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In the Requiem For A Dream (2000) which is based on a novel written in '78, The grandma uses rainbow pills for weight loss and after overdosing on them. She loses Her sanity and ends up getting ECT.

According to some internet resource I have read. "As any first year pharmacist (or seasoned drug user) can tell you: mixing uppers with downers is a very, very bad idea. (Think pharmaceutical grade speedball.) "So what exactly are uppers and downers? Why is it a bad idea to mix them?

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"Uppers" and "downers" are colloquial terms for drugs with stimulant effects versus depressive effects, respectively.

The primary acute health concern with either (i.e., what tends to kill people in an overdose) is overstimulation or oversuppression of the cardiovascular/respiratory systems.

One recreational combination of upper/downer is a "speedball" of cocaine and heroin/morphine. The combination can provide a substantial euphoria, and a reduced perception of impairment and other side effects because of counteracting stimulant/depressive effects. Therefore, a drug user may underestimate how intoxicated they are and is more able to use more of each at the same time.

However, these drugs do not have the same time course. When the immediate stimulant effects wear off, the respiratory depressive effects of the opioid persist, plus any rebound effect from withdrawal from the stimulant. The result is more respiratory depression than would be expected, leading to respiratory arrest and death.

There have been many deaths of famous people (and many more not-so-famous) attributable to these drug combinations, including people who were long-time drug users beforehand.

Ethanol (alcohol) can be even worse because of paradoxical drug reactions: alcohol is typically a depressant, but can also have dis-inhibitory effects as well. Simultaneous alcohol and cocaine use is also strongly associated with overdose death.

More generally, combinations of stimulant and depressive drugs are likely to mask side effects that occur prior to the level at which the outcomes are dangerous, and individuals prescribed one category of drug likely have contraindications for the other. There is also increased potential for abuse due to larger combined euphoric effects and combined chronic effects depending on the specific drugs.


Coffin, P. O., Galea, S., Ahern, J., Leon, A. C., Vlahov, D., & Tardiff, K. (2003). Opiates, cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990–98. Addiction, 98(6), 739-747.

Ellinwood, E. H., Eibergen, R. D., & Kilbey, M. M. (1976). Stimulants: interaction with clinically relevant drugs. Annals of the New York Academy of Sciences, 281(1), 393-408.

Farré, M. A. G. I., De la Torre, R., Llorente, M., Lamas, X., Ugena, B., Segura, J., & Camí, J. O. R. D. I. (1993). Alcohol and cocaine interactions in humans. Journal of Pharmacology and Experimental Therapeutics, 266(3), 1364-1373.

O'Driscoll, P. T., McGough, J., Hagan, H., Thiede, H., Critchlow, C., & Alexander, E. R. (2001). Predictors of accidental fatal drug overdose among a cohort of injection drug users. American Journal of Public Health, 91(6), 984.

Ochoa, K. C., Hahn, J. A., Seal, K. H., & Moss, A. R. (2001). Overdosing among young injection drug users in San Francisco. Addictive Behaviors, 26(3), 453-460.

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