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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.
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