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Nausea and Vomiting
1. What research has been done and what is known about the possible
medical uses of
marijuana?
There is a large body of clinical research on the use of cannabinoids for
chemotherapy-related
nausea and vomiting. Most of this work was conducted during the early 1980s.
The
majority of reports deal with oral dronabinol rather than smoked marijuana.
These studies
demonstrated that dronabinol was superior to placebo in controlling nausea and
vomiting caused
by chemotherapy that induces a moderate amount of emesis (Sallan et al. 1975).
Several studies
compared oral dronabinol with prochlorperazine (Sallan et al. 1980). Mixed
results were
reported from these studies, but generally dronabinol was found equivalent.
Gralla and colleagues (1984) examined metoclopramide versus dronabinol in
patients given
cisplatin in a randomized double-blind trial. These investigators reported
poorer antiemetic
control and more side effects with dronabinol than with the metoclopramide.
None of these studies compared oral dronabinol or smoked marijuana with what
are now
considered the most effective antiemetic regimens, the combination of a specific
serotonin
antagonist (like ondansetron, granisetron, or dolasetron) plus dexamethasone,
which were
introduced in the early 1990s. This combination has demonstrated complete
protection from
vomiting during the initial 24 hours after cisplatin (the most potent emetic
stimulus) in 79
percent of patients treated (Italian Group for Antiemetic Research 1995).
Without antiemetic
protection, 98 percent of similar patients vomit a median of six times within the
first 24 hours
alone after cisplatin (Kris 1996). Side effects of these newer antiemetic
regimens are negligible
and would permit a patient to drive or return to his or her job immediately after
receiving
chemotherapy.
Only two clinical trials have formally addressed the effectiveness of smoked
marijuana. Levitt
and colleagues (1984) conducted a random-order assignment crossover study
comparing smoked
marijuana and dronabinol in 20 subjects, 15 men and 5 women. Twenty-five percent
of the
subjects were free of vomiting and 15 percent were free of nausea. As to
individual preference
for the route of administration, 45 percent of the patients had no preference, 35
percent preferred
oral dronabinol, and 20 percent preferred smoked marijuana.
Vinciguerra and colleagues (1988) studied smoked marijuana in an open trial in
74 patients who
previously had no improvement with standard antiemetic agents. Nearly 25 percent
of patients
who initially consented to participate later refused treatment citing bias
against smoking, harshness of
smoke, and preference for oral dronabinol. Of the remaining 56 patients, 18 (34
percent) rated it
very effective and 26 (44 percent) moderately effective. Twelve (22 percent)
noted no benefit.
Sedation occurred in 88 percent, dry mouth in 77 percent, and dizziness in 39
percent. Only
13 percent were free of adverse effects.
2. What are the major unanswered scientific questions?
No scientific questions have been definitively answered about the efficacy of
smoked marijuana
in chemotherapy-related nausea and vomiting. A comparison of the efficacy of
smoked marijuana
versus oral dronabinol would also be of interest. In addition, further
information on appropriate
dosage and frequency, side effects, tolerability, and patient acceptability for
smoked marijuana
would need to be established.
3. What are the diseases or conditions for which marijuana might have
potential as a treatment
and which merit further study?
Inhaled marijuana has the potential to improve chemotherapy-related nausea and
vomiting.
Because the combination of a serotonin antagonist plus dexamethasone prevents
chemotherapy-related nausea and vomiting in the majority of patients,
investigation of smoked marijuana as a
treatment for the minority of patients who vomit despite receiving the current
best regimens
(i.e., rescue therapy in refractory patients) might be an initial focus. Another
line of investigation
could be the efficacy of inhaled marijuana in delayed nausea and vomiting due to
chemotherapy.
An add-on design in which smoked marijuana or placebo would be administered to
incomplete
responders to standard combination therapy would be appropriate. A dronabinol
capsule group
should also be included. Stratification should be done for naive versus
experienced marijuana
smokers. Nausea severity, vomiting prevention, and CNS effects assessments
should be primary
endpoints.
Inhaled marijuana merits testing in controlled, double-blind, randomized trials for the above indications.
References
Gralla, R.J.; Tyson, L.B.; Bordin, L.A.; Clark, R.A.; Kelsen, D.P.; Kris, M.G.; Kalman, L.B.; and Groshen, S. Antiemetic therapy: A review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treat Rep 68(1):163-172, January 1984.
Italian Group for Antiemetic Research. Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis. Ann Oncol 6:805-810, 1995.
Kris, M.G.; Cubeddu, L.X.; Gralla, R.J.; Cupissol, D.; Tyson, L.B.; Venkatraman, E., and Homesley, H.D. Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin. Cancer 78:2193-2198, 1996.
Levitt, M.; Faiman, C.; Hawks, R.; and Wilson, A. Randomized double-blind comparison of delta-9-tetrahydrocannabinol (THC) and marijuana as chemotherapy antiemetics. Proc Am Soc Clin Oncol 3:91, 1984.
Sallan, S.E.; Zinberg, N.E.; and Frei, III, E. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 293:795-797, 1975.
Sallan, S.E.; Cronin, C.; Zelen, M.; and Zinberg, N.E. Antiemetics in patients receiving chemotherapy for cancer--a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med 302:135-138, 1980.
Vinciguerra, V.; Moore, T.; and Brennan, E. Inhalation marijuana as an antiemetic for cancer chemotherapy. NY State Med J 88(10):525-527, October 1988.
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