“…habitual use of marijuana alone does not appear to lead to significant abnormalities in lung function, except for possible increases in lung volumes… no clear link to chronic obstructive pulmonary disease has been established… findings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use… In summary, the accumulated weight of evidence implies far lower risks for pulmonary complications of even regular heavy use of marijuana compared with the grave pulmonary consequences of tobacco.” http://www.ncbi.nlm.nih.gov/pubmed/23802821
Category Archives: Lung Cancer
Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors.
“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…
Activation of cannabinoid receptors on tissue-resident macrophages might be a novel strategy to modulate macrophage-assisted vascular remodeling in cancer and chronic inflammation.”
Δ-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.
“Lung cancer is the major cause of cancer-related mortality worldwide.
Many of these over-express epidermal growth factor receptor (EGFR), and are usually highly aggressive and resistant to chemotherapy.
Recent studies have shown that Δ-9 Tetrahydrocannabinol (THC), the major component of Cannabis sativa, possess anti-tumor properties against various types of cancers.
However, not much is known about its effect on lung cancer. In this study, we sought to characterize the effect of THC on EGF-induced growth and metastasis of human non small lung cancer cell (NSCLC) lines A549 and SW-1573.
We demonstrate that these cell lines and primary tumor samples derived from lung cancer patients express cannabinoids receptors CB1 and CB2, the known targets for THC action.
We further show that THC inhibits EGF-induced growth in these cell lines.
In addition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.
Next we characterized the effect of THC on in vivo lung cancer growth and metastasis in a murine model. A549 cells were implanted in SCID mice (n=6 per group) through subcutaneous and intravenous injections to generate subcutaneous and lung metastatic cancer, respectively. THC (5mg/kg body wt.) was administered once daily through intraperitoneal injections for 21 days. The mice were analyzed for tumor growth and lung metastasis.
A significant reduction (~50%) in tumor weight and volume were observed in THC treated animals compared to the vehicle treated animals.
THC treated animals also showed a significant (~60%) reduction in macroscopic lesions on the lung surface in comparison to vehicle treated control.
Immunohistochemical analysis of the tumor samples from THC treated animals revealed anti-proliferative and anti-angiogenic effects of THC with significant reduction in staining for Ki67, a proliferative marker and CD31, an endothelial marker indicative of vascularization. Investigation into the signaling events associated with reduced EGF-induced functional effects revealed that THC also inhibits EGF-induced Akt phosphorylation. Akt is a central signaling molecule of EGFR-mediated signaling pathways and it regulates a diverse array of cellular functions, including proliferation, angiogenesis, invasion and apoptosis.
Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”
http://cancerres.aacrjournals.org/content/67/9_Supplement/4749.short
The use of cannabinoids as anticancer agents.
“It is well-established that cannabinoids exert palliative effects on some cancer-associated symptoms. In addition evidences obtained during the last fifteen years support that these compounds can reduce tumour growth in animal models of cancer.
Cannabinoids have been shown to activate an ER-stress related pathway that leads to the stimulation of autophagy-mediated cancer cell death.
In addition, cannabinoids inhibit tumour angiogenesis and decrease cancer cell migration.
The mechanisms of resistance to cannabinoid anticancer action as well as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer have also started to be explored.
In this review we will summarize these observations (that have already helped to set the bases for the development of the first clinical studies to investigate the potential clinical benefit of using cannabinoids in anticancer therapies) and will discuss the possible future avenues of research in this area.” http://www.ncbi.nlm.nih.gov/pubmed/26071989
“… cannabinoids have been shown to alleviate nausea and vomit induced by chemotherapy and several cannabinoid-based medicines [Marinol (THC) and Cesamet (nabilone, a synthetic analogue of THC)] are approved for this purpose. Cannabinoids also inhibit pain, and Sativex (a standardized cannabis extract) has been approved in Canada for the treatment of cancer-associated pain. Other potential palliative effects of cannabinoids in oncology include appetite stimulation and attenuation of wasting. In addition to these palliative actions of cannabinoids in cancer patients, THC and other cannabinoids exhibit antitumour effects in animal models of cancer… a large body of scientific evidences strongly support THC and other cannabinoid agonists exert anticancer actions in preclinical models of cancer… In conclusion there exist solid scientific evidences supporting that cannabinoids exhibit a remarkable anticancer activity in preclinical models of cancer. Since these agents also show an acceptable safety profile, clinical studies aimed at testing them as single agents or in combinational therapies are urgently needed.” http://www.sciencedirect.com/science/article/pii/S0278584615001190
The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.
“As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes.
Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy.
During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.
In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors.
For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer.
This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells.
We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.”
Association Between Marijuana Exposure and Pulmonary Function over 20 Years
“Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.
Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms.
Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840897/
https://jamanetwork.com/journals/jama/fullarticle/1104848
“A common misconception about medical marijuana is that if inhaled, it will have detrimental effects on the patient’s lungs. However, according to a 2012 study published in the Journal of the American Medical Association (JAMA), this notion is simply untrue; in fact, this study points to an idea quite the opposite: that medical marijuana just might improve lung health under certain conditions.” HTTPS://AGRIMEDINDUSTRIES.COM/2018/06/08/STUDY-SHOWS-MARIJUANA-HAS-A-POSITIVE-IMPACT-ON-LUNG-HEALTH-UNDER-CERTAIN-CONDITIONS/
Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.
“We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI).
In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation.
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 pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 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.”
CANNABINOIDS INCREASE LUNG CANCER CELL LYSIS BY LYMPHOKINE-ACTIVATED KILLER CELLS VIA UPREGULATION OF ICAM-1.
“Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action…
Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody…
ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol (THC) and R(+)-methanandamide, a stable endocannabinoid analogue…
Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell susceptibility to LAK cell-mediated cytolysis.
These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.”
CANNABINOIDs INHIBIT angiogenic capacities of Endothelial cells via release of Tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells.
“Cannabinoids inhibit tumor neovascularisation as part of their tumorregressive action.
However, the underlying mechanism is still under debate. In the present study the impact of cannabinoids on potential tumor-to-endothelial cell communication conferring anti-angiogenesis was studied…
Collectively, our data suggest a pivotal role of the anti-angiogenic factor TIMP-1 inintercellular tumor-endothelial cell communication resulting in anti-angiogenic features of endothelial cells.”
COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.
“Within the last decade, evidence has been accumulated to suggest an antitumorigenic action of cannabinoids elicited via induction of apoptosis and alternative anticarcinogenic mechanisms… cannabidiol has been shown to elicit pronounced proapoptotic or autophagic effects on different types of tumor cells
This study investigates the role of COX-2 and PPAR-γ in cannabidiol’s proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis… our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ…
Collectively, our data strengthen the notion that activation of PPAR-γ may present a promising target for lung cancer therapy.
In addition and to the best of our knowledge, this is the first report to provide an inhibitor-proven tumor-regressive mechanism of cannabidiolin vivo as well as a proapoptotic mechanism confirmed by use of primary lung tumor cells.
Against this background and considering recent findings supporting a profound antimetastatic action of cannabidiol, this cannabinoid may represent a promising anticancer drug.”