As one poster indicated, the danger lies in the fact that a speedball can allow for the user to assume he has not taken too much of the opioid, where in fact he has, but does not know this on account of the given stimulant's counter-effects, which stimulate the CNS. When the stimulant wears off, the counter-effects wear off, too, and the CNS stimulation which was keeping the user from respiratory or cardiac problems/arrest is no longer there to 'protect' the user from the large dose of the opioid. Often, the danger can be thought to be particularly present when the user re-doses while still affected by the stimulant, and the user miscalculates how much of the opioid he is using is safe for he feels subjectively 'okay' to dose again, when in reality he is not. With almost any upper-downer mix, the danger is not so much in any 'stress' or 'strain' on the CNS itself or the heart or some such, not that many drugs cannot strain the heart, for they can obviously, but that would be done anyhow otherwise, in combination or alone.