💊Placebos: A spoonful of weird science

We think we know placebos. They’re sham medicines that delude patients into feeling better. They have predictable, purely psychological effects. And they make great controls in clinical drug trials. But a growing body of research suggests that we might have placebos all wrong. PET scans show that placebos have [measurable, physiological effects on brain chemistry](. Pharmaceutical companies have discovered that drugs that outperform placebos in one country fail in another. And puzzlingly, the placebo effect seems to have [grown steadily stronger]( in clinical trials since the 1990s—[but only in the United States](. The fickleness of the placebo effect isn’t just a medical curiosity; it’s a big problem for Big Pharma. Prospective drugs are now much less likely to beat increasingly stiff competition from placebos, biting into pharmaceutical profits and [slowing drug discovery](. Meanwhile, drug companies have [outsourced their clinical trials]( to more friendly arenas overseas, where the placebo effect is weaker than in the United States. Sit down. This may be hard to swallow. 🐦 [Tweet this!]( 🌐 [View this email on the web]( Sponsored by [Quartz Obsession] Placebos December 17, 2018 Empty promises? --------------------------------------------------------------- We think we know placebos. They’re sham medicines that delude patients into feeling better. They have predictable, purely psychological effects. And they make great controls in clinical drug trials. But a growing body of research suggests that we might have placebos all wrong. PET scans show that placebos have [measurable, physiological effects on brain chemistry](. Pharmaceutical companies have discovered that drugs that outperform placebos in one country fail in another. And puzzlingly, the placebo effect seems to have [grown steadily stronger]( in clinical trials since the 1990s—[but only in the United States](. The fickleness of the placebo effect isn’t just a medical curiosity; it’s a big problem for Big Pharma. Prospective drugs are now much less likely to beat increasingly stiff competition from placebos, biting into pharmaceutical profits and [slowing drug discovery](. Meanwhile, drug companies have [outsourced their clinical trials]( to more friendly arenas overseas, where the placebo effect is weaker than in the United States. Sit down. This may be hard to swallow. 🐦 [Tweet this!]( 🌐 [View this email on the web]( Ready to go deeper? --------------------------------------------------------------- We’re tired of all the shouting matches and echo chambers on social media, and thought you might be, too. On the new Quartz app, we’ve gathered a community of curious thinkers and doers to have high-quality discussions about the most important stories each day. It’s like an ongoing conversation with CEOs like Richard Branson, Punit Renjen, Arianna Huffington, and many more. Now available for iOS and Android. [Try the Quartz app!]( Reuters/Srdjan Zivulovic By the digits [27%:]( How much more effective new pain medications were than placebos in 1996 [9%:]( How much more effective new pain medications were than placebos in 2013 [90%:]( Share of potential pain drugs failed to outperform placebos between 2005 and 2015 [$14.95:]( Price of 45 Zeebo pills, which contain no active ingredients, marketed as “honest placebos” [46%:]( Share of American doctors that report regularly prescribing placebo treatments Sponsored by Citrix Today’s workforce has a productivity problem. --------------------------------------------------------------- Thanks to technology, today’s workforce is more connected than ever -- but that’s not entirely a good thing. The complexity of office technology is hurting worker productivity: people are actually doing less work with more tech.[Listen to two experts discuss the productivity paradox]( Giphy EXPLAIN IT LIKE I’M 5! Why do placebos work? --------------------------------------------------------------- Here’s what we know: if you give a patients a phony treatment and a reasonable expectation that it will work, they tend to report feeling better—especially if they suffer from conditions like chronic pain or anxiety. But doctors and researchers still aren’t totally sure what mechanism is creating that improvement. They have a few competing theories. Regression to the mean: Patients come in for treatment when their symptoms are particularly bad, but with time their malady gets better on its own. In depression, for example, about a third of patients [get better without drugs or a placebo](. Unreliable self-reports: Thanks to confirmation bias, after getting treated, patients may be on the lookout for signs that they are improving and ignore signs that their condition is getting worse. Or patients may not feel much different at all, but report that their condition has improved to make their doctor happy. Pavlovian conditioning: If you give a patient a real drug, its active ingredient may trigger a physical response from the patient’s body—for example, decreasing the production of interleukin, a crucial protein in the immune system. But, as [one 2012 study showed]( if you secretly swap out the real pill for a placebo after a few days, patients’ bodies will still respond by producing less interleukin. Just as Pavlov’s dogs started to salivate at the sound of the bell, patients’ bodies suppressed their immune systems because of their associations with the act of taking a pill. Giphy Pop quiz What color pills make the best placebo tranquilizers? RedBlueYellowWhite Correct. Unless you’re treating Italian men, who associate the color with their national soccer team. Incorrect. If your inbox doesn’t support this quiz, find the solution at bottom of email. Fun fact! Placebos have an “evil twin”—[nocebos]( trick patients into feeling worse instead of better. Some researchers blame the nocebo effect for the [recent rise of gluten sensitivity](. Have a friend who would enjoy our Obsession with Placebos? [ [Forward link to a friend](mailto:?subject=Thought you'd enjoy.&body=Read this Quartz Obsession email – to the email – Brief history [14th century:]( “Placebo” enters the language as a word for hired mourners, after the first word of the Catholic Office of the Dead, a cycle of prayers sung at funerals. [18th century:]( The word, which comes from the Latin for “I will please,” enters medical jargon to refer to prescriptions given to placate patients. [1784:]( Benjamin Franklin performs what might be the first ever single-blind placebo-controlled study, demonstrating that the healing powers of Franz Anton Mesmer’s “animal magnetism” were a sham. [1889:]( Charles Brown-Séquard begins selling a wildly popular “elixir of life” made from the testicular extracts of dogs and guinea pigs. [1955:]( Henry Beecher publishes “The Powerful Placebo,” arguing for placebo-controlled randomized clinical trials. [1962:]( The American Food and Drug Administration requires that drugs be proven effective before they’re sold to the public, prompting pharmaceutical companies to begin using placebo-controlled trials. [2011:]( Harvard Medical School establishes a program in placebo studies. AP Photo/Darron Cummings Quotable “One of the most successful physicians I have ever known, has assured me, that he used more bread pills, drops of colored water, & powders of hickory ashes, than of all other medicines put together. It was certainly a pious fraud.” —Thomas Jefferson, in [a June 21, 1807 letter]( to physician and friend Caspar Wistar Watch this! Two PBS reporters explain what traditional medicine can teach us about how our expectations—and the theater of medicine—can affect our perception of pain. Giphy BREAK IT DOWN The wide world of shams --------------------------------------------------------------- When you think of placebos, you probably picture sugar pills. But placebo treatments come in many forms to better mimic a wide range of medical interventions. Sham surgeries: Patients undergo all the usual pre-surgery rituals of fasting, donning a hospital gown, receiving anesthesia, and giving themselves over to the care of a surgeon. But while the patient is under, the doctor just makes an incision and stitches it back up. A [2014 analysis of 53 clinical trials]( found that three-quarters of the time, the sham surgeries helped—and about half the time, they were as effective as the real procedure. Saline injections: Patients get an injection of salt water with about the same level of salinity as their blood and most tissues, instead of a drug. In a [2017 analysis of 13 studies]( placebo injections were found to make a clinically meaningful improvement in patients’ osteoarthritis as long as six months after the fake shots. Fake acupuncture: In [a 2009 study]( Harvard medical researcher Ted Kaptchuk treated patients with irritable bowel syndrome by giving them fake acupuncture, using retractable needles that never broke the skin. One group of patients interacted with a warm practitioner who asked many questions and expressed optimism that the treatment would work. Another group interacted with a cold practitioner who didn’t say much. And a third got no placebo treatment at all. Kaptchuk found that the different “doses” of placebo yielded different levels of relief—those with a warm practitioner felt better than those with a cold one, and those who got fake acupuncture felt better than those who went untreated. Phony salves: Last year, Stanford researchers gave 164 subjects a histamine skin-prick meant to provoke an allergic reaction, then rubbed the spot with a placebo cream. [They found]( that how warm the doctor was, and whether they said the cream would help or hurt, affected the size of the lump that showed up on patients’ skin. Jargon watch Enter the placebome --------------------------------------------------------------- As if teasing out how the placebo effect wasn’t hard enough, researchers are studying whether some people are genetically more susceptible to it than others. [“Placebome”]( is the term they chose for the genetic biomarkers that might play a role. Giphy Million-dollar question Why is the placebo effect getting stronger in the US? --------------------------------------------------------------- There are two main theories. First, the country allows direct-to-consumer drug ads, which could give Americans [more faith in prescription drugs generally]( and thus more sensitivity to the effect. Second, drug trials have gotten [longer and more sophisticated]( with more patient support, which may have the same effect. It has profound implications for treatment [if the power of the placebo can be harnessed]( but meanwhile it’s raised the bar for companies getting new drugs to market. take me down this 🐰 hole! Harvard medical researcher Ted Kaptchuk believes the placebo effect isn’t just a nuisance to be controlled for in clinical studies—it’s an understudied but crucial piece of how health workers heal patients. The New York Times Magazine explores [his obsessive quest]( to prove the value of placebos to the medical community. Reuters/Amir Cohen Poll Would you take an honest placebo to cure what ails you? [Click here to vote]( Self-delusion is my strong suitOnly if a doctor prescribed itI prefer drugs, thank you 💬let's talk! 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