Medical Marijuana: Effects of Cannabis on Lungs
Cannabis is one of the most popular drugs consumed worldwide. According to statistical data marijuana is the first most commonly used illegal substance in the world. The way weed is consumed can be of a myriad of ways. Cannabis can be smoked by rolling it in a cigarette known as joint, from a pipe, inhaled from a bong or by a more healthy way with a special vaporizer. Weed can also be eaten if cooked in oil, and is often included into a lot of recipes like muffins.
However, weed is rather smoked. This way has raised medical concerns and above all a growing scientific interest. As everybody knows every kind of smoke inhaled involountarily or not produces a bad effect on the lungs.
Studies have been conducted regarding several aspects by which marijuana's effects can be evaluated on a pathophysiological and pathological basis, the comparison was made between four groups including marijuana smokers (MS), tobacco smokers (TS), marijuana and tobacco smokers (MTS) and a control group of nonsmokers (NS). Evidence suggests, that frequent marijuana use has a harmful effect on epithelial cells of the lungs, thus increasing the risk to develop cancerous malformations. On the other hand a clear view on how cannabis smoke increases the likelihood of developing Chronic Obstructive Pulmonary Disease (COPD) is still inconstistent on an epidemiologic platform, and still requires further evidence and studies. Researchers have also found decreased lung immune function in marijuana users, this state could facilitate the exposure to lung infections. Anormal respiratory symptoms like cough, increased sputum production, wheezing are also reported.
Acute effects of smoked marijuana cause short-term bronchodilation that could be an effective treatment for asthmatic people. In contrast, tobacco smoking causes modest transient bronchoconstriction.
What are the effects on respiratory symptoms?
The purpose of this study was to determine if a statistical significance of negative respiratory symptoms between four groups of questioned groups of subjects was present.
The results were evident, as 2% of NS group reported on average two episodes of acute bronchitis within the preceding 3 years compared to 13% of cannabis smokers, 21% of MS subjects reported occurrence of chronic cough and sputum release compared to 2-5% of non-smokers.
Are there additive effects if marijuana is combined with tobacco?
Additive effects seen inside MTS group didn't seem to play a crucial role in worsening of respiratory symptoms. However, regular use of marijuana similar to tobacco smoking demonstrated a risk of developing chronic and/or acute episodes of bronchitis.
- Spirometry is the most common test to evaluate pulmonary function, specifically the amount (volume) of air and the speed (flow) of it being inhaled and exhaled.
- Closing volume or closing capacity is the volume of lungs when air become exhaled. Normally, this value is greater than residual volume. Residual volume is a determined amount of air that remains in the lungs until death and prevent them from pathological collapse. Closing volume slowly decreases because of aging process, however pulmonary diseases such as asthma can also contribute to this impairment.
In this section spirometry, measurement of closing volume, density-dependence of flow indices and diffusing capacity is evaluated.
Does marijuana affect lung function?
In three studies made in Los Angeles, Tucson and Dunedin showed conflicting results.
In Los Angeles cohort, no potentially harmful long-term effects were demonstrated. Moreover, a particular value named FEV1 showed no particular changes in marijuana only smokers in contrast with tobacco smokers who demonstrated a gradual decrease in lung function, more precisely in air expiratory abilities.
However in the latter two studies, a slight impairment of lung function showed an evidence of mild airflow obstruction, that can lead to development of COPD if the smoking habit remains unchanged over time.
Visual Evidence of Airway Injury
In both tobacco and marijuana smokers visual airway injuries were noted by the application of a procedure called fiberoptic bronchoscopy. The purpose was to examine the tracheobronchial mucosa by videotaping it.
What kind of visual injuries have been revealed during the procedure?
Signs of erythema, edema and increased secretions were noticed. In additon increased number and size of submucosal blood vessels have been diagnosed.
- Hyperplasia means an increase in the number of cells within a tissue or generally an organ. Hyperplasia is associated with enlargement of an organ, or benign tumors in worse cases. However, hyperplasia is thought to be a natural adaptive reaction to a damage, an inflammatory status or hormonal changes within a specified location inside the body.
- Metaplasia means a reversible conversion of one cell type into another. Similar to hyperplastic phenomenon, cell metaplasia can be a normal or abnormal response to a stimulus coming both from external and internal environmental changes.
- Nuclear atypia is a common definition in cyto- and histopathology. It refers to an abnormal, pleomorphic appearance of cell nucleus showing differences in size and shape from the normal ones. Atypia can be a sign of a preneoplastic change that can lead to cancerous changes of the cells if left untreated. Healthy lifestyle is thought to be the best way to convert these cellular states.
- Nuclear/cytoplasmic ratio or NC ratio is the proportion between the size of the nucleus and the surrounding cytoplasm inside the cell.
During bronchoscopy, small tissue samples of bronchial mucosa were taken in order to examine the exposed tissue on cellular levels. The biopsy results revealed under light microscopy severe histological alterations in MS and TS subjects compared to those of nonsmokers.
What kind of histological alterations have been revealed?
Epithelial tissues of marijuana smokers showed few pathological alterations and inflammatory states that eventually over time could lead to malignancies such as various forms of lung cancer. The results proved the presence of:
- goblet cell hyperplasia
- reserve cell hyperplasia
- squamous metaplasia
- cellular disorganization
- nuclear atypia
- increased mitotic index
- increased nuclear/cytoplasmic ratio
- inflammatory changes
What about genes?
By performing bronchial biopsy, immunohistochemical methods were applied in order to evalute alterations in genes responsible for cellular growth that may hinder further consequences of developing malignancies. A striking overexpression of Epidermal Growth Factor Receptor (EGFR) and a protein responsible for nuclear proliferation called Ki-67 has been observed.
The dramatic results showed a greater numerical occurrence of these abnormal processes in marijuana users compared to nonsmokers and even if differences were slight, the abnormal genetic responses were higher than those in tobacco smokers.
This evidence points out the risk to development of cancerous malformations. As the epithelial cells become injured in the airways, and cellular dysregulation becomes significant, an increased risk of having a certain type of lung cancer may manifest.
Effects on Alveolar Macrophages
Along with functional and histopathological examinations, alveolar macrophages being the principal immune cells responsible for elimination of dust and microorganisms inside the lungs were retrieved and put under examination with a procedure called bronchoalveolar lavage.
At first glance, alveolar macrophage cytoplasm showed an abnormal amount of inclusion bodies both in MS and TS groups. MTS group showed to carry additional harmful changes in macrophage function, since the tar amount is significantly greater.
Does THC protect against emphysema? Is it true that this molecule suppress pulmonar immune function?
There has been speculation about the role of the principal psychoactive substance in marijuana, Tetrahydrocannabinol (THC) also known as Delta-9-tetrahydrocannabinol (Δ9-THC). THC appears to act as a double-edged sword on alveolar macrophages. On one side thc suppress certain inflammatory responses of the immune system decreasing the defense against disease causing microorganisms, however, this effect is thought to decrease the development of emphysema, a chronic and progressive lung disease affecting the ability and effectiveness of breathing and gas exchange.
Several immune processes have been examined such as:
- Fungicidal activity against Candida Tropicalis and Albicans;
- Bactericidal and phagocytic activity against Staphylococcus Aureus;
- Production of superoxides and nitrate intermediates against fungi and bacteria;
- Tumoricidal activity and production of cytotoxic substances against precancerous cells.
Significant findings are summarized in the table below.
Alveolar Macrophage Function in TS and MS Compared to NS
Fungicidal activity against Candida Albicans and Candida Tropicalis
Phagocytotic and bactericidal activity against Staphylococcus Aureus
Basal superoxide production
Generation of nitric oxide
Generation of proinflammatory cytokines (TNF-alpha, GM-CSF)
Major harmful substances found in tobacco and cannabis smoke
- Polyacyclic aromatic hydrocarbons (PAHs) like Benzo(a)pyrene
- Vinyl Chlories
- Reactive oxygen species
- Mitochondria (singulat Mitochondrion) are known as the power plant of the cell. This organelle is involved in serving the cell with adenosine triphosphate (ATP) an essential source for chemical energy.
Does Marijuana Cause Cancer?
Since marijuana smoke contains almost the same carcinogens and co-carcinogens as tobacco smoke, it has been shown that along a certain group of harmful substances present equivalently, a compund of benzopyrene family, benzo(a)pyrene is present in far greater amounts than tobacco smoke.
Deposition of tar and smoking habits
Tar deposition from marijuana is estimated to be 4 fold greater than tobacco. This is understandable by the fact, that joints usually contain no filter compared to industrially controlled cigarettes with appropriate filtering.
Various experiments with hamsters being exposed for circa 2 years to marijuana smoke, showed evidence of precancerous cellular changes, meaning a risk for development of bronchial carcinoma.
Protein Overexpression and DNA instability
Human bronchial biopsies showed various cellular changes and genetic instabilities, clear signs of precancerous malformations.
Apoptosis and Mitochondrial Function
Another significant revealing, was the negative toxic effect of THC to mitochondrial organelles causing disturbances in mictochondrial electron transport and depletion of ATP. This phenomenon could inhibit programmed cell death, leading to formation of cancerous cells.
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