 I expected quite a bit of pushback in my recent video. I have encountered marijuana proponents before, but they still managed to surprise me. There was a lot of anger, a lot of defensiveness, a fair share of personal attacks on me and my character or motivations, and one death threat that was disturbingly specific. That was not the norm, though. For the most part, I was pleasantly surprised by the rationality of the responses. People disagreed, some suggested I might be unconsciously biased on the topic, and others asked some really great questions. There were also a few people who shared with me stories and personal anecdotes, either for or against points raised in the video. Some said they would forward the vid to friends or relatives. A few even said that I gave them some motivation to quit. I want to extend a heartfelt thank you to everyone who watched, considered the content and participated in the discussion. I want to start off with one apology. I think it's been correctly pointed out that I misrepresented the LD50 data comparison to nicotine. One was for oral and one was for inhaled dose in the comparison. That's a bit sloppy, and that whole section was not well received. Let me just amend that part to say that an LD50 for THC has been established. By my best estimates, the median lethal dose of marijuana is somewhere on the order of 50 joints, or 6 grams of THC. So far as I know, no one has ever had their heart stop because they smoke too much marijuana. There are documented overdoses from synthetic cannabinoids. I really only intended to address the old saying that it's impossible to overdose from THC because it's so safe. It's certainly impractical, but what protects the user is not the safety or non-toxicity of THC, but the low density of the drug and how it affects the body. There are also two really important issues raised as deficits in the video. One, I didn't address the threshold of usage, how much pot is abused and how much is okay. Two, are the other forms of use, things like vaporizing and ingesting safer. The short answer to both is, I don't know. There's not much data on very low consumption, and the definition changes from paper to paper. Any amount of the drug is going to have effects on the brain, but not all DNA damage necessarily leads to cancer. Human clinical studies are not very good at detecting very small differences in risk and behavior because there are so many variables in the way people live their lives. I can only say that smoking is probably never a good idea, that we don't know how much is too much, and you'd be better off with a healthy habit instead of a bad one. I'm going to address the accusations of cherry picking at the end of this video, because I found that to be the most common and frankly the most offensive accusation. It's important that a scientist always be ready to concede bias, but I want to let you, the viewer, decide if I unfairly cherry pick studies, or if I'm fairly representing the most recent research on harmful effects of smoked marijuana. Before I get to that, there were a couple of common misconceptions that I want to address. There were a lot of people who were quite insistent that marijuana is less harmful than tobacco or alcohol, and that somehow invalidated the research presented. Let every drug be considered on its own merits. Just because heroin is worse than cigarettes doesn't make cigarettes a safe alternative to heroin. Just because you suspect that marijuana is better than cigarettes does not make marijuana a safe alternative to tobacco. One of the best questions asked in comments was how marijuana and cigarettes compared, especially in cancer risk. It seemed like I was saying that they were equal per unit mass, like one cigarette equals one joint, but that's not the case. One joint contains twice the cancer causing compounds of cigarettes, but the method of smoking is much worse. The New Zealand study in 2008 did a case control study of about 400 people. After they made corrections for tobacco smoking, the risk of lung cancer was increased by 8% for every joint per day they smoked. This was the same risk increase as smoking a pack of cigarettes a day. The people in the study who smoked the most pod were also the most likely to develop lung cancer. I want to be very clear that older studies have failed to find the same correlation in other populations. The ratio of the studies I looked at was about 2 to 1 in favor of pot smoking increasing risk. The biggest differences in the studies are the age of the subjects. Lung cancer is a long term development, but before cancer develops, people who smoke marijuana exhibit abnormal cells in their lungs, specifically alveolar macrophages, the kind of abnormalities that can progress to cancer. The hardest part of studying this is untangling the cigarette and marijuana use of people who use both. However, scientists are not stupid. There are statistical methods specifically for accounting for multiple variables, and researchers think through their models very carefully. Two, a lot of people inform me that I was wrong about marijuana being addictive. They base this on their intuitive knowledge or their personal experience. I can only say that repeated studies have demonstrated that a percentage of people experience withdrawal, and many people are actually unable to quit. Why do the scientists think they know better than YouTube commenters? Because they send out surveys, they interview users, and study behaviors of patients in recovery. Now you are welcome to dismiss this research because it conflicts with your personal experience. You can accuse the researchers of being dumb, being biased, or making the results up. You can even dismiss all research as being invalid. However, if you give yourself that kind of easy excuse, you can dismiss anything you disagree with out of hand. It's a rationalization, and it causes you to lose your objectivity. Better to face evidence with honest openness, even when you disagree, where the results are hard to hear. The other common objection to cannabis addiction is that everything is addictive, including sugar and love, or that marijuana addiction is just people missing their emotional crutch. You're welcome to use this argument as well, but be sure to apply it consistently. The symptoms of withdrawal in marijuana are very similar to the symptoms of withdrawal in cigarettes. They are physiological changes in the organ systems of the body. Would you say that cigarettes are only psychologically addictive? Three, the schizophrenia link was contested by a lot of people as well. The most common argument was that marijuana couldn't cause psychoses, but it can make the symptoms of a preexisting disorder worse. It's actually an interesting paradox. Some diagnosed schizophrenics actually benefit from marijuana when compared to their non-drug state. A common cause of self-medication is to cope with hallucinations. However, the mechanism of how marijuana acts as a component cause is well documented. Let me define that term. Component cause is a cause that is not sufficient alone to cause the disease, but in context with other risk factors is actually causative. More on this at the end. Four, there were a lot of anecdotes shared with me about how marijuana made a friend smarter or cured his emphysema or removed her warts. I think that's great, but A, it's not relevant for the harmful effects, and B, anecdotes are interesting but not always useful in objective analysis. If you're a student of human psychology, you know that people tend to be very poor at determining causation. We remember the hits and forget the misses. Your experience may not be typical, which is why scientists use large populations randomly selected and aggregate their results. Now we get to your chance to judge my bias. What I'm going to show you here are the first 10 papers for cannabis and schizophrenia found on PubMed Central. Let me be very clear. I typed in the terms cannabis and schizophrenia in the search bar. And these are the first 10 hits in the database of full text research papers from around the world. I'm not asking if you agree with the findings of these papers. I'm asking if an honest person could read through these 10 papers and still agree with the conclusion that cannabis is addictive and plays a role in the development of schizophrenia. I invite you to follow the link in the bar below and verify that I'm not manipulating anything here. Now am I cherry picking or accurately representing the body of knowledge? One, the environment and susceptibility to schizophrenia. A considerable amount of data supports cannabis use in adolescents, migration on favorable neighborhood environments, and possibly infections at different points in the lifespan as risk factors for schizophrenia. Two, cannabis dependence in the San Francisco family study, age of onset of use, DSM, four symptoms, withdrawal, and heritability. These findings suggest that within this population that cannabis use and dependence, as well as individual cannabis dependence symptoms, have a significant heritable component, that cannabis dependence is more likely to occur when use begins during adolescence, and that cannabis dependence syndrome includes a number of heritable untoward psychiatric side effects, including withdrawal. Also, chronic use of cannabis is associated with both physical and mental health problems. Persistent use poses health problems similar to those of tobacco. Three, do patients think cannabis causes schizophrenia? A qualitative study on the causal beliefs of cannabis using patients with schizophrenia. There still is a debate among the research community whether cannabis use may cause schizophrenia, and whether cannabis use of patients with schizophrenia might lead to a more untoward outcome, like earlier and more frequent relapses. Four, cannabis and psychosis schizophrenia, human studies. The association between cannabis use and psychosis has long been recognized. Recent advances in knowledge about cannabinoid receptor functions have renewed interest in this association. Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative, and cognitive symptoms in some healthy individuals. Also clear is that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. It is likely that cannabis exposure is a component cause that interacts with other factors to cause schizophrenia or a psychotic disorder, but it is neither necessary nor sufficient to do so alone. Five, cannabis use and cognition in schizophrenia. The relationship between cannabis and schizophrenia seems fairly specific to schizophrenia as compared to other mental disorders and cannot be explained by potentially confounding factors like pre-morbid disorders, drug use, intoxication, personality traits, sociodemographic markers, and intellectual ability. An alternative explanation is what can be called reversed causality, namely that schizophrenia patients use cannabis as a form of self-medication, although existing data does not seem to support this hypothesis. Thus, taken together, the available data seemed to point to cannabis use as increasing psychotic symptoms and increasing the vulnerability for a psychotic outbreak. Six, using the matrix to guide development of a preclinical cognitive test battery for research in schizophrenia. The use of cannabis, of which the psychoactive ingredient, delta-9-THC, acts as an agonist on cannabinoid receptors, is a known risk factor for schizophrenia and cognitive dysfunction in schizophrenia patients. Seven, cannabis and cognitive dysfunction parallels with endophenotypes of schizophrenia. Cannabis intoxication impairs cognitive processes. There is an increasing body of outage demonstrating that cannabis users show persistent deficits in specific cognitive functions beyond the period of acute intoxication. The extent of persistence of these deficits is still a matter of contention. In this paper, we integrate this evidence within the framework of endophenotypes of schizophrenia and propose that the similarity between the cognitive dysfunctions associated with cannabis use in schizophrenia is more than purely coincidental. Eight, cannabis withdrawal is common among treatment-seeking adolescents with cannabis dependence and major depression, and is associated with rapid relapse to dependence. Cannabis withdrawal has the most commonly reported cannabis dependence criterion among the 104 subjects in our sample, with cannabis dependence being noted in 92% of subjects using a two symptom cutoff for determination of cannabis withdrawal. The most common withdrawal symptoms among those with cannabis dependence were craving, irritability, restlessness, anxiety, and depression. Cannabis withdrawal symptoms were reported to have been associated with rapid reinstatement of cannabis dependence symptoms. Nine, a perspective study of cannabis use as a risk factor for non-adherence and treatment dropout in first episode schizophrenia. Results indicate that cannabis use is a risk factor for non-adherence to medication and dropout from treatment. Treatment for first episode schizophrenia may be more effective if providers address the issue of cannabis use with patients throughout the early years of treatment, especially for those with existing cannabis abuse slash dependence. Ten, increased cortical inhibition deficits in first episode schizophrenia with comorbid cannabis use. Comorbid cannabis abuse may potentiate the reduced intracortical inhibition and enhanced ICF observed in first episode schizophrenia patients in some previous studies. This finding suggests an increased alteration of GABA and MDA receptor activity in cannabis abusing first episode patients as opposed to schizophrenia patients with no history of substance abuse. This may constitute a distinct vulnerability factor in this special population. Those are the top 10 hits on PubMed Central. I could repeat this exercise for cannabis and lung cancer, cannabis and addiction, cannabis and heart disease, etc. For now, I'm done with marijuana. It's been a pretty painful experience facing down dozens of angry denialists. I've been asked to do a video on alcohol and its harmful effects and then possibly for cigarettes. I doubt that I will have to face so much rationalization so I'm actually looking forward to it. In the short term, I have an essay by Einstein, a discussion of MSG and food and I'm also looking into Aspartame. You can also look for a discussion of evolution and a little bit about my work with NASA. Again, I want to thank those of you who have reached out to me in a positive way. I make the videos on topics you request, even if it kills me. Thanks for watching.