COPD - 26 MARIJUANA RESEARCH PAPERS - 2000-2017
Chronic Obstructive Pulmonary Disease (COPD) – Medical Marijuana Research Overview 2017
These research studies are intended to further the knowledge of both patient and health care professional alike - and is not intended to specifically treat any patient's condition.
We first start with an introduction and commentary. Readers can page down to jump to the list of research papers ... from worldwide sources.
COMMENDARY AND OVERVIEW
COPD Chronic Obstructive Pulmonary Disease is the third leading cause of death in the United States. COPD is a group of lung diseases that block airflow, which makes breathing difficult. A wealth of research indicates that cannabis can help patients manage the pulmonary diseases by reducing airway inflammation, which is the root cause of bronchodilation.
In Chronic Obstructive Pulmonary Disease, less air flows in and out of the airways because, either tissues lose its elastic quality, or it produces an excess of mucus, which chronically clogs bronchial tubes. This is called bronchitis. When the walls of the bronchial tubes become thick and inflamed, as seen In emphysema, the walls between the air sacs are destroyed which catastrophically reduces the supply of oxygen to the body.
"In Washington DC, any condition can be approved for medical marijuana, so as long as a DC-licensed physician recommends if for therapeutical purposes."
THE CAUSE - TISSUE DAMAGE FROM FOREIGN AGENTS
Chronic Obstructive Pulmonary Disease is usually caused by a long-term exposure to irritating particulate matter, chemicals, gases, sometimes in conjunction with low grade infection. The number one cause of Chronic Obstructive Pulmonary Disease is cigarette smoking,air pollution and workplace exposure to dust, particulate and smoke also poses problems. The disease is insidious and develops slowly. Symptoms get worse over time until even basic physical activities, like walking or cooking become a chore.
The symptoms associated with Chronic Obstructive Pulmonary Disease typically include the coughing up of large amounts of mucus, shortness of breath, wheezing, and chest tightness. Symptoms often don’t appear until significant damage to the lungs has already occurred. A major cause of disability, Chronic Obstructive Pulmonary Disease is most commonly diagnosed in middle-aged or older adults.
Chronic Obstructive Pulmonary Disease has been shown to increase the risk of respiratory infections, heart problems, lung cancer, high blood pressure and depression.
"Cannabidiols improved lung function and inflammation in mice with acute lung injury."
NO CURE FOR COPD? - MAYBE THERE IS
According to medical orthodoxy, there is presently no cure for Chronic Obstructive Pulmonary Disease and as damage to the airways and lungs is seen as irreversible. However, treatment can help control symptoms and reduce the risk of complication and exacerbation.
Bronchodilators are medications that can be used to relax the muscles around the airways. Inhaled steroids help reduce airway inflammation. With that said, there are a variety of new therapies that promise to repair lung tissue and airways Therapies include stem cells and perhaps cannabis based medicines.
SUMMARY FINDINGS THE EFFECTS OF CANNABIS BASED MEDICINES ON COPD
Studies indicate that cannabis could potentially be beneficial therapeutically - for managing acute attacks of airway constriction - due to inflammation, thereby acting as a preventative for patients with Chronic Obstructive Pulmonary Disease. The efficacy of Cannabis was shown through numerous studies to reducing inflammation, suggesting effectiveness in managing inflamed airways in chronic bronchitis.
Two of the major cannabinoids found in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD) have shown in several studies to have anti-inflammatory benefits through a variety of mechanisms. THC and CBD interact with one another, the endocannabinoid system’s cannabinoid receptors CB1 & CB2 are modulated to better maintain homeostasis. The activation of both the CB1 & CB2 receptors has shown to reduce airway inflammation.
A review of the literature shows a consensus opinion; that CBD is a potent anti-inflammatory and also improves lung function, and suggests it could well be a useful therapeutic tool for the treatment of inflammatory lung diseases. In animal studies, CBD was shown to have anti-inflammatory effects following acute lung injury. Other studies have also found that terpenes, the aromatic compounds found in cannabis have anti-inflammatory benefits as well.
Some research has also shown that the cannabinoids found in cannabis can have bronchodilatory effects, thereby decreasing resistance in the respiratory airway and increasing airflow to the lungs. One study found that cannabinoids’ activation of the CB1 receptor inhibits contraction of the smooth muscle surrounding the lungs to dilate the bronchial tubes and further open up the airways.
CONCLUSION - CANNABIS OPENS AIRWAYS - REDUCES BLOCKAGE FACTORS
It’s important to note that the conclusion of several studies, suggesting that smoking of marijuana may increase the prevalence of acute and chronic bronchitis due to irritants entering the lungs. However, these studies are in the majority, and are usually funded by groups that are searching for negatives, rather than being unbiased. These negative studies focus on the worst case scenario, fanatical marijuana smokers who mix weed with tobacco and god knows what.
CANNABIS PROPERTS - PERFECT FOR COPD
Rather, vapor delivery is the most promising of all delivery methods. Cannabinoids, THC and the others, and especially the terpenes, dilate the bronchial tubes, help clear phlegm and mucous, while delivering its anti-bacterial, anti-fungal, and antiviral effects, all properties of a perfect tonic for lung conditions.
Certainly, in a random marijuana sample of street weed, there may be pesticides, there is tar, and other non-desirable products of combustion. Ideally, these toxic agents should and can be removed. Using extraction and distillation, the medicinal ingredients, the terpenes and cannabinoids can be collected and separated from the heavy tar. By using proper organic growing methods and by choosing the right strain (with both CBD and THC), a distillate containing nothing but medical desirables can be produced.
Therefore, therapy and study for COPD of cannabis based medicines should concentrate on the efficacy of both distillate via inhaler (vape) or via, oral route and in combination.
"Recent Studies on the effect of Cannabis’ in Chronic Obstructive Pulmonary Disease show that CBD has a potent anti-inflammatory effect and it also improves lung function These findings suggest that CBD may be a useful therapeutic tool in the treatment of inflammatory lung diseases."
FED GOVERNMEN, BIG PHARMA AND NEGATIVE STUDIES
The wealth of negative studies, as uncontrolled and biased as they are, have shown that marijuana smoker's lungs are slightly better than non-smokers, and only a small fraction of long time abusers show any ill effects. Taking into account that the subjects in the study include abusers and some of the marijuana used by the subjects very likely was tainted with fungus and sprays in many cases, the positive results from smoking marijuana are even more impressive.
Further uncontrolled worst case scenario studies should be discontinued, or at a minimum, the results thrown out altogether. We suggest that cannabis based medicines should be studied in the clinic, with definitive testing done on the medicine with ingredients known (cannabinoid profile, pesticide, microbial, terpene).
YOUR DOCTOR AND MEDICAL MARIJUANA
While no state has approved medical marijuana specifically for the treatment of Chronic Obstructive Pulmonary Disease, several states approve of medical marijuana for treatment of COPD under the umbrella categorization of "other conditions". This is the case in both California and Nevada, where the law has a clause in it that allows physicians may prescribe medical marijuana as they see fit.
“The illegality of cannabis is outrageous, an impediment to full utilization of a drug which helps produce the serenity and insight, sensitivity and fellowship so desperately needed in this increasingly mad and dangerous world.” - Carl Sagan
26 MMJ RESEARCH STUDIES WORLDWIDE 2000-2017
1 Effects of cannabis on pulmonary structure, function & symptoms. Thorax, 62, 1058–1063. Aldington, S., Williams, M., Nowitz, M., Weatherall, M., Pritchard, A., McNaughton, A., Robinson, G., & Beasley, R. (2007). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094297/.
2 Preclinical assessment of novel therapeutics on the cough reflex:cannabinoid agonists as potential antitussives. Lung, 186, Suppl 1, S66-9.Belvisi, M.G. (2008). Gathered from https://link.springer.com/article/10.1007/s00408-007-9028-8.
3 β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation & PPARγ Pathway. The American Journal of Pathology, 178, 1153–1166. Bento, A. F., Marcon, R., Dutra, R. C., Claudino, R. F., Cola, M., Pereira Leite, D. F., & Calixto, J. B. (2011). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070571/.
4 Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors. Immunobiology, 216(4), 466-76. Braun, A., Engel, T., Aguilar-Pimentel, J.A., Zimmer, A., Jakob, T., Behrendt, H, & Mempel, M. (2011, April). Gathered from https://www.sciencedirect.com/science/article/pii/S0171298510001592.
5 Cannabinoids, Endocannabinoids, & Related Analogs in Inflammation. The AAPS Journal, 11(1), 109. Burstein, S. H., & Zurier, R. B. (2009). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664885/.
6 Chronic Obstructive Pulmonary Disease. (2016). Mayo Clinic. Gathered from https://www.mayoclinic.org/diseases-conditions/copd/home/ovc-20204882. Inhibition Attenuates Acute Lung Injury in Mice. PLoS ONE, 8, e 77706. Costola-de-Souza, C., Ribeiro, A., Ferraz-de-Paula, V., Caleffi, A.S., Aloia, T.P.A., Gimenes-Júnior, J.A., de Almedia, V.I., Pinheiro, M.L., & Palermo-Neto, J. (2013). Monoacylglycerol Lipase (MAGL) Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808422/.
7 CB2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma. Allergy, doi: 10.1111/all.13107. Ferrini, M.E., Hong, S., Stierle, A., Stierle, D., Stella, N., Roberts, K., & Jaffar, Z. (2016, December 19). Gathered from https://onlinelibrary.wiley.com/wol1/doi/10.1111/all.13107/full.
8 Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors. British Journal of Pharmacology, 171, 2767–2777.Grassin-Delyle, S., Naline, E., Buenestado, A., Faisy, C., Alvarez, J.C., Salvator, H., Abrial, C., Advenier, C., Zemoura, L., Devillier, P. (2014). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243853/.
9 Bronchodilator Effect of d9 -Tetrahydrocannabinol. British Journal of Clinical Pharmacology, 5, 523-535. Hartley, J.P.R., Nogrady, S.G., & Graham, J.D.P. (1978).Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1429361/pdf/brjclinpharm00292-0050.pdf.
10 The effects of marijuana exposure on expiratory airflow. A study of adults who participated in the U.S. National Health & Nutrition Examination Study. Annals of American Thoracic Society, 12, 135-41.Kemper, J.A., Honig, E.G., & Martin, G.S. (2015, February). Gathered from https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201407-333OC.
11 Cannabinoids Δ9-Tetrahydrocannabinol & Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB & Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells. The Journal of Biological Chemistry, 285, 1616–1626.Kozela, E., Pietr, M., Juknat, A., Rimmerman, N., Levy, R., & Vogel, Z. (2010). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/.
12 Inhibition of guinea-pig & human sensory nerve activity & the cough reflex in guinea-pigs by cannabinoid (CB2) receptor activation. British Journal of Pharmacology, 140(2), 261–268. Patel, H.J., Birrell, M.A., Crispino, N., Hele, D.J., Venkatesan, P., Barnes, P.J., Yacoub, M., & Belvisi, M.G. (2003). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574031/.
13 Cannabinoid effects on ventilation & breathlessness: a pilot study of efficacy & safety. Chronic Respiratory Disease, 8, 109-18. Pickering, E.E., Semple, S.J., Nazir, M.S., Murphy, K., Snow, T.M., Cummin, A.R., Moosavi, S.H., Guz, A., & Holdcroft, A. (2011). Gathered from https://journals.sagepub.com/doi/pdf/10.1177/1479972310391283.
14 Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor. European Journal of Pharmacology, 678, 78-85. Ribeiro, A., Ferraz-de-Paula, V., Pinheiro, M.L., Vitoretti, L.B., Mariano-Souza, D.P, Quinteiro-Filho, W.M., Akamine, A.T., Almeida, V.I., Quevedo, J., Dal-Pizzol, F., Hallak, J.E., Zuardi, A.W., Crippa, J.A., & Palermo-Neto, J. (2012, March). Gathered from https://www.sciencedirect.com/science/article/pii/S0014299912000052.
15 Cannabidiol improves lung function & inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacology & Immunotoxicology, 37, 35-41. Ribeiro, A., Almeida, V.I., Costola-de-Souza, C., Ferraz-de-Paula, V., Pinheiro, M.L., Vitoretti, L.B., Gimenes-Junior, J.A., Akamine, A.T., Crippa, J.A., Tavare-de-Lima, W., & Palermo-Neto, J. (2015, February). Gathered from https://www.tandfonline.com/doi/full/10.3109/08923973.2014.976794?needAccess=true.
16 Human lung-resident macrophages express CB1 & CB2 receptors whose activation inhibits the release of angiogenic & lymphangiogenic factors. Journal of Leukocyte Biology, 99(4), 531-40. Staiano, R.I., Loffredo, S., Borriello, F., Iannotti, F.A., Piscitelli, F., Orlando, P., Secondo, A., Granata, F., Lepore, M.T., Fiorelli, A., Varricchi, G., Santini, M., Triggiani, M., Di Marzo, V., & Marone, G. (2016, April). Gathered from https://www.jleukbio.org/content/99/4/531.long.
17 Marijuana & chronic obstructive lung disease: a population-based study. CMAJ?: Canadian Medical Association Journal, 180(8), 814–820. Tan, W.C., Lo, C., Jong, A., Xing, L., FitzGerald, M.J., Vollmer, W.M., Buist, S.A., & Sin, D.D., for the Vancouver Burden of Obstructive Lung Disease (BOLD) Research Group. (2009). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665947/.
18 Acute effects of smoked marijuana & oral delta9-tetrahydrocannabinol on specific airway conductance in asthmatic subjects. The American Review of Respiratory Disease, 109(4), 420-8. Tashkin, D.P., Shapiro, B.J., & Frank, I.M. (1974, April). Gathered from https://www.atsjournals.org/doi/pdf/10.1164/arrd.19184.108.40.2060.
19 Respiratory & immunologic consequences of marijuana smoking. Journal of Clinical Pharmacology, 42 (11 Suppl), 71S-81S. Tashkin, D.P., Baldwin, G.C., Sarafian, T., Dubinett, S., & Roth, M.D. (2002, November).Gathered from https://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.2002.tb06006.x/abstract.
20 Does smoking marijuana increase the risk of chronic obstructive pulmonary disease? CMAJ?: Canadian Medical Association Journal, 180(8), 797–798. Tashkin, D.P. (2009). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665954/.
21 Effects of marijuana smoking on the lung. Annals of American Thoracic Society, 10(3), 239-47. Tashkin, D.P. (2013, June). Gathered from https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201212-127FR.
22 Impact of cannabis, cannabinoids, & endocannabinoids in the lungs. Frontiers in Pharmacology, 7, 317. Turcotte, C., Blanchet, M.R., Laviolette, M., & Flamand, N. (2016, September 15). Gathered from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023687/.
23 What is Chronic Obstructive Pulmonary Disease? (2014, May 22). National Heart, Lung, & Blood Institute. Gathered from https://www.nhlbi.nih.gov/health/health-topics/topics/copd.
24 Damaging Effects of Cannabis Use on the Lungs. Advances in Experimental Medicine & Biology, 952, 31-34.Yayan, J., & Rasche, K. (2016). Gathered from https://link.springer.com/chapter/10.1007%2F5584_2016_71.
25 HIGHLIGHTED PAPER
Cannabidiol is the most abundant non-psychoactive cannabinoid in most strains of the plant, and it and analogs of CBD have been studied more extensively in recent years. Thus, CBD reduces joint inflammation in collagen-induced arthritis (CIA) in mice and carrageenan paw edema in rats . CBD treatment also suppressed release of tumor necrosis factor (TNF) α from synovial cells isolated from the mice. In addition, oral administration of CBD (2.5–20 mg/kg) reduces neuropathic (sciatic nerve constriction) and inflammatory (intraplantar injection of complete Freund’s adjuvant) pain in rats, effects reversed by vanilloid but not CB receptor antagonists .
Although CBD did not reduce inducible nitric oxide synthase (iNOS) in these studies, others have reported that CBD does inhibit iNOS in a beta-amyloid-induced murine model of neuroinflammation. In contrast to these receptor studies, increased activation of rat mast cells by CBD was not mimicked by a full agonist of vanilloid receptor type 1 . In addition, CBD is an antagonist of CB receptor agonists in mouse brain and in membranes from cells transfected with human CB2 receptors.
Binding of CBD and its analogs to the cannabinoid receptors CB1 and CB2 appears to be negligible . The dimethylheptyl-7-oic-acid analog of CBD (DMH-CBD) reduces joint inflammation, including cartilage degradation and bone erosion in murine CIA. CBD also reduces intestinal inflammation in mice .
In addition to its ability to suppress production of the inflammatory cytokine TNFα, CBD appears to exert anti-inflammatory activity by suppressing fatty acid amidohydrolase (FAAH) activity, thereby increasing concentrations of the anti-inflammatory endocannabinoid anandamide. CBD and CBD-DMH have been hydrogenated to give four different epimers. The complex mechanisms whereby these compounds exert their effects is illustrated by the fact that hydrogenation at different double bonds has different effects on bioactivities, none of which appear dependent on CB1 activation.
Further, insight into mechanisms whereby CBD exerts therapeutic effects is provided by experiments which indicate that CBD attenuates inflammation induced by high glucose in diabetic mice (21). Specifically, CBD treatment reduces mitochondrial superoxide, iNOS, nuclear factor kappa B (NF-κB) activation, and transendothelial migration of monocytes. Another potential therapeutic use of CBD may lie in its ability to counter some undesirable effects of THC (sedation, psychotropic effects, tachycardia), thus suggesting that if given together with THC, it may allow higher doses of THC . THC and CBD have been administered as an oral mucosal spray to 58 patients with rheumatoid arthritis . Treated patients had significant reduction in pain and improvement in sleep compared to patients given placebo.
The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of proinflammatory cytokines (TNF and IL6) and chemokines (MCP1 and MIP2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.