Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain
Director of Research The Harry R Horvitz Center for Palliative Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, R35, Cleveland OH 44195, USA. Expert Opinion on Investigational Drugs
(Impact Factor: 5.53).
02/2008; 17(1):85-95. DOI: 10.1517/135437184.108.40.206
Nabilone has been approved to treat chemotherapy-induced nausea and vomiting. Recent studies have explored cannabinoids in pain management.
To review the evidence for the use of cannabinoids in general and nabilone in particular; i) in managing chemotherapy-induced nausea and vomiting; and ii) in treating pain.
A systematic review of published English literature used the terms: cancer, cannabinoid, nabilone, nausea, pain, tetrahydrocannabinol and vomiting as search terms. Reviews, meta-analyses and treatment trials were reviewed.
Nabilone is superior to placebo, domperidone and prochlorperazine but not metoclopramide or chlorpromazine. Cannabinoids do not add to benefits of 5-HT(3) receptor antagonists. Side effects are greater for nabilone than for prochlorperazine, in most studies patients prefered nabilone over prochlorperazine. Nabilone is ineffective in acute pain but benefits in neuropathic pain and central hypersensitization. Recent guidelines place nabilone as a second to fourth line drug for neuropathic pain.
Available from: Annette Conzelmann
- "The eCB system is involved in various psychiatric disorders , such as mood disorders, addiction, pain, and anxiety disorders (Monteleone et al. 2009; Parolaro et al. 2010; Sipe et al. 2002). FAAH inhibitors are promising pharmacological agents in the treatment of pain and anxiety without drugseeking side effects (Davis 2008). Accordingly, this study contributes to an area of substantial interest for the development of psychological and psychopharmacological treatments and asks for further research to clarify the bidirectionality of the eCB system's influence on emotion processing. "
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ABSTRACT: RATIONALE: The endocannabinoid (eCB) system is implicated in several psychiatric disorders. Investigating emotional-motivational dysfunctions as underlying mechanisms, a study in humans revealed that in the C385A polymorphism of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the eCB anandamide (AEA), A carriers, who are characterized by increased signaling of AEA as compared to C/C carriers, exhibited reduced brain reactivity towards unpleasant faces and enhanced reactivity towards reward. However, the association of eCB system with emotional-motivational reactivity is complex and bidirectional due to upcoming compensatory processes. OBJECTIVES: Therefore, we further investigated the relationship of the FAAH polymorphism and emotional-motivational reactivity in humans. METHODS: We assessed the affect-modulated startle, and ratings of valence and arousal in response to higher arousing pleasant, neutral, and unpleasant pictures in 67 FAAH C385A C/C carriers and 45 A carriers. RESULTS: Contrarily to the previous functional MRI study, A carriers compared to C/C carriers exhibited an increased startle potentiation and therefore emotional responsiveness towards unpleasant picture stimuli and reduced startle inhibition indicating reduced emotional reactivity in response to pleasant pictures, while both groups did not differ in ratings of arousal and valence. CONCLUSIONS: Our findings emphasize the bidirectionality and thorough examination of the eCB system's impact on emotional reactivity as a central endophenotype underlying various psychiatric disorders.
Available from: Iwan Dwiprahasto
- "Nabilone as anti-emetic was superior to placebo, domperidone and prochlorperazine in preventing CINV, but not superior not metoclopramide or chlorpromazine. Nabilone also did not increase the benefit of 5-HTRAs as anti-emetic in CINV .The use of cannabinoids and olanzapine have been suggested as potentially useful interventions, but data from phase III clinical trials are still lacking . "
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ABSTRACT: Nausea and vomiting are the most distressful side effects of cytotoxic drugs in cancer patients. Antiemetics are commonly used to reduce these side effects. However, the current antiemetic efficacy is about 70-80% in patients treated with highly-emetogenic cytotoxic drugs. One of the potential factors explaining this suboptimal response is variability in genes encoding enzymes and proteins which play a role in metabolism, transport and receptors related to antiemetic drugs. Aim of this review was to describe the pharmacology and pharmacogenetic concepts of of antiemetics in oncology.
Pharmacogenetic and pharmacology studies of antiemetics in oncology published between January 1997 and February 2010 were searched in PubMed. Furthermore, related textbooks were also used for exploring the pharmacology of antiemetic drugs. The antiemetic drugs which were searched were the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs), dopamine antagonists, corticosteroids, benzodiazepines, cannabinoids, antihistamines and neurokinin-1 antagonists.
The 5-HT3RAs are widely used in highly emetogenic chemotherapy in combination with dexamethasone and a neurokinin-1 antagonist, especially in acute phase. However, the dopamine antagonists and benzodiazepines were found more appropriate for use in breakthrough and anticipatory symptoms or in preventing the delayed phase of chemotherapy induced nausea and vomiting. The use of cannabinoids and antihistamines need further investigation. Only six articles on pharmacogenetics of the 5-HT3RAs in highly emetogenic chemotherapy are published. Specifically, these studies investigated the association of the efficacy of 5-HT3RAs and variants in the multi drug resistance 1 (MDR1) gene, 5-HT3A,B and C receptor genes and CYP2D6 gene. The pharmacogenetic studies of the other antiemetics were not found in this review.
It is concluded that pharmacogenetic studies with antiemetics are sparse. It is too early to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice: confirmation of early findings is required.
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ABSTRACT: Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as antiemetic, appetite modulating, and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. As opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis-based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.
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