Pack of 2 [English] works by Yuki Seto (also written “Yuuki Seto”) : 375 (Minako) and Bookmark

The most basic thing is that these drugs are dangerous, especially if used repeatedly and over a protracted period. The main hypnotics strong enough to be used as date-rape drugs are the more powerful benzodiazepines, which are sometimes used to treat severe insomnia. They are addictive, and repeated use can build tolerance. They're also generally short-acting, since the long-acting ones have residual effects. Oh, and the side effects: we're talking seizures, psychosis, mood disorders, exhaustion due to deteriorating sleep quality, insomnia, confusion, cognitive and learning impairment, gastrointestinal issues (your gut has a lot of neurotransmitter receptors, so this is common for psychoactive drugs), and respiratory depression or arrest. Of course, most drugs have a long catalog of rare side effects, but for hypnotics, they're not so rare. In general, more powerful hypnotics have worse side effects — for instance, Rohypnol is very effective, but insomniacs who use it may suffer rebound effects even after a few days of use. If drugs like these are being used on someone night after night, they're going to be suffering intense side effects and addiction, and at some point the drug will start to fail.

Most sleeping pills and drugs, though, simply aren't that strong. They don't conk you out, because being conked out can be really dangerous, and it's not really what happens to you when you sleep normally. And general anaesthesia, which is strong enough, simply isn't safe to use unless you're an anaesthesiologist. For reference, they can't use it in a medical setting if you've eaten recently, because there's a decent chance that you'll choke to death because you're unable to vomit. It's what they put you under with for surgery — little more explanation is needed.

GHB is a weird case, being neither of those – it's a chemical that occurs naturally in your blood. It's still dangerous, though, and has been associated with respiratory arrest, vomiting death, and addiction. It's also got a strong salty flavor, enough that it would be hard to miss in something like tea (date rapists often hide it in mixed drinks, or other things which will overpower the taste).

Note that I'm not a medical professional — I read a lot of wikipedia, and I've been around a lot of people who use prescription psychoactive drugs, so I've picked some things up.