73), 85% continued

(90% of inhaled, 82% of oral).

Anticipatory Symptoms

Pre-cannabinoid scores on nausea and vomiting were evaluated

to assess presence or absence of anticipatory nausea and

vomiting. ANOVA of these variables with post-cannabinoid scores

were not significant, suggesting no connection between

anticipatory nausea and vomiting and therapeutic response to

cannabinoids.

Because of the retrospective nature of the baseline nausea

and vomiting scores, patients initially gave two ratings of these

symptoms, once when requesting entry into the program and the

second just before receiving cannabinoid. Data was available for

74 patients and showed no difference between the two ratings. The

median time between the two scorings was 11 days (range 0-150

days).

Side Effects

The presence or absence of eight side effects was tallied

before and hourly after cannabinoid dosing for the four hour

observation period: euphoria, sleepiness, agitation, depression,

fearfulness, anxiety, visual and auditory hallucinations. Table

III lists frequencies. Reported effects parallel the known

pharmacodynamics of the oral and inhaled forms.

Three patients experienced side effects requiring medical

intervention. Two had paranoid/fear responses (panic attacks) and

one had an episode of paroxysmal atrial tachycardia.

Sallan et al (1) indicated that euphoria from cannabinoids

seemed necessary to attain anti-emesis. Chi-square analysis for

euphoria vs any improvement in nausea was not significant. For

euphoria vs improvement of two or more (defined as clinically

significant) there was still no significant association. Results

for vomiting were the same. Prior use of marijuana predicted

presence of euphoria (chi-square =10.87, p < .001), but showed no

association with either type of response measure.

As previously noted, 90% of patients elected to continue the

drug after initial dosing. Patient's reasons for later

discontinuation were tabulated. Reasons included: not effective,

side effects, and other (death of patient, ending or changing

chemotherapy to less emetogenic forms, unknown). At the data

analysis cut-off, 15 patients were actively receiving

cannabinoids (6 oral, 9 inhaled). Chi-square analysis of route vs

the four groups was significant. This was due to the greater

number of drop outs among oral cannabinoid users. Of the 154

patients, 44 stopped the drug because it was not effective, not

as effective as expected, or no more effective than conventional

anti-emetics. Thirty-four were on oral drug (77%) and ten were

using inhaled. twenty-two patients stopped due to side effects,

seventeen on oral (77%) drug. Eighty-eight patients quit because

of other reasons: changed or discontinued chemotherapy (N=41;

oral=18), death (N=21; oral=10), and unknown (N=26;oral=9).

An approach to assessing the long term efficacy of the

cannabinoids is to determine the amount of drug ingested by

patients. Although such data can be difficult to accurately

obtain, prescriptions, returns of unused portions to the pharmacy

and patient follow-up allow estimation of the amounts likely

ingested. Since the initial dosing was 15 mg four times a day for

two days, we assumed that less than 120 mg total usage was

evidence against pharmacologic efficacy or acceptance, whereas

larger amounts implied the opposite. A chi-square analysis of

total, dose vs route was significant (p < .0003). Thirty-six of

168

patients used less than 120 mg total. Twenty-nine of these were

on oral drug (80.6%). One hundred thirty-two patients used more

than 120 mg, 64 (48% were on oral form). Ninety percent of prior

users ingested over 120 mg versus 69% of non-prior users. Ninety-

one percent on inhaled used the larger amount vs 67% on oral.

Eighty-four percent of males used larger amounts vs 72% of

females. Extrapolating from total use, the mean total use was

735 mg per patient, with oral drug at 526 mg and inhaled at 908

mg.

DISCUSSION

Results acquired under the State of New Mexico's Controlled

Substances Therapeutic Research Act indicate that oral THC and

inhaled marijuana are both effective anti-emetics and anti-

nauseants. This conclusion is based on data gathered at the time

of the initial dose. The efficacy of the inhaled form is superi-

or to the oral form, but this difference is statistically signi-

ficant for vomiting only. This may be due partially or wholly to

the tendency of the capsules to be regurgitated during chemother-

apy, or to the sesame oil vehicle failing to consistently dissi-

pate in the GI tract, thus preventing optimal absorption. Effi-

cacy is related to the severity of chemotherapy with most im-

provement occurring in the mild subgroup than in the moderate or

severe ones. Prior use of marijuana (at least once) had no

effect on initial efficacy. Prior use only predicted nausea

scores at application, with non-prior users reporting signifi-

cantly higher levels. The latter suggests that prior users did

not exaggerate their symptoms just to get marijuana.

Immediately before drug ingestion, anticipatory nausea and

vomiting were evident, with the mild chemotherapy group being

highest on nausea. All three groups had comparable scores on

vomiting. The oral-mild subgroup had highest pre-THC nausea and

vomiting scores.

When applying for admission to the study, the mild chemo-

therapy subgroup reported levels of nausea and vomiting com-

parable to the other two groups. The oral THC-mild chemotherapy

subgroup had significantly lower vomiting scores at application

than the other five groups. At four hours post-THC patients on

severe chemotherapy had significantly higher nausea and vomiting

scores than the mild and moderate categories.

Prior users of marijuana were more likely to be on the

inhaled form of THC and more likely to continue after the first

dose, whether on oral or inhaled. Non-prior users were more

likely to continue if on inhaled than oral. Patients receiving

severe chemotherapy were more likely to drop out, especially if

on oral drug.

Lack of complete random assignment of dose form requires

caution in data interpretation. Still, efficacy of both forms

appears comparable, although the inhaled form may be especially

useful with vomiting unresponsive to other anti-emetic agents.

Euphoria ("high") was not required for reduction of nausea

or vomiting. Side effects were predominantly euphoria,

sleepiness, and anxiety, and appeared well-tolerated by most

patients. Oral cannabinoid use resulted in more drop outs due to

side effects or ineffectiveness. Mean cannabinoid use on the

program was 735 mg, which is actually an upper limit of

ingestion.

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vomiting. In Wiernik PH (Ed) Mediguide to Oncology, Vol 2, No

5, New York, Lawrence Delia Corte Publication, 1982

17. Stevens JP: Power of the multivariate analysis of variance

tests. Psychol Bull 1980;88:728-737

18. Cohen J: Statistical Power Analysis for the Behavioral

Sciences. Revised Edition. New York, Academic Press, 1977

Table 1

Age N %

_____ __ ____

10-19 15 8.9

20-29 28 16.6

30-39 31 18.3

40-49 24 14.2

50-59 34 20.1

60-69 22 13.0

70+ 15 8.9

___ ____

169 100.0

Sex

____

Male 76 45.0

Female 93 55.0

THC Group

__________

Oral 94 55.6

Inhaled 75 44.4

Marijuana

__________

Prior Use 69 41.1

No Prior Use 99 58.9

Tumor Stage

____________

Local 16 9.4

Regional 28 16.6

Metastatic 125 74.0

Tumor Site

___________

Breast 30 17.8

Ovary 30 17.8

Lung 17 10.1

Gastrointestinal 11 6.5

Genitourinary 27 15.9

Leukemia/Lymphoma 37 21.9

Other 17 10.0

Chemotherapy

______________

Mild 20 11.8

Moderate 73 43.2

Severe 73 43.2

Not Reported 3 1.8

Group x Chemotherapy N % Mean Range Age

____________________ ___ ___ __________ ___

Oral-mild 8 4.8 45.8 19-64

Oral-moderate 42 25.3 48.3 13-78

Oral-severe 44 26.5 42.9 12-76

Inhaled-mild 12 7.2 54.7 35-76

Inhaled-moderate 31 18.7 42.2 17-73

Inhaled-severe 29 17.5 35.7 16-73

Table 1. Frequencies and descriptive statistics of selected

variables.

TABLE 2

________

N SEX AGE AGE x SEX

__ ___ ___ __________

M F M F

Oral 94 39 55 45.6 yrs 39.1 50.2

Inhaled 75 37 38 41.9 yrs 37.2 46.9

CHEMOTHERAPY SEVERITY PRIOR USE

______________________ __________

Mild Moderate Severe No Yes

Oral 8 42 44 68 26

Inhaled 12 31 29 31 43

CANCER STAGE

______________

Local Regional Metastatic

Oral 11 11 72

Inhaled 5 17 53

Table 2. Oral versus inhaled groups: descriptive variable

comparison

TABLE 3

_______

NAUSEA VOMITING

______ ________

TIME Mean (SD) Mean (SD)

____ ____ ____ ____ ____

0 Baseline 4.53 (0.73) 4.26 (1.04)

1 Pre-THC 2.26 (1.39) 1.67 (1.27)

2 Post-THC 2.03 (1.22) 1.73 (1.24)

Time 1 - Time 0 -2.25 (1.52) -2.56 (1.58)

Time 2 - Time 0 -2.50 (1.32) -2.52 (1.46)

(Time 2 - Time 0) vs Group

Oral -2.46 -2.40

Inhaled -2.54 -2.69

(Time 2 - Time 0) VS Chemotherapy Severity

Mild -2.76 -2.59

Moderate -2.77 -2.84

Severe -2.14 -2.19

(Time 2 - Time 0) vs Prior Use

Prior Use -2.39 -2.42

No Prior Use -2.56 -2.60

(Time 2 - Time 0) vs Randomization

Randomized -2.57 -2.55

Non-randomized -2.47 -2.51

Table 3. Means and standard deviations of pertinent variables.

TABLE 4

_______

EUPHORIA SLEEPY AGITATION

________ _______ __________

Time No Yes ? No Yes ? No Yes ?

0 142 4 2 59 28 61 124 21 3

1 78 67 3 38 52 58 131 14 3

2 81 64 3 27 68 53 126 19 3

3 98 47 3 40 54 54 136 9 3

4 94 27 27 34 42 72 115 5 28

DEPRESSION FEARFUL ANXIOUS

__________ _______ _______

Time No Yes ? No Yes ? No Yes ?

0 122 24 2 123 22 3 80 65 3

1 141 4 3 136 9 3 115 30 3

2 136 9 3 139 6 3 118 26 4

3 140 5 3 139 5 4 128 16 4

4 113 3 29 115 4 29 106 13 29

Table 4. Side effect frequencies derived from patients responding

to at least four of the five times assessed. Time 0= Pre-

THC; 1-4 is one to four hours post-THC.