Cannabinoid and Cancer / Septiembre 2016

Cannabis is the most widely smoked illicit substance in the world. It can be smoked alone in its plant form, marijuana, but it can also be mixed with tobacco. The specific effects of smoking cannabis are difficult to assess accurately and to distinguish from the effects of tobacco; however its use may produce severe consequences.

Cannabinoid and Cancer

1. Damaging Effects of Cannabis Use on the Lungs.

Yayan J(1), Rasche K(2).

> Author information:

(1)Department of Internal Medicine, Division of Pulmonary, Allergy, and Sleep Medicine, HELIOS Clinic Wuppertal, Witten/Herdecke University, Heusner 40, 42283, Wuppertal, Germany. .

(2)Department of Internal Medicine, Division of Pulmonary, Allergy, and Sleep Medicine, HELIOS Clinic Wuppertal, Witten/Herdecke University, Heusner 40, 42283, Wuppertal, Germany.

Cannabis is the most widely smoked illicit substance in the world. It can be smoked alone in its plant form, marijuana, but it can also be mixed with tobacco. The specific effects of smoking cannabis are difficult to assess accurately and to distinguish from the effects of tobacco; however its use may produce severe consequences. Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, and hyperinflation. It can also cause serious lung diseases with increasing years of use.
Cannabis can weaken the immune system, leading to pneumonia. Smoking cannabis has been further linked with symptoms of chronic bronchitis. Heavy use of cannabis on its own can cause airway obstruction. Based on immuno-histopathological and epidemiological evidence, smoking cannabis poses a potential risk for developing lung cancer. At present, however, the association between smoking cannabis and the development of lung cancer is not decisive.

2. Am J Physiol Gastrointest Liver Physiol. Endocannabinoids in the gut.

Lee Y(1), Jo J(1), Chung HY(2), Pothoulakis C(3), Im E(4).

> Author information:

(1)Pusan National University.

(2)College of pharmacy, Pusan national university.

(3)David Geffen School of Medicine at UCLA. (4)Pusan National University

The endocannabinoid system mainly consists of endogenously produced cannabinoids (endocannabinoids) and two G protein-coupled receptors (GPCRs), cannabinoid receptors 1 and 2 (CB1 and CB2). This system also includes enzymes responsible for the synthesis and degradation of endocannabinoids and molecules required for the uptake and transport of endocannabinoids. In addition, endocannabinoid-related lipid mediators and other putative endocannabinoid receptors, such as transient receptor potential channels and other GPCRs have been identified. Accumulating evidence indicates that the endocannabinoid system is a key modulator of gastrointestinal physiology, influencing satiety, emesis, immune function, mucosal integrity, motility, secretion, and visceral sensation.

In light of therapeutic benefits of herbal and synthetic cannabinoids, the vast potential of the endocannabinoid system for the treatment of gastrointestinal diseases has been demonstrated. This review focuses on the role of the endocannabinoid system in gut homeostasis and in the pathogenesis of intestinal disorders associated with intestinal motility, inflammation and cancer. Finally, links between gut microorganisms and the endocannabinoid system are briefly discussed.

Copyright © 2015, American Journal of Physiology-Gastrointestinal and Liver Physiology.

3. Ann Otol Rhinol Laryngol. 

Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial.

Côté M(1), Trudel M(2), Wang C(3), Fortin A(4).


> Author information:

(1)Department of Otolaryngology, Head and Neck Surgery, CHU de Québec, Quebec City, QC, Canada Faculty of Medicine, Laval University, Quebec City, QC, Canada. 

(2)Department of Otolaryngology, Head and Neck Surgery, CHU de Québec, Quebec City, QC, Canada Faculty of Medicine, Laval University, Quebec City, QC, Canada

(3)Department of Radiation Oncology, CHU de Sherbrooke, QC, Canada. (4)Faculty of Medicine, Laval University, Quebec City, QC, Canada Department of Radiation Oncology, CHU de Québec, QC, Canada.

OBJECTIVES: Patients treated for head and neck carcinomas experience a significant deterioration of their quality of life during treatments because of severe side effects. Nabilone has many properties that could alleviate symptoms caused by radiotherapy and improve patients' quality of life. The aim of the present study was to compare the effects of nabilone versus placebo on the quality of life and side effects during radiotherapy for head and neck carcinomas.

METHODS: Fifty-six patients were randomized to nabilone or placebo. Patients filled the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H&N35; three independent questionnaires assessing appetite, nausea, and toxicity; and a visual analog scale for pain. These data were collected before radiotherapy, each week during radiotherapy, and 4 weeks after radiotherapy. Patients were weighed every week. 

RESULTS: Nabilone did not lengthen the time necessary for a 15% deterioration of quality of life (P = .4279), and it was not better than placebo for relieving symptoms like pain (P = .6048), nausea (P = .7105), loss of appetite (P = .3295), weight (P = .1454), mood (P = .3214), and sleep (P = .4438).

CONCLUSION: At the dosage used, nabilone was not potent enough to improve the patients' quality of life over placebo.


4. J Leukoc Biol. 

Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors.

Staiano RI(1), Loffredo S(1), Borriello F(1), Iannotti FA(1), Piscitelli F(1), Orlando P(1), Secondo A(1), Granata F(1), Lepore MT(1), Fiorelli A(1), Varricchi G(1), Santini M(1), Triggiani M(1), Di Marzo V(2), Marone G(2).

> Author information:

(1)Departments of *Translational Medical Sciences and Center for Basic and Clinical Immunology Research and Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy; Endocannabinoid Research Group, Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Naples, Italy; Thoracic Surgery Unit, Second University of Naples, Naples, Italy; Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy; and Consiglio Nazionale delle Ricerche Institute of Experimental Endocrinology and Oncology "G. Salvatore," Naples, Italy.

(2)Departments of *Translational Medical Sciences and Center for Basic and Clinical Immunology Research and Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy; Endocannabinoid Research Group, Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Naples, Italy; Thoracic Surgery Unit, Second University of Naples, Naples, Italy; Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy; and Consiglio Nazionale delle Ricerche Institute of Experimental Endocrinology and Oncology "G. Salvatore," Naples, Italy

Comment in
 J Leukoc Biol.

Macrophages are pivotal effector cells in immune responses and tissue remodeling by producing a wide spectrum of mediators, including angiogenic and lymphangiogenic factors. Activation of cannabinoid receptor types 1 and 2 has been suggested as a new strategy to modulate angiogenesis in vitro and in vivo. We investigated whether human lung-resident macrophages express a complete endocannabinoid system by assessing their production of endocannabinoids and expression of cannabinoid receptors. Unstimulated human lung macrophage produce 2-arachidonoylglycerol,N- arachidonoyl-ethanolamine,N- palmitoyl-ethanolamine, and N-oleoyl-ethanolamine. On LPS stimulation, human lung macrophages selectively synthesize 2-arachidonoylglycerol in a calcium-dependent manner. Human lung macrophages express cannabinoid receptor types 1 and 2, and their activation induces ERK1/2 phosphorylation and reactive oxygen species generation. Cannabinoid receptor activation by the specific synthetic agonists ACEA and JWH-133 (but not the endogenous agonist 2-arachidonoylglycerol) markedly inhibits LPS-induced production of vascular endothelial growth factor-A, vascular endothelial growth factor-C, and angiopoietins and modestly affects IL-6 secretion. No significant modulation of TNF-α or IL-8/CXCL8 release was observed.

The production of vascular endothelial growth factor-A by human monocyte-derived macrophages is not modulated by activation of cannabinoid receptor types 1 and 2. Given the prominent role of macrophage-assisted vascular remodeling in many tumors, we identified the expression of cannabinoid receptors in lung cancer-associated macrophages. Our results demonstrate that cannabinoid receptor activation selectively inhibits the release of angiogenic and lymphangiogenic factors from human lung macrophage but not from monocyte-derived macrophages. Activation of cannabinoid receptors on tissue-resident macrophages might be a novel strategy to modulate macrophage-assisted vascular remodeling in cancer and chronic inflammation.

© Society for Leukocyte Biology.

5. J Pain. 

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).

Ware MA(1), Wang T(2), Shapiro S(3), Collet JP(4); COMPASS study team.

> Collaborators: Boulanger A, Esdaile JM, Gordon A, Lynch M, Moulin DE, O'Connell C.

> Author information:

(1)Department of Anesthesia, McGill University, Montreal, Quebec, Canada; Department of Family Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..

(2)Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.

(3)Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Centre for Clinical Epidemiology, Jewish General Hospital, Montreal, Quebec, Canada.

(4)Department of Pediatrics, University of British Columbia; Child and Family Research Institute, Vancouver, British Columbia, Canada.

Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among individuals with chronic non-cancer pain. A standardized herbal cannabis product (12.5% tetrahydrocannabinol) was dispensed to eligible individuals for a 1-year period; controls were individuals with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events and non-serious adverse events. Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 216 controls (chronic pain but no current cannabis use) from 7 clinics across Canada. The median daily cannabis dose was 2.5 g/d. There was no difference in risk of serious adverse events (adjusted incidence rate ratio = 1.08, 95% confidence interval = .57-2.04) between groups. Medical cannabis users were at increased risk of non-serious adverse events (adjusted incidence rate ratio = 1.73, 95% confidence interval = 1.41-2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year, appears to have a reasonable safety profile. Longer-term monitoring for functional outcomes is needed.STUDY

REGISTRATION: The study was registered with (ISRCTN19449752).

PERSPECTIVE: This study evaluated the safety of cannabis use by patients with chronic pain over 1 year. The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day.


Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.