Among psychonauts, a hardhead is someone who needs a high dose of a substance to achieve the same subjective effects as another person of similar mass and sex (that is, hardheadedness is figured on mg/kg, not on raw dose). Some people see hardheadedness as a virtue (e.g., people who brag about how much they can drink before passing out); more serious users instead value working with the ASC. More pragmatically, given the artificial scarcity and high cost of most psychoactives, being a hardhead has distinct disadvantages.
A hardhead generally is resistant to most, or to a wide variety of, drugs. People who can take a lot of one particular drug, especially if they commonly use it, are said to have a tolerance.
Some reasons a person might be a hardhead:

•unusually efficient metabolism of a class of chemicals
•Low population of a relevant receptor
• precence of an endogenous chemical that blocks the relevant receptor
•unusually good homeostatic mechanisms
habituation to altered states
•Blunted perception of relevant bodily symptoms
•Habitually low awareness of emotional changes (alexithymia)
machismo or other motive for minimizing reports of drug's effects
•unusual degree of control over state of consciousness (coupled with some reason to minimize drug effects)