Basically the best predictor of serious drug abuse is whether someone had a highly adverse childhood. Those who do are 4600% more likely to use injection drugs then those who didn't. Essentially every single street level drug addict was abused as a child. If you didn't suffer serious abuse as a child then you could use the same drug without developing an abusive relationship with it. (Listen to the public radio interview with the Mator Gabe I linked to, and also read the adverse childhood experience study and specifically the analysis of the drug addiction portion.)
2) The norms of a person's peer group and also why the person is using the drug are also very good predictors of how likely a person is to get addicted. E.g. someone using a drug to escape from emotional pain is much more likely to get addicted to a drug than someone using it for analgesic or spiritual purposes.
3) The method of consumption also plays an enormous role in how likely someone is to become addicted. The faster the drug hits you, the more likely you are to become addicted. Taking a drug transdermally is less addictive than eating it, eating a drug is less addictive than taking it sublingually or snorting it, snorting a drug is less addicting than injecting it, and injecting a drug is less addictive than smoking it. That's why you can drink coca tea several times a day indefinitely without becoming addicted, whereas people smoking crack get addicted extremely quickly.
4) There are basically two components of addiction, physical addiction and 'moreishness'. Physical addiction is a result of how increasing your neurotransmitter levels decreases your density of receptors for those neurotransmitters, so once you stop taking a drug you don't have enough neurotransmitters anymore so you can be in enormous pain (depending on the drug, the method of administration, etc.)[1]. The vast majority of people can just deal with the pain and it's not a big deal. But for those with severe depression, a history of abuse, or other mental problems, they don't have enough inner strength to deal with this pain so they just keep using the drug until it kills them. It's actually very very similar to the studies on 'learned helplessness' that they do with rats, where they see how long they swim before they drown. (The rats with depression just give up and drown much faster than the normal rats, even though they can physically swim just as well.)
The second issue is with the 'moreishness' of a drug. There are a few drugs, especially stimulants, where there is a very short high followed by a ridiculously wicked comedown. With these drugs people tend to just keep doing the drug until they run out of it. The best example of this is probably MDPV, which is usually marketed as 'bath salts'. When people tell you that quitting crack is a joke compared to quitting this drug, you know it's probably bad news. But again, those without severe mental issues do eventually manage, they're just in a world of pain for about a week.
5) The worst drugs to quit if you've been severely addicted are benzos (e.g. xanax, ativan, valium, etc.), and also methadone and some of the other synthetic opiates. Even heroin addicts get through the worst of their symptoms in a week or so, whereas xanax addicts can't sleep for up to a year or more. And what's worse, they feel like they're constantly being electrocuted over and over, they can't think straight, and there are plenty of other horrific issues as well. So basically you don't want to get addicted to drugs with horrific physical withdrawals like xanax, and you don't want to use drugs that are ridiculously moreish, like MDPV, but other than that drug addiction is almost entirely a function of the person and not the molecule.
Obviously you want to follow best practices when using any drug. E.g. if you want to try psychedelics then read Neal Goldsmith's new book Psychedelic Healing, which explains how to use the substances safely and effectively. But if you don't have any mental issues, and if you know how to use a given drug safely, then the risks can be minimal as long as you're disciplined enough to actually do everything correctly every time. (Not unlike driving, rock climbing, skiing, etc.)
That's not to say that everyone should go out and start using drugs. But the fact is that according to government estimates, around 89% of Americans use illegal drugs at some point during their lives (at least once). And making poor decisions about drug usage (including legal drugs) kills around 30% of Americans.[2] So while people say you should eat healthy and exercise, and they're right, in fact learning how to use drugs safely has a much better bang for your buck in terms of improving your overall expected health and lifespan.
It's undeniable that when used properly drugs can have enormous benefits for treating medical issues, relaxing, socializing, gaining spiritual understanding, etc. And what's more, I would argue that if you haven't read extensively about and also tried (for most of them) the drugs that have shaped western civilization (alcohol, tobacco, cannabis, sugar, chocolate, tea, coffee, cocaine, lsd, psilocybin, MDMA, mescaline, and opium), you aren't even really fully capable of understanding the world we live in and why society is the way it is.[3] Which isn't to say that everyone should use all the drugs I just mentioned, but I think taking the time to understand not only the health aspects of drugs, but also how these drugs have affected art, architecture, music, the law, medicine, philosophy, psychology, technology, etc. is probably the single best investment one could make in terms of becoming a self-actualized and well-educated person.
[1] With opiates you also get oxidative damage to receptors. It's effectively the same as having their density reduced, but it's worth mentioning because it can be largely preventing with certain supplements, and also possibly reversed with ibogaine.
[2] http://news.ycombinator.com/item?id=1877771. N.b. it's possible that alcohol-related fatalities have been wildly exaggerated by the NHTSA.
[3] I might actually add ayahuasca to this list as well, though I didn't include it because it hasn't really had any impact on western civilization, at least not yet. It seems like smoked DMT may end up being important as well, though as of yet its contributions have been fairly peripheral.
Do you characterize people with other drug sensitivities as "unable to handle their [Advil/Codeine/Penicillin/Accutane/etc]" ?
A drug makes 1% or 0.1% of its users go insane can still reasonably be characterized as very dangerous.
> And what sorts of drugs will not mess you up when taken in "recreational" dosages?
Alcohol is one, if we change "not addictive" to "not always addictive".
Alcohol certainly can be powerfully addictive, but you can also use it periodically in small doses throughout your adult life without becoming dependent.
Alcohol certainly can be massively destructive, but, depending on your definition of a recreational dose, it not. It can actually have health benefits, and is associated with longevity.
The Psychedelics Experience by Peter Stafford
Pikhal by Alexander Shulgin
Acid Dreams by Lee and Shlain
The Illuminatus Trilogy by Shea and Wilson
Plants of the Gods by Richard Evans Schultes
The Archaic Revival by Terrence McKenna
The Psychedelic Explorer's Guide by James Fadiman
That should get you started. Good luck, and have a safe trip.