The reverse placebo effect comes about when a course of drug treatment is less effective then it ought to be because the patient pessimistically questions whether the treatment will be effective on them. By way of example, a typical somebody with a typical headache given a typical ibuprofen will experience some relief from the headache. At least part of the relief experienced, and perhaps more of it in especially optimistic and placebo-prone people, will arise from the recipient’s expectation of relief. But to the person experiencing a negative placebo effect, their expectation will be that their system is especially nonreceptive to this treatment, and that it will not really offer all that much relief. And so they will experience diminished relief. In effect, they will shrug and mutter, “this isn't going to help me much.” And so it will not. The headache will persist, even if to a lessened magnitude, simply because they believe the headache will persist.

This is somewhat similar to the nocebo effect (and the latter is sometimes defined so as to encompass the former), though that possibility usually focuses on the mentally stimulated experience of negative side effects and similar newly-introduced negative experiences due to the taking of the medication. Whereas the reverse placebo effect is simply a reduction in the effectiveness of actual medication to treat the actual condition. Naturally, there is a limit to the capacity of the human mind to reject the effect of a drug on the body. Try offering somebody who thinks drugs don't work on them a tab of LSD, and see how quickly their conviction that this won't have any effect on them will give way to the transformation of reality into dancing spiderwebs of eleventh dimensional colors of light.