Yup, medication can get in the way (such as antipsychotics that prevent you from tripping), otherwise typical reasons are:
- Low or non-existent dose (very common, and to quote House: 'people lie')
- An imposter drug: if you swallowed the blotter and your friend kept it in his mouth for a while, a NBOMe compound could explain what happened (unfortunately: common nowadays)
- 'Unnatural' tolerance: if you took certain drugs in the week prior, this can prevent you from tripping (common)
- Certain set & settings: there are situations that sober you up, especially if the effects were not strong to start with (uncommon)
- Indeed uneven dosing of the blotter (not that common AFAIK)
- 'Natural' tolerance: some people are just hardheaded, although in some cases people may think that but it just turns out to be one of the reasons above. (uncommon)