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A selective review of medical cannabis in cancer pain management

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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 op-tions. 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 neu-ropathic 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.
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© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2017apm.amegroups.com
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
1MedReleaf, 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: ablake@medreleaf.com.
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 efcacy 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 identied ve 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 signicant 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
conicting 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 efcacy 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
Cancer patients often present with chronic pain, which may
stem from direct tumour involvement, or present as a side
effect of cancer treatment (1). As pain negatively impacts the
physical, functional, and emotional domains of life, effective
pain management strategies are essential for restoring
and maintaining quality of life of cancer patients (2).
Unfortunately, the current standard treatment regimens for
chronic or neuropathic pain in end-stage cancer patients
rely heavily on opioid analgesics, which are problematic
for some patients (3,4). This can be due to a combination
of factors, including differences in individual responses to
these drugs, and the presence of serious side effects such as
severe constipation, that may prevent the administration
2Blake et al. Cannabis cancer pain
© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2017apm.amegroups.com
of sufficient doses for pain relief (3). In addition,
imprudent dosing runs the dangerous risk of patients
developing dependency, or overdosing on opioids (4).
Therefore, identifying alternative classes of analgesics that
can effectively manage pain in cancer patients is of great
importance.
Alternative pharmacological interventions include
prescription medications such as acetaminophen, or
nonsteroidal anti-inflammatory drugs like ibuprofen (5).
Non-medicated approaches include therapies such
as acupuncture, physical therapy, in addition to
psychological or behavioural approaches (6). In addition
to the management strategies listed above, compounds
derived from the plant species Cannabis Sativa L. have
demonstrated the potential to alleviate pain. The most
commonly studied examples include tetrahydrocannabinol
(THC), and cannabidiol (CBD) from the family of
compounds known as cannabinoids (7). These compounds
are commonly administered via inhalation, orally as oils or
oil-filled capsules, or oromucosally via sprays containing
either THC alone, or a combination of THC:CBD (8).
Several pre-clinical studies have been conducted in animal
models, investigating the mechanism of cannabinoid
modulation of pain pathways (9,10). One of the identied
mechanisms is the interaction of these compounds with
one of the body’s endogenous signalling systems, known
as the “endocannabinoid” system (11). This system acts
independently of the opioid pathway to control pain
signalling, immune activation, and inflammation (11).
While there is an abundance of existing anecdotal evidence
of the analgesic properties of medical cannabis, its efcacy
has not yet been validated through high-quality clinical
studies that provide strong evidence supporting its utility in
the clinical setting (12).
This selective review is an overview of clinical studies
conducted historically and up until the present day that
aimed to investigate the efficacy of medical cannabis in
managing pain in advanced cancer patients.
Methods
A search of literature published on Medline between 1975
and 2017 through using key words including “cannabis”,
“THC”, “CBD”, “Nabiximol”, “cancer”, and “pain” was
conducted. Five clinical studies that evaluated the effect of
THC or CBD on controlling cancer pain were evaluated
for a selective review. Information regarding the study
population, interventions, pain response, and side effects
was reviewed and summarised.
Results
Patient populations and selection criteria
Five studies were selected based on their evaluation of
cannabinoids to manage chronic pain in advanced cancer
patients. An early pilot study conducted in 1975 by Noyes
et al. assessed pain in ten advanced cancer patients (eight
women and two men, average 51 years old) (13). In a similar
pain management study, Noyes et al. compared the effects
of THC and codeine in 36 cancer patients (consisting of
26 women and 10 men) (14). Non-study medications were
withheld from patients from both studies by Noyes et al.
during the study period (13,14). Johnson et al. conducted a
multicenter, double-blind, randomized, placebo-controlled,
parallel-group study of the efcacy, safety, and tolerability
of nabiximols and THC in patients with intractable
cancer-related pain, using a well-distributed population
of 177 advanced cancer patients, who recorded non-study
breakthrough analgesics (15). In this study, the mean age,
gender, primary disease sites, and pain classification were
distributed similarly between the three treatment arms;
THC, nabiximols, and placebo (15). In 2012, Portenoy et al.
conducted a randomized, placebo-controlled, graded-dose
trial involving 360 patients with advanced cancer, looking
at the efcacy of THC or nabiximols. Patients were chosen
based on having previously responded poorly to opioid
analgesics, but were allowed to take breakthrough opioid
analgesics as required (16). Patients who had received long-
term methadone treatment for pain were excluded. Pain
characteristics were categorized as mixed (48%), bone
(24%), visceral (15%), and neuropathic (11%), and were
distributed approximately equally across the study arms.
Finally, Lynch et al. conducted a double-blind, placebo-
controlled, crossover pilot trial including 16 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
treatment for 14 days prior to study initiation, and were not
taking breakthrough analgesics.
Evaluation of pain
In the clinical studies of cannabinoids for cancer pain
management included in this review, several methods of
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measuring changes in pain intensity were employed. Early
studies by Noyes et al. used a 4-point pain scoring system
in which 0= absent, 1= mild, 2= moderate, and 3= severe
(13,14). Since then, many studies have employed the
numerical rating scale (NRS) to evaluate pain on a 0–10
scale, with “0” representing “no pain” to “10” representing
“pain as bad as you can imagine”. Patients with neuropathic
pain studied by Lynch et al. completed the NRS at baseline,
and the last day of each week of dosing (17). The change
in NRS score from baseline to the week in which a stable
dose was reached was used as the primary endpoint in
determining cannabis efcacy. In the study by Johnson et al.,
patients used the NRS in addition to recording their
long-term and break-through pain medications in a pain
diary (15). Portenoy et al. asked patients to report their
average pain on the brief pain inventory (BPI), as well as
through an interactive voice recording system (16). The two
remaining studies used the BPI to assess change in pain as
the primary endpoint (18,19).
Efcacy of interventions
Overall, four out of the ve studies found that cannabis was
signicantly associated with a decrease in cancer-associated
pain. Table 1 presents a summary of the efcacy of THC or
CBD on cancer pain.
THC oil capsules and THC, CBD oromucosal sprays
Studies included in this review assessed the efficacy of
THC oil capsules, and oromucosal sprays containing THC
extract, or THC:CBD extract, also known as nabiximols.
Since nabiximols have CBD in addition to THC, they may
potentially target more pain pathways when compared to
THC extract alone.
Two early clinical studies on the efcacy of THC extract
in sesame oil capsules were published by Noyes et al. in
1975 (13,14). The first was a pilot study that identified a
correlation between higher doses of THC and increased
pain relief (P<0.001) (13). The second study found a
signicant difference in pain reduction between placebo and
20 mg THC (P<0.05), in favour of THC treatment (14).
Oromucosal sprays have been a common method
of administration for cannabinoid-based medicines in
clinical investigations, to date (12). Both THC extracts
and nabiximols, administered oromucosally, were studied
by Johnson et al. (15). They did not observe a significant
change in mean pain score from baseline for THC spray
compared to placebo, but did report a statistically signicant
change in favour of nabiximols treatment compared to
placebo (P=0.024). In addition, they reported that patients
taking nabiximols required significantly fewer doses of
breakthrough pain medications when compared to placebo
(P=0.004). Portenoy et al. found that compared to placebo,
nabiximols were significantly more effective for reducing
average daily pain when comparing scores from baseline to
the end of the study period (P=0.038) (16). These ndings
are in contrast with the study by Lynch et al. in which there
was no statistically significant difference between placebo
and nabiximols treatment groups amongst the 16 patients
experiencing cancer-related neuropathic pain (17).
Dosage
Studies assessed the efcacy of different doses of medication,
or allowed patients to self-titrate up to a maximum dose, as
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
pain relief increased with dose (13). Out of 10 patients in
each cohort, 5 received substantial relief from 15 mg, and
7 patients received substantial relief from 20 mg. In the
second study by Noyes et al., two different THC doses
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
many pain types, including cancer pain (20). A significant
difference in pain reduction was observed with the
administration of 20 mg THC when compared to placebo
(P<0.05). Additionally, no signicant difference in pain relief
was observed when comparing the 10 mg THC cohort
to those receiving 60 mg codeine (P<0.05). This suggests
the non-inferiority of 10 mg of THC in comparison to a
commonly used opioid treatment.
Evaluation of the efcacy of THC oromucosal spray by
Johnson et al. followed a self-titration method of dosing (15).
Patients who used THC sprays used an average of
8.3 sprays/day, corresponding to 22.5 mg of THC/day
following dose titration up to a ceiling dose of 48 sprays/day.
Patients were considered to have reached their optimal
dose upon experiencing relief of pain, or the development
of side-effects. The authors found the optimal dose of
THC reached across patients provided greater pain relief
compared with placebo as measured by the average NRS
pain score reduction (THC −1.01 vs. placebo −0.69)
however, statistical signicance was not reached (P=0.245).
4Blake et al. Cannabis cancer pain
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Table 1 An overview of randomized controlled trials (RCTs) involving medical cannabis for cancer pain
Reference Year Type of
study Total subjects Treatment arms and doses Duration Outcome measure Pain response
Noyes
et al. (13)
1975 RCT 10 advanced cancer
patients
(I) THC: 5, 10, 15, and 20 mg in oil
capsules; (II) placebo
6 hours Self-reported pain
severity, pain relief, side
effects, subjective effects
questionnaires
Correlation between higher doses
of THC and increased pain relief
(P<0.001)
Noyes
et al. (14)
1975 RCT 36 advanced cancer
patients
(I) THC: 10 and 20 mg in oil
capsules; (II) codeine: 60 mg and
120 mg; (III) placebo
6 hours Self-reported pain
severity, pain relief, side
effects, subjective effects
questionnaires
Significant difference in pain
reduction between placebo and
20 mg THC (P<0.05), in favour
of THC treatment; no significant
difference in pain relief was
observed when comparing the
10 mg THC cohort to those
receiving 60 mg codeine (P<0.05)
Johnson
et al. (15)
2010 RCT 177 advanced cancer
patients
(I) Nabiximols: ceiling dose of
8 sprays/3-hour period (21.6 mg
THC, 20 mg CBD); (II) THC: ceiling
dose of 48 sprays/day (130 mg/day);
average dose of 8.3 sprays/day
(22.5 mg/day); (III) placebo
2 weeks Self-reported pain score,
BPI-SF, EORTC QLQ-C30;
Self-recorded background
medication and
breakthrough analgesics
No significant change in mean pain
score from baseline for THC spray
compared to placebo; statistically
significant change in favour of
nabiximols treatment compared to
placebo (P=0.024); patients taking
nabiximols required significantly
fewer doses of breakthrough pain
medications when compared to
placebo (P=0.004)
Portenoy
et al. (16)
2012 RCT 263 advanced cancer
patients
(I) Low dose nabiximols
(1–4 sprays/day, or 2.7–10.8 mg
THC, 2.5–10.0 mg CBD); (II) medium
dose nabiximols (6–10 sprays/day,
or 10.8–16.2 mg THC, 10.0–15 mg
CBD); (III) high dose nabiximols
(11–16 sprays/day, or 29.7–43.2 mg
THC, 27.5–40 mg CBD); (IV) Placebo
5 weeks Self-reported pain,
sleep disruption, BPI-
SF, EORTC QLQ-C30,
MADRS; self-recorded
medications for
breakthrough pain
Compared to placebo, low and
medium dose nabiximols were
significantly more effective for
reducing average daily pain when
comparing scores from baseline
to the end of the study period
(low dose P=0.008, medium dose
P=0.038); insignificant for high
dose
Lynch
et al. (17)
2014 RCT 18 cancer patients
with chronic
neuropathic pain
after taxol-based
chemotherapy
(I) Nabiximols: ceiling dose of
12 sprays/day, or 32.4 mg THC,
30 mg CBD); (II) placebo
4 weeks Self-reported NRS-PI pain
scale, SF-36, adverse
events; QST
No statistically significant
difference between placebo and
nabiximols treatment groups
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.
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In the three studies on nabiximols included in this
review, self-titration was recommended up to a maximum
dose of 8 sprays/3-hour period (15), and 11–16 sprays/day
(16,17). In one of the studies, patients were divided into
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),
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
mg THC, 27.5–40 mg CBD) (16). The doses found
to produce significant pain relief include an average of
8.75 sprays/day (15), 1–4 sprays/day (16), and 6–
10 sprays/day (16). It was observed that the high dose group
of patients who utilised 11–16 sprays/day did not experience
signicant pain relief compared to placebo. Similarly, Lynch
et al. found that at a high dose of an average of 8 sprays/day
there was no signicant pain relief observed in comparison
to placebo (17).
Side effects and adverse events
Side effects reported in studies included in this review were
consistent with those reported in literature investigating
the use of cannabinoid-based therapies for several other
indications (7). Table 2 summarises the ve most commonly
reported side effects of the ve studies. In both studies by
Noyes et al., side effects of 15 and 20 mg of THC included
mental clouding (60–70%), drowsiness (70–100%), and
euphoria (40–50%) (13,14). Not all side effects were
experienced by all patients, and side effects tended to
become more prevalent with higher doses.
Common treatment-related adverse events reported by
Johnson et al. include somnolence (nabiximols 13%, THC
14%, placebo 10%), dizziness (nabiximols 12%, THC
12%, placebo 5%), confusion (nabiximols 7%, THC 2%,
placebo 2%), nausea (nabiximols 10%, THC 7%, placebo
7%), and hypotension (nabiximols 5%, THC 0%, placebo
0%) (15). These were reportedly more frequent in patients
receiving the nabiximols extract and the THC only extract,
when compared with placebo. The adverse events identied
by Portenoy et al. were significantly more frequent in the
higher nabiximols dose group, whereas little difference was
observed between the low dose and placebo groups (17).
Lynch et al. identified fatigue (nabiximols n=7, placebo
n=0), dry mouth (nabiximols n=5, placebo n=1), dizziness
(nabiximols n=6, placebo n=0), and nausea (nabiximols n=6,
placebo n=1) to be the most common side effects, which
were more often observed in the treatment arm compared
to placebo, although the significance of this difference
was not assessed. However, patients also reported that the
majority of side effects were transient and mild, and could
be reduced through adjusting treatment dose. Side effects
did not lead to any study drop-outs (13-17).
Discussion
The paucity of clinical data available on medical cannabis
for treatment of cancer pain is partly due its classication
as a schedule I agent by the Controlled Substances Act
in 1970, which restricted its investigation as a potential
medical product (8). However, the few studies that were
produced on the use of medical cannabis for cancer pain
management have results that suggest it does possess
therapeutic potential, and is at least worthy of further
investigation.
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
management, but does not produce intolerable side effects.
However, there are challenges in establishing this optimal
dose in the advanced cancer patient population. One of
these is inter-patient variability, in keeping with results
from studies on narcotics and other prescription analgesics.
As optimal doses were found to vary from patient to
patient, physicians need to understand how to determine
the correct dosage when prescribing to a new patient. In
addition, advanced cancer patients are likely to present with
complex symptomologies that make it difcult to accurately
assess side effects derived from cannabis treatments, and
are often taking multiple concurrent medications. That
said, a number of these studies reported that observed side-
effects tended not to be treatment-limiting, and could be
controlled through dose titration, with pain relief in as little
administration of 2.7–10.8 mg THC in combination with
2.5–10.0 mg CBD (17). This highlights the importance
of establishing and validating a titration protocol that will
allow researchers to identify effective and tolerated dosages
in a safe and controlled manner.
Several studies presented in this review were underpowered
due to small sample sizes, with three out of the ve studies
reviewed enrolling less than 50 patients. Therefore, the
generalizability of the results may be limited, and future
studies on medical cannabis are warranted to establish its
efcacy and side effect prole in the cancer pain population.
This includes additional efforts to identify the efcacies of
specic cannabis compounds and their combinations, as well
as ideal methods of administration through the assessment
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© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2017apm.amegroups.com
of relevant endpoints. Subsequent clinical trials should also
consider the differences in cannabinoid pharmacokinetics
and pharmacodynamics among individuals. Moreover,
standardized and validated evaluation and reporting of
cannabis-associated side effects is warranted in order
to enable more accurate comparisons across studies.
Table 2 Summary of most common side effects
Most common side effects (reference),
number of patients Percentage of patients experiencing side effect in each treatment arm (%)
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
(all dose)
Placebo
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.
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Ultimately, this will contribute to the development of
clinical guidelines for the dosing and administration of
cannabis as a pain medication for the large population of
cancer patients in need of pain management, particularly
those for whom alternative analgesics are insufficient,
intolerable, or unsafe.
Conclusions
Current research shows that there is a potential role for
medical cannabis in cancer pain management. However,
the scale and quality of studies conducted to date are
somewhat limited (12). Therefore, further research is
needed to establish the efcacy of medical cannabis, either
as an alternative to opiates or as an adjunctive therapy, and
to identify the most appropriate methods of administration
to achieve optimal therapeutic efficacy with minimal side
effects.
Acknowledgements
We thank the generous support of Bratty Family Fund,
Michael and Karyn Goldstein Cancer Research Fund, Joey
and Mary Furfari Cancer Research Fund, Pulenzas Cancer
Research Fund, Joseph and Silvana Melara Cancer Research
Fund, and Ofelia Cancer Research Fund. This study was
conducted in collaboration with MedReleaf.
Footnote
Conicts of Interest: The authors have no conicts of interest
to declare.
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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. doi: 10.21037/apm.2017.08.05
... Em pacientes oncológicos, a dor neuropática está relacionada diretamente com a neoplasia em 60 a 90% dos casos, em decorrência da invasão ou da compressão de estruturas orgânicas, e em 5 a 20% dos casos, a dor oncológica está relacionada ao tratamento (radioterapia, neuropatia pós-quimioterapia, pósoperatório) e apenas em 3 a 10% dos casos, esta dor não tem relação com a malignidade [6] . Além disso, aproximadamente 5 a 10% dos sobreviventes do câncer, após o tratamento, permanecem com dor crônica severa que interfere significativamente em suas funções orgânicas e sociais [6] . ...
... Em pacientes oncológicos, a dor neuropática está relacionada diretamente com a neoplasia em 60 a 90% dos casos, em decorrência da invasão ou da compressão de estruturas orgânicas, e em 5 a 20% dos casos, a dor oncológica está relacionada ao tratamento (radioterapia, neuropatia pós-quimioterapia, pósoperatório) e apenas em 3 a 10% dos casos, esta dor não tem relação com a malignidade [6] . Além disso, aproximadamente 5 a 10% dos sobreviventes do câncer, após o tratamento, permanecem com dor crônica severa que interfere significativamente em suas funções orgânicas e sociais [6] . ...
... Esse avanço propiciou a descoberta do sistema "canabinérgico" endógeno, posteriormente denominado de sistema endocanabinoide (SEC) ou canabinoide endógeno. Diversas evidências clínicas e experimentais vêm sugerindo a participação do SEC na modulação da dor [6] . ...
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A dor oncológica configura-se como uma problemática atual de alta prevalência e difícil manejo. Logo, na busca por novas perspectivas para o alívio dos níveis álgicos de pacientes oncológicos, o uso da Cannabis surge como uma alternativa terapêutica. Diante disso, objetivou-se destacar, neste estudo, o potencial farmacológico da planta Cannabis sativa L. (cannabaceae) no tratamento da dor oncológica. Assim, realizou-se uma revisão da literatura através das bases de dados: SciELO, LILACS, Science direct e PubMed, considerando trabalhos publicados entre 2007 e 2020. Após a aplicação dos critérios de inclusão e exclusão, 25 artigos foram selecionados. Observa-se que a potencialidade farmacológica da Cannabis sativa está ligada ao grande número de substâncias químicas presentes em sua composição, sendo a principal classe denominada canabinoides. Tais compostos possuem inúmeras propriedades biológicas, como atividade antiemética, neuroprotetora, anti-inflamatória e anticâncer, podendo ser benéfica no tratamento da dor oncológica e distúrbios psíquicos. Atualmente, há um medicamento em uso clínico derivado dos canabinoides, sendo utilizado para aliviar algias oncológicas, porém encontra-se limitado ao Canadá.
... Other reports based on clinical trials conducted to date suggest considering cannabinoids, both CBD and THC, as a potential therapeutic option and adjuvant therapy in chronic, neuropathic and cancer pain management, highlighting they are relatively safe and rarely cause severe adverse effects [27,29,30,34,[37][38][39][40][41]. Cannabinoids show a moderate analgesic effect in patients with neuropathic pain, which is weaker than that of tricyclic antidepressants (TCA), but stronger than that of selective serotonin reuptake inhibitors (SSRI) and gabapentin [24,25]. ...
... As a result, the use of cannabis has been clinically evaluated in the treatment of a number of illnesses such as glaucoma, depression, anxiety, Alzheimer's disease, MS, and alleviation of symptoms of HIV/AIDS and cancer [4,88]. Of the aforementioned illnesses, CBD has been shown to have benefits in anxiety-related disorders and Alzheimer's disease, as well as the alleviation of pain in HIV/AIDS and cancer [5,16,[89][90][91][92]. ...
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PurposePrior research studies have shown that the endocannabinoid system, influenced by CBD and THC, plays a role in bone remodeling. As both the research on cannabis and use of cannabis continue to grow, novel medicinal uses of both its constituents as well as the whole plant are being discovered. This review examines the role of cannabinoids on osteoporosis, more specifically, the endocannabinoid system and its role in bone remodeling and the involvement of the cannabinoid receptors 1 and 2 in bone health, as well as the effects of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and synthetic cannabinoids on bone.MethodsA comprehensive literature search of online databases including PUBMED was utilized.ResultsA total of 29 studies investigating the effects of cannabis and/or its constituents as well as the activation or inactivation of cannabinoid receptors 1 and 2 were included and discussed.Conclusion While many of the mechanisms are still not yet fully understood, both preclinical and clinical studies show that the effects of cannabis mediated through the endocannabinoid system may prove to be an effective treatment option for individuals with osteoporosis.
... In recreational users of cannabis, coughing fits, anxiety and paranoia were the most common adverse reactions [28]. In the clinical trial setting, oral, gastrointestinal, or sublingual administered cannabis, was associated with nausea, fatigue, vertigo/hallucinations, diarrhea, constipation, and dry mouth [29][30][31][32][33]. In our study, the administration of a nanoparticle water soluble cannabis-based medicine resulted in mild drowsiness, fatigue, and nausea. ...
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This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h −1 (1.1, 6.6) and 0.65 ng mL.h −1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.
... Furthermore, there is an increasing body of literature supporting the use of various cannabis-based medicinal products (CBMPs) to treat cancer-related pain. A helpful summary can be found here (Blake et al., 2017). ...
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A 49-year-old woman was diagnosed with an ER + , PR-, HER2 + , BRCA- invasive ductal carcinoma which progressed metastatically to include bone, liver, and lymph node involvement. Standardised care included a 26-month treatment period with targeted chemotherapy and a ketogenic diet. The patient also began a course of cannabinoid-based therapy, consisting initially of a titrated high-dose protocol of mixed cannabidiol (CBD) and d9-tetrahydrocannabinol (THC) chemotypes, as well as psilocybin-assisted psychotherapy at macro and intermittent micro-doses. At the end of the five-month treatment period PET/CT investigations revealed no evidence of metastatic disease and chemotherapy was withdrawn. A one year follow up CT investigation concluded no evidence of residual or recurrent disease. A recurrence of disease was noted at 18 months follow up. Over these 18 months the cannabis regimen was titrated down to 60% of the initial protocol. This was subsequently increased to the initial dosing protocol following detection of recurrent disease and this titration occurred over a 10-month period where it remained stable. 16 months following the detection of recurrence of disease, favourable results were observed in the patient with evidence of receding cancer progression. Over the last 15 years there has been a considerable body of in-vitro and in-vivo evidence supporting the anti-neoplastic properties of cannabinoids and more recently psychedelics. Indeed, growing anecdotal and real-world evidence is reported of the therapeutic effect of cannabinoids and psychedelics in reducing both tumour proliferation and aiding as a palliative medicine to treat pain and psychological distress associated with cancer and chemotherapy. The data presented here indicate the potential therapeutic utility of such adjunctive pharmacological interventions in an individual with metastatic breast cancer.
... También existe literatura para el tratamiento del dolor oncológico con cannabis medicinal (17,18), así como también en menor medida para tratar el dolor asociado con la fibromialgia y el dolor de origen reumático (19). ...
... In fact, although being considered as an neuropathic pain, current pharmacological treatments for this condition (tricyclic antidepressants, anticonvulsants, etc.) are slightly effective in CIPN or have undesirable reactions (Hou et al., 2018), such as dizziness, nausea, somnolence and vomiting (Lee et al., 2021). Therefore, identifying alternative classes of analgesics that can effectively manage pain in cancer patients is of great importance (Blake et al., 2017). ...
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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition.
... En 2017 se publicó una revisión de estudios clínicos comparativos, desde pequeños estudios piloto conducidos en 1975 a ensayos clínicos aleatorizados de 2014, que evaluaban la eficacia de terapias basadas en cannabis con THC y CBD en reducir el dolor asociado al cáncer (13). Esta revisión de la literatura encontró únicamente 5 estudios que evaluaban cápsulas de aceite de THC, espráis oromucosos de THC:CBD (nabiximol) o espráis oromucosos de THC en el control del dolor oncológico. ...
Article
Background The use of medical cannabis has rapidly increased among cancer patients worldwide. Cannabis is often administered concomitantly with cancer medications, including immune checkpoint inhibitors (ICIs). As the cannabinoid receptors are abundantly expressed and modulate immune cells, it has been hypothesized that cannabis may attenuate the activity of ICIs. We aimed to assess the effect of cannabis on ICIs' efficiency in NSCLC patients. Method The murine model of CT26 tumor-bearing mice treated with an anti-PD-1 antibody and Δ9-tetrahydrocannabinol (THC) was used to evaluate the interaction between THC and ICIs in vivo. Correlation between use of medical cannabis and clinical outcome was evaluated in a cohort of 201 consecutive metastatic NSCLC patients treated with monotherapy pembrolizumab as a first line treatment. Results Median overall survival (OS) of the mice receiving a control vehicle, tetrahydrocannabinol (THC), anti-PD-1 antibody, or their combination was 21, 24, 31, 54 days, respectively (p<0.05 for the combination treatment compared to a control vehicle), indicating that THC did not reduce efficacy of anti-PD-1 therapy. Of 201 NSCLC patients treated with first-line monotherapy pembrolizumab for metastatic disease, 102 (50.7%) patients received license for cannabis within the first month of treatment. Cannabis-treated patients were younger compared to the cannabis naïve patients (median age 68 vs.74, p=0.003), with female predominance (62, 60.8% vs. 34, 34.3%, p=0.002) and with more prevailing brain metastasis (15.7% vs. 5%, p=0.013). Similar distribution of histology, smoking status, ECOG and PDL1 expression was noted between the groups. Liver metastases were marginally significant (19.6% vs. 10.1%, p=0.058). The most common indication for cannabis was pain (71%) followed by loss of appetite (34.3%). Time to progression (TTP) was similar for cannabis-naïve and cannabis-treated patients (6.1 vs. 5.6 months, respectively, 95% confidence interval [CI], 0.82 to 1.38, p=0.386), while OS was numerically higher in the cannabis-naïve group (54.9 vs. 23.6 months,) but did not reach statistical significance (95% CI 0.99 to 2.51, p=0.08). In Multivariate analyses we did not identify cannabis use as an independent predictor factor for mortality. Conclusions Preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first line monotherapy for advanced NSCLC. The differences in OS can be most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting.
Chapter
Palliative care is an essential component of comprehensive cancer care. Palliative care is given concurrently with other disease‐modifying, life‐prolonging, and curative therapy. Palliative medicine specialists focus on helping patients and their families with a variety of care needs including symptom control, psychosocial support, physician–patient communication, addressing care goals in relation to the patient's condition, prognosis, values, and preferences, as well as with transitions in care. Cancer patients often experience significant symptom distress either from the illness itself or from the associated treatments. The beneficial effects of palliative care have been well documented. When integrated into early oncologic care, palliative care is associated with a significant improvement in quality of life, depression, and survival. As such, palliative care should be given throughout the trajectory of cancer care whether during early‐stage disease in which the focus is on cure or in more advanced disease when the focus is on maximizing quality of life. Currently, national and international organizations have clinical guidelines that recommend palliative care be routinely integrated into comprehensive cancer care.
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Depression and pain co-exist in almost 80% of patients and are associated with impaired health-related quality of life, often contributing to high mortality. However, the majority of patients who suffer from the comorbid depression and pain are not responsive to pharmacological treatments that address either pain or depression, making this comorbidity disorder a heavy burden on patients and society. In ancient times, this depression-pain comorbidity was treated using extracts of the Cannabis sativa plant, known now as marijuana and the mode of action of Δ9‑tetrahydrocannabinol, the active cannabinoid ingredient of marijuana, has only recently become known, with the identification of cannabinoid receptor type 1 (CB1) and CB2. Subsequent investigations led to the identification of endocannabinoids, anandamide and 2-arachidonoylglycerol, which exert cannabinomimetic effects through the CB1 and CB2 receptors, which are located on presynaptic membranes in the central nervous system and in peripheral tissues, respectively. These endocannabinoids are produced from membrane lipids and are lipohilic molecules that are synthesized on demand and are eliminated rapidly after their usage by hydrolyzing enzymes. Clinical studies revealed altered endocannabinoid signaling in patients with chronic pain. Considerable evidence suggested the involvement of the endocannabinoid system in eliciting potent effects on neurotransmission, neuroendocrine, and inflammatory processes, which are known to be deranged in depression and chronic pain. Several synthetic cannabinomimetic drugs are being developed to treat pain and depression. However, the precise mode of action of endocannabinoids on different targets in the body and whether their effects on pain and depression follow the same or different pathways, remains to be determined.
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Unlabelled: Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Significance statement: Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids.
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Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Twenty-eight databases from inception to April 2015. Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
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Introduction: Cancer pain is one of the most important symptoms of malignant disease, which has a major impact on the quality of life of cancer patients. Therefore, it needs to be treated appropriately after a careful assessment of the types and causes of pain. Areas covered: The mainstay of cancer pain management is systemic pharmacotherapy. This is, in principle, still based on the WHO guidelines initially published in 1986. Although these have been validated, they are not evidence-based. The principles are a stepladder approach using non-opioids, weak and then strong opioids. In addition, adjuvants can be added at any step to address specific situations such as bone or neuropathic pain. Patients, even if they are on long-acting opioids, need to be provided with immediate-release opioids for breakthrough pain. In case of inefficacy or severe adverse effects of one opioid, rotation to another opioid is recommended. Expert opinion: There is a major need for more and better randomized controlled trials in the setting of cancer pain as the lack of evidence is hampering the improvement of current treatment guidelines.
Article
Background: Pain is very common in patients with cancer. Opioid analgesics, including codeine, play a significant role in major guidelines on the management of cancer pain, particularly for mild to moderate pain. Codeine is widely available and inexpensive, which may make it a good choice, especially in low-resource settings. Its use is controversial, in part because codeine is not effective in a minority of patients who cannot convert it to its active metabolite (morphine), and also because of concerns about potential abuse, and safety in children. Objectives: To determine the efficacy and safety of codeine used alone or in combination with paracetamol for relieving cancer pain. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2014, Issue 2), MEDLINE and EMBASE from inception to 5 March 2014, supplemented by searches of clinical trial registries and screening of the reference lists of the identified studies and reviews in the field. Selection criteria: We sought randomised, double-blind, controlled trials using single or multiple doses of codeine, with or without paracetamol, for the treatment of cancer pain. Trials could have either parallel or cross-over design, with at least 10 participants per treatment group. Studies in children or adults reporting on any type, grade, and stage of cancer were eligible. We accepted any formulation, dosage regimen, and route of administration of codeine, and both placebo and active controls. Data collection and analysis: Two review authors independently read the titles and abstracts of all studies identified by the searches and excluded those that clearly did not meet the inclusion criteria. For the remaining studies, two authors read the full manuscripts and assessed them for inclusion. We resolved discrepancies between review authors by discussion. Included studies were described qualitatively, since no meta-analysis was possible because of the small amount of data identified, and clinical and methodological between-study heterogeneity. Main results: We included 15 studies including 721 participants with cancer pain due to diverse types of malignancy. All studies were performed on adults; there were no studies on children. The included studies were of adequate methodological quality, but all except for one were judged to be at a high risk of bias because of small study size, and six because of methods used to deal with missing data or high withdrawal rates. Three studies used a parallel group design; the remainder were cross-over trials in which there was an adequate washout period, but only one reported results for treatment periods separately.Twelve studies used codeine as a single agent and three combined it with paracetamol. Ten studies included a placebo arm, and 14 included one or more of 16 different active drug comparators or compared different routes of administration. Most studies investigated the effect of a single dose of medication, while five used treatment periods of one, seven or 21 days. Most studies used codeine at doses of 30 mg to 120 mg.There were insufficient data for any pooled analysis. Only two studies reported our preferred responder outcome of 'participants with at least 50% reduction in pain' and two reported 'participants with no worse than mild pain'. Eleven studies reported treatment group mean measures of pain intensity or pain relief; overall for these outcome measures, codeine or codeine plus paracetamol was numerically superior to placebo and equivalent to the active comparators.Adverse event reporting was poor: only two studies reported the number of participants with any adverse event specified by treatment group and only one reported the number of participants with any serious adverse event. In multiple-dose studies nausea, vomiting and constipation were common, with somnolence and dizziness frequent in the 21-day study. Withdrawal from the studies, where reported, was less than 10% except in two studies. There were three deaths, in all cases due to the underlying cancer. Authors' conclusions: We identified only a small amount of data in studies that were both randomised and double-blind. Studies were small, of short duration, and most had significant shortcomings in reporting. The available evidence indicates that codeine is more effective against cancer pain than placebo, but with increased risk of nausea, vomiting, and constipation. Uncertainty remains as to the magnitude and time-course of the analgesic effect and the safety and tolerability in longer-term use. There were no data for children.
Article
Background: Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. Methods: We evaluated antiallodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1 knockout (CB1KO), CB2 knockout (CB2KO), and wild-type (WT) mice. Comparisons were made with the prototypic classic cannabinoid Δ(9)-THC. We also explored the site and possible mechanism of action of AM1710. Results: Paclitaxel-induced mechanical and cold allodynia developed to an equivalent degree in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ(9)-THC suppressed established paclitaxel-induced allodynia in WT mice. In contrast to Δ(9)-THC, chronic administration of AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Antiallodynic efficacy of systemic administration of AM1710 was absent in CB2KO mice and WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal administration of AM1710 also attenuated paclitaxel-induced allodynia in WT mice, but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 antiallodynic efficacy. Finally, both acute and chronic administration of AM1710 decreased messenger RNA levels of tumor necrosis factor-α and monocyte chemoattractant protein 1 in lumbar spinal cord of paclitaxel-treated WT mice. Conclusions: Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects.
Article
This review examines evidence for psychological factors that affect pain across the cancer continuum from diagnosis through treatment and long-term survivorship or end of life. Evidence is convincing that emotional distress, depression, anxiety, uncertainty, and hopelessness interact with pain. Unrelieved pain can increase a desire for hastened death. Patients with cancer use many strategies to manage pain, with catastrophizing associated with increased pain and self-efficacy associated with lower pain reports. A variety of psychological and cognitive behavioral treatments can reduce pain severity and interference with function, as indicated in multiple meta-analyses and high-quality randomized controlled trials. Effective methods include education (with coping skills training), hypnosis, cognitive behavioral approaches, and relaxation with imagery. Exercise has been tested extensively in patients with cancer and long-term survivors, but few exercise studies have evaluated pain outcomes. In survivors post-treatment, yoga and hypnosis as well as exercise show promise for controlling pain. Although some of these treatments effectively reduce pain for patients with advanced disease, few have been tested in patients at the end of life. Given the clear indicators that psychological factors affect cancer pain and that psychological and behavioral treatments are effective in reducing varying types of pain for patients with active disease, these methods need further testing in cancer survivors post-treatment and in patients with end-stage disease. Multidisciplinary teams are essential in oncology settings to integrate analgesic care and expertise in psychological and behavioral interventions in standard care for symptom management, including pain.
Article
Context: Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life. Chemotherapeutic neuropathy responds poorly to conventional treatments, and there is an urgent medical need for new treatments. Recent preclinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy. Objectives: This was a pilot trial to begin to investigate a currently available cannabinoid agent, nabiximols (oral mucosal spray containing cannabinoids), in the treatment of chemotherapy-induced neuropathic pain. Methods: A randomized, placebo-controlled crossover pilot study was done in 16 patients with established chemotherapy-induced neuropathic pain. A 0-10 point numeric rating scale for pain intensity (NRS-PI) was used as the primary outcome measure. Results: When examining the whole group, there was no statistically significant difference between the treatment and the placebo groups on the NRS-PI. A responder analysis demonstrated that there were five participants who reported a two-point or greater reduction in pain that trended toward statistical significance and the number needed to treat was five. Conclusion: Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments. This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five "responders" (as compared with a decrease of 0.6 with placebo) and supports that it is worthwhile to study nabiximols in a full randomized, placebo-controlled trial of chemotherapy-induced neuropathic pain.
Article
Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.