Review Article

A selective review of medical cannabis in cancer pain management

Alexia Blake1, Bo Angela Wan2, Leila Malek2, Carlo DeAngelis2,3, Patrick Diaz2, Nicholas Lao1,
Edward Chow2, Shannon O’Hearn1
1
MedReleaf, Markham, Ontario, Canada; 2Odette Cancer Centre, Sunnybrook Health Sciences Centre, 3Leslie Dan Faculty of Pharmacy, University
of Toronto, Toronto, Ontario, Canada
Contributions: (I) Conception and design: A Blake, E Chow, S O’Hearn; (II) Administrative support: BA Wan, L Malek, P Diaz; (III) Provision
of study materials or patients: N Lao; (IV) Collection and assembly of data: A Blake, BA Wan, L Malek, S O’Hearn; (V) Data analysis and
interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Correspondence to: Ms. Alexia Blake, MSc. MedReleaf Corp, Markham Industrial Park, Markham, Ontario, Canada. Email: [email protected].

Abstract: Insufficient management of cancer-associated chronic and neuropathic pain adversely affects
patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects
from the use of traditional analgesics are in need of alternative therapeutic options. Anecdotal evidence
suggests that medical cannabis has potential to effectively manage pain in this patient population. This
review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to
double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based
therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated
pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that
evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised.
Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC
oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety
of doses ranging from 2.7–43.2 mg/day THC and 0–40 mg/day CBD were administered. Higher doses of
THC were correlated with increased pain relief in some studies. One study found that significant pain relief
was achieved in doses as low as 2.7–10.8 mg THC in combination with 2.5–10.0 mg CBD, but there was
conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include
drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that
medical cannabis reduces chronic or neuropathic pain in advanced cancer patients. However, the results of
many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there
is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in
order to establish the optimal dosage and efficacy of different cannabis-based therapies.

Keywords: Medical cannabis; cancer; pain

Submitted Jul 04, 2017. Accepted for publication Aug 03, 2017.
doi: 10.21037/apm.2017.08.05
View this article at: http://dx.doi.org/10.21037/apm.2017.08.05

Introduction Unfortunately, the current standard treatment regimens for

chronic or neuropathic pain in end-stage cancer patients
Cancer patients often present with chronic pain, which may
stem from direct tumour involvement, or present as a side rely heavily on opioid analgesics, which are problematic
effect of cancer treatment (1). As pain negatively impacts the for some patients (3,4). This can be due to a combination
physical, functional, and emotional domains of life, effective of factors, including differences in individual responses to
pain management strategies are essential for restoring these drugs, and the presence of serious side effects such as
and maintaining quality of life of cancer patients (2). severe constipation, that may prevent the administration

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216 Blake et al. Cannabis cancer pain

of sufficient doses for pain relief (3). In addition, population, interventions, pain response, and side effects
imprudent dosing runs the dangerous risk of patients was reviewed and summarised.
developing dependency, or overdosing on opioids (4).
Therefore, identifying alternative classes of analgesics that
Results
can effectively manage pain in cancer patients is of great
importance. Patient populations and selection criteria
Alternative pharmacological interventions include
Five studies were selected based on their evaluation of
prescription medications such as acetaminophen, or
cannabinoids to manage chronic pain in advanced cancer
nonsteroidal anti-inflammatory drugs like ibuprofen (5).
patients. An early pilot study conducted in 1975 by Noyes
Non-medicated approaches include therapies such
et al. assessed pain in ten advanced cancer patients (eight
a s a c u p u n c t u r e , p h y s i c a l t h e r a p y, i n a d d i t i o n t o
women and two men, average 51 years old) (13). In a similar
psychological or behavioural approaches (6). In addition
pain management study, Noyes et al. compared the effects
to the management strategies listed above, compounds
of THC and codeine in 36 cancer patients (consisting of
derived from the plant species Cannabis Sativa L. have 26 women and 10 men) (14). Non-study medications were
demonstrated the potential to alleviate pain. The most withheld from patients from both studies by Noyes et al.
commonly studied examples include tetrahydrocannabinol during the study period (13,14). Johnson et al. conducted a
(THC), and cannabidiol (CBD) from the family of multicenter, double-blind, randomized, placebo-controlled,
compounds known as cannabinoids (7). These compounds parallel-group study of the efficacy, safety, and tolerability
are commonly administered via inhalation, orally as oils or of nabiximols and THC in patients with intractable
oil-filled capsules, or oromucosally via sprays containing cancer-related pain, using a well-distributed population
either THC alone, or a combination of THC:CBD (8). of 177 advanced cancer patients, who recorded non-study
Several pre-clinical studies have been conducted in animal breakthrough analgesics (15). In this study, the mean age,
models, investigating the mechanism of cannabinoid gender, primary disease sites, and pain classification were
modulation of pain pathways (9,10). One of the identified distributed similarly between the three treatment arms;
mechanisms is the interaction of these compounds with THC, nabiximols, and placebo (15). In 2012, Portenoy et al.
one of the body’s endogenous signalling systems, known conducted a randomized, placebo-controlled, graded-dose
as the “endocannabinoid” system (11). This system acts trial involving 360 patients with advanced cancer, looking
independently of the opioid pathway to control pain at the efficacy of THC or nabiximols. Patients were chosen
signalling, immune activation, and inflammation (11). based on having previously responded poorly to opioid
While there is an abundance of existing anecdotal evidence analgesics, but were allowed to take breakthrough opioid
of the analgesic properties of medical cannabis, its efficacy analgesics as required (16). Patients who had received long-
has not yet been validated through high-quality clinical term methadone treatment for pain were excluded. Pain
studies that provide strong evidence supporting its utility in characteristics were categorized as mixed (48%), bone
the clinical setting (12). (24%), visceral (15%), and neuropathic (11%), and were
This selective review is an overview of clinical studies distributed approximately equally across the study arms.
conducted historically and up until the present day that Finally, Lynch et al. conducted a double-blind, placebo-
aimed to investigate the efficacy of medical cannabis in controlled, crossover pilot trial including 16 cancer patients
managing pain in advanced cancer patients. who had persistent neuropathic pain 3 months after their
cancer treatment (17). These patients had an average 7-day
pain intensity ≥4 on 0–10 NRS, stable concurrent analgesic
Methods
treatment for 14 days prior to study initiation, and were not
A search of literature published on Medline between 1975 taking breakthrough analgesics.
and 2017 through using key words including “cannabis”,
“THC”, “CBD”, “Nabiximol”, “cancer”, and “pain” was
Evaluation of pain
conducted. Five clinical studies that evaluated the effect of
THC or CBD on controlling cancer pain were evaluated In the clinical studies of cannabinoids for cancer pain
for a selective review. Information regarding the study management included in this review, several methods of

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Annals of Palliative Medicine, Vol 6, Suppl 2 December 2017 217

measuring changes in pain intensity were employed. Early compared to placebo, but did report a statistically significant
studies by Noyes et al. used a 4-point pain scoring system change in favour of nabiximols treatment compared to
in which 0= absent, 1= mild, 2= moderate, and 3= severe placebo (P=0.024). In addition, they reported that patients
(13,14). Since then, many studies have employed the taking nabiximols required significantly fewer doses of
numerical rating scale (NRS) to evaluate pain on a 0–10 breakthrough pain medications when compared to placebo
scale, with “0” representing “no pain” to “10” representing (P=0.004). Portenoy et al. found that compared to placebo,
“pain as bad as you can imagine”. Patients with neuropathic nabiximols were significantly more effective for reducing
pain studied by Lynch et al. completed the NRS at baseline, average daily pain when comparing scores from baseline to
and the last day of each week of dosing (17). The change the end of the study period (P=0.038) (16). These findings
in NRS score from baseline to the week in which a stable are in contrast with the study by Lynch et al. in which there
dose was reached was used as the primary endpoint in was no statistically significant difference between placebo
determining cannabis efficacy. In the study by Johnson et al., and nabiximols treatment groups amongst the 16 patients
patients used the NRS in addition to recording their experiencing cancer-related neuropathic pain (17).
long-term and break-through pain medications in a pain
diary (15). Portenoy et al. asked patients to report their
Dosage
average pain on the brief pain inventory (BPI), as well as
through an interactive voice recording system (16). The two Studies assessed the efficacy of different doses of medication,
remaining studies used the BPI to assess change in pain as or allowed patients to self-titrate up to a maximum dose, as
the primary endpoint (18,19). dictated by study protocols.
Evaluation of the effect of 5, 10, 15, and 20 mg of THC
in oil capsules by Noyes et al. found that the amount of
Efficacy of interventions
pain relief increased with dose (13). Out of 10 patients in
Overall, four out of the five studies found that cannabis was each cohort, 5 received substantial relief from 15 mg, and
significantly associated with a decrease in cancer-associated 7 patients received substantial relief from 20 mg. In the
pain. Table 1 presents a summary of the efficacy of THC or second study by Noyes et al., two different THC doses
CBD on cancer pain. of 10 and 20 mg were compared to placebo and 60 mg
codeine (14). A 60 mg dose of codeine is a standard daily
opioid analgesic regimen used in the management of
THC oil capsules and THC, CBD oromucosal sprays
many pain types, including cancer pain (20). A significant
Studies included in this review assessed the efficacy of difference in pain reduction was observed with the
THC oil capsules, and oromucosal sprays containing THC administration of 20 mg THC when compared to placebo
extract, or THC:CBD extract, also known as nabiximols. (P<0.05). Additionally, no significant difference in pain relief
Since nabiximols have CBD in addition to THC, they may was observed when comparing the 10 mg THC cohort
potentially target more pain pathways when compared to to those receiving 60 mg codeine (P<0.05). This suggests
THC extract alone. the non-inferiority of 10 mg of THC in comparison to a
Two early clinical studies on the efficacy of THC extract commonly used opioid treatment.
in sesame oil capsules were published by Noyes et al. in Evaluation of the efficacy of THC oromucosal spray by
1975 (13,14). The first was a pilot study that identified a Johnson et al. followed a self-titration method of dosing (15).
correlation between higher doses of THC and increased Patients who used THC sprays used an average of
pain relief (P<0.001) (13). The second study found a 8.3 sprays/day, corresponding to 22.5 mg of THC/day
significant difference in pain reduction between placebo and following dose titration up to a ceiling dose of 48 sprays/day.
20 mg THC (P<0.05), in favour of THC treatment (14). Patients were considered to have reached their optimal
Oromucosal sprays have been a common method dose upon experiencing relief of pain, or the development
of administration for cannabinoid-based medicines in of side-effects. The authors found the optimal dose of
clinical investigations, to date (12). Both THC extracts THC reached across patients provided greater pain relief
and nabiximols, administered oromucosally, were studied compared with placebo as measured by the average NRS
by Johnson et al. (15). They did not observe a significant pain score reduction (THC −1.01 vs. placebo −0.69)
change in mean pain score from baseline for THC spray however, statistical significance was not reached (P=0.245).

© Annals of Palliative Medicine. All rights reserved. apm.amegroups.com Ann Palliat Med 2017;6(Suppl 2):S215-S222
 Table 1 An overview of randomized controlled trials (RCTs) involving medical cannabis for cancer pain
Type of 218
Reference Year Total subjects Treatment arms and doses Duration Outcome measure Pain response
study

Noyes 1975 RCT 10 advanced cancer (I) THC: 5, 10, 15, and 20 mg in oil 6 hours Self-reported pain Correlation between higher doses
et al. (13) patients capsules; (II) placebo severity, pain relief, side of THC and increased pain relief
effects, subjective effects (P<0.001)
questionnaires

Noyes 1975 RCT 36 advanced cancer (I) THC: 10 and 20 mg in oil 6 hours Self-reported pain Significant difference in pain
et al. (14) patients capsules; (II) codeine: 60 and severity, pain relief, side reduction between placebo and
120 mg; (III) placebo effects, subjective effects 20 mg THC (P<0.05), in favour
questionnaires of THC treatment; no significant
difference in pain relief was
observed when comparing the
10 mg THC cohort to those

© Annals of Palliative Medicine. All rights reserved.

receiving 60 mg codeine (P<0.05)

Johnson 2010 RCT 177 advanced cancer (I) Nabiximols: ceiling dose of 2 weeks Self-reported pain score, No significant change in mean pain
et al. (15) patients 8 sprays/3-hour period (21.6 g THC, BPI-SF, EORTC QLQ-C30; score from baseline for THC spray
20 mg CBD); (II) THC: ceiling dose Self-recorded background compared to placebo; statistically
of 48 sprays/day (130 mg/day); medication and significant change in favour of
average dose of 8.3 sprays/day breakthrough analgesics nabiximols treatment compared to
(22.5 mg/day); (III) placebo placebo (P=0.024); patients taking
nabiximols required significantly
fewer doses of breakthrough pain
medications when compared to
placebo (P=0.004)

Portenoy 2012 RCT 263 advanced cancer (I) Low dose nabiximols 5 weeks Self-reported pain, Compared to placebo, low and

apm.amegroups.com
et al. (16) patients (1–4 sprays/day, or 2.7–10.8 mg sleep disruption, BPI- medium dose nabiximols were
THC, 2.5–10.0 mg CBD); (II) medium SF, EORTC QLQ-C30, significantly more effective for
dose nabiximols (6–10 sprays/day, MADRS; self-recorded reducing average daily pain when
or 10.8–16.2 mg THC, 10.0–15 mg medications for comparing scores from baseline
CBD); (III) high dose nabiximols breakthrough pain to the end of the study period
(11–16 sprays/day, or 29.7–43.2 mg (low dose P=0.008, medium dose
THC, 27.5–40 mg CBD); (IV) Placebo P=0.038); insignificant for high
dose

Lynch 2014 RCT 18 cancer patients (I) Nabiximols: ceiling dose of 4 weeks Self-reported NRS-PI pain No statistically significant
et al. (17) with chronic 12 sprays/day, or 32.4 mg THC, scale, SF-36, adverse difference between placebo and
neuropathic pain 30 mg CBD); (II) placebo events; QST nabiximols treatment groups
after taxol-based
chemotherapy
BPI-SF, Brief Pain Inventory-Short Form; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Version 3.0;
MADRS, Montgomery-Åsberg Depression Rating Scale; NRS-PI, Numerical Rating Score-Pain Intensity; SF-36, 36-Item Short Form Health Survey; QST, quantitative
sensory testing; RCT, randomized controlled trial; THC, tetrahydrocannabinol; CBD, cannabidiol.

Ann Palliat Med 2017;6(Suppl 2):S215-S222

Blake et al. Cannabis cancer pain
Annals of Palliative Medicine, Vol 6, Suppl 2 December 2017 219

In the three studies on nabiximols included in this was not assessed. However, patients also reported that the
review, self-titration was recommended up to a maximum majority of side effects were transient and mild, and could
dose of 8 sprays/3-hour period (15), and 11–16 sprays/day be reduced through adjusting treatment dose. Side effects
(16,17). In one of the studies, patients were divided into did not lead to any study drop-outs (13-17).
three dose groups categorized by titration ranges of mild
(1–4 sprays/day, or 2.7–10.8 mg THC, 2.5–10.0 mg CBD),
Discussion
moderate (6–10 sprays/day, or 10.8–16.2 mg THC, 10.0–
15 mg CBD), and high (11–16 sprays/day, or 29.7–43.2 The paucity of clinical data available on medical cannabis
mg THC, 27.5–40 mg CBD) (16). The doses found for treatment of cancer pain is partly due its classification
to produce significant pain relief include an average of as a schedule I agent by the Controlled Substances Act
8.75 sprays/day (15), 1–4 sprays/day (16), and 6– in 1970, which restricted its investigation as a potential
10 sprays/day (16). It was observed that the high dose group medical product (8). However, the few studies that were
of patients who utilised 11–16 sprays/day did not experience produced on the use of medical cannabis for cancer pain
significant pain relief compared to placebo. Similarly, Lynch management have results that suggest it does possess
et al. found that at a high dose of an average of 8 sprays/day therapeutic potential, and is at least worthy of further
there was no significant pain relief observed in comparison investigation.
to placebo (17). There is a lack of dosing guidelines for the use of
cannabinoid-based therapies in clinical practice. The
ideal dosage would be one that provides effective pain
Side effects and adverse events
management, but does not produce intolerable side effects.
Side effects reported in studies included in this review were However, there are challenges in establishing this optimal
consistent with those reported in literature investigating dose in the advanced cancer patient population. One of
the use of cannabinoid-based therapies for several other these is inter-patient variability, in keeping with results
indications (7). Table 2 summarises the five most commonly from studies on narcotics and other prescription analgesics.
reported side effects of the five studies. In both studies by As optimal doses were found to vary from patient to
Noyes et al., side effects of 15 and 20 mg of THC included patient, physicians need to understand how to determine
mental clouding (60–70%), drowsiness (70–100%), and the correct dosage when prescribing to a new patient. In
euphoria (40–50%) (13,14). Not all side effects were addition, advanced cancer patients are likely to present with
experienced by all patients, and side effects tended to complex symptomologies that make it difficult to accurately
become more prevalent with higher doses. assess side effects derived from cannabis treatments, and
Common treatment-related adverse events reported by are often taking multiple concurrent medications. That
Johnson et al. include somnolence (nabiximols 13%, THC said, a number of these studies reported that observed side-
14%, placebo 10%), dizziness (nabiximols 12%, THC effects tended not to be treatment-limiting, and could be
12%, placebo 5%), confusion (nabiximols 7%, THC 2%, controlled through dose titration, with pain relief in as little
placebo 2%), nausea (nabiximols 10%, THC 7%, placebo administration of 2.7–10.8 mg THC in combination with
7%), and hypotension (nabiximols 5%, THC 0%, placebo 2.5–10.0 mg CBD (17). This highlights the importance
0%) (15). These were reportedly more frequent in patients of establishing and validating a titration protocol that will
receiving the nabiximols extract and the THC only extract, allow researchers to identify effective and tolerated dosages
when compared with placebo. The adverse events identified in a safe and controlled manner.
by Portenoy et al. were significantly more frequent in the Several studies presented in this review were underpowered
higher nabiximols dose group, whereas little difference was due to small sample sizes, with three out of the five studies
observed between the low dose and placebo groups (17). reviewed enrolling less than 50 patients. Therefore, the
Lynch et al. identified fatigue (nabiximols n=7, placebo generalizability of the results may be limited, and future
n=0), dry mouth (nabiximols n=5, placebo n=1), dizziness studies on medical cannabis are warranted to establish its
(nabiximols n=6, placebo n=0), and nausea (nabiximols n=6, efficacy and side effect profile in the cancer pain population.
placebo n=1) to be the most common side effects, which This includes additional efforts to identify the efficacies of
were more often observed in the treatment arm compared specific cannabis compounds and their combinations, as well
to placebo, although the significance of this difference as ideal methods of administration through the assessment

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220 Blake et al. Cannabis cancer pain

Table 2 Summary of most common side effects

Most common side effects (reference),
Percentage of patients experiencing side effect in each treatment arm (%)
number of patients

Noyes et al. (13), n=10 THC (20 mg) THC (15 mg) THC (10 mg) THC (5 mg) Placebo

Drowsiness 100 70 50 70 30

Slurred speech 80 80 40 40 20

Blurred vision 70 70 40 20 0

Mental clouding 60 70 40 50 20

Dizziness 60 40 40 20 10

Noyes et al. (14), n=34 THC (10 mg) THC (20 mg) Codeine (60 mg) Codeine (120 mg) Placebo

Dizziness 97 59 59 24 26

Sedation 94 71 50 47 29

Dry mouth 76 74 65 59 35

Blurred vision 65 41 24 12 9

Mental clouding 53 32 24 12 9

Johnson et al. (15), n=177 Nabiximols THC Placebo – –

Somnolence 13 14 10 – –

Dizziness 12 12 5 – –

Nausea 10 7 7 – –

Vomiting 5 7 3 – –

Confusion 7 2 2 – –

Portenoy et al. (16) n=263 Nabiximols Placebo – – –

(all dose)

Nausea 22 13 – – –

Dizziness 19 13 – – –

Neoplasm progression 18 14 – – –

Disorientation 17 1 – – –

Vomiting 16 8 – – –

Lynch et al. (17), n=18 Nabiximols Placebo – – –

Fatigue 39 0 – – –

Dry mouth 28 6 – – –

Dizziness 33 0 – – –

Nausea 33 6 – – –

Increased appetite 11 0 – – –
THC, tetrahydrocannabinol.

of relevant endpoints. Subsequent clinical trials should also standardized and validated evaluation and reporting of
consider the differences in cannabinoid pharmacokinetics cannabis-associated side effects is warranted in order
and pharmacodynamics among individuals. Moreover, to enable more accurate comparisons across studies.

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Annals of Palliative Medicine, Vol 6, Suppl 2 December 2017 221

Ultimately, this will contribute to the development of 6. Syrjala KL, Jensen MP, Mendoza ME, et al. Psychological
clinical guidelines for the dosing and administration of and behavioral approaches to cancer pain management. J
cannabis as a pain medication for the large population of Clin Oncol 2014;32:1703-11.
cancer patients in need of pain management, particularly 7. Grotenhermen F, Müller-Vahl K. The therapeutic
those for whom alternative analgesics are insufficient, potential of cannabis and cannabinoids. Dtsch Arztebl Int
intolerable, or unsafe. 2012;109:495-501.
8. Borgelt LM, Franson KL, Nussbaum AM, et al. The
pharmacologic and clinical effects of medical cannabis.
Conclusions
Pharmacotherapy 2013;33:195-209.
Current research shows that there is a potential role for 9. Ward SJ, McAllister SD, Kawamura R, et al. Cannabidiol
medical cannabis in cancer pain management. However, inhibits paclitaxel-induced neuropathic pain through
the scale and quality of studies conducted to date are 5-HT(1A) receptors without diminishing nervous system
somewhat limited (12). Therefore, further research is function or chemotherapy efficacy. Br J Pharmacol
needed to establish the efficacy of medical cannabis, either 2014;171:636-45.
as an alternative to opiates or as an adjunctive therapy, and 10. Deng L, Guindon J, Cornett BL, et al. Chronic
to identify the most appropriate methods of administration cannabinoid receptor 2 activation reverses paclitaxel
to achieve optimal therapeutic efficacy with minimal side neuropathy without tolerance or cannabinoid receptor
effects. 1-dependent withdrawal. Biol Psychiatry 2015;77:475-87.
11. Huang WJ, Chen WW, Zhang X. Endocannabinoid
system: Role in depression, reward and pain control
Acknowledgements
(Review). Mol Med Rep 2016;14:2899-903.
We thank the generous support of Bratty Family Fund, 12. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids
Michael and Karyn Goldstein Cancer Research Fund, Joey for Medical Use: A Systematic Review and Meta-analysis.
and Mary Furfari Cancer Research Fund, Pulenzas Cancer JAMA 2015;313:2456-73.
Research Fund, Joseph and Silvana Melara Cancer Research 13. Noyes R Jr, Brunk SF, Baram DA, et al. Analgesic effect
Fund, and Ofelia Cancer Research Fund. This study was of delta-9-tetrahydrocannabinol. J Clin Pharmacol
conducted in collaboration with MedReleaf. 1975;15:139-43.
14. Noyes R Jr, Brunk SF, Avery DA, et al. The analgesic
properties of delta-9-tetrahydrocannabinol and codeine.
Footnote
Clin Pharmacol Ther 1975;18:84-9.
Conflicts of Interest: The authors have no conflicts of interest 15. Johnson JR, Burnell-Nugent M, Lossignol D, et al.
to declare. Multicenter, double-blind, randomized, placebo-
controlled, parallel-group study of the efficacy, safety,
and tolerability of THC:CBD extract and THC extract
References
in patients with intractable cancer-related pain. J Pain
1. Kumar SP. Cancer Pain: A Critical Review of Mechanism- Symptom Manage 2010;39:167-79.
based Classification and Physical Therapy Management in 16. Portenoy RK, Ganae-Motan ED, Allende S, et al.
Palliative Care. Indian J Palliat Care 2011;17:116-26. Nabiximols for opioid-treated cancer patients with poorly-
2. Katz N. The impact of pain management on quality of life. controlled chronic pain: a randomized, placebo-controlled,
J Pain Symptom Manage 2002;24:S38-47. graded-dose trial. J Pain 2012;13:438-49.
3. Trang T, Al-Hasani R, Salvemini D, et al. Pain and 17. Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-
Poppies: The Good, the Bad, and the Ugly of Opioid blind, placebo-controlled, crossover pilot trial with
Analgesics. J Neurosci 2015;35:13879-88. extension using an oral mucosal cannabinoid extract for
4. Nersesyan H, Slavin KV. Current aproach to cancer pain treatment of chemotherapy-induced neuropathic pain. J
management: Availability and implications of different Pain Symptom Manage 2014;47:166-73.
treatment options. Ther Clin Risk Manag 2007;3:381-400. 18. Daut RL, Cleeland CS, Flanery RC. Development of
5. Schug SA, Chandrasena C. Pain management of the cancer the Wisconsin Brief Pain Questionnaire to assess pain in
patient. Expert Opin Pharmacother 2015;16:5-15. cancer and other diseases. Pain 1983;17:197-210.

© Annals of Palliative Medicine. All rights reserved. apm.amegroups.com Ann Palliat Med 2017;6(Suppl 2):S215-S222
222 Blake et al. Cannabis cancer pain

19. Cleeland CS, Ryan KM. Pain assessment: global use 20. Straube C, Derry S, Jackson KC, et al. Codeine, alone
of the Brief Pain Inventory. Ann Acad Med Singapore and with paracetamol (acetaminophen), for cancer pain.
1994;23:129-38. Cochrane Database Syst Rev 2014;(9):CD006601.

Cite this article as: Blake A, Wan BA, Malek L, DeAngelis C,

Diaz P, Lao N, Chow E, O'Hearn S. A selective review of
medical cannabis in cancer pain management. Ann Palliat Med
2017;6(Suppl 2):S215-S222. doi: 10.21037/apm.2017.08.05

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