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Here's an example of a real difference in the brain that predicts an interesting relationship with psychoactive substances, both endogenous and exogenous: the OPRM1 A118G SNP. There's evidence that it predicts (i) a much greater risk of alcohol dependence; (ii) a much greater chance that naltrexone can be used to successfully treat said alcoholism once it happens; and (iii) a requirement for dramatically more opioid pain medication to achieve equal pain relief after surgery. This is a functional polymorphism that changes the way beta-endorphin binds in the brain; i.e. it's a real physical thing that you're born with. FAAH 385A is another interesting one.