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

August 2008
Journal of Palliative Medicine 11(6):929-34

DOI:10.1089/jpm.2008.9880

Source
PubMed

Authors:

University of Toronto

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.

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JOURNAL OF PALLIATIVE MEDICINE

Volume 11, Number 6, 2008

DOI: 10.1089/jpm.2008.9880

Nabilone for the Treatment of Paraneoplastic Night Sweats:

A Report of Four Cases

VINCENT MAIDA, M.D., B.Sc., ABHPM

ABSTRACT

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.

929

INTRODUCTION

ATIENTS WITH ADVANCED STAGES

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).

Similarly,

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.

Al-

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

cluster.

7,8

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-

fects.

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

corticosteroids.

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-

tients.

5,10

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,

nabilone.

METHODS

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-

tients.

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-

ness.

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.

RESULTS

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-

enon.

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-

MAIDA

930

ABLE

1. C

HARACTERISTICS OF

ATIENTS WITH

ARANEOPLASTIC

IGHT

WEATS

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,

osteoporosis

#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 (p0.03; 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 (p0.01; Fig. 2). None of the patients expe-

rienced any significant burden of side effects from the

addition of nabilone.

DISCUSSION

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).

10,13

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.

14–17

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-

MAIDA

932

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 (p0.03, 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

antagonist.

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.

Nabilone

has also been shown to reduce prostaglandin induced

inflammation in a rat model via agonism of CB2 re-

ceptors.

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.

SUMMARY

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-

NABILONE FOR THE TREATMENT OF PARANEOPLASTIC NIGHT SWEATS 933

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 (p0.01, t-test).

uated through prospective, randomized, controlled

trials.

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Jul 2021

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.

Skin Symptoms

Chapter

Apr 2019

Palliative Performance Scale (PPS): A new tool

Article

Full-text available

Feb 1996

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.

Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: A double-blind placebo-controlled crossover trial

Article

Jan 2006

Nabilone: An Effective Antiemetic in Patients Receiving Cancer Chemotherapy

Article

Aug 1981
J CLIN PHARMACOL

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.

Nutzen einer Add-On-Therapie mit dem synthetischen Cannabinomimetikum Nabilone bei Patienten mit chronischen Schmerzzuständen – eine randomisierte kontrollierte Studie

Article

Jun 2006

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.

Superiority of Nabilone over Prochlorperazine as an Antiemetic in Patients Receiving Cancer Chemotherapy

Article

Jul 1979

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: A potent antiemetic cannabinol with minimal euphoria

Article

Jan 1978
Biomedicine

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.

Nabilone: An effective antiemetic agent in patients receiving cancer chemotherapy

Article

Jan 1983
CANCER TREAT REV

L H Einhorn

Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton symptom assessment scale

Article

May 2000

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.

The Cannabinoid System and Cytokine Network

Article

Nov 2000

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.

The use of thalidomide in the management of severe sweating in patients with advanced malignany: Trial report

Article