Chapter 7: Pulmonary Health and Disease

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Human Pulmonary System

The human pulmonary also commonly known as the respiratory system is a series of organs responsible for delivering in oxygen through diffusion and expelling carbon dioxide. The system is made up of three main parts:

  1. Airway: Includes the nose, mouth, pharynx, larynx, trachea, bronchi and bronchioles. The airway transports air between the lungs and the exterior.
  2. Lungs:  Are functional organs that carry out the exchange of gases during breathing.
  3. Respiration muscles: Include the diaphragm and intercostal muscles which pump air in and out of the lungs during breathing.

Several health problems may lead to respiratory diseases that impair the ability of the body to exchange carbon dioxide for oxygen. The endocannabinoid system is essential in maintaining the function of the pulmonary system. Throughout the respiratory system,  there are CB1 and CB2 receptors scattered; hence clinical endocannabinoid deficiencies can contribute to the development of chronic and malignant disease in the respiratory system.1, 2, 4, 6, 7, 9, 10

The Role of Cannabidiol in Pulmonary Diseases

Experiments in rodent models of inflammation have shown that CBD has desireable immunosuppressive and anti-inflammatory properties. In cases of acute lung injury (ALI), preventive treatment with cannabidiol inhibited the inflammatory lung response. Both acute lung injury and its severe manifestation of acute respiratory distress syndrome (ARDS) are rigorous and challenging public health concerns. CBD represents a promising approach to their prevention and treatment.3, 5, 8, 10

Asthma

Asthma is a chronic lung disease that inflames and narrows the airways; it causes recurring periods of wheezing, chest tightness, shortness of breath, and coughing. Persistent asthma usually occurs with reactive airway disease which can swiftly become lethal if not attended. Asthma is both genetic and idiopathic autoimmune clinical endocannabinoid deficiency (CECD).

CB1 and CB2 receptors allow the endocannabinoid system to manage the inflammatory response in asthma. Active CB1 receptors can induce bronchodilator effects that ease respiratory distress by relaxing smooth muscle. Activated CB2 receptors regulate the lungs immunological responses. With activated CB1 and CB2 receptors, the endocannabinoid system can modulate the potential hyperactive response to an antigen.

Studies propose that increasing anandamide levels within the pulmonary system reduces the morbidity of asthma. Cannabidiol administration can increase anandamide levels and hence modulate the inflammatory response in asthma.11

Emphysema

Emphysema is a long-term, progressive lung disease that primarily causes shortness of breath due to overinflation of the alveoli (the air sacs in the lung). It is also known as a chronic obstructive pulmonary disease (COPD) and effects not only the respiratory system but also the cardiovascular and neurological systems. Lung tissue in emphysema is damaged; as a result, the lungs elastic function that returns it to its relaxed state after stretching is impaired; air remains trapped in the lungs.

Emphysema is an acquired clinical endocannabinoid deficiency and is closely associated with cigarette smoke. Tobacco smoke carries high concentrations of oxidants and produces a variety of free radicals including reactive oxygen species (ROS). Cannabidiol contains anxiolytic and anti-inflammatory properties that can ease and prevent the symptoms of emphysema, by activating CB1 and CB2 receptors in the respiratory system.18

Lung Cancer

Lung cancer is a malignancy which is commonly acquired due to cigarette smoking. The use of tobacco can cause early genetic malformations, however, developing into malignancies may take years. Lung cancer is an acquired clinical endocannabinoid deficiency, where both CB1 and CB2 receptors are affected by tobacco usage. The endocannabinoid system is critical in sustaining homeostasis of the immunological system.

Clinical research has shown that lung cancer responds to cannabidiol administration; CBD oil inhibits metastasis of lung cancer, preventing it from spreading to usually the brain and spine. The preventive treatment with cannabidiol reduces the risk of lung cancer, especially after being exposed to secondhand smoke. CBD may even prove valuable in the treatment of highly invasive lung cancer.12-15

Pneumonia

Pneumonia is a lung infection that varies in severity from mild to severe. It occurs when the alveoli (lung air sacs) are filled with fluid or pus that limit the amount of oxygen reaching the blood. In individuals with underlying chronic and autoimmune diseases, pneumonia can cause distress and respiratory dysfunction.

The clinical endocannabinoid deficiency associated with pneumonia affects the immunological response that is regulated by CB2 receptors. The effects include failure to prevent overactivity of white blood cells; this may lead to allergy and autoimmunity, further inhibiting the functionality of the respiratory system. Overactivity of white blood cells can be inhibited by cannabidiol administration, consequently reducing inflammation and improving lung function. CBD can also hasten recovery time from acute lung infections. Therapeutic administration of cannabidiol can also minimize the risk of viral and bacterial infections associated with pneumonia.1, 4, 6, 7, 10, 16

Pulmonary Hypertension

Pulmonary hypertension is a complex chronic and lethal disease that manifests as high blood pressure in the lungs. Hypertension or high blood pressure arteries throughout the body have higher pressure than usual. In pulmonary hypertension the blood vessels in the lungs are specifically affected; they can become stiff and damaged and require the heart to exert more force to pump blood through. These effects increase the risk of vessel rupture and fatality.

The phytocannabinoid cannabidiol can induce relaxation in the vessel walls and hence reduce systemic blood pressure. Studies have shown that the CBD administration in subjects with pulmonary hypertension reduces the pressure in arteries by enhancing binding capabilities of CB1 receptors. Cannabidiol is a promising supplement for individuals diagnosed with pulmonary hypertension or at risk of it.17

References:

  1. Russo E. B, Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Available at https://www.ncbi.nlm.nih.gov/pubmed/15159679
  2. Scarabino, T., Salvolini, U. Atlas of Morphology and Functional Anatomy of the Brain. Springer-Verlag Berlin Heidelberg, (2006).
  3. George W. Booz, Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress, Free Radical Biology and Medicine, Volume 51, Issue 5, 2011, Pages 1054-1061, ISSN 0891-5849, available at: http://www.sciencedirect.com/science/article/pii/S0891584911000116
  4. Smith SC, Wagner MS. Clinical endocannabinoid deficiency (CECD) revisited: can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2014; 35(3): 198 – 201. Available at https://www.ncbi.nlm.nih.gov/pubmed
  5. Tatiana Barichello, Renan A. Ceretta, Jaqueline S. Generoso, Ana Paula Moreira, Lutiana R. Simões, Clarissa M. Comim, João Quevedo, Márcia Carvalho Vilela, Antonio Waldo Zuardi, José A. Crippa, Antônio Lucio Teixeira, Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis, European Journal of Pharmacology, Volume 697, Issues 1–3, 2012, Pages 158-164, ISSN 0014-2999, available at https://doi.org/10.1016/j.ejphar.2012.09.053
  6. Baron, E. P. (2015), Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been …. Headache: The Journal of Head and Face Pain, 55: 885-916. Available at https://doi.org/10.1111/head.12570
  7. Fitzcharles, MA., Baerwald, C., Ablin, J. et al. Schmerz (2016) 30: 47. Available at https://doi.org/10.1007/s00482-015-0084-3
  8. Stanley, C. P., Hind, W. H., & O’Sullivan, S. E. (2013). Is the cardiovascular system a therapeutic target for cannabidiol? British Journal of Clinical Pharmacology, 75(2), 313–322. Available at http://doi.org/10.1111/j.1365-2125.2012.04351.x
  9. Alison Ribeiro, Viviane Ferraz-de-Paula, Milena L. Pinheiro, Luana B. Vitoretti, Domenica P. Mariano-Souza, Wanderley M. Quinteiro-Filho, Adriana T. Akamine, Vinícius I. Almeida, João Quevedo, Felipe Dal-Pizzol, Jaime E. Hallak, Antônio W. Zuardi, José A. Crippa, João Palermo-Neto, Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A2A receptor, European Journal of Pharmacology, Volume 678, Issues 1–3, 2012, Pages 78-85, ISSN 0014-2999, available at https://doi.org/10.1016/j.ejphar.2011.12.043.
  10. A. Ribeiro, V. I. Almeida, C. Costola-de-Souza, V. Ferraz-de-Paula, M. L. Pinheiro, L. B. Vitoretti, J. A. Gimenes-Junior, A. T. Akamine, J. A. Crippa, W. Tavares-de-Lima & J. Palermo-Neto (2014) Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury, Immunopharmacology and Immunotoxicology, 37:1, 35-41, available at https://doi.org/10.3109/08923973.2014.976794
  11. Vuolo, F., Petronilho, F., Sonai, B., Ritter, C., Hallak, J. E. C., Zuardi, A. W., … Dal-Pizzol, F. (2015). Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators of Inflammation, 2015, 538670. Available at http://doi.org/10.1155/2015/538670
  12. Robert Ramer, Jutta Merkord, Helga Rohde, Burkhard Hinz, Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1, Biochemical Pharmacology, Volume 79, Issue 7, 2010, Pages 955-966, ISSN 0006-2952, available at https://doi.org/10.1016/j.bcp.2009.11.007
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  14. Robert Ramer, Katharina Bublitz, Nadine Freimuth, Jutta Merkord, Helga Rohde, Maria Haustein, Philipp Borchert, Ellen Schmuhl, Michael Linnebacher, and Burkhard Hinz, The FASEB Journal 2012 26:4, 1535-1548, available at https://doi.org/10.1096/fj.11-198184
  15. Robert Ramer, Katharina Heinemann, Jutta Merkord, Helga Rohde, Achim Salamon, Michael Linnebacher and Burkhard Hinz, COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells, Mol Cancer Ther January 1 2013 (12) (1) 69-82; available at http://mct.aacrjournals.org/content/12/1/69.long
  16. Karmaus, P. W. F., Wagner, J. G., Harkema, J. R., Kaminski, N. E., & Kaplan, B. L. F. (2013). Cannabidiol (CBD) Enhances Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation in C57BL/6 Mice. Journal of Immunotoxicology, 10(3), 321–328. Available at http://doi.org/10.3109/1547691X.2012.741628
  17. Hanna Kozłowska; Marta Baranowska; Eberhard Schlicker; Mirosław Kozłowski; Jerzy Laudański; Barbara Malinowska, Identification of the vasodilatory endothelial cannabinoid receptor in the human pulmonary artery, Journal of Hypertension. 25(11):2240–2248, NOV 2007, available at https://insights.ovid.com/pubmed?pmid=17921818

Ribeiro, L. I., & Ind, P. W. (2016). Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review. NPJ Primary Care Respiratory Medicine, 26, 16071–. Available at http://doi.org/10.1038/npjpcrm.2016.71

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