 In part 1 of this series, I covered some very basic information on cannabis and cannabinoids. In this video, I'm going to review just the health effects of smoking cannabis on the lungs. Along the way, I'll address the belief that cannabis has never killed anyone. Let's start with a quick review. There are two primary receptors for cannabinoids, CB1 and CB2. CB1 is mostly found in the brain and is responsible for most of cannabis's psychotropic effects. The second receptor, CB2, is found in a lot of other places, including our immune system and the lungs. Plant-based phytocannabinoids generally bind our receptors more strongly and with less specificity than the endocannabinoids that our bodies produce. Let's start with a central question for this video. Is smoking cannabis harmful to the lungs? First we'll look at the composition of cannabis smoke. In a 2008 study by a group of Canadian researchers using standardized methodologies for evaluating the chemical composition of smoke products, a comparison was made between the smoke of a marijuana joint and tobacco cigarette on a mechanical smoking machine typically used in this kind of research. Their findings were, quote, ammonia was found in mainstream marijuana smoke at levels up to 20-fold greater than that found in tobacco. Hydrogen cyanide, nitrogen monoxide, other nitrous oxides, and some aromatic amines were found in marijuana smoke at concentrations 3 to 5 times those found in tobacco smoke. They also found that polyaromatic hydrocarbons, PACs, were present at higher levels in sidestream cannabis smoke. In a follow-up study by the same Canadian group, they took smoke condensate from joints and cigarettes and ran standard lab tests for cytotoxicity, the ability to kill normal cells, mutagenicity, the ability for a substance to damage DNA, and teratogenicity, the ability to cause birth defects. In this case they were testing for the ability to cause chromosomal abnormalities associated with birth defects. I'll quote their conclusions. The marijuana condensates were all found to be more cytotoxic and mutagenic than the matched tobacco condensates. So pot smoke has at least as much cancer-causing potential as cigarettes. We know from other studies that cannabis produces twice as much tar as the same weight of tobacco, and because the smoke is held longer, about 4 times as much tar as delivered to the lungs of a smoker by cannabis than by tobacco. That's the chemical analysis. Let's move to the anatomic and cellular impact of cannabis smoke on animal models and humans. Two types of experiments can be done on living subjects, lung lavage and bronchoscope exams. Lung lavage is the washing of cells from the airway and lungs using sterile saline. These done where non-smokers are compared to people who only smoke tobacco, only smoke cannabis or smoke both, found that more cells and more inflammation are recovered from any kind of smoker, and that the only difference in the airways of cannabis-only and tobacco-only smokers are the presence of inflammatory white blood cells called neutrophils. Cells recovered from cannabis-only smokers show the same kind of pre-cancerous changes observed in tobacco-only smokers. Let's stop and review the evidence so far. Cannabis smoke is more toxic, has more cancer potential than tobacco. In the human lung, it damages cells and causes the same kinds of pre-cancerous changes that we see with tobacco use. And yet, as we're about to see, the evidence from epidemiological studies looking at the correlation between cannabis use and lung cancer is mixed and inconclusive. There are four studies I want to look at. First, a pooled analysis of multiple populations in North Africa, which found that smoking cannabis at any level increased lung cancer odds by 2.4 fold. The problem with this study is that 100% of the cannabis smokers were also tobacco smokers. And while the researchers compensated for this in statistical analysis, it's possible that the increased risk was the result of confounding, or a relationship to a second variable. The second study was in New Zealand, a case control study done from the National Cancer Registry there. The results, quote, the risk of lung cancer increased 8% for each joint year of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% for each pack year of cigarette smoking. That is, they found that smoking a joint a day carried with it a higher risk of lung cancer than smoking a pack of cigarettes a day. Let's add to these two definitively positive studies, the largest study at the time, done in 2006 at UCLA Medical Center. 1,200 cancer cases were matched to 1,000 cancer-free controls. And after removing the confounding from cigarette smoking, no increased cancer risk could be detected. That was as surprising to the authors as it is to me. There is one caveat, the population was all under the age of 60, an intentional decision, because cannabis use became more mainstream about 40 years ago in the US in the 1960s youth culture. Populations of cannabis users from people who were young in the 1950s or before are more likely to be part of unusual, non-representative subgroups. The problem here is that the median age of diagnosis for lung cancer is 72, with over two-thirds of cases diagnosed after age 65. It's a disease that's usually diagnosed in people that are older than anyone included in the study. I don't think the results are invalid, but there's a possibility that the design was only looking at a very low-risk population and is underpowered as a result, even with large population sizes. The fourth study is a pooled analysis by the International Lung Consortium, using 2,000 lung cancer cases and 3,000 matched controls. The overall finding was only an extremely weak association between cannabis-only smoking and lung cancer risk, and only for specific types of lung cancer, although they didn't have enough heavy users to find here is 10 joint years to be certain of the risk increase. Cannabis smoke is more carcinogenic than cigarette smoke. We know it's causing pre-cancerous changes in the airway, and yet the evidence for a link to cancer isn't yet clear. How could that be? There are two possible explanations, and I suspect both of these are true. One, the absence of nicotine as a co-carcinogen, and two, the presence of cannabinoids. Nicotine is more than just addictive. It also contributes to the carcinogenic potential of tobacco smoke by preventing cells with damaged DNA from self-destructing, by encouraging cell growth, and by promoting the formation of new blood vessels in tumors. The simple absence of nicotine in cannabis probably makes it less likely to form the kinds of cancer that are life-threatening. Meanwhile, the presence of cannabinoids in cannabis smoke can have the effect of causing cells in the airway to undergo necrosis, a type of cell death where the cell just falls apart, as opposed to apoptosis, which is a tightly controlled self-destruct mechanism for the cell. Why would that be a good thing? One of the changes that often occurs in cancer is damage to that self-destruct mechanism, resulting in a cell that should die but doesn't. We might say the more cytotoxic cannabis smoke balances out its increased carcinogenic potential. It kills cells as fast as it mutagenizes them, while tobacco keeps them from dying, allowing damaged cells to go on to become tumors. Lung cancer is not the only health risk associated with cannabis use. The action of THC on the immune system is generally immunosuppressive, which can predispose people with already weak immune systems to infection, including life-threatening pneumonia. It does this both by turning off normal immune responses, but also by causing the death of a specific type of immune cell in the lining of the lungs. Cannabis smoking also produces the full range of chronic bronchitis symptoms, including wheezing, mucus production, cough, and acute attacks. But surprisingly, doesn't cause COPD, or chronic obstructive pulmonary disease, where airflow is blocked, making it hard to breathe. In fact, it may cause something of the reverse, bullis emphysema, which is where the alveoli of the lung become hyper-extended and over-inflated. Bullis emphysema may require surgical removal of part of the lungs, and there are some documented cases in young people where the only cause that couldn't be eliminated was heavy chronic cannabis use. Lastly, I want to address the idea that cannabis has never killed anyone. It's absolutely true that acute life-threatening reactions to cannabis ingestion are rare, but so are acute reactions to cigarettes. Very few people, if any, die from uncomplicated cigarette overdose every year. It would not be accurate to say that as a result, cigarettes are harmless. The bigger disease burden is created by the chronic effects of tobacco use. In the case of tobacco, the death toll annually from overdose might be less than 100, while the deaths from smoking are around 6 million per year. In a future video, I'll talk about some of the deaths attributed to acute cannabis toxemia or overdose, but it's clear that to assess the public health cost of cannabis, we need to tally up what is called the attributable risk. Given that cannabis is a likely but not confirmed source of lung cancer, and given that it has other pulmonary consequences like increased infection and chronic bronchitis, there's no doubt that cannabis is killing people. If the actual increase in cancer risk for a typical user is no more than four-fold, and I think that's likely, and the percent of regular users is about 7% or 22 million people in the U.S., that would mean up to an additional 3,000 people dying every year in the U.S. from cannabis smoking. That's directly tied to the risk of smoking, but even with non-smoked cannabis, there's an increased risk of stroke, heart attack, arterial disease, and other life-threatening consequences of chronic use. While not inhaling the smoke from burning plant material is always a good idea, the risks are not completely mitigated in vaporizers, edibles, and oils. In the next video, we'll examine cannabis in the cardiovascular system. How does cannabis interact with your heart and blood vessels, and what risks does that carry? Thanks for watching.