 Death by drug overdose has been on the rise in the US with a 2.2-fold increase from 2002 to 2015. But what is the most dangerous drug in the world? If we're simply talking about the most lethal substances, scientists use something called the median lethal dose, or LD50, which measures how much of a substance is required to kill half the members of a tested population. So something like coffee requires around 13 grams to kill a 70 kilogram person, while the venom of an inland type hand snake requires much less with only 0.00175 grams. Using this method, the most deadly substance on Earth? Bautchilineum toxin, or Botox. Oral ingestion would require only 0.0000007 grams to kill a 70 kilogram person. However, most dangerous doesn't always mean most lethal. In the UK, a group of experts decided to look at how much harm the most common recreational drugs cause using 16 parameters, including types of physical, psychological, and social harm. For example, a drug may cause physical damage but not be lethal. It could cause you to become completely dependent. It can be more likely to cause loss of relationships or decreased mental functioning. And these are all forms of harm. Using these criteria, they concluded that the most dangerous drug to an individual is heroin. Heroin can be injected, snorted, or smoked, and enters the brain rapidly, particularly when injected into the bloodstream. Here, it attaches to opioid receptors, creating a surge of pleasurable sensations. It's also highly addictive, with intense withdrawal symptoms that begin with an hours of a hit, including insomnia, cold flashes, muscle and bone pain, nausea, and vomiting. Receptors in the brainstem are also affected, impacting important physiological processes, such as breathing and blood pressure, which is why overdosing causes breathing to slow or stop entirely, leading to the accumulation of CO2 in the blood and ultimately death. And since heroin is unregulated, it is especially difficult for users to know the strength of the dose, making the risk of odying high. Additionally, the drug can be mixed with other compounds like fentanyl, making it even more dangerous. Fentanyl, like heroin, is an opiate, but is 50 to 100 times as strong because it is very lipophilic, meaning it penetrates our fatty brain more easily. And in terms of lethality alone, it's much more dangerous than heroin to users. It was initially used as a prescription pain reliever, but because of its addictiveness, it was mostly used in end-of-life cases. It is since emerged as a recreational drug where the number of reported fentanyl-related overdoses has increased seven times from 2012 to 2014 in the US and continues to see more widespread use worldwide. But there is an even more dangerous drug. Though crack cocaine and methamphetamine topped the list of harm to an individual just after heroin, finding the most dangerous drug overall involves studying 20 different popular drugs and also looking at the harm they place on others. This includes the physical and psychological harm, crime, degradation to families and communities, and economic costs. And in the end, it turns out the most dangerous drug in the world is alcohol. To ensure this wasn't simply a UK phenomenon, a European group attempted the same process, putting more emphasis on individual harm and less on economic harm, and even with the different weightings, the two groups found largely the same result. A large contributor to the danger of alcohol is its wide use. The majority of the world does drink and drink a lot, with an average of 17 liters of pure alcohol consumed per person per year. The World Health Organization found 3.3 million deaths worldwide were caused by dangerous alcohol consumption in 2012, meaning alcohol kills one person every 10 seconds. But experts don't recommend a prohibition stance on alcohol. By all accounts, the war on drugs has been deemed a failure, and nations who have stepped away from hardline policies and implemented decriminalization, harm reduction and education have seen significant declines of drug abuse. If you'd like to learn more about the failure of the war on drugs, check out in a nutshell's video who so brilliantly helped us animate this video. A huge thanks to them for helping out, and continuing to inspire us with their intelligent and well-designed videos. You can also check out our drug series if you'd like to learn more about the impact of specific drugs like marijuana, cocaine and LSD on your brain.