Cannabinoid and Cancer / MARZO 2017

Cannabinoids and Cancer

1. Cancer Chemother Pharmacol. 2017

Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting. Pergolizzi JV Jr(1), Taylor R(1), LeQuang JA(2), Zampogna G(1), Raffa RB(3).

Author information:

(1)NEMA Research, Inc., 868 106th Ave North, Naples, FL, 34108, USA.

(2)NEMA Research, Inc., 868 106th Ave North, Naples, FL, 34108, USA.

(3)University of Arizona College of Pharmacy, Tucson, AZ, USA.

Chemotherapy-induced nausea and vomiting (CINV) is a prevalent, distressing, and burdensome side effect of cancer chemotherapy. It is estimated to affect the majority of patients receiving certain anti-cancer drug regimens and can be treatment-limiting, even for life-saving medications. Despite seemingly numerous options, such as antimuscarinic anticholinergics, antihistamines, 5-HT3 receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists, preventative therapies are often inadequately effective, particularly for "delayed CINV"-leaving an important unmet clinical need.
Cannabinoid receptor agonists, by virtue of their unique mechanism of action and efficacy and safety data reported in clinical trials, appear to offer a useful additional option. The mechanistic value of cannabinoids has been well known for many years, but these agents may have been underutilized in the past because of the notoriety and legal status of marijuana. While botanical marijuana contains nearly 500 components, including the psychoactive tetrahydrocannabinol (THC), nabilone is an established, single-entity synthetic cannabinoid receptor agonist that has become the focus of renewed interest. We review the basic pharmacology and clinical trial data of nabilone for use in prophylaxis and treatment of CINV.


2. J Chromatogr B Analyt Technol Biomed Life Sci. 2017

Ultra-high performance liquid chromatography tandem mass-spectrometry for simple and simultaneous quantification of cannabinoids. Jamwal R(1), Topletz AR(2), Ramratnam B(3), Akhlaghi F(4).

Author information:

(1)Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, United States.

(2)Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, United States; COBRE Center for Cancer Research Development and Lifespan Clinical Research Centre, Rhode Island Hospital, Brown University, Providence, RI, United States.

(3)COBRE Center for Cancer Research Development and Lifespan Clinical Research Centre, Rhode Island Hospital, Brown University, Providence, RI, United States.

(4)Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, United States.

Cannabis is used widely in the United States, both recreationally and for medical purposes. Current methods for analysis of cannabinoids in human biological specimens rely on complex extraction process and lengthy analysis time. We established a rapid and simple assay for quantification of Δ(9)-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-hydroxy Δ(9)-tetrahydrocannabinol (11-OH THC) and 11-nor-9-carboxy-Δ(9)-tetrahydrocannbinol (THCCOOH) in human plasma by U-HPLC-MS/MS usingΔ9-tetrahydrocannabinol-D3 (THC-D3) as the internal standard. Chromatographic separation was achieved on an Acquity BEH C18 column using a gradient comprising of water (0.1% formic acid) and methanol (0.1% formic acid) over a 6 min run-time. Analytes from 200μL plasma were extracted using acetonitrile (containing 1% formic acid and THC-D3). Mass spectrometry was performed in positive ionization mode, and total ion chromatogram was used for quantification of analytes. The assay was validated according to guidelines set forth by Food and Drug Administration of the United States. An eight-point calibration curve was fitted with quadratic regression (r(2)>0.99) from 1.56 to 100ngmL(-1) and a lower limit of quantification (LLOQ) of 1.56ngmL(-1) was achieved. Accuracy and precision calculated from six calibration curves was between 85-115% while the mean extraction recovery was >90% for all the analytes. Several plasma phospholipids eluted after the analytes thus did not interfere with the assay. Bench-top, freeze-thaw, auto-sampler and short-term stability ranged from 92.7 to 106.8% of nominal values. Application of the method was evaluated by quantification of analytes in human plasma from six subjects. Copyright © 2017 Elsevier B.V. All rights reserved.


3. J Clin Pharm Ther. 2017

Cannabidiol: an alternative therapeutic agent for oral mucositis? Cuba LF(1,)(2), Salum FG(1), Cherubini K(1), Figueiredo MA(1). Author information:

(1)Division of Oral Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

(2)Division of Oral Medicine, Paranaense University (UNIPAR), Francisco Beltrão, Brazil. WHAT IS KNOWN AND OBJECTIVE: Chemo- and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects. Oral mucositis is especially of concern, due to the morbidity that it causes. We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis. METHODS: We searched the PubMed database and selected complete articles published in English that met the inclusion criteria for the period 1998-2016. The search terms 'cannabinoids', 'cannabidiol', 'oxidative stress', 'antioxidants' and 'oral mucositis' were used. RESULTS AND DISCUSSION: The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, anti-inflammatory and analgesic properties. WHAT IS NEW AND CONCLUSIONS: The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stress-mediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged. © 2017 John Wiley & Sons Ltd.


4. J Transl Int Med. 2016

Corticosteroids, the oldest agent in the prevention of chemotherapy-induced nausea and vomiting: What about the guidelines? Van Ryckeghem F(1).

Author information:

(1)Department of Medical Oncology, Ghent University Hospital, Belgium. Chemotherapy-induced nausea and vomiting (CINV) remains one of the most disturbing side effects of cancer treatment. Research in antiemetic therapy has progressed gradually since the early eighties, and the development of antiemetic agents continues. This review focuses on the current management of CINV based on the most recent guidelines, and adherence to the latter is examined more carefully. Setrons (5HT3 receptor antagonists), corticosteroids, and NK-1 receptor antagonists are the cornerstones of antiemetic therapy. Corticosteroids are one of the oldest agents in the prevention of CINV. They are highly effective, increase the effect of other antiemetic agents, and are cost-effective. The latest developed 5HT3 receptor antagonist palonosetron led to an update of the guidelines of CINV. Other types include benzodiazepines, cannabinoids, and olanzapine.
Various factors contribute to the overall risk of developing CINV, such as patient characteristics, emetogenic potency of the chemotherapeutic agents, and correct prevention of CINV. Current guidelines determine which is the right preventive regimen for each cancer patient at risk for experiencing CINV. Adherence to these guidelines and implementation in daily practice seem to be below the optimal level.
In Belgium, authorities use the guidelines as a base for reimbursement and this has increased the level of implementation.


5. Front Mol Neurosci. 2017 Jan 24;10:14. doi: 10.3389/fnmol.2017.00014. eCollection 2017. Modulation of Human Peripheral Blood Mononuclear Cell Signaling by Medicinal Cannabinoids. Utomo WK(1), de Vries M(2), Braat H(1), Bruno MJ(1), Parikh K(3), Comalada M(4), Peppelenbosch MP(1), van Goor H(2), Fuhler GM(1).

Author information:

(1)Department of Gastroenterology and Hepatology, Erasmus MC, Erasmus University of Rotterdam Rotterdam, Netherlands.

(2)Department of Surgery, Radboud University Medical Center Nijmegen, Netherlands.

(3)Department of Cell Biology, University Medical Center Groningen Groningen, Netherlands.

(4)Institute for Research in Biomedicine Barcelona, Spain. Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis.
However, the mechanistic aspects and properties of cannabis remain remarkably poorly characterized.
In this study we aimed to investigate the immune-cell modulatory properties of medical cannabis. Healthy volunteers were asked to ingest medical cannabis, and kinome profiling was used to generate comprehensive descriptions of the cannabis challenge on inflammatory signal transduction in the peripheral blood of these volunteers.

Results were related to both short term and long term effects in patients experimentally treated with a medical marijuana preparation for suffering from abdominal pain as a result of chronic pancreatitis or other causes. The results reveal an immunosuppressive effect of cannabinoid preparations via deactivation of signaling through the pro-inflammatory p38 MAP kinase and mTOR pathways and a concomitant deactivation of the pro-mitogenic ERK pathway.
However, long term cannabis exposure in two patients resulted in reversal of this effect. While these data provide a powerful mechanistic rationale for the clinical use of medical marijuana in inflammatory and oncological disease, caution may be advised with sustained use of such preparations.