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Cancer Management and Research 2016:8 49–55
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REVIEW
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/CMAR.S81425
Dronabinol for chemotherapy-induced nausea and
vomiting unresponsive to antiemetics
Megan Brafford May1
Ashley E Glode2
1Department of Pharmacy, Baptist
Health Lexington, Lexington, KY, USA;
2Department of Clinical Pharmacy,
Skaggs School of Pharmacy and
Pharmaceutical Sciences, University of
Colorado Anschutz Medical Campus,
Aurora, CO, USA
Abstract: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common
symptoms feared by patients, but may be prevented or lessened with appropriate medications.
Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists,
and neurokinin receptor antagonists are the classes most commonly used in the prevention of
CINV. There are many alternative drug classes utilized for the prevention and management of
CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine
receptor antagonists. Medications belonging to these classes generally have lower efficacy and
are associated with more adverse effects. They are also not as well studied compared to the
aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid
class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally
occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is
the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence
for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combina-
tion with ondansetron, and in combination with prochlorperazine.
Keywords: dronabinol, cannabinoids, antiemetic, chemotherapy-induced nausea and vomiting
Introduction
Chemotherapy-induced nausea and vomiting (CINV) is one of the most common
symptoms feared by patients, but may be prevented or lessened with appropriate
medications.1 CINV is categorized as acute, delayed, anticipatory, breakthrough,
or refractory.2 Acute-onset CINV may occur within a few minutes to several hours
after treatment administration and typically resolves within the first 24 hours. Risk
factors for the development of this kind of nausea include female sex, age <50
years, environment of administration, lack of history of chronic alcoholism, his-
tory of motion sickness, previous incidence of nausea and vomiting, emetogenicity
of agent(s) administered, dose of emetogenic agent(s), infusion rate, duration of
therapy, number of cycles, and efficacy of preventive antiemetic regimen. Delayed-
onset CINV generally occurs in patients more than 24 hours after medication
administration and may last 6–7 days. This type of nausea unfortunately tends to be
more common, severe, and treatment resistant. Factors impacting the incidence of
delayed CINV include dose and emetogenicity of chemotherapy agent(s), incidence
of acute CINV, patient age, sex, and prophylactic antiemetics used. Anticipatory
nausea and/or vomiting is considered a conditioned response and may occur after a
negative prior experience with chemotherapy. This happens before a patient receives
Correspondence: Megan Brafford May
Baptist Health Lexington, 1740
Nicholasville Road, Lexington, KY,
40503, USA
Email megan.may@bhsi.com
Journal name: Cancer Management and Research
Article Designation: REVIEW
Year: 2016
Volume: 8
Running head verso: May and Glode
Running head recto: Dronabinol for CINV unresponsive to antiemetics
DOI: http://dx.doi.org/10.2147/CMAR.S81425
This article was published in the following Dove Press journal:
Cancer Management and Research
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May and Glode
their next cycle of treatment. This type of CINV is more
common in younger patients due to the aggressive nature
of treatment. Breakthrough emesis is considered vomiting
that occurs even with prophylactic treatment and/or requires
the addition of “rescue” antiemetics. Refractory emesis is
classified as vomiting that occurs with subsequent treatment
when prophylactic antiemetics and/or rescue medications
have been ineffective in previous cycles.
CINV may have a significant negative impact on a
patient’s quality of life (QoL) as well as lead to increased
indirect and direct costs. When a patient’s QoL is impacted
in a negative manner, it may result in poor compliance
with future treatment. The development of CINV has been
reported to have a significant impact on QoL in 55%–60%
of chemotherapy cycles administered to patients.1 The inten-
sity of CINV and duration of CINV were the most notable
factors linked to a more significant influence on QoL. In a
study analyzing cost associated with the development of
CINV, it was noted that the average cost was nearly $800 per
patient for the first 5 days of the first cycle of chemotherapy.3
The cost analysis included overall direct and indirect costs:
direct medical, missed work, productivity loss, and cost of
any antiemetic medications taken on the day of treatment.
Indirect costs were greater for patients with more severe
CINV due to work absence for longer periods of time and
reduced productivity. Additional undesirable effects of CINV
to consider include metabolic imbalances, decline in self-care
and functional ability, nutrient depletion, anorexia, worsen-
ing of the patient’s performance status and mental status,
wound dehiscence, esophageal tears, and withdrawal from
potentially useful or curative treatment.2
It is reported that chemotherapy-induced vomiting can
be prevented in more than two-thirds of patients if antiemet-
ics are used correctly.1 Nausea remains difficult to prevent
and manage and is typically more commonly reported than
emesis: 54.9% versus 45.1% at any cycle. Several treatment
guidelines exist published by reliable institutions providing
recommendations to optimize CINV prevention and manage-
ment, yet CINV remains an issue. In a recent report, despite
prophylactic antiemetics, approximately 60% of patients who
received moderately and highly emetogenic chemotherapy
regimens still experienced some form of CINV; delayed being
more common (58% versus 34%).3 Improvements in CINV
management are needed.
Current antiemetic treatment
Several antiemetic options exist to manage CINV. Cortico-
steroids, serotonin receptor antagonists (5-HT3 RAs), and
neurokinin receptor antagonists (NK1 RAs) are the classes
most commonly used in the prevention of CINV.
Corticosteroids have been utilized as an effective anti-
emetic for over 30 years, with dexamethasone being the
most common agent.4 This class may be used for acute and
delayed CINV and are effective when given in combination
for prevention of CINV in moderately and highly emetogenic
regimens. A meta-analysis of over 5,000 patients receiving
highly or moderately emetogenic chemotherapy assessed
the efficacy of dexamethasone as prophylaxis for CINV. In
the majority of trials included, dexamethasone was given
in combination with other antiemetics, such as 5-HT3 RAs,
or metoclopramide. Dexamethasone was determined to be
superior to placebo or no treatment in terms of complete
protection (no vomiting or retching) for both acute (odds
ratio: 2.22, 95% confidence interval: 1.89–2.60) and delayed
(odds ratio: 2.04, 95% confidence interval: 1.63–2.56) vom-
iting. Corticosteroids are usually well tolerated when used
as a short-term antiemetic. Moderate-to-severe insomnia
(45%), gastrointestinal discomfort (27%), agitation (27%),
increased appetite (19%), weight gain (16%), and acne (15%)
have been reported by patients taking dexamethasone for the
prevention of delayed CINV.
Selective 5-HT3 RAs have been incorporated into the
management of CINV for over the last 20 years.4 In the
United States, the following agents are approved: dolasetron,
granisetron, ondansetron, and palonosetron, with palonose-
tron having a significantly longer half-life, making it excep-
tionally useful in the prevention of delayed CINV. Various
studies have shown this class of agents to be effective in the
prevention of acute and delayed CINV. One meta-analysis
including ten studies revealed an 8.2% absolute risk reduction
compared to placebo for the development of delayed CINV.
One of the more notable adverse effects of this class is the
potential development of electrocardiogram abnormalities,
including QT prolongation. Additional side effects reported
with these medications include headache, constipation, and
abdominal pain.
One of the newer classes of medications approved for the
prevention of CINV is the NK1 RAs. Agents from this class
should be administered in combination with dexamethasone
and a 5-HT3 RA to prevent acute and delayed CINV associ-
ated with moderately and highly emetogenic chemotherapy.2
A meta-analysis including nearly 9,000 patients receiving
moderately and highly emetogenic chemotherapy expe-
rienced a significant improvement in CINV in the acute,
delayed, and overall phases (P<0.001) when NK1 RAs were
added to 5-HT3 RAs and corticosteroids.4 Medications from
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Dronabinol for CINV unresponsive to antiemetics
this class tend to be well tolerated with minimal side effects.
It is important to note the potential for drug interactions
with medications metabolized through the cytochrome P450
enzyme system.
Olanzapine is the latest unique agent to be added to the
treatment guidelines.2 Olanzapine works on several neu-
rotransmitters involved in the development of CINV such
as dopamine, serotonin, histamine, and acetylcholine.4 Data
support its role for the prevention of acute and delayed CINV
as well as for the management of breakthrough CINV. Caution
should be employed when using this agent in elderly patients
with dementia-related psychosis as it may place them at an
increased risk of death.
There are many alternative drug classes utilized for the
prevention and management of CINV such as antihistamines,
benzodiazepines, anticonvulsants, cannabinoids, and dopa-
mine receptor antagonists. Medications belonging to these
classes generally have lower efficacy and are associated
with more adverse effects. They are also not as well studied
compared to the agents mentioned above. The remainder of
this review will focus on dronabinol, a member of the can-
nabinoid class, and its role in CINV.
Pharmacology of dronabinol
Cannabis sativa L. (also known as marijuana) contains
naturally occurring delta-9-tetrahydrocannibinol (delta-9-
THC). The synthetic version of delta-9-THC is the active
ingredient in dronabinol that makes dronabinol an orally
active cannabinoid.
There are at least two types of cannabinoid receptors, CB1
and CB2.5 CB1 receptors are located throughout the central
nervous system, whereas CB2 receptors are present on the
brainstem neurons but mostly concentrated in the periphery,
primarily on immunocytes and mast cells.6 These receptors
can be activated not only by cannabis-derived and synthetic
agonists, but also by endogenous cannabinoids produced in
mammalian tissues.5 The mediating effects of dronabinol
and other cannabinoids occur through these cannabinoid
receptors located in neural tissues.7
Dronabinol has an onset of action of approximately 0.5–1
hour, with a peak effect at 2–4 hours, lasting a total of 4–6
hours with the psychoactive effects. After a single dose of
dronabinol, 90%–95% of the medication is systemically
absorbed; however, only 10%–20% enters the systemic cir-
culation due to the high lipid solubility and first-pass hepatic
metabolism. Dronabinol has a large volume of distribution,
approximately 10 L/kg, which allows for the metabolites to
be released over a prolonged period of time at low levels. It
undergoes first-pass hepatic metabolism, leading to active
and inactive metabolites. The clearance for dronabinol varies
greatly, with an average of 0.2 L/kg/h. Dronabinol metabolites
have been detected after a single dose more than 5 weeks
after administration in the urine and feces. The major route
of elimination for dronabinol is through the feces, with
approximately 35%–50% removed by this route; however,
about 10%–15% is found in the urine.7
Evidence for clinical efcacy of
dronabinol in CINV
Dronabinol was approved by the US Food and Drug Admin-
istration (FDA) in 1985 for the treatment of CINV in patients
who have failed to respond adequately to conventional anti-
emetic treatment.7
The endogenous cannabinoid system is an important
pathway involved in the emetic response. Cannabinoids
can prevent chemotherapy-induced emesis by acting at
central CB1 receptors by preventing the proemetic effects of
endogenous compounds such as dopamine and serotonin.8 In
addition, by acting as an agonist to CB1, cannabinoids used
as a treatment results in an antiemetic effect.9 Cannabinoids
have been used effectively for treating CINV since 1985.10
Monotherapy
A meta-analysis evaluated a total of 1,366 patients with 30
randomized clinical trials between 1975 and 1996.10 Three dif-
ferent cannabinoids were evaluated among the 30 trials, with 16
trials investigating nabilone, 13 investigating dronabinol, and
one investigating intramuscular levonantradol. The controls
included prochlorperazine, metoclopramide, chlorproma-
zine, thiethylperazine, haloperidol, domperidone, alizapride,
and placebo. The data showed that cannabinoids were more
effective with completely controlling CINV than the active
comparators or placebo in all the trials (number needed to
treat [NNT] =6 for nausea and NNT =8 for nausea). In patients
receiving a low or highly emetogenic chemotherapy regimen,
cannabinoids were similar in efficacy of complete control of
CINV versus the control; however, in patients receiving mod-
erate emetogenic risk chemotherapy regimens, cannabinoids
performed better than the control.
The three cannabinoids resulted in greater adverse drug
effects compared to the controls.10 There was a significant
increase in the number of patients who withdrew from the
studies due to intolerable adverse drug effects in 19 of the
30 trials. The increased adverse drug effects were described
as being beneficial or harmful. The beneficial adverse effects
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May and Glode
included sensation of a “high”, euphoria, drowsiness, seda-
tion, and somnolence. The harmful adverse effects included
dysphoria, depression, hallucination, and paranoia. Can-
nabinoids also increased the risk of arterial hypotension
(>20% decrease in blood pressure from baseline) in patients.
This meta-analysis showed that one in eleven patients would
stop chemotherapy treatment if taking a cannabinoid for
antiemesis compared to no patients discontinuing treatment
if prescribed another antiemetic.
Rocha et al’s11 meta-analysis evaluated 13 randomized
clinical trials. Five trials included dronabinol, six included
nabilone, and two included levonantradol. Ten of the trials
used prochlorperazine as a comparator, with the remain-
ing using alizapride, chlorpromazine, or domperidone.
Dronabinol’s ability for antiemetic efficacy was determined
to show statistical significance over the comparator (P=0.03,
NNT =3.4). The difference in antiemetic efficacy with nabi-
lone or levonantradol compared to controls was not statisti-
cally significant (P=0.21 and P=0.60, respectively).
Patients in the cannabinoids group reported paranoid
delusions, hallucinations, dysphoria, and depression.11 These
adverse drug effects occurred exclusively in the cannabinoids
group. Other adverse drug effects such as a “high” sensation,
sleepiness, sedation, and euphoria occurred more frequently
and more intensely in the cannabinoids group. However,
only 30% of the 400 patient dropouts were due to toxicities.
Dronabinol in combination with
ondansetron
Meiri et al8 conducted a randomized, double-blind, placebo-
controlled, parallel group trial that enrolled 64 patients receiv-
ing moderate or highly emetic chemotherapy.8 The objective
of this study was to determine if 4 days after chemotherapy,
adding dronabinol to a prophylactic regimen for acute CINV
and continuing treatment either alone or in combination with
ondansetron can help prevent delayed CINV. The four parallel
groups were dronabinol monotherapy (D; n=17), ondansetron
monotherapy (O; n=17), combination with dronabinol and
ondansetron (D + O; n=16), and placebo (n=14). Patients
in all four groups received dexamethasone 20 mg PO (by
mouth) and ondansetron 16 mg intravenous prechemotherapy
on day 1. In the three active treatment groups, patients also
received dronabinol 2.5 mg PO both prechemotherapy and
postchemotherapy on day 1. Day 2 consisted of fixed doses
with dronabinol 2.5 mg PO four times daily and/or ondanse-
tron 8 mg PO twice daily in the respective groups. Days 3–5
were flexible dosing days, with patients being allowed to take
dronabinol 2.5–5 mg PO four times a day and/or ondansetron
4–8 mg PO twice daily depending on tolerability. In the pla-
cebo group, a placebo was matched with the doses of dronabi-
nol and/or ondansetron. In all groups, patients were provided
with rescue medications consisting of metoclopramide PO,
prochlorperazine PO, and prochlorperazine suppository to
be used on days 1–8 for intolerable nausea and vomiting or
retching after the maximum prescribed study doses.
In this trial, there were more females (37 out of 61
patients, 61%) compared to males (24 out of 61 patients,
39%).8 The two most common cancer diagnoses were breast
cancer (26 out of 64 patients, 41%) and non-small-cell lung
cancer (14 out of 64 patients, 22%). Among all four groups,
29 patients (45%) took all of the appropriate study medica-
tions in the correct dosages over the 5-day trial period. A
total response was defined as no vomiting and/or retching,
intensity of nausea less than 5 mm on a 100 mm visual analog
scale (VAS), and no rescue medications. VAS is ranked from
0 to 100 mm, with 0 mm meaning no nausea and 100 mm
meaning intractable nausea. For day 1 results, the three active
treatment groups were combined and compared to the placebo
group. The total response during active treatment on day 1
for the combined active treatment (CAT) group was 79%
compared to 40% for the placebo group. For days 2–5, the
total response for the D, O, D + O, and placebo groups were
54%, 58%, 47%, and 20%, respectively. The percentage of
patients without nausea on day 1 in CAT group was 79% and
in the placebo group 38%. For days 2–5, the percentages were
71%, 64%, 53%, and 15% in the D, O, D + O, and placebo
groups, respectively. The reported VAS for nausea intensity
was 7.65 in the CAT group and 30.67 in the placebo group.
For days 2–5, the VAS was 10.1 in the D group, 24 in the
O group, 14.3 in the D + O group, and 48.4 in the placebo
group. Overall, the complete response rate was 62% in the
D group, 58% in the O group, 60% in the D + O group, and
20% in the placebo group. In addition, the active treatment
groups reduced the number of vomiting episodes to zero and
decreased the duration of vomiting and retching to 0 hours
by days 4 and 5. The duration of nausea was comparable
between all four groups. On the flexible dosage days, the
median dosage in the D group was 20 mg/d of dronabinol,
16 mg/d of ondansetron in the O group, and 17.5–20 mg/d
of dronabinol and 12–16 mg/d of ondansetron in the D + O
group. Rescue medications were used in all four groups (24%
in D, 31% in O, 12% in D + O, and 43% in placebo groups).
Treatment-emergent adverse drug effects were reported
in all four groups, with the largest percentage in the ondan-
setron group.8 Adverse drug effects were reported in 82% in
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Dronabinol for CINV unresponsive to antiemetics
the D group, 88% in the O group, 71% in the D + O group,
and 50% in the placebo group. The percentage of patients
who permanently discontinued a study medication because
of a treatment-emergent adverse drug effect was 6% in the
D group, 13% in the O group, 18% in the D + O group, and
no patients in the placebo group.
Dronabinol in combination with
prochlorperazine
Lane et al12 conducted a multicentered, randomized, paral-
lel group, double-blind trial that enrolled 62 patients. All
the patients had previously received chemotherapy and
antiemetics. Patients were eligible for the trial if they were
receiving any chemotherapy agents except high-dose cisplatin
(>60 mg/m2). The most common chemotherapy agents were
doxorubicin and cyclophosphamide (n=26), 5-fluorouracil
(n=14), vincristine (n=13), and etoposide (n=10). Two or three
drug chemotherapy regimens were given to 79% of patients.
Patients were randomized to one of three arms: dronabinol 10
mg PO every 6 hours with placebo (n=21), prochlorperazine
10 mg PO every 6 hours with placebo (n=21), or dronabinol
10 mg PO every 6 hours with prochlorperazine 10 mg PO
every 6 hours (n=20). Patients started the prescribed anti-
emetic 24 hours prior to starting chemotherapy and continued
it until 24 hours after the last dose of chemotherapy.
The overall complete response rate was defined as no
episodes of nausea or vomiting and occurred in 41% in the
dronabinol group and 30% in the prochlorperazine group
(P<0.0001).12 No complaints of nausea or vomiting occurred
in 41% in the dronabinol group, 30% in the prochlorperazine
group, and 47% in the combination group. Two or fewer
nausea or vomiting episodes occurred in 71%, 45%, and
65% in the dronabinol, prochlorperazine, and combination
groups, respectively. The median duration per episode of
nausea or vomiting was 2 minutes in the combination group
compared to 5 minutes in the dronabinol and prochlorpera-
zine groups (P<0.001). In addition, the severity of the nausea
was less in the combination group versus the dronabinol
and prochlorperazine groups (P<0.001). The duration per
episode of nausea or vomiting in the dronabinol group was
2 and 10 minutes versus 4 and 15 minutes in the prochlor-
perazine group. However, the total duration of nausea and
vomiting episodes did not differ between the three treatment
groups. Eleven patients reported anticipatory nausea (30%
in dronabinol group, 0% in the prochlorperazine group, and
26% in the combination group).
Thirty-four patients reported adverse drug effects in the
dronabinol (n=16), prochlorperazine (n=7), and combination
(n=11) groups.12 The difference of reported adverse drug
effects was statistically significant between the dronabinol
and prochlorperazine groups (P<0.01). Most of the adverse
drug effects reported were mild to moderate. The most
common type of adverse effects reported were neuropsycho-
tropic, seen in a total of 48% of patients. The incidence of
neuropsychotropic adverse drug effects that was reported in
the dronabinol and prochlorperazine groups was 62% versus
29% (P=0.06). In the combination group, it was reported in
55% of patients. Overall, 14 patients withdrew (ten patients
in dronabinol group and four in combination group) due to
adverse drug effects, with neuropsychotropic effects being
the most common reason and beginning during the preche-
motherapy phase.
Indicated dronabinol dosage
Dronabinol is typically prescribed at a dosage of 5 mg PO
three or four times daily to control CINV.7 On the basis of
the patient’s response after each chemotherapy cycle, the
dose may be increased or decreased as tolerated. Another
option for dosing dronabinol is 5 mg/m2 PO every 1–3 hours
prechemotherapy and then every 2–4 hours for a total of 4–6
doses/d. The maximum individual dose is 15 mg/m2.
Patient perspectives of dronabinol
CB1/CB2 receptor agonists can produce adverse effects in
patients, and many of these are likely caused by the activa-
tion of central CB1 receptors rather than CB2 or peripheral
CB1 receptors.5
In 18 cross-over trials included in the Tramer et al10 meta-
analysis, when patients were questioned which antiemetic
was preferred, 38%–90% of patients preferred cannabinoids.
Four trials compared cannabinoids to placebo. Out of 202
patients, 153 patients preferred cannabinoids versus 27
patients preferring the placebo (NNT =1.6). In ten additional
trials comparing cannabinoids to an active control, 371 out
of 604 (61%) preferred cannabinoids versus 156 patients
(26%) preferring the active control.
In the Rocha et al’s11 meta-analysis, 18 double-blind
and cross-over trials (n=1,138) included an analysis of the
patient’s preference of cannabinoids, and it resulted in a
statistically significant difference in favor of cannabinoids
(NNT =1.8, P<0.00001). The cannabinoids included in
the different trials included dronabinol, nabilone, and
levonantradol compared to the controls of prochlorperazine,
chlorpromazine, domperidone, haloperidol, alizapride, meto-
clopramide, and placebo. A relationship was determined with
the control drug that was utilized.
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May and Glode
It is suggested that patients prefer the “beneficial” adverse
drug effects associated with dronabinol, such as, sedation,
sensation of a “high”, and somnolence.10,11 These adverse
drug effects might provide relief while receiving chemo-
therapy.11 Another view is since CINV has such a major
impact on the patient’s QoL and can cause such discomfort
to the patient, the patients prefer cannabinoids’ adverse drug
effects instead of the conventional medications that might be
less effective in preventing and relieving the CINV.11
Medical marijuana
Many states have legalized marijuana for medical use,
including the condition of cancer.13 The legal limit of the
amount allowed for a patient to possess varies by state.
Technically marijuana contains more than 60 pharma-
cologically active cannabinoids, with the primary active
cannabinoids being THC and cannabidiol. The therapeutic
effect depends on the concentration of THC in addition to
the THC-to-cannabidiol ratio. Various strains of marijuana
are engineered to have different concentrations and ratios to
achieve desired pharmacologic effects. Medical marijuana
may be purchased from dispensaries in various dosage forms
as well, and is most commonly dispensed in the form used
to smoke as “cigarettes” or with a water pipe.14 It may also
be inhaled through a vaporizer, eaten in food, or applied
topically as a lotion.
It is important to note that adverse effects on the cardio-
vascular, respiratory, and central nervous system have been
associated with marijuana use. Marijuana smoke has been
reported to contain more carcinogens than cigarette smoke,
and may lead to head and neck cancer, lung cancer, as well as
bronchitis.9 The development of atrial fibrillation, myocardial
infarction, stroke, drowsiness, dizziness, nightmares, diffi-
culty sleeping, acute toxic psychosis, anxiety, and depression
among many other adverse effects has been associated with
marijuana use.9,14 Another concern in cancer patients is the
reported immunosuppressive properties of marijuana.
Few studies have evaluated medical marijuana alone or
in combination to treat nausea and vomiting related to che-
motherapy. The published studies that have been conducted
have mixed results. One study of 15 patients receiving
adjuvant high-dose methotrexate for sarcoma were random-
ized to three paired trials of placebo-THC or THC-placebo
with the patients serving as their own control.15 THC was
administered as capsules and cigarettes or matching placebos.
Fourteen of the 15 patients reported a reduction in nausea and
vomiting when using THC. Another study conducted by the
same group in eight patients receiving adjuvant doxorubicin
and cyclophosphamide for sarcoma were randomized to
THC-placebo or placebo-THC in paired trials to serve as
their own control.16 THC was administered as oral capsules
and cigarettes compared to matching placebos. Although the
investigators used the same trial design and THC regimen, a
beneficial effect of THC was not seen in this patient popula-
tion. The lack of benefit in this trial is thought to potentially
be from lower THC concentrations achieved in this group of
patients and presence of anticipatory nausea and vomiting
in half of the patients.
The largest account of patients receiving marijuana for
CINV was published by Musty and Rossi in 2001.17 This
group compiled a report of state-run clinical trials that had
been conducted evaluating Cannabis sativa (smoked mari-
juana and/or delta-9-tetrahydrocannabinol capsules) efficacy
in reducing CINV. Six trials were included in the analysis
comprising 748 patients who smoked marijuana prior to and/
or after chemotherapy and 345 patients who used oral THC
capsules. For the patients who smoked marijuana, 70%–100%
experienced relief from nausea and vomiting, and 76%–88%
of those who ingested the oral THC capsules experienced
relief. Short-term side effects reported included sedation, a
“high”, and smoke intolerance. More studies are needed in
this area to evaluate the efficacy and safety as additional states
approve medical marijuana and more patients gain access to
this management option.
Future directions
Dronabinol is utilized for breakthrough CINV based upon
available evidence already discussed and recommendations
by major oncology guidelines. Dronabinol is currently
being investigated in a few studies for additional roles in the
management of CINV. A completed, not published study has
investigated the use of dronabinol versus standard ondanse-
tron antiemetic therapy in the prevention of delayed CINV or
retching after moderate-to-high emetogenic chemotherapy.18
Patients were randomized to ondansetron, dronabinol,
combination therapy, or placebo. The study outcome was to
measure response of nausea and vomiting/retching, intensity,
and use of rescue medication. An additional study completed,
but yet to be published, has investigated palonosetron and
dexamethasone with or without dronabinol in the preven-
tion of CINV with moderately emetogenic chemotherapy.19
Patients were assessed for protection against the develop-
ment of vomiting, nausea, and use of rescue therapy. In an
ongoing study of patients with primary glioma receiving
chemotherapy, dronabinol is being administered to assess
its tolerability, toxicity, and impact on QoL.20 Assessment
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55
Dronabinol for CINV unresponsive to antiemetics
of emesis will be completed by patients filling out a daily
appetite and nausea/vomiting log as well as a QoL functional
living index emesis scale.
With medical marijuana remaining a schedule I substance
on a federal level, no studies are registered with clnicaltri-
als.gov to investigate its role in the management of CINV.
Anecdotally patients report benefit, but more research is
needed to identify the most appropriate dose, dosage form,
drug–drug interactions, and safety concerns with its use
before a role for medical marijuana can be elucidated in the
management of CINV.
Conclusion
Current guidelines as well as the FDA-approved indications
consider dronabinol’s role to be in the management of break-
through CINV. Dronabinol has a unique mechanism of action
and adverse effect profile that should be considered when
treating a patient with this medication. Unfortunately, there
are few ongoing studies evaluating the role of dronabinol in
the management of CINV. Two completed, yet unpublished,
studies have evaluated dronabinol in combination with a
5-HT3 RA as a prophylactic strategy. At this time, there is
insufficient data to support the routine use of dronabinol as an
antiemetic in all chemotherapeutic regimens. Data do support
the beneficial effects of dronabinol in the breakthrough CINV
setting. Further study of the scope of dronabinol’s potential
efficacy is warranted.
Disclosure
The authors report no conflicts of interest in this work.
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