SCIENCE AND PRACTICE

Journal of the American Pharmacists Association xxx (2019) 1e4

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RESEARCH NOTES
Effect of cannabis on opioid use in patients with cancer receiving
palliative care
Elizabeth R. Pritchard, Lindsey Dayer, Jennifer Belz, Brittany Forseth,
Sarah E. Harrington, Jacob T. Painter*

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Opioids are the primary therapy for cancer-related pain in patients receiving
Received 27 June 2019 palliative care. More states are legalizing medical cannabis, which may provide a pain man-
Accepted 28 October 2019 agement alternative for some of these patients. This study aimed to estimate the effect of
cannabis on opioid use in patients with cancer receiving palliative care.
Methods: This was a retrospective cohort study of patients with cancer at an academic medical
center palliative care clinic. The primary outcome was change in morphine equivalent daily
dose (MEDD) from baseline to 84-day follow-up in the cannabis plus opioid group compared
to that in the opioid-only group.
Results: A total of 83 patients were included: 61 in the opioid monotherapy group and 22 in
the cannabis plus opioid group. An increase in MEDD from the baseline to 84 days was seen in
both the opioid monotherapy and opioid plus cannabis group (28.8 vs. 10.8); however, the
study lacked power to detect a statistical difference.
Conclusion: A possibly meaningful difference in MEDD increase was seen when comparing the
opioid monotherapy group with the opioid plus cannabis group. However, the study was not
powered to test this hypothesis; the findings suggest that further research is warranted to
determine the impact of cannabis use on opioid dosing in patients receiving palliative care for
cancer.
© 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.

Background mediated by inhibiting prostaglandin synthesis (a hormone

produced in response to injury or inflammation) and acts on
Cannabis is a natural compound used for alleviating pain-sensing pathways in the brain.3
symptoms in many disease states. Its effects are mainly pro- When treating patients for cancer-related pain, the primary
duced through the actions of the endocannabinoid system. The pain-relieving therapy is opioid medications.4,5 For patients
2 main active phytochemicals are D9-tetrahydrocannabinol with pain that is not well controlled, alternative or adjunctive
(THC) and cannabidiol (CBD).1 THC is the cannabinoid pri- therapies, such as cannabis, have been used. The legal status of
marily responsible for psychoactive effects (euphoria or cannabis varies from state to state; the medical use of cannabis
dysphoria) and causes relaxation and has anti-inflammatory is currently legal in 14 states including Arkansas. The effects of
effects. CBD does not have psychoactive effects, but it has cannabis on pain management have been studied in other
some anti-inflammatory effects.2 In addition to its anti- populations such as patients with human immunodeficiency
inflammatory effects, CBD has pain-relieving effects virus and those with chronic pain.6-8 This literature suggests
that cannabis-based therapies have benefits in managing pain.
A study conducted outside of the United States followed
oncology patients who received a medical cannabis permit.
Disclosure: The authors declare no relevant conflicts of interest or financial Sixty-nine of 113 patients reported an improvement in pain
relationships.
management along with overall well-being.9 Another pro-
* Correspondence: Jacob T. Painter, PharmD, MBA, PhD, University of
Arkansas for Medical Sciences, 4301 W Markham St., Little Rock, AR 72205. spective study outside the United States followed more than
E-mail address: jtpainter@uams.edu (J.T. Painter). 3000 patients with various types of cancer receiving medical

https://doi.org/10.1016/j.japh.2019.10.013
1544-3191/© 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.
SCIENCE AND PRACTICE
E.R. Pritchard et al. / Journal of the American Pharmacists Association xxx (2019) 1e4

cannabis. At a 6-month follow-up survey, pain intensity and the change in MEDD between the opioid plus cannabis group
quality of life were assessed; only 4.6% reported an intensity of and the opioid monotherapy group from the baseline to the
8-10 (scale, 0-10) compared with 52.9% before treatment 84-day follow-up. MEDD change was calculated by subtracting
initiation, whereas 69.5% reported good quality of life the patient’s MEDD at the baseline from that at the 84-day
compared with 18.7% who reported good quality of life at the follow-up. In addition, the group average MEDD at the base-
beginning of the study.10 line, 84-day follow-up, and 180-day follow-up was compared.
Although an increasing number of states have legalized Total average MEDD was calculated on the basis of conversions
medical cannabis, evidence on its effectiveness is lacking. provided by the Centers for Disease Control and Prevention.14
Studies have examined the use of medical cannabis in patients In addition, medication use for depression, anxiety, and
with cancer, but evidence supporting the use in patients with chemotherapy-induced nausea and vomiting at the baseline
cancer receiving palliative care is lacking. Palliative care ser- and follow-up were recorded.
vices aim to decrease patient suffering and to provide the best The PCC did not have a sufficient number of patients to
possible quality of life for patients and their families. Palliative support a hypothesis-driven statistical analysis. Descriptive
care can include hospice and nonhospice care. Although defi- statistics are reported, and test statistics for nonparametric
nitions vary, here, palliative care refers to nonhospice care unadjusted comparisons are provided in the tables. This study
offered for patients with serious disease or illness and may be was approved by the local institutional review board.
given along with life-prolonging or curative treatment.11-13
The purpose of this study was to examine the effect of con- Results
current opioid and cannabis use when compared with opioid
use alone in patients with cancer receiving palliative care. A total of 159 patients were seen in the PCC, and 83 patients
met the criteria for inclusion in the final analysis: 61 patients
in the opioid monotherapy group and 22 patients in the opioid
Methods
plus cannabis group. Demographics of both the groups are
shown in Table 1. The median age of patients in the opioid plus
This retrospective cohort study was performed using data
cannabis group was 48 years and in the opioid monotherapy
from the palliative care clinic (PCC) at an academic medical
group was 55 years.
center. The pharmacist’s role at this practice site includes
For the primary end point (Table 2), the change in MEDD
helping to monitor the urine drug screen (UDS) of patients in
from the baseline to the 84-day follow-up in the opioid
the PCC. In addition, it includes providing a detailed medica-
monotherapy group was an increase of 28.8 morphine milli-
tion reconciliation to help aid in medication safety and choice
gram equivalents (MME) with an increase of only 10.8 MME in
of medication or dose. The pharmacist provides patient and
the opioid plus cannabis group. The total average MEDD was
caregiver education regarding the use of cannabis and opioids.
Data were abstracted from the electronic medical records
Table 1
(EMRs) of patients enrolled in the PCC between October 2014 Baseline characteristics
and October 2017. Inclusion criteria were as follows: patients
Variable Opioid only Opioid plus THC P value
with a diagnosis of cancer seen in the PCC; patients aged 18
(n ¼ 61) (n ¼ 22)
years or older; and patients who had a UDS in clinic within 28
Age, mean ± SD, y 55 ± 11.06 48 ± 12.16 0.014
days of the initial PCC visit, an opioid prescription listed in the
Sex
EMR with a valid morphine equivalent daily dose (MEDD) Female 23 12 0.524
measurement at the initial PCC visit, and a follow-up Male 38 10 d
appointment within 84 days of the initial PCC visit. The UDS Race
used in this project screened for amphetamine, metham- White 41 16 0.633
phetamine, barbiturates, benzodiazepines, THC, cocaine, Other 20 6 d
No. patients on specific opioid at baseline
methadone, opiates, and phencyclidine (PCP). Patients with a
Morphine IR 11 2 0.498
positive UDS for illicit substances, defined as amphetamine or Morphine ER 20 3 0.102
methamphetamine (unless patients had current prescription Oxycodone IR 33 15 0.251
for a central nervous system stimulant), barbiturates, cocaine, Oxycodone ER 2 2 0.285
or PCP, and patients on dronabinol or nabilone therapy were Hydromorphone 12 3 0.749
excluded. In addition, patients who received any of the Fentanyl 4 5 0.051
following medications during the study period, as determined Hydrocodone 4 2 0.653
Methadone 12 5 0.761
by review of the EMR, were excluded: codeine, tramadol,
Oxymorphone d d d
tapentadol, buprenorphine, or pentazocine. These therapies Other medications at baseline
were excluded owing to their limited use in pain management SSRI 4 5 0.051
in the PCC. On the basis of UDS results, patients were assigned SNRI 7 3 0.720
to the opioids plus cannabis group or opioid monotherapy TCA 1 2 0.170
group. Baseline characteristics abstracted from the EMR Bupropion d d d
Mirtazapine 3 3 0.187
included demographic and medication use characteristics.
Benzodiazepine 10 5 0.528
The exposure of interest for the study was the presence of MEDD at baseline 119.21 (100.31) 144.32 (129.19) 0.57
THC on the 28-day UDS report. Patients positive for THC on
Abbreviations used: IR, immediate release; ER, extended release; MEDD,
UDS were considered to comprise the opioid plus cannabis morphine equivalent daily dosage; SSRI, selective serotonin reuptake inhibi-
group, whereas those with a THC-free, 28-day UDS made up tor; SNRI, serotonin-norepinephrine reuptake inhibitor; TCA, tricyclic anti-
the opioid-only group. The primary end point of the study was depressant; THC, D9-tetrahydrocannabinol.

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 SCIENCE AND PRACTICE
Cannabis effect on opioid use in cancer patients

Table 2
Outcomes

Variable Opioid only (n ¼ 61) Opioid plus THC (n ¼ 22) P value

Primary outcome, mean ± SD
MEDD change from initial visit to 84-day follow-up 28.84 ± 90.07 10.80 ± 113.48 0.686
Secondary outcomes, mean ± SD
MEDD change from initial visit to 180-day follow-up 46.24 ± 151.66 99.61 ± 149.45 0.353
MEDD average at 84-day follow-up 148.06 ± 128.03 155.11 ± 136.07 0.955
MEDD average at 180-day follow-up 165.58 ± 162.30 232.84 ± 199.87 0.328
Other medications at 84th day of follow-up
SSRI 4 4 0.199
SNRI 1 0 1.00
TCA 3 2 0.605
Bupropion d d d
Mirtazapine 1 1 0.695
Benzodiazepine 9 2 0.719
Abbreviations used: MEDD, morphine equivalent daily dosage; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin-norepinephrine reuptake inhibitor;
TCA, tricyclic antidepressant.

lower overall in the opioid monotherapy group than that in the able to correlate changes with possible disease progression or
opioid plus cannabis group at baseline (119.2 vs. 144.3). In- other life events that may affect their scoring.
crease in MEDD from baseline to the 180-day follow-up was Studying cannabis has many inherent limitations. The
46.2 MME in the opioid monotherapy group (n ¼ 31) and 99.6 amount, type, and frequency of its use are usually unknown.
MME in the opioid plus cannabis group (n ¼ 13). No clear Cannabis is currently a schedule I substance per the U.S. Drug
changes were observed for the groups between baseline and Enforcement Agency,16 making it difficult to perform clinical
follow-up for adjuvant medication. research. The investigators chose to study cannabis because
many patients in the PCC use cannabis or have reported use in
Discussion the past.

This retrospective cohort study saw an MEDD increase of Conclusion

approximately 25% from baseline to the 84-day follow-up in
the opioid monotherapy group and an increase of only 7.5% in In conclusion, this retrospective cohort study examining
the opioid plus cannabis group. Although this estimated dif- patients with cancer receiving palliative care saw a difference
ference had a high level of uncertainty, if the observed dif- with the increase in MEDD between baseline and follow-up
ference was to hold in a larger study, it would be clinically and between patients treated with opioids alone and those
meaningful. The observed difference in MEDD change may be who were concurrently using opioids and cannabis; however,
due to cannabis providing pain relief by suppressing neuro- the study was not adequately powered to detect an effect with
transmitter release and mechanisms causing neuropathic precision. A larger, more robust study could test this hypoth-
pain15; however, there was no indication in the data as to esis while controlling for potential confounding factors due to
whether the pain experienced by the patient was neuropathic differences in baseline patient characteristics.
in nature. It must be noted that the average baseline MEDD
was higher in the opioid plus cannabis group. Moreover, the Acknowledgments
effect of differences in prescriber behavior as a result of
patient-level variation not observed in this study cannot be The authors thank the Arkansas Clinical Data Repository
ruled outdfor example, patients who test positive for THC (AR-CDR) for providing assistance in data collection. Data for
may exhibit behaviors that prescribers see as risky, and thus, the study were provided by AR-CDR maintained by the
opioid prescriptions do not increase at the same rate. Department of Biomedical Informatics of the College of Med-
There are several limitations to this study, including the icine at the University of Arkansas for Medical Sciences
retrospective nature of data analysis and the sample size. In (UAMS). AR-CDR is approved to operate as an enterprise data
addition, at the 180-day follow-up, many patients could not be resource to support research across UAMS. Data in AR-CDR
analyzed because they did not arrive for their follow-up ap- come from the UAMS Electronic Medical Record, tumor reg-
pointments, were transitioned into hospice care and were no istry, billing, and cancer genomic data and comprises en-
longer followed at the PCC, or died. Other study limitations counters since January 5, 2014.
include how patients were assigned into treatment groups on
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