It's Not Just In Your Head—It's In Your Body's Power: The Placebo Effect

The conventional narrative goes something like this: a doctor gives a patient a sugar pill but tells them it's medicine. The patient believes it will help, and somehow, mysteriously, they feel better. It's been framed as "the lie that heals"—effective but fundamentally dishonest.

This framing created an ethical dilemma: beneficence versus autonomy. Is it okay to mislead someone, even if it helps them feel better? For over a century, medical professionals have wrestled with this question.

But emerging research reveals something revolutionary: placebos can work even when patients know they're taking an inactive substance. Studies on "open-label placebos" show significant improvements in conditions ranging from irritable bowel syndrome to chronic back pain, migraines, and even ADHD—all while patients are fully informed they're taking sugar pills.

What's happening here isn't trickery. It's biology. ... continue reading the article

This is Heliox: Where Evidence Meets Empathy

Independent, moderated, timely, deep, gentle, clinical, global, and community conversations about things that matter.  Breathe Easy, we go deep and lightly surface the big ideas.

Thanks for listening today!

Four recurring narratives underlie every episode: boundary dissolution, adaptive complexity, embodied knowledge, and quantum-like uncertainty. These aren’t just philosophical musings but frameworks for understanding our modern world. 

We hope you continue exploring our other podcasts, responding to the content, and checking out our related articles on the Heliox Podcast on Substack. 

Transcript

0:25

This is Heliox, where evidence meets empathy. Independent, moderated, timely, deep, gentle, clinical, global, and community conversations about things that matter. Breathe easy. We go deep and lightly surface the big ideas. Okay, so we often hear placebo effect and immediately think, you know, sugar pill. Right. Believing makes it work. Right. But what if that's like just scratching the surface? What if it's really about tapping into our own body's power? Yeah. Maybe even without any deception. Exactly. That's where the conversation is heading now. For a long time, though, it was really framed as the lie that heals. You look back to the early 1900s, Richard Cabot and others. The view is pretty negative, fundamentally dishonest, basically. And that stuck around. Oh, absolutely. Even more recently, you see descriptions framing placebos as sort of unethical trickery, not really serious science. But, yeah, our understanding is definitely shifting. And the big ethical fight was always kind of doing good versus letting someone know what's actually going on, right? Beneficence versus autonomy. That was the core tension, yes. Is it okay to mislead someone, even if it helps them feel better? And then you layer on the nocebo effect. Which is the opposite. Bad expectations leading to bad outcomes. Precisely. And that brings up tough questions about informed consent. Like, how much do you tell someone about potential side effects without actually causing those side effects through suggestion? It's tricky. But this new angle you mentioned, the stuff we looked at, it really suggests we don't need the lie. That's the exciting part. The idea is that these placebo responses, the body's beneficial changes, can be activated, can be harnessed openly, honestly. Giving people more agency, you could say. Yes, exactly. Agency in sense of having a greater capacity to act, to do something that helps relieve their own suffering. Okay, so if we zoom out a bit, how do these responses actually happen? Is there agreement on the mechanisms? Broadly, yes. Scientists generally agree on the main pathways that produce these effects, even if they categorize them slightly differently sometimes. And it's key to remember it doesn't work for everything. Pain, mood, anxiety, those seem quite responsive. But not like a virus or a tumor. Right. The placebo isn't shrinking a tumor directly. It affects our experience, our symptoms, our internal environment. So what are these pathways? You mentioned conditioning earlier. Yes, classical conditioning. Think Pavlov's dogs, but for our own physiology. If you consistently pair something neutral, say, a specific taste or smell, with an active drug that causes a biological effect. Like an immunosuppressant. Exactly. Over time, the body can learn to produce that same immune response just from the taste alone without the drug. Wow. And we don't even realize it's happening. Often, no. These conditioned responses, especially in the endocrine and immune systems, don't seem to rely much on our conscious beliefs about them. But you said it gets complicated with pain. It can, yeah. With pain, especially sudden, sharp pain, strong negative expectations, like really believing it's going to hurt more, can sometimes override any positive conditioning that might be there. Okay, so conditioning is one piece. What else? Expectations are huge. What we believe will happen, what we're told, the whole context. So if the doctor says this will really help. That matters. Verbal cues, prior experiences, beliefs, they all shape our expectations. And those expectations demonstrably impact symptoms. Like examples. Sure. Pain relief treatments often work better when people know they're receiving them versus when they're hidden. Right. In depression trials, you tend to see stronger placebo responses when there are more active treatment arms, maybe because people feel more hopeful they're getting something effective. And there was that fascinating low back pain study where patient expectations were actually a better predictor of outcome than which treatment they got. Seriously. Wow. OK, so conditioning, expectations. What else? The human element, the relationship, the interaction. You mean like how nice the doctor is? Essentially, yes. Warmth, empathy, trust in that clinical encounter, these effective components can absolutely produce placebo effects. That makes intuitive sense. And it probably extends beyond the clinic, too. Good social support networks likely offer similar benefits for mental health, maybe even cardiovascular health. Is there research on that? There is. Studies linking practitioner empathy to how long a cold lasts or physician characteristics to the strength of the placebo response. It's quite compelling. Okay, this next one really threw me. Open label placebos. Yeah. People knowing they're taking a placebo. Yeah. And still getting better. It sounds completely backwards, doesn't it? Yeah. But the research is building. seeing improvements in things like IBS, migraines, allergic rhinitis, chronic low back pain, even ADHD. When patients are told up front, this is a placebo. Yes. Ted Kaptuk's trial with IBS is a famous example. They gave people placebo pills, told them what they were, but also explained the power of the placebo effect itself, encouraging them to engage with that idea. And they saw significant improvements in symptoms. How? I mean, if you know it's inert, what's the mechanism? That's the million dollar question, really. And the truth is, we don't know for sure yet. It's likely a mix of things. Like what? Maybe some conditioning is still happening. Maybe the ritual of taking the pill, the positive framing, still shapes expectations. Maybe it relates to feeling cared for, taking action. Some theories involve embodied cognition or even complex ideas about how the brain predicts and regulates bodily states, like Bayesian predictive processing. It's an active area of research. So still some mystery there. Are there other factors that seem to play a role, even if we don't fully get why? Yeah, a few interesting ones. Things like having a choice in your painkiller seems to boost the effect. Okay. The perceived cost of a treatment more expensive seeming more potent. How invasive it is, an injection often has a stronger placebo effect than a pill. How often you get the treatment, how consistently you take it. Adherence matters. Right. And even social learning, seeing others benefit, can influence your own response. Oh. Lots of subtle factors. Okay, so pulling this together, if these effects aren't just about being fooled, how can we actively use this, turn it into a tool for agency? Great question. Let's look at those mechanisms again. Take conditioning. We could potentially pair an active medication with a specific cue, a taste, a smell, a routine, and over time maybe use that cue to get a similar effect, but with a lower dose of the actual drug. To reduce side effects or cost. Exactly. This has shown promise for things like antihistamines, methadone for opioid dependence, melatonin, even corticosteroids and some antipsychotics. It could be really beneficial for people struggling with affordability, side effects or just complex drug regimens. And you said awareness doesn't necessarily stop those conditioned immune or hormone responses. Generally, no, though the pain caveat still applies strong negative expectations can interfere. Okay. What about managing our own expectations? Can we steer those? I think so. It's not just about what doctors tell us. We can actively seek out reliable information, positive stories, maybe join support groups where people share successful experiences. Right. Choosing treatments we genuinely believe in that resonate with us could also help foster positive expectations and hope. And the relationship part. That seems straightforward. No deception needed there. Absolutely not. Fostering warmth, trust, empathy. That's just good clinical practice, right? And building strong social support systems in our lives. These things are inherently valuable and likely tap into these beneficial placebo pathways. And the open label approach seems like the most direct route to agency, in a way. It really does. Actively engaging with the idea that your mind and body can produce healing responses, even with an inert substance, is pretty empowering. And again, think of the potential benefits regarding cost, side effects, polypharmacy. What about those other fuzzier factors, like invasiveness or frequency? Can we leverage those? It's more speculative, but maybe. Could intentionally pairing a treatment with stronger sensory input make a difference? Could using reminders to boost adherence enhance the effect? Could seeking out success stories amplify social learning? It's possible these things could subtly nudge outcomes. This really shifts the conversation, doesn't it? It's not just about the ethics of deception anymore. Far from it. Once you see placebo responses as part of our inherent capacity, you start seeing potential mechanisms everywhere. Outside the clinic. Definitely. Think about online health communities, workplace wellness programs, school environments, even just supportive friendships. The principles of expectation, social support, feeling understood, they operate broadly. And it makes you look differently at alternative or traditional medicine, too. For sure. It's highly likely that many CHAM practices derive a significant portion of their benefit from these very mechanisms, building strong expectations, fostering hope, and providing a very empathetic relational context. Like that homeopathy study you mentioned. Right, where the consultation itself, the therapeutic alliance, the listening, the hope generated seem to be the most potent factor, more so than the homeopathic remedy itself. Which raises ethical questions about how those are regulated and presented. It does, including things like, could you ethically offer open-label placebo homeopathy, focusing purely on the ritual and consultation? It's complex. But we absolutely need to be careful about the limits, right? Placebos don't cure cancer. Critically important. We must differentiate conditions that are placebo-responsive, like pain, mood, IBS symptoms, from those that require specific, targeted biomedical intervention, like infections, tumors, broken bones. Because the danger is equating them. Exactly. Suggesting an alternative therapy that helps with, say, anxiety will also cure cancer is incredibly dangerous. We see the tragic consequences when people forego effective conventional treatments. Vaccine hesitancy is another area where misapplying ideas about natural healing can be harmful. So responsible communication is key. Vital. From researchers reporting findings clearly to integrative medicine practitioners being honest about what their approaches can and cannot do. And another crucial point you raised, enhancing agency shouldn't mean enhancing blame. Yes. Thank you for bringing that up again. It's so important. We empower people by showing them their potential influence, but we must not make them feel responsible or guilty if they're still suffering. Especially with nocebo effects or those conditions often called psychosomatic. Right. Those conditions often respond well to placebos, but they also carry a terrible stigma, this idea of it being all in your head, just because we lack a clear biomarker or physiochemical explanation yet. We need compassion, not blame. It really is amazing how far the science has come, moving beyond it's just belief to actually looking at the biology. It's a major shift. We now understand that concepts we used to think of as purely subjective expectation value, meaning have concrete physiological bases. They literally change brain activity and body chemistry, modulating perception, emotion and health. So let's dig into that a bit. Yeah. What's happening, say, in the brain during placebo pain relief? A key player is the body's own opioid system, the endogenous opioids, like endorphins. Our natural painkillers. Exactly. When you expect pain relief, your brain can actually release these opioids. We know this because the drug naloxone, which blocks opioid receptors, can actually block or reverse placebo-induced pain relief. There's also another chemical, CCK, that seems to work against the placebo effect. Blocking CCK can enhance placebo analgesia. And studies have literally found higher concentrations of endorphins in the cerebrospinal fluid of people who respond well to placebos. And brain scans show this too. Yes. PE scans show increased activity in brain regions like the rostral anterior cingulate cortex, both when people take actual opioid drugs and when they experience pain relief from a placebo. So the brain is acting similarly. There's significant overlap in the activated regions. And remember, this opioid system does more than just dull pain. It's involved in stress responses, hormone regulation, reacting to important stimuli. So the placebo effect taps into this fundamental system. It seems to, yes. Activating these opioid pathways appears to reduce both the intensity and the unpleasantness of pain, increasing tolerance. The key brain areas involve prefrontal cortex, anterior cingulate, insula, are hotspots for this natural opioid activity. What about other conditions? You mentioned Parkinson's disease earlier as a model. Right. Parkinson's is useful because the underlying issue involves dopamine. And sometimes researchers can even measure activity in single neurons in patients undergoing surgery. Okay. PET scans have shown that placebo treatments can trigger dopamine release in the striatum of Parkinson's patients. Just from the expectation. Apparently so. And interestingly, one study found more dopamine release when patients thought there was a 75% chance of getting the real drug compared to when they were 100% certain. That's wild. So uncertainty or hope played a bigger role. It suggests expectation is a really powerful modulator of these neurochemical systems. And in depression, do placebos change the brain there too? Yes. Neuroimaging studies show changes with both active antidepressants and placebos. A common finding is a normalization of activity patterns in the frontal parts of the brain. Similar to the drugs. In some ways, yes, but there also seem to be differences. The specific patterns of brain activation with placebo often look different from those seen with psychotherapies like CBT or IPT. Suggesting different mechanisms are at play. Possibly, yes. Brain regions involved in reward processing and expectation, like the ventral striatum and orbitofrontal cortex, are thought to be involved in placebo responses in depression, linking back to that idea of anticipation and value. You also mentioned that the context, the ritual, seems important. more invasive procedures having bigger effects. Absolutely. It stands to reason, doesn't it? An injection, or especially something like sham surgery, involves much more interaction, more sensory input, more patient investment, and anticipation. And maybe a stronger belief that something physically significant is being done. That's likely part of it. There's data showing sham acupuncture often outperforms a placebo pill for pain. Okay. And remarkably, for many orthopedic conditions, like certain knee surgeries, Studies have found sham surgery to be just as effective as the real procedure for pain and function in the long run. That's astonishing. Even in sham spine procedures for chronic low back pain, the placebo effect size is estimated to be quite large, maybe around 53%. Which circles back to the open label findings, knowing it's a placebo doesn't negate the effect. Right. It reinforces the idea that belief, context, and the therapeutic ritual itself are incredibly powerful, even independent of a pharmacologically active ingredient. Like that study on opioid use disorder. Yeah, the Belcher et al. study. They used conditioned open-label placebo pairing placebo with counseling cues and found it helped people stay in treatment longer and improved their sleep. Again, telling people didn't ruin it. Exactly. Like the IBS studies, educating patients about the placebo effect doesn't necessarily diminish it. We should quickly touch on the nocebo effect again, the dark side. Yes, absolutely crucial. Negative expectations create negative realities. In drug trials, you routinely see people in the placebo group reporting side effects. That mimic the actual drug side effects. Often, yes. Sometimes they even report side effects that only the placebo group experienced. It just underscores how profoundly our expectations shape our physical experience, for better or worse. And why clear, careful communication from doctors is so vital. Absolutely. To maximize placebo and minimize nocebo. It does sound like researching all this must be incredibly challenging. Oh, it is. For one thing, if your placebo response is really high in a trial, it makes it harder to prove that your new drug actually works better than the placebo. Right, the bar gets higher. And the trial setting itself is different from routine care. Patients in trials often get more attention, more interaction. Which could inflate the placebo response compared to real-world practice. Potentially, yes. Plus, there are all the usual challenges of controlling variables, accounting for patient and researcher expectations, potential biases in reporting, and the ethical tightrope of using placebos when effective treatments exist. It's complex. But despite the hurdles, the goal now is finding ways to use this ethically. That's the push. Things like transparency through open-label placebos, skillful communication to manage expectations positively, maybe using conditioning to reduce drug doses like we discussed. Any other promising areas? Post-operative recovery seems like a big one. Leveraging expectations and context to potentially speed healing or reduce reliance on pain medication after surgery. So wrapping this all up, it feels like the big takeaway is that the placebo effect isn't just noise or a trick. It's real. It's biological. Absolutely. It has neurobiological underpinnings. It's a genuine phenomenon. And crucially, it can be a source of our own agency, our own power to influence health. And it doesn't always need deception to work. That's the empowering message, I think. It really invites us to appreciate the profound mind-body connection in healing. So thinking about all this, how might you, listening now, reevaluate your own views on healing, on the power of belief, the importance of the relationship with caregivers, all the factors inside and outside medicine that shape well-being? What part of this deep dive makes you most curious to learn more? It's definitely given me a lot to think about. Thanks for listening today. Four recurring narratives underlie every episode. Boundary dissolution, adaptive complexity, embodied knowledge, and quantum-like uncertainty. These aren't just philosophical musings, but frameworks for understanding our modern world. We hope you continue exploring our other podcasts, responding to the content, and checking out our related articles at heliocspodcast.substack.com.