 Even as proponents of cannabis legalization contend that marijuana is a harmless natural substance that improves quality of life, a growing body of evidence links it in a small but significant number of users to the induction or aggravation of psychosis. Psychotic disorders are arguably the most serious of mental illnesses, the best known being schizophrenia. Schizophrenia is an illness characterized by delusions, hallucinations, odd behavior, and is among the top 10 leading causes of disability in the United States, affecting approximately 1% of the general population. Can cannabis cause it? Nearly 2,000 studies have been published on this topic over the last half century, and we hear about the pro-psychotic effects, but how clear is that link? Well, population studies have consistently demonstrated a strong dose-dependent association between cannabis use and the risk of psychotic disorders. This is what they mean by a dose response, studies showing that the more cannabis people used, the more likely they were to be psychotic. But that doesn't mean cannabis is the cause, it could just be a correlation, or even a consequence of the disease. Yeah, the link between cannabis and psychosis is well established, but maybe that's just because patients with mental health problems self-medicate with cannabis to relieve their distress. But there isn't just a link between cannabis and psychosis in snapshot and time cross-sectional studies, but in cohort studies as well, where people are followed over time, and so you can see the cannabis use often precedes the psychosis and not the other way around. Now, it goes without saying that the vast majority of people who use cannabis do not develop schizophrenia and many schizophrenics have never used cannabis, but overall these studies are considered to be strong enough evidence to warrant a public health warning. There is another potential explanation, though, even though cannabis use precedes schizophrenia, maybe whatever genes drive schizophrenia also just make it more likely you start smoking pot? The biggest strike against the cannabis schizophrenia link are country-by-country ecological studies that don't seem to show more disease in areas where there's more use, and overall schizophrenia rates seem to have remained stable or even gone down worldwide since the 60s, even though there's been a big bump in cannabis use since then. I mean, if about 10% of schizophrenia cases are attributable to marijuana use and there's been a four-fold increase in use, why hasn't there been a 40% increase in the prevalence of schizophrenia? The problem with that argument is that there's apparently little reliable evidence on the true trends in the incidence of schizophrenia. Or maybe it's more of a potency issue rather than just cannabis in general. The bottom line is you just don't know when to you put it to the test. You can't just randomize kids to cannabis, but in a way mother nature set up a natural experiment for us. There are genes that kids randomly get that can increase their likelihood of smoking pot. Do those kids then go on to have a higher risk of schizophrenia? Yes, supporting all those population studies that suggest cannabis plays a cause and effect role in the development of schizophrenia. Okay, but by how much? Let's break it down. Even if cannabis use doubles risk, that would only mean going from like a 7 in 1,000 chance of going crazy to like 14 in 1,000, so like a 1 in 140 chance to a 1 in 70 chance. Now if it runs in your family that's different and that doubling could mean going from like 1 in 10 to 1 in 5, but on a population scale it could take thousands of users quitting to prevent a single case of schizophrenia. So from a public health standpoint, addiction is a far more common problem and people are probably 9 times more likely to become addicted to marijuana, even though that itself is relatively rare than to develop psychosis in their lifetime.