Not really...it's all in how you are wired. I can handle E, coke, percs without blinking. Im not a "downer" type person....I find them boring and annoying
Oh it is, you see it doesn't matter how you are wired you are abnormal. For example if I line 100 people up give them amphetamine I predict they will all be energetic etc. Some may become paranoid some become excited and hypomanic, that is the indivdual response, the pharmacokinetics are the same. Sativa's are energizing, they improve dopaminergic tone, paranoia is too much dopamine.
Yes you don't like downers but they still tranquilize you, regardless of your feeling about the effects, some like being sedated you do not.
It's not really as complex as indivdual neurochemistry, preference for drugged states is important.