How drugs you don't take can hurt you

Most of us have heard of the placebo effect: something makes you feel better because you think it will. Like how that first sip of coffee wakes you up in the morning, though the caffeine hasn’t hit your bloodstream. And how your headache feels better 10 minutes after popping some Advil, even though the biochemical effect won’t set in for another 20 minutes. What you might not know as much about is the nocebo effect - or how drugs you didn't take can cause side effects and even death!

The Placebo Effect

The placebo effect (Latin for "I will please") is extensively used in clinical trials. The most common setup for testing  a drug is to divide subjects into two groups, one of which gets the test drug for their condition, the other of which gets a sugar pill. The individual patients and the doctors monitoring the trial don’t know which people got which treatment.

The efficacy of placebos is sometimes called the “expectancy effect.” I.e., if a patient really believes it will work, it does (at least for a while). Researchers have shown that you can give the same placebo to two groups, telling one group that it will have one effect (such as muscle relaxation) and the other group that it will have the opposite effect (muscle tension) and you will observe relaxation in the first group and tension in the second. Another contributor to expectation is size and cost of placebo drugs – the more a patient pays for a placebo, they better it will work!

How does this work? An interesting hint comes from a study showing that the placebo painkiller effect can be blocked by using an opioid antagonist. This suggests that endogenous (i.e. genetically produced) opioids like endorphins are released because you  expect pain relief, but this effect tends to wear off over time, because you’re not receiving real drug to relieve pain.

The placebo effect can last for a long time, depending on the condition. Placebo painkillers have been reported to last as long as 8 weeks, and placebos for rheumatoid arthritis for as long as 2 years!

The Nocebo Effect: 

But the flip side of the expectancy effect is the “nocebo” effect (Latin for "I will harm"). In a clinical trial for painkillers, for example, the placebo group will often display side effect from the drug as well as pain relief – even though they only took a sugar pill!

A retrospective study in Pain looked at 73 studies of painkiller vs. placebo trials for migrains that used three classes of pain drugs (NSAIDS, triptans and anticonvulsants). This study analyzed side effects experienced by placebo patients in all trials, and found that the side effects they experienced matched the drug they believed they were receiving!

Another nocebo study assessed subjects who believed they got headaches from cell phone radio frequencies. Subjects were then allowed to watch TV and received calls from researchers on a cell phone. Some subjects had a phone that output normal cell phone radio waves, while others had a sham phone that did not emit radio waves. In fact, subjects with sham phones reported worse side effects than people with the real phones!

Yet another nocebo effect is “MSG sensitivity.” Certain people reported migraines, hyperactivity and other symptoms in connection with MSG consumption. However, a double-blind placebo-controlled study found only one reaction to MSG – but wait! That patient had eaten placebo! Expectations strike again!

The nocebo effect can be more sinister, for example patients who know they are diagnosed as terminal may die faster than those who don’t know. Some researchers believe that the nocebo effect may also explain why curses from black magic can adversely effect those who believe in it and know they have been cursed.