Are Americans more gullible than other people? A recent McGill University analysis finds Americans respond more to placebo pain pills during clinical trials, and, even more, that response has grown stronger over time.

The placebo effect is a well-known phenomenon. A placebo is defined as an inert, innocuous substance that has no effect on your body, yet when patients are told a placebo is an actual drug, some will feel better as a result of taking the fake pill. While most of us believe Psychology 101 can neatly explain this, the deeper mysteries of placebo effect are more extensive than you might expect.

For instance, the McGill University study involved a review of the results from 84 clinical trials of drugs conducted around the world between 1990 and 2013. Pain reduction in the placebo group increased steadily during that period, reaching an average of 30 percent decrease in pain levels by 2013. While past studies recorded a similar increase in placebo response during trials of antidepressants and antipsychotic drugs, the pain review showed one important difference: Americans were the main driver of this effect. (Importantly, the research on antidepressant and antipsychotic placebos did not compare effects around the world.)

“It remains to be determined why the United States is an outlier with respect to its clinical trials,” Alexander Tuttle, a doctoral student in psychology and co-first author of the paper, said in a McGill press release.

He and his colleagues speculate all the direct-to-consumer advertising for drugs (only New Zealand also allows drug ads) has increased Americans’ expectations of the benefits of drugs and creates stronger placebo effects, too. Tuttle and his co-researchers also say it could be the fact that United States’ drug trials are longer, bigger, and probably cost more, and these factors may enhance patients' expectations.

Though that may sound far-fetched, other studies offer proof that the placebo effect can be altered by a variety factors, including nationality. Here are five more:

High Costs Can Create Stronger Effects

“Perceptions of cost are capable of altering the placebo response in clinical studies,” wrote the researchers behind one study involving Parkinson’s patients. This may be explain why many people believe they have a stronger response to a brand drug than a (cheaper) generic.

In this study published earlier this year, University of Cincinnati researchers gave all 12 participants with moderately advanced Parkinson’s first one placebo and then the second placebo. In this case, both the placebos were identical saline injections, but with one twist: One placebo was referred to as “expensive” the other “cheap.” According to the researchers, the “expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than,” the actual drug.

Pills vs. Shots

Generally, injections work better than pills in eliciting a curative response. In at least six clinical trials, the shot trumped the pill when participants were given placebo injections and compared to those given placebo pills, according to Harvard researchers. The various studies examined effects on patients with rheumatoid arthritis, osteoarthritis, and high blood pressure.

Interestingly, a similar study conducted on 64 schizophrenic patients did not share in these results. In this case, patients were told their sham pills or shots would either lead to increased activity or decreased activity. Whether given a placebo pill or placebo shot, the behavior of these 64 patients did not change in the least.

Placebo Surgery is a Thing… and it Works

Pills, ointments, even mildly invasive shots are one thing, but it’s hard to imagine experiments where real people receive sham surgery. However, that’s exactly what one group of mad scientists in Finland did with 146 patients between the ages of 35 and 65. While all the participants suffered persistent knee pain, none had responded to conservative treatment. After tests, each showed evidence of a tear in the medial meniscus. So the researchers randomized these participants to receive either the most common orthopedic surgery performed in the U.S. (arthroscopic partial meniscectomy) or placebo surgery.

“The outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure,” wrote the authors in their conclusion. Imagine that.

Even Infertility Can Be Solved With a Placebo

A placebo appeared to boost the fertility rates of women with polycystic ovarian syndrome. A 2010 study found that 15 percent (5 of 33 women) got pregnant while taking placebo over a six-month period, compared with 22 percent (7 of 32) who took metformin, a fertility drug. This, according to the Wall Street Journal, is a statistically insignificant difference, one that may be due to the fact that the women given a placebo felt some much-needed stress relief. Fertility issues take a toll.

Man’s Best Friend, Other Animals Also Respond to Placebos

A 2010 joint effort from North Carolina State University and University of Minnesota found that even dogs respond to placebos. In the 2010 study, 34 dogs with epilepsy were observed by researchers who recorded and averaged each dog's weekly number of seizures. Then, 28 of the dogs were given placebo treatment while other dogs received either surgical implants or drugs. Of the placebo treated dogs, 79 percent demonstrated a decrease in weekly number of seizures and 29 percent showed a decrease in seizure frequency by 50 percent or more.

The scientists speculate the hopes of the owner and how that translated into treatment of the dog during the study might have favorably impacted seizure frequency. That said, placebo effect has been demonstrated on laboratory animals as well, the authors note.

History Lesson

The term "placebo" became part of medical jargon in 1772 when a Scottish physician and pharmacologist, William Cullen, introduced the term in his lectures. By 1785, the word first appeared in a medical dictionary which described a placebo as “a commonplace method or medicine,” according to the Merck Manual; two editions later, it was described as “make-believe” medicine. However, placebos were used long before they were officially named or defined.

According to one scholar, family doctors often gave demanding patients useless pills or ointments simply to satisfy their expectations: no one wants to go home empty handed. In most cases these placebos were not “pure,” instead they were more usually some mild medicine deemed powerless or ineffective in treating the condition at hand.

Henry K. Beecher is given credit for developing what we refer to as the “double-blind trial,” where neither patient nor doctor knows whether or not a given treatment is a real drug or an inert substance. In 1955, he published a paper outlining his thoughts on the necessity of creating such a complex ruse as a way to control the psychological variables when testing new treatments.