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Nabilone for the Treatment of Paraneoplastic Night Sweats: A Report of Four Cases



ABSTRACT Night sweats are one of many symptoms experienced by patients with advanced cancer. The prevalence of night sweats ranges from 10%-48% in cancer patients. Persistent night sweats tend to decrease quality of life through interference with sleep. A recent study has demonstrated that night sweats occur as part of a symptom pattern, and are associated with the anorexia-cachexia symptom cluster. In addition, night sweats represent one of the symptoms that displays a tendency not to improve as patients with advanced cancer approach end of life. This paper serves to report on the successful management of four patients suffering from persistent paraneoplastic night sweats using the synthetic orally administered cannabinoid nabilone. The four patients had been referred to a regional consultative palliative medicine program and identified night sweats as one of their most significant symptomatic concerns reported on their Edmonton Symptom Assessment System (ESAS) questionnaires.
Volume 11, Number 6, 2008
© Mary Ann Liebert, Inc.
DOI: 10.1089/jpm.2008.9880
Nabilone for the Treatment of Paraneoplastic Night Sweats:
A Report of Four Cases
Night sweats are one of many symptoms experienced by patients with advanced cancer. The preva-
lence of night sweats ranges from 10%–48% in cancer patients. Persistent night sweats tend to de-
crease quality of life through interference with sleep. A recent study has demonstrated that night
sweats occur as part of a symptom pattern, and are associated with the anorexia–cachexia symp-
tom cluster. In addition, night sweats represent one of the symptoms that displays a tendency not
to improve as patients with advanced cancer approach end of life. This paper serves to report on
the successful management of four patients suffering from persistent paraneoplastic night sweats
using the synthetic orally administered cannabinoid nabilone. The four patients had been referred
to a regional consultative palliative medicine program and identified night sweats as one of their
most significant symptomatic concerns reported on their Edmonton Symptom Assessment System
(ESAS) questionnaires.
of cancer suffer
from a multitude of symptoms. Night sweats oc-
cur in 10% to 14% of patients with advanced-stage
cancer as a result of disease progression.
In patients
with Hodgkin’s lymphoma, night sweats, which per-
sist with fluctuating fevers for weeks in some patients,
may be the only presenting symptom.
A retrospective
study among 63 patients with metastatic hormone-re-
sistant prostate cancer identified night sweats, along
with fever, back pain, and fatigue, as common signs
of systemic inflammatory syndrome (SIS).
in patients with liver metastases, night sweats were re-
ported as a symptom in 48%.
The differential diag-
nosis of night sweats in cancer patients includes in-
fection (pneumonia, tuberculosis, endocarditis, urinary
tract infection, etc), drugs (allergic or hypersensitivity
reactions), graft-versus-host-disease (GVHD), hor-
monal withdrawal, and paraneoplastic syndromes.
Night sweats are capable of reducing the quality of life
of cancer patients through interference with sleep.
terations in sleep patterns are associated with daytime
fatigue, hypersomnolence, and depression, and de-
creased functional capacity.
In addition, night sweats
are associated with the anorexia–cachexia symptom
Tsai et al.
reported that night sweats are part of a
symptom pattern in patients with advanced cancer that
displays a tendency to remain static and eventually de-
teriorate as patients approach end of life. This suggests
that treatments to date have been largely ineffective in
the management of night sweats. Numerous therapies
have been used to treat night sweats such as selective
serotonin reuptake inhibitors, -adrenergic agonists, -
blockers, antidopaminergic agents, soy phytoestrogens,
Division of Palliative Medicine, William Osler Health Centre, University of Toronto, Toronto, Canada.
Case Discussions
in Palliative Medicine
Feature Editor: James Hallenbeck
vitamin E, and thalidomide.
Yet, the use of these
agents is limited by lack of efficacy and/or side ef-
In a small proportion of cases, early sympto-
matic relief may be achieved with the use of nonste-
roidal anti-inflammatory drugs (NSAID) and/or
Emerging data suggest the cannabi-
noids, which are approved in the United States for the
treatment of refractory chemotherapy-induced nausea
and vomiting and appetite stimulation in patients with
acquired immune deficiency syndrome (AIDS), and
for the treatment of neuropathic pain in patients with
multiple sclerosis in Canada, may be effective in the
polysymptom management of advanced cancer pa-
The following describes a case series of four
patients with advanced-stage cancer who were suffer-
ing from paraneoplastic night sweats and successfully
treated, “off-label,” with the synthetic cannabinoid,
All four patients were referred to a specialist out-
patient consultative palliative medicine program that
serves a population of over 750,000 in the northwest
quadrant of Toronto, Canada. None of the patients
were being considered for further attempts with dis-
ease-modulating therapies as their advanced disease
states and co-morbidities precluded such options. In
addition, all patients expressed the wish for their care
to be focused strictly on comfort and dignity measures,
to be achieved exclusively through pain and symptom
management. All patients were found to be mentally
competent at baseline and provided informed consent
for an empiric trial of “off-label” cannabinoid therapy.
They completed the Edmonton Symptom Assessment
System (ESAS) questionnaire on initial consultation
and at 48-hour intervals thereafter. The ESAS, a 10-
item, patient- or caregiver-rated, validated tool, was
developed to assess symptoms in palliative care pa-
The severity of the symptoms is rated on an
11-point scale where 0 indicates absence of the symp-
tom and 10 reflects worst possible severity. The tenth
item on the ESAS is “other,” where patients can cite
a symptom not on the questionnaire that is particularly
bothersome. The four patients in this case series re-
ported night sweats as being their most bothersome
“other” symptom. Their overall performance status
was assessed using the Palliative Performance Scale,
version 2 (PPSv2). This tool measures a patient’s over-
all performance status through the composite evalua-
tion of ambulation, activity level, self-care capacity,
evidence of disease, intake, and level of conscious-
Performance is scored as a percentage in 10%-
step increments from 0% to 100%, and a lower score
indicates greater impairment in performance and func-
tion. Data were analalyzed using MS Windows based
SAS 9.1 software (SAS Institute, Cary, NC). Com-
parisons were made using the Student’s ttest. The
study protocol was approved by the hospital’s research
ethics board.
Three of the four patients were men, and all were
older than age 66 years (Table 1). Two patients had
non-Hodgkin’s lymphoma, one had acute lymphocytic
leukemia, and one suffered from gastrointestinal stro-
mal tumor (GIST). Despite advanced-stage disease and
several comorbidities, three of the four patients dem-
onstrated relatively good performance and function-
ing, as reflected by a PPSv2 score of 60% or higher.
At baseline, all patients underwent a medical work-up
that included blood cultures, hemogram, biochemical
profile, urinalysis, urine culture, chest radiograph, and
abdominal ultrasound. None of the patients presented
with clinical or laboratory evidence to suggest infec-
tion or febrile neutropenia. None of their concurrent
medications were known to cause night sweats. There-
fore, through a process of exclusion it was concluded
that their night sweats were a paraneoplastic phenom-
All patients reported experiencing night sweats for at
least 2 weeks prior to referral. Patient 1 and patient 4 had
reported experiencing low-grade elevated oral tempera-
tures between 37°C and 38°C. Both patients experienced
a normalization of their oral temperatures with nabilone
therapy. Unfortunately, consistent serial temperature
measurements were not documented during the follow-
up period. Two patients (patients 1 and 3) reported no
improvement with the NSAID, ibuprofen (400–800
mg/d), while two patients (patients 2 and 4) reported no
improvement with the NSAID naproxen (250–750
mg/d). All NSAID agents were used for at least 7 to 10
days and were discontinued prior to the baseline assess-
ment. Patient 2 was prescribed prednisone 5 mg daily 4
weeks prior to baseline, and patient 3 began taking pred-
nisone 10 mg daily 2 weeks prior to baseline. Both pa-
tients 2 and 3 continued with their original dosage of
prednisone during the follow-up period. Three of the pa-
tients had hepatosplenomegaly, while the fourth had liver
metastases. Three of the patients displayed lymphade-
nopathy in the periphery, abdomen, or mediastinum.
All patients were prescribed nabilone on the date of
their initial (baseline) assessment. Two patients (pa-
1. C
Age at referral PPSv2 at Nabilone
Patient Gender (yrs) Primary diagnosis Medical history Current co-morbidities referral Concomitant medications dosage
#1 F 93 Metastatic Vertebral compression, fracture, Anemia, CHF, diabetes, COPD, liver 65 hydromorphone, 1 mg qhs
Gastrointestinal hypertension, hyperlipidemia, metastases, RP adenopathy, DVT lorazepam,
Stromal Tumour hypothyroidism, CVA, OA, oxycodone,
(GIST) depression, right shoulder rotator heparin
cuff tear, vertigo, hysterectomy,
cholecytectomy, appendectomy,
#2 M 66 Non-Hodgkin’s Appendectomy, tonsillectomy, Chronic lymphocytic leukemia, 70 prednisone, 1 mg qhs
lymphoma peptic ulcer disease thrombocytopenia, mediastinal nodes, hydromorphone,
peripheral adenopathy, pleural lorazepam,
effusion, chronic renal failure, oxycodone
hepatosplenomegaly, RP adenopathy
#3 M 82 Non-Hodgkin’s Hernia surgery, TURP, hypertension, Acute leukemia, diabetes, anemia, RP 60 prednisone, 1 mg bid
lymphoma OA, hyperlipidemia, blunt facial adenopathy, mesenteric adenopathy, hydromorphone,
trauma, hypothyroidism, varicose pleural effusions, hepatosplenomegaly, lorazepam,
veins mediastinal adenopathy oxycodone
#4 M 78 Acute lymphocytic Left knee injury, CABG, gout, OA CAD, COPD, diabetes, 40 lorazepam, 1 mg bid
leukemia hepatosplenomegaly morphine sulfate
Laboratory results
Patient Uh (g/L) WBC (10
/L) Platelets (10
/L) ESR (mm/hr) CRP (mg/L) Albumin (g/L)
#1 93 7.7 387 127 52.7 25
#2 109 4.1 9 67 47 23
#3 95 11 22 40 4 37
#4 86 1.6 41 24 38 38
CABG, coronary artery bypass grafting; CAD, coronary artery disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; CVA,
cardiovascular accident; DVT, deep venous thrombosis; ESR, erythrocyte sedimentation rate; GIST, gastrointestinal tumor; Hb, hemoglobin; OA, osteoarthritis; PPSv2, Palliative Perfor-
mance Scale, version 2; RP, retroperitoneal; TURP, transurethral resection of the prostate; WBC, white blood cell.
tients 1 and 2) were prescribed nabilone at a dose of
1 mg, taken at bedtime, while the other two (patients
3 and 4) were given nabilone at a dose of 1 mg twice
daily. Patients 3 and 4 were prescribed a higher
nabilone dosage because of their reported high levels
of pain, nausea, and anorexia. All patients reported im-
provement within 48 hours of initiating therapy with
nabilone. At 48 hours after baseline, there was an av-
erage 5.00 (2.58) point decrease in their ESAS score
pertaining to night sweats (p0.03; Fig. 1). At 14
days after baseline, there was an average 5.75 (2.65)
point decrease in their ESAS score pertaining to night
sweats (p0.01; Fig. 2). None of the patients expe-
rienced any significant burden of side effects from the
addition of nabilone.
Treatment of four patients with advanced cancer
with the synthetic orally administered cannabinoid,
nabilone, resulted in the successful management of
persistent symptomatic paraneoplastic night sweats.
This is evidenced by statistically significant reductions
in their ESAS scores pertaining to the “other” symp-
tom that they identified as night sweats. The im-
provement occurred within 48 hours of initiating ther-
apy and demonstrated further improvement after 2
weeks. The limitations of this study include the small
sample size, lack of a control group, and possible
placebo effect.
Nabilone, a synthetic analogue of -9-tetrahydroxy-
cannabinol (
-THC), is a potent agonist at cannabi-
noid receptors (CB1 and CB2).
It has demon-
strated efficacy in reducing spasticity-related pain and
chronic pain, and decreasing the frequency of vomit-
ing and lessening the severity of nausea associated
with chemotherapy.
The significant reduction in
the severity of night sweats experienced by the four
patients described herein suggests nabilone may offer
additional benefits to patients with cancer.
Given their association with the anorexia–cachexia
syndrome, it is postulated that paraneoplastic night
sweats are also caused by pro-inflammatory cytokines
such as tumor necrosis factor-(TNF-) , interleukin-
1 (IL-1), IL-6, and prostaglandins secreted both by
cancer cells and inflammatory cells.
In one study of
patients with prostate cancer with SIS, IL-6 was ele-
vated, which is a common finding in patients with hor-
mone-refractory disease.
The cannabinoid ligand,
anandamide, modulates the production of IL-6, as well
as cellular responses to IL-6.
Cannabinoids have
demonstrated anticytokine activity in a number of an-
imal models.
An additional mechanism for the ob-
FIG. 1. Reduction in nights sweats in cancer patients receiving nabilone at 48 hours after baseline. The mean baseline
Edmonton Symptom Assessment System (ESAS) score for night sweats in four cancer patients was 7.75 (0.50). At 48 hours
after baseline, the mean score was 2.75 (2.50), a mean change of 5.00 (2.58) from baseline (p0.03, t-test).
served reduction in night sweats may relate to the abil-
ity of cannabinoids to produce relative hypothermia
via CB1 agonism. Investigators showed that adminis-
tration of
-THC induced hypothermia in mice, an
effect that was reversed by the administration of a CB1
Although many patients with cancer ex-
perience nocturnal fevers in conjunction with their
night sweats, only two of four patients in this case se-
ries reported having fevers on a subjective basis. It is
also interesting to note that hepatosplenomegaly
and/or adenopathy was present in all four patients in
the case series. CB2 receptors are found in greatest
density in the spleen, as well as in the liver, lymph
nodes, white blood cells, and mast cells.
has also been shown to reduce prostaglandin induced
inflammation in a rat model via agonism of CB2 re-
The interrelationship among these factors,
as well as others, might explain, at least in part, the
effects of nabilone on paraneoplastic night sweats in
the four patients described.
Paraneoplastic night sweats are a relatively preva-
lent symptom experienced by advanced cancer pa-
tients. They are part of a symptom pattern that tends
to deteriorate as patients approach end of life. This
symptom is also associated with the anorexia–cachexia
symptom cluster. Night sweats may impact negatively
on the functional capacity and quality of life of af-
fected patients. Beyond disease-modulating therapies,
few effective palliative modalities are available to
manage symptoms such as paraneoplastic night
sweats. The significant and rapid reduction in parane-
oplastic night sweats in a case series of four advanced
cancer patients referred for palliative care might have
important implications in regards to managing this
symptom in patients with earlier stages of their ma-
lignancies. Further research is needed to elucidate their
exact mechanism of action in this context. In addition,
validation of the efficacy of nabilone should be eval-
FIG. 2. Reduction in nights sweats in cancer patients receiving nabilone at 14 days after baseline. The mean baseline Edmon-
ton Symptom Assessment System (ESAS) score for night sweats in four cancer patients was 7.75 (0.50). At 14 days after base-
line, the mean score was 2.00 (2.00), a mean change of 5.75 (2.65) from baseline (p0.01, t-test).
uated through prospective, randomized, controlled
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... These night sweats result in physical and emotional fatigue, depression, and reduced function, promoting a vicious cycle associated with the anorexia-cachexia syndrome that often afflicts cancer patients. [1][2][3][4] Hot flashes affect 50-85% of menopausal women, 5 with an incidence of 65-85% in breast cancer patients due to antiestrogen therapies. 6 An association between night sweats and sleep disruptions, including awakenings for pain, has been reported in male patients. ...
... 1,2 Regardless of etiology, these symptoms present a key problem in treatment of this population based on both their prevalence and disruption of quality of life. 1 Various treatments have been proposed and studied to address night sweats. Traditional treatment options include both hormonal and non-hormonal pharmacotherapies, as well as integrative therapies such as cognitive-based therapy, yoga, acupuncture, and relaxation techniques. ...
... 20 Some studies support the use of nabilone, a synthetic analogue of 9tetrahydroxycannabinol (9-THC), in the treatment of night sweats in cancer patients as well. 1 Nabilone is an agonist at CB1 and CB2 receptors that has been used outside the United States for the treatment of hot flushes in cancer patients. Cannabinoids have been shown to modulate cytokine activity as well as produce hypothermia in mouse models, and it is possible that nabilone is effective in mitigating night sweats by these methods. 1 However, since nabilone is unavailable in the United States, dronabinol should be investigated as a potential candidate for palliation of night sweats because it is available and works by a similar mechanism. ...
Background: Night sweats significantly impact the quality of life for cancer patients and are often resistant to treatment. Cannabinoids have been shown to modulate cytokine activity and produce hypothermia in animal models, suggesting that they may be a promising candidate for palliation of night sweats in patients with oncologic disease. Objective: Assess efficacy of the oral cannabinoid, dronabinol, for palliation of night sweats in cancer patients. Design: A retrospective record search identified five cancer patients who had tried oral dronabinol for palliation of their night sweats between 2013 and 2016 and subjectively reported on its efficacy. Setting/Subjects: A convenience sample of five patients from the outpatient consultative palliative medicine program at Stanford Medical Center was chosen from a search of past records. Patients were included if they had a cancer diagnosis and complained of night sweats that subjectively interfered with their quality of life. All agreed to try oral dronabinol for palliation of their night sweats. Measurements: Patients self-reported the effect of oral synthetic dronabinol on their night sweats. Results: Treatment of five patients with advanced cancer with synthetic orally administered dronabinol resulted in the successful management of persistent symptomatic paraneoplastic night sweats. Conclusion: Dronabinol and/or medicinal cannabis are promising therapies for palliation of night sweats in cancer patients.
... CBM was prescribed BID either THC:CBD (2.4 mg:1 mg) or THC (2.5 mg) for cancer-related anorexia [31]. Nabilone (Cesamet®) was dosed between 2 and 4 mg QD for quality of life measures [33,45]. Bedrocan® was dosed at 1 g, infused as a tea in 200 ml of water QD to investigate potential interaction with anticancer drugs [29]. ...
... CBM THC:CBD or CBD only was scheduled before lunch and dinner, with milk for cancerrelated anorexia [31]. For quality of life including management of nocturnal hyperhidrosis, nabilone (Cesamet®) was scheduled before bed for the hypothesised management of hyperhidrosis associated with cancer or scheduled once a day before the first radiotherapy treatment [33,45]. The CBM Bedrocan® was prescribed once daily, in the evening for drug interactions study [29]. ...
Full-text available
Purpose This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology. Methods A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology. Results Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified. Conclusions There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.
... Although numerous sources outside of evidence-based medicine report on the treatment of excessive sweating with cannabinoids (10), there is an acute lack of clinical studies corroborating this effect, as we have found. In some palliative patients, cannabinoids, such as nabilone and dronabinol, were effective in reducing paraneoplastic night sweats and improving patient quality of life (11,12). To consolidate the literature, we conducted this scientific investigation of cannabinoids therapy in a case of therapy-refractive primary hyperhidrosis. ...
Full-text available
Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids. We found a remarkable reduction in the volume of sweat and an improvement to the patient's quality of life using this novel low-cost and low-impact approach.
... The second important objective of our study was to determine possible factors associated with the prevalence of each orphan symptom. Sweating is controlled by a center in the preoptic and anterior regions of the hypothalamus where thermosensitive neurons are located and may be influenced by various factors, such as infection, hormonal withdrawal, endocrine disorders, lymphoma, carcinoid syndrome, and drugs including withdrawal [6,16,24]. In our study, sweating was associated with opioid use, especially morphine. ...
Full-text available
Purpose The aims of this study were to examine the prevalence of myoclonus, sweating, pruritus, hiccup, and vesical and rectal tenesmus, and to explore associated factors in patients with advanced cancer. Methods This multicenter prospective cohort study was conducted in 23 inpatient hospices/palliative care units in Japan from January to December 2017. The prevalence and characteristics of each symptom were assessed on admission and in the 3 days before death. We selected factors that might influence the occurrence of each symptom and investigated the association. Results A total of 1896 patients were enrolled. The prevalence of orphan symptoms rose from admission to the 3 days before death: myoclonus 1.3 to 5.3% (95% CI 0.9–1.9%/4.3–6.5%), sweating 1.8 to 4.1% (95% CI 1.3–2.6%/3.1–5.1%), hiccup 1.1 to 1.8% (95% CI 0.7–1.7%/1.2–2.6%), and tenesmus 0.7 to 0.9% (0.4–1.2%/0.5–1.5%). Prevalence of pruritus fell from 3.5 to 2.5% (95% CI 2.7–4.4%/1.8–3.4%). Sweating, pruritus, and hiccups persisted throughout the day in nearly half of the patients. Myoclonus was significantly associated with brain tumors, sweating with opioids and antipsychotics, pruritus with liver and biliary tract cancer, cholestasis and severe diabetes, hiccup with male gender, digestive tract obstruction, severe diabetes, and renal failure. Vesical tenesmus was associated with urinary cancer, antipsychotics, and anticholinergics and rectal tenesmus with pelvic cavity cancer. Conclusion We found that orphan symptoms occurred in 0.5–5.0% of patients, increased over time except for pruritus, and persisted in half of the patients.
Context : Palliative care aims to improve the quality of life (QoL) in patients with incurable illness. Medicinal cannabis (MC) has been used in the palliative care setting to address multiple symptoms in patients. Objectives : To evaluate the full scope of available literature investigating the effects and potential harms of MC on symptom management and QoL in palliative care. Methods : PubMed, Embase, The Cochrane Library and were searched for eligible articles, published between 1960 and September 09, 2021. Quality of the evidence was assessed in accordance with Grading of Recommendations, Assessment, Development and Evaluations. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials and the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for non-randomized trials. Results : Fifty-two studies (20 randomised; 32 non-randomised) with 4786 participants diagnosed with cancer (n=4491), dementia (n=43), AIDS (n=235), spasticity (n=16), NORSE syndrome (n=1) were included. The quality of evidence was ‘very low’ or ‘low’ for all studies, and low for only two RCTs. Positive treatment effects (statistical significance with P<0.05) were seen for some MC products in pain, nausea and vomiting, appetite, sleep, fatigue, chemosensory perception and paraneoplastic night sweats in patients with cancer, appetite and agitation in patients with dementia and appetite, nausea and vomiting in patients with AIDS. Meta-analysis was unable to be performed due to the wide range of cannabis products used and the heterogeneity of the study outcomes. Conclusion : While positive treatment effects have been reported for some MC products in the palliative care setting, further high quality evidence is needed to support recommendations for its use in clinical practice.
Background and objective: Although cannabinoid-based medications are increasingly used by older adults, their safety and tolerability in this age group remain unclear. The purpose of this systematic review was to examine the safety and tolerability of cannabinoid-based medications by conducting a meta-analysis of open-label observational studies of cannabinoid-based medications for all indications in individuals with a mean age of ≥50 years. Methods: A systematic search was conducted on PubMed, PsycINFO, MEDLINE, EMBASE and CINHAL. Study quality was assessed using an adapted version of the Grading of Recommendations Assessment, Development and Evaluation criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. We included studies that (a) were published from 1990 onwards; (b) included older adults (mean age ≥50 years); and (c) provided data on the safety and tolerability of medical cannabinoids. Data were pooled using a random-effects approach. Risk of adverse events, serious adverse events and withdrawals was computed as the incidence rate (IR). Separate analyses were conducted by the cannabinoid-based medication used, for delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and a combination of THC and CBD (THC:CBD). Results: Thirty-eight studies were identified (THC = 23; CBD = 6; THC:CBD = 9; N = 2341, mean age: 63.19 ± 8.08 years, men: 53.86%). THC had a very low incidence of all-cause and treatment-related adverse events (IR: 122.18, 95% confidence interval [CI] 38.23-253.56; IR: 84.76, 95% CI 0.13-326.01, respectively) and negligible serious adverse events (IR = 0). Similar IRs for CBD (all cause, IR: 111.91, 95% CI 1.24-495.93; treatment related, IR: 1.76, 95% CI 4.63-23.05) and no serious adverse events (IR = 0). CBD was not associated with a risk of treatment-related withdrawals. THC had a low risk of all-cause and treatment-related withdrawals (IR: 25.18, 95% CI 12.35-42.52; IR: 7.83, 95% CI 3.26-14.38, respectively). The THC:CBD treatment had a low risk of all-cause and treatment-related adverse events (IR: 100.72, 95% CI 0.25-383.00; IR: 55.38, 95% CI 8.61-142.80, respectively), but reported a risk of all-cause and treatment-related serious adverse events (IR: 21.32, 95% CI 0.18-93.26; IR: 3.71, 95% CI 0.21-11.56, respectively), and all-cause and treatment-related withdrawals (IR: 78.63, 95% CI 17.43-183.90; IR: 34.31, 95% CI 6.09-85.52, respectively). Significant heterogeneity (I2 >55%) was present in most analyses. Conclusions: Although cannabinoid-based medications were generally safe and acceptable to adults aged over 50 years, these estimates are limited by the lack of a control condition and considerable heterogeneity. Nevertheless, they complement and are consistent with comparable evidence from randomised controlled trials.
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The Palliative Performance Scale (PPS), a modification of the Karnofsky Performance Scale, is presented as a new tool for measurement of physical status in palliative care. Its initial uses in Victoria include communication, analysis of home nursing care workload, profiling admissions and discharges to the hospice unit, and, possibly, prognostication. We assessed 119 patients at home, of whom 87 (73%) had a PPS rating between 40% and 70%. Of 213 patients admitted to the hospice unit, 175 (83%) were PPS 20%-50% on admission. The average period until death for 129 patients who died on the unit was 1.88 days at 10% PPS upon admission, 2.62 days at 20%, 6.70 days at 30%, 10.30 days at 40%, 13.87 days at 50%. Only two patients at 60% or higher died in the unit. The PPS may become a basis for comparing drug costs at home and for studying the effects of treatments (e.g. hypodermoclysis) at various levels of physical performance. Validity and reliability testing are currently being undertaken.
Eighty evaluable patients receiving chemotherapy were entered on a random prospective double-blind study to evaluate the effectiveness of nabilone, a synthetic cannabinoid, compared to prochlorperazine. Most of these patients received cisplatin, a drug that universally produces severe nausea and vomiting, as part of a combination chemotherapy regimen. The patients served as their own controls, receiving either nabilone or prochlorperazine during two consecutive treatment courses with the identical chemotherapy. Side effects consisting of hypotension and lethargy were more pronounced with nabilone. Toxicity, in general, did not preclude antiemetic treatment and in no way interfered with chemotherapy. Sixty patients (75 per cent) reported nabilone to be more effective than prochlorperazine for relief of nausea and vomiting. Of these 60 patients, 46 required further chemotherapy and continued taking nabilone as the antiemetic of choice.
RATIONALE: Ziel der Studie war die Überprüfung der Wirksamkeit und Sinnhaftigkeit einer Add-On-Therapie mit dem synthetischen Cannabinomimetikum Nabilone bei Patienten mit chronischen Schmerzzuständen. Dabei standen die Evaluierung des Therapieeinflusses auf Schmerzzustand und Lebensqualität sowie die subjektive Abwägung von Wirkungen und Nebenwirkungen durch die Studienteilnehmer im Vordergrund. METHODEN: Die Placebo-kontrollierte doppelblinde Pilotstudie gliederte sich in einen 14-wöchigen Cross-Over-Abschnitt (2-mal 4-wöchige Medikationsphasen plus Wash-Out-Phasen) und einen anschließenden 16-wöchigen Medikations-Switch-Abschnitt mit freier Wahl der als Präparat A und Präparat B bekannten Prüfmedikation durch die Studienteilnehmer. Vorrangiges Einschlusskriterium waren chronische therapierefraktäre Schmerzzustände in kausalem Zusammenhang mit pathologischen Zuständen des Stütz- und Bewegungsapparates. Die Studienteilnehmer bestimmten die Prüfpräparat-Dosierung (zwischen 1 und 4 Kapseln/Tag, entspricht bei Nabilone ¼–1 mg/Tag) selbst. Schmerzintensitäten wurden mittels einer visuellen Analogskala (VAS), die Lebensqualität mittels des QOL-Scores von Mezzich & Cohen erhoben. ERGEBNISSE: Insgesamt wurden 30 Patienten in die Studie aufgenommen und ausgewertet. Die Ergebnisse zeigten im Cross-Over-Abschnitt durchwegs Vorteile der Nabilone-Therapie (Mediane [Quartile]: Nabilone/Placebo): Verringerung der durchschnittlichen Wirbelsäulen (WS)-Schmerzintensität in den letzten 4 Wochen (ΔVAS) 0,9 [0,0; 2,0] / 0,5 [0,0; 1,7], Verringerung der aktuellen WS-Schmerzintensität (ΔVAS) 0,6 [0,0; 2,5] / 0,0 [−1,0; 1,0] (p = 0,006), Verringerung der durchschnittlichen Kopfschmerzintensität in den letzten 4 Wochen (ΔVAS) 1,0 [−1,0; 2,4] / 0,2 [−0,9; 1,0], Erhöhung der Anzahl an kopfschmerzfreien Tagen in den letzten 4 Wochen 2,0 [0,0; 6,5] / 0,0 [−5,0; 4,0], Verbesserung der Lebensqualität (ΔQOL-Score) 5,0 [0,8; 10,8] / 2,0 [−2,3; 8,0]. Im Medikations-Switch-Abschnitt wurde eine mehrheitliche Nabilone-Einnahme (≥85% aller Medikationstage) von mehr als viermal so vielen Studienteilnehmern gewählt wie eine mehrheitliche Placebo-Einnahme. Die Anzahl der Tage mit Nabilone-Einnahme war klar höher als jene mit Placebo-Einnahme (Mediane: 89% vs. 11% aller Medikationstage, p = 0,003). SCHLUSSFOLGERUNGEN: Insgesamt lassen die Studienergebnisse den Schluss zu, dass die Nabilone-Einnahme zusätzlich zur Standardtherapie von einer Mehrheit an Patienten mit chronischen Schmerzzuständen als eine Maßnahme mit positiver individueller Nutzen-Risiko-Relation gesehen wird und somit eine interessante und attraktive Bereicherung des analgetischen Behandlungskonzepts darstellen kann. OBJECTIVE: The aim of this study was to investigate the efficacy and efficiency of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain. Of major interest were the evaluation of the influence the treatment had on pain and on quality of life as well as the subjective assessment of positive effects and side effects by the study participants. METHODS: The placebo-controlled double-blinded pilot study was divided into a 14 week cross-over period (two 4 week medication phases plus wash-out phases) followed by a 16 week medication switch period with free choice of the study drugs (drug A and drug B) by the study participants. The principal inclusion criterion was chronic therapy-resistant pain in causal relationship with a pathologic status of the skeletal and locomotor system. The study participants chose the dosage of the study drug themselves (between 1 und 4 capsules/day, in the case of nabilone this corresponds to ¼–1 mg/day). Pain intensity was assessed by a visual analogue scale (VAS), quality of life by the Mezzich & Cohen QOL-score. RESULTS: Altogether, 30 patients were included and analyzed. From the results, it is obvious that throughout the cross-over periods the nabilone treatment was superior (medians [25%-; 75%-percentiles]: nabilone/placebo): decrease of the average spinal pain intensity within the last 4 weeks (ΔVAS) 0.9 [0.0; 2.0] / 0.5 [0.0; 1.7], decrease of the current spinal pain intensity (ΔVAS) 0.6 [0.0; 2.5] / 0.0 [−1.0, 1.0] (p = .006), decrease of the average headache intensity within the last 4 weeks (ΔVAS) 1.0 [−1.0; 2.4] / 0.2 [−0.9; 1.0], increase of the number of days without headache within the last 4 weeks 2.0 [0.0; 6.5] / 0.0 [−5.0; 4.0], increase of the quality of life (ΔQOL-Score) 5.0 [0.8; 10.8] / 2.0 [−2.3; 8.0]. In the medication switch period, the number of study participants who favoured nabilone (nabilone intake ≥85% of all medication days) was more than 4 times higher than those who favoured placebo. The number of days with nabilone intake was clearly higher than the number with placebo intake (medians: 89% vs. 11% of all medication days, p = .003). CONCLUSION: In summary, the study results allow the conclusion that a majority of patients with chronic pain classify nabilone intake in addition to the standard treatment as a measure with a positive individual benefit-riskratio. Thus, this kind of treatment may be an interesting and attractive enrichment of analgetic therapy concepts.
Two double-blind, crossover trials comparing the antiemetic effectiveness of nabilone, a new synthetic cannabinoid, with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy. Of 113 patients evaluated, 90 (80 per cent) responded to nabilone therapy, whereas only 36 (32 per cent) responded to prochlorperazine (P less than 0.001). Complete relief of symptoms was infrequent, occurring only in nine patients (8 per cent) given nabilone. When both drugs were compared, both nausea (P less than 0.01) and vomiting episodes (P less than 0.001) were significantly lower in patients given nabilone. Moreover, patients clearly favored nabilone for continued use (P less than 0.001). Predominant side effects noted by patients were similar for both agents and included somnolence, dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone. In addition, four patients (3 per cent) taking nabilone had side effects (hallucinations in three, hypotension in one) that required medical attention. Euphoria associated with nabilone was infrequent (16 per cent) and mild.
Nabilone is a cannabinol derivative which has potent central antiemetic effects in animals. We observed that the drug significantly reduced the nausea and vomiting induced by cancer chemotherapy in 10 of 13 patients who were refractory to conventional antiemetics. A dose-response effect was apparent. The drug was generally well-tolerated, although it also had sedative effects. Additionally, dizziness, decreased coordination and postural hypotension were observed in some patients. Euphoric effects of the agent were minimal at antiemetic dosage levels.
Eighty evaluable patients receiving chemotherapy were entered on a random prospective double-blind study to evaluate the effectiveness of nabilone, a synthetic cannabinoid, compared to prochlorperazine. Most of these patients received cisplatin, a drug that universally produces severe nausea and vomiting, as part of a combination chemotherapy regimen. The patients served as their own controls, receiving either nabilone or prochlorperazine during two consecutive treatment courses with the identical chemotherapy. Side effects consisting of hypotension and lethargy were more pronounced with nabilone. Toxicity, in general, did not preclude antiemetic treatment and in no way interfered with chemotherapy. Sixty patients (75 per cent) reported nabilone to be more effective than prochlorperazine for relief of nausea and vomiting. Of these 60 patients, 46 required further chemotherapy and continued taking nabilone as the antiemetic of choice.
The Edmonton Symptom Assessment Scale (ESAS) is a nine-item patient-rated symptom visual analogue scale developed for use in assessing the symptoms of patients receiving palliative care. The purpose of this study was to validate the ESAS in a different population of patients. In this prospective study, 240 patients with a diagnosis of cancer completed the ESAS, the Memorial Symptom Assessment Scale (MSAS), and the Functional Assessment Cancer Therapy (FACT) survey, and also had their Karnofsky performance status (KPS) assessed. An additional 42 patients participated in a test-retest study. The ESAS "distress" score correlated most closely with physical symptom subscales in the FACT and the MSAS and with KPS. The ESAS individual item and summary scores showed good internal consistency and correlated appropriately with corresponding measures from the FACT and MSAS instruments. Individual items between the instruments correlated well. Pain ratings in the ESAS, MSAS, and FACT correlated best with the "worst-pain" item of the Brief Pain Inventory (BPI). Test-retest evaluation showed very good correlation at 2 days and a somewhat smaller but significant correlation at 1 week. A 30-mm visual analogue scale cutoff point did not uniformly distinguish severity of symptoms for different symptoms. For this population, the ESAS was a valid instrument; test-retest validity was better at 2 days than at 1 week. The ESAS "distress" score tends to reflect physical well-being. The use of a 30-mm cutoff point on visual analogue scales to identify severe symptoms may not always apply to symptoms other than pain.
Many advances have been made in the last few years concerning our understanding of the receptors and ligands composing the cannabinoid system. Likewise, the science surrounding cytokine biology has advanced enabling us to measure these proteins more precisely as well as understand and interpret the meaning of changes in their levels. Scientists wishing to study the health consequences of smoking marijuana as well as understand the possible role of endogenous cannabimimetic ligands in immune regulation have continued to study the influence of these substances on the regulation and development of the cytokine network. Research has shown that two major cannabinoid receptor subtypes exist and that subtype 1 (CB1) is expressed primarily in the brain whereas subtype 2 (CB2) is expressed primarily in the periphery. A variety of ligands for these receptors based on the cannabinoid structure have been synthesized and studied as well as low affinity compounds, noncannabinoid ligands, and endogenous ligands derived from fatty acid eicosanoids. Highly selective receptor antagonists have also been introduced and studied. Synthetic, low affinity ligands such as (+)-HU-211 and DMH-11C have been shown to cause anti-inflammatory effects possibly through inhibiting the production and action of TNF-alpha and other acute phase cytokines. In addition, suppression of TNF and other cytokines such as GM-CSF, IL-6, IFNgamma, and IL-12 has also been seen following exposure to high affinity and psychoactive ligands such as marijuana and THC. However, some of these ligands have also been shown to increase rather than decrease interleukins such as IL-1, IL-4, IL-10, and IL-6, cytokines such as TNF-alpha, and chemokines such as IL-8, MIP-1, and RANTES. The endogenous ligand, anandamide, has been shown in culture to either suppress the proliferation response to prolactin or enhance the response to cytokines such as IL-3 and IL-6. This eicosanoid has also been shown to increase the production of interleukins and other cytokines. Cannabinoid receptors have been shown to be involved in some but not all of these effects. It is clear that psychoactive and nonpsychoactive compounds have demonstrated effects in vivo and in vitro on the production and function of a variety of cytokines. Depending upon the model system, these effects are often conflicting, and the involvement of cannabinoid receptors is unclear. However, enough evidence exists to suggest that the cannabinoid system significantly impacts the functioning of the cytokine network, and this association may provide clues to the mechanisms of certain immune diseases and form the basis for new immunotherapies.