CANNABINOIDS AND CANCER AGOSTO 2018

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1. Biochem Pharmacol. 2018 Aug

Cannabinoid pharmacology and therapy in gut disorders.

Uranga JA(1), Vera G(2), Abalo R(3).

Author information: 
(1)Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la
Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; Unidad Asociada
I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), 
Spain; Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo
Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Spain.
(2)Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la
Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; Unidad Asociada
I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), 
Spain; Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Spain;
Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar 
de Investigación y Tratamiento del Dolor (i+DOL), Spain.
(3)Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la
Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; Unidad Asociada
I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), 
Spain; Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Spain;
Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar 
de Investigación y Tratamiento del Dolor (i+DOL), Spain. Electronic address:
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Cannabis sp and their products (marijuana, hashish...), in addition to their
recreational, industrial and other uses, have a long history for their use as a
remedy for symptoms related with gastrointestinal diseases. After many reports
suggesting these beneficial effects, it was not surprising to discover that the
gastrointestinal tract expresses endogenous cannabinoids, their receptors, and
enzymes for their synthesis and degradation, comprising the so-called
endocannabinoid system. This system participates in the control of tissue
homeostasis and important intestinal functions like motor and sensory activity,
nausea, emesis, the maintenance of the epithelial barrier integrity, and the
correct cellular microenvironment. Thus, different cannabinoid-related
pharmacological agents may be useful to treat the main digestive pathologies. To 
name a few examples, in irritable bowel syndrome they may normalize dysmotility
and reduce pain, in inflammatory bowel disease they may decrease inflammation,
and in colorectal cancer, apart from alleviating some symptoms, they may play a
role in the regulation of the cell niche. This review summarizes the main recent 
findings on the role of cannabinoid receptors, their synthetic or natural ligands
and their metabolizing enzymes in normal gastrointestinal function and in
disorders including irritable bowel syndrome, inflammatory bowel disease, colon
cancer and gastrointestinal chemotherapy-induced adverse effects
(nausea/vomiting, constipation, diarrhea).

Copyright © 2018 Elsevier Inc. All rights reserved.


2. Biochem Pharmacol. 2018 Jul
Chronic pain and cannabinoids. great expectations or a christmas carol.

Pascual D(1), Sánchez-Robles EM(1), García MM(1), Goicoechea C(2).

Author information: 
(1)Farmacología y Nutrición. Facultad de Ciencias de la Salud, Universidad Rey
Juan Carlos, Spain; Grupo de Excelencia investigadora URJC-Banco de
Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor
(i+Dol), Spain; Unidad Asociada CSIC-IQM. Alcorcón, Spain.
(2)Farmacología y Nutrición. Facultad de Ciencias de la Salud, Universidad Rey
Juan Carlos, Spain; Grupo de Excelencia investigadora URJC-Banco de
Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor
(i+Dol), Spain; Unidad Asociada CSIC-IQM. Alcorcón, Spain. Electronic address:
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The discovery of the endocannabinoid system nearly three decades ago generated
great interest among pain scientists. Moreover, its analogy with the opioid
system in terms of evolutionary preservation, tissue localization and analgesic
activity enabled a vast new field for the development of medicines addressed to
those types of pain that still nowadays are difficult to manage. However, the
main disadvantage that hampers the use of cannabinergic drugs as analgesics is
their identification with recreational use, besides their psychotomimetic
actions. Pain has traditionally been classified attending to the ailment duration
(acute or chronic) and drugs are used according to the intensity of the pain to
treat, but it is also important to target the mechanism involved despite the
intensity or duration of pain. The present chapter reviews the study and use of
cannabinoids attending separately to four classic types of pain: nociceptive,
inflammatory, neuropathic and oncological, considering basic research (pain
animal models) as well as clinical practice.

Copyright © 2018 Elsevier Inc. All rights reserved.


3. Pediatr Blood Cancer. 2018 Jul
Safety and efficacy of nabilone for acute chemotherapy-induced vomiting
prophylaxis in pediatric patients: A multicenter, retrospective review.

Polito S(1), MacDonald T(2)(3), Romanick M(4)(5), Jupp J(4)(6), Wiernikowski
J(7), Vennettilli A(8), Khanna M(8), Patel P(9)(10), Ning W(10), Sung L(11)(12), 
Dupuis LL(8)(9)(10).

Author information: 
(1)Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, 
Canada.
(2)Department of Pharmacy, IWK Health Centre, Halifax, Nova Scotia, Canada.
(3)College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.
(4)Pharmacy Services, Alberta Health Services,, Edmonton, Alberta, Canada.
(5)Stollery Children's Hospital, Edmonton, Alberta, Canada.
(6)Alberta Children's Hospital, Calgary, Alberta, Canada.
(7)Department of Paediatrics, Faculty of Health Sciences, McMaster Children's
Hospital, McMaster University, Hamilton, Ontario, Canada.
(8)Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
(9)Department of Pharmacy, The Hospital for Sick Children, Toronto, Ontario,
Canada.
(10)Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario,
Canada.
(11)Research Institute and Department of Paediatrics, The Hospital for Sick
Children, Toronto, Ontario, Canada.
(12)Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

OBJECTIVES: To describe the safety and efficacy of nabilone given to pediatric
patients to prevent acute chemotherapy-induced nausea and vomiting (CINV).
METHODS: A multicenter, retrospective review of pediatric patients who received
nabilone for acute CINV prophylaxis between December 1, 2010 and August 1, 2015
was undertaken. One course of nabilone was evaluated per patient. Adverse effects
associated with nabilone use were noted. The proportion of patients who
experienced complete acute chemotherapy-induced vomiting (CIV) control during the
acute phase was determined. The acute phase was defined as starting with the
first chemotherapy dose and continuing until 24 h after administration of the
last chemotherapy dose of the chemotherapy block.
RESULTS: One hundred ten eligible patients (median age: 14.0 years, range:
1.1-18.0 years; 65 male) were identified. Most (109/110) received nabilone plus a
5-HT3 antagonist for CINV prophylaxis. Adverse effects associated with nabilone
were experienced by 34% (37/110) of children. All were of CTCAE Version 4.03
Grade 2 or less. Sedation (20.0%), dizziness (10.0%), and euphoria (3.6%) were
the most commonly reported adverse events. Nabilone was discontinued in 10
patients due to an adverse event. The proportions of patients receiving highly or
moderately emetogenic chemotherapy who experienced complete acute CIV control
were 50.6% (42/83) and 53.8% (14/26), respectively.
CONCLUSION: Adverse events associated with nabilone were common but of minor
clinical significance. Acute CIV control in children receiving nabilone as a part
of their antiemetic regimen was poor. Future work should focus on implementation 
of guideline-consistent CINV prophylaxis and treatment.

© 2018 Wiley Periodicals, Inc.


4. Chem Biol Interact. 2018 Jul

Therapeutic applications of cannabinoids.

Maurya N(1), Velmurugan BK(2).

Author information: 
(1)School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal,
India.
(2)Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City,
Vietnam. Electronic address: bharath.kumar.velmurugan@tdt.edu.vn.

The psychoactive property of cannabinoids is well known and there has been a
continuous controversy regarding the usage of these compounds for therapeutic
purposes all over the world. Their use for medical and research purposes are
restricted in various countries. However, their utility as medications should not
be overshadowed by its negative physiological activities. This review article is 
focused on the therapeutic potential and applications of phytocannabinoids and
endocannabinoids. We further highlights their mode of action, overall effects on 
physiology, various in vitro and in vivo studies that have been done so far and
the extent to which these compounds can be useful in different disease conditions
such as cancer, Alzheimer's disease, multiple sclerosis, pain, inflammation,
glaucoma and many others. Thus, this work is an attempt to make the readers
understand the positive implications of these compounds and indicates the
significant developments of utilizing cannabinoids as therapeutic agents.

Copyright © 2018 Elsevier B.V. All rights reserved.


5. Br J Pharmacol. 2018 Jul 17.

Anti-tumoural actions of cannabinoids.

Hinz B(1), Ramer R(1).

Author information: 
(1)Institute of Pharmacology and Toxicology, Rostock University Medical Center,
Schillingallee 70, D-18057, Rostock, Germany.

The endocannabinoid system has emerged as a considerable target for the treatment
of diverse diseases. In addition to the well-established palliative effects of
cannabinoids in cancer therapy, phytocannabinoids, synthetic cannabinoid
compounds as well as inhibitors of endocannabinoid degradation have attracted
attention as possible systemic anticancer drugs. As a matter of fact,
accumulating data from preclinical studies suggest cannabinoids elicit effects on
different levels of cancer progression, comprising inhibition of proliferation,
neovascularisation, invasion and chemoresistance, induction of apoptosis and
autophagy as well as enhancement of tumour immune surveillance. Although the
clinical use of cannabinoid receptor ligands is limited by their psychoactivity, 
nonpsychoactive compounds, such as cannabidiol, have gained attention due to
preclinically established anticancer properties and a favourable risk-to-benefit 
profile. Thus, cannabinoids may complement the currently used collection of
chemotherapeutics, as a broadly diversified option for cancer treatment, while
counteracting some of their severe side effects.

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