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Brilliant is offering all SciShow  viewers a 30 day free trial and 20% off an annual premium subscription for the first 200 people who  sign up at Brilliant.org/SciShow. You might have heard of the placebo effect.

It’s when you feel better because  you think you’re being treated for something, but you never  really got the medicine. You might have received a sugar pill  or a salt-water injection instead. But here’s the mind-blowing part: Those two placebos would affect  your body in different ways.

Because there’s more than one placebo effect. As it turns out, it’s not just a matter  of believing it’s working or not. Different imaginary treatments actually make you release different chemicals,  creating different results.

And it often depends on what  they’re pretending to be. An oxygen placebo works differently  from an anti-inflammatory placebo, which works differently  from an opioid placebo. And some objectively work better  than others!

So if not all placebos are created equal, Doc, gimme  the strongest placebo you’ve got. [♪ INTRO] Let’s start at the beginning. Placebos work. I know it may sound odd that  you sometimes feel better after not receiving a treatment that’s  been clinically demonstrated to be effective.

But, yeah,  that’s the placebo effect. A meta-analysis covering  152 publications including almost 25,000 participants found that placebos can be just as effective as drugs. That doesn’t mean that  you’ll feel better every time you take a placebo.

But in some  situations, they do the job. If you use a placebo to reduce  pain, there’s a good chance it will work similarly to real  treatment. On the other hand, if you use a placebo to reduce  nausea, it might be less effective.

And here’s why: Your experience of pain is not  something that a doctor can observe and report on without you describing it to them. It’s your subjective experience. And you can have varying amounts of pain.

So you could be one of those  slightly frowny faces on the chart. But when it comes to something  like losing your lunch, well, that either happens or it  doesn’t. It’s a binary outcome.

And placebos are better at treating subjective, continuums of concern, like pain,  than binary concerns, like puking. So part of what determines  how effective a placebo is is what you’re trying to treat. Another part of the puzzle is  which placebo you’re taking.

Just like how not every drug  is as effective as the next, some placebos are more effective than others. And some of it comes down to packaging. For instance, placebos that are presented as being “more expensive” reduce pain better.

That’s a real finding from a real study. The researchers administered  painful, but not too painful, shocks to the study participants  and had them rate their pain. Then they gave them opioid  placebo pills and readministered the shock to see if the pain changed.

And to be clear, these were  placebos pretending to be opioids. The researchers told some participants  that they were getting pills that cost about what you’d  expect an opioid to cost. And they told other participants  that they were getting significantly cheaper opioid pills… like… “Here, take this pill we paid 10 cents for.” And the cheap placebos were significantly less effective at reducing pain.

So you have to trust that the pill will work. And maybe that’s part of why brand name products get to be so expensive. Another study focused on the brand effect by using placebos to treat  a different kind of pain.

This time, they heated up  the participants’ forearms for 20 seconds, at which  point it became painfully hot. Then they told the participants  they’d get either Aspirin or the made up generic 1A Pharma pill prior to the heat being applied again. And the Aspirin placebo took away more pain than the 1A Pharma placebo did.

So there’s a brand name effect.  But this study didn’t stop there. They also used a functional  magnetic resonance imaging machine, or an fMRI, to see how people’s brains responded to brand name and generic placebos. One part of the brain in  particular was way more active when they got the brand name  placebo than the generic placebo.

And that’s the prefrontal cortex, which takes care of decision making and working memory. It’s like you’re deciding  whether Aspirin or a generic pill would work better while  you’re taking the placebo. But aside from what placebo you take, how often you take it also influences how well it works.

A meta-analysis of over  3,000 patients being treated for ulcers found that taking  more doses of a placebo was associated with feeling better faster. On average, significantly more people who took placebos four times per day were fully recovered by four weeks than people who  took them two times per day. Now, this is a correlation across several studies, so we can’t say exactly  what’s driving these results.

But one idea proposed by the  researchers is that receiving more treatment puts you in a state of mind of being cared for and healing,  which then causes your body to go through changes to make that happen. Like, your body could boost its immune system and start making more compounds  called prostaglandins, which are involved in healing  wounds and infections. But we need more research to say  definitively if that’s how it works.

All we know is that you could  get the exact same placebo as someone else and have  drastically different results because of how you interpret  the care you’re receiving. So just imagine how different the results become when you get a different placebo. For example, there are several different ways to take away an altitude headache.

That’s because these headaches come from the drop in oxygen when you reach really high elevations, which can initiate a few different  pathways to headache-town. Like, at low oxygen levels,  you could end up making more prostaglandins than usual, which open up your blood vessels  and may provoke headaches. Or, because there’s not as much oxygen, you could start hyperventilating,  which may also provoke headaches.

Those two pathways would be  treated with different approaches. You’d take something like aspirin to stop prostaglandins from being made, while an oxygen mask would be more helpful to stop you from hyperventilating. So one study took advantage  of those two mechanisms to compare the effectiveness  of different placebos.

In this case, the participants were conditioned to expect a particular  effect from their treatment. So instead of just giving them  a pill and saying it’s aspirin, the researchers gave them real aspirin, which really stopped prostaglandins from being made and got rid of their headaches. Then they did it again and  gave them the placebo pill.

And they did the same preconditioning with a real oxygen mask followed by a placebo oxygen mask. So these people’s bodies already had generated a response to the real treatments. Then, when the real stuff  was swapped out for placebos, their bodies kept up the response as if they were getting the original treatment.

The placebo aspirin affected a bunch of prostaglandins that the  placebo oxygen mask didn’t. And the placebo oxygen mask  got rid of hyperventilation, which the placebo aspirin didn’t. So different placebos can have totally different effects on your body!

And since the real oxygen mask was better at reducing altitude headaches than real aspirin, the placebo oxygen mask worked  better than the placebo aspirin. These results are pretty incredible. But taking a pill and putting on an oxygen mask are very different experiences.

Surely, if you got one injection that’s pretending to be a non-steroidal  anti-inflammatory drug, or NSAID, and another injection that’s  pretending to be an opioid, you wouldn’t respond any differently because you're getting a shot either way. Well… this next study might  prove that suspicion wrong. This time around, researchers went back to the tried and true arm pain metric.

And to reduce that pain,  they gave participants either the NSAID ketorolac tromethamine or the opioid drug morphine hydrochloride. Just like in the last experiment,  these are both effective pain killers despite initiating different  chemical pathways in the body. And just like the last experiment,  participants were preconditioned to know what response would come from the real deal before switching to a placebo.

Once they stopped getting the  drugs and started getting saline, or salt-water placebos, they still felt better. So the saline placebos worked for both the NSAID and the opioid drugs. And even though everyone was  getting the placebo at this point, we know from the last study that  preconditioned placebos can still activate the specific chemical  pathways that the real treatment did.

So when the researchers gave their  participants the anti-opioid drug, naloxone, it brought the pain  back for the people who were taking the morphine placebo  but not the ketorolac placebo. Because naloxone isn’t  relevant to how NSAIDs work. Which means that even the exact same saline injection can make your body respond in different ways depending on how  you’ve been preconditioned for it.

A placebo that comes after  preconditioning seems to use whatever pathways that real drug  used to make you feel better. But preconditioning isn’t the only  way to get the placebo effect. Sometimes, you’re just told  it’s a strong pain reliever, without getting the real pain reliever first.

In those cases, naloxone  also brought back the pain. So that kind of placebo without preconditioning probably uses an opioid  pathway to take your pain away. Ultimately, placebos can make your body respond in a ton of different ways.

And it’s not all smoke and mirrors. When a researcher comes out and tells you that you’re getting a placebo, it still works. It just might not work as  well as if they’d told you you were getting a different one.

So think twice before calling  placebos “fake” medicine. The complex effects they have  on your body are very real. Placebos are a brilliant medical tool.

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We both love spreading knowledge  about awesome stuff in the world. So you can learn about LLMs and  all sorts of other cool stuff at Brilliant.org/SciShow or the  link in the description down below. That link also gives the  first 200 people who sign up 20% off an annual premium Brilliant subscription.

And you’ll get your first 30 days for free! Thanks to Brilliant for  supporting this SciShow video! [♪ OUTRO]