I believe that Fentanyl has been a pretty major killer. Because of the high potency only a small amount is needed to overdose. Bad people lace drugs with them because its cheaper than the drug people think they're buying.
This may be the ratio of how much more powerful fentanyl is and how much is needed to OD. Don't quote me on that though. I'm sure there are people with more knowledge who will post.
RE: What's The Number One Killer of Americans Under Age 50? Hint: Not Guns, Not Vehicle Accidents