Is the placebo effect a purely psychological effect?

Question

The placebo effect plays a crucial role in clinical trials and in our understanding of medicine, but I have always had some difficulty in understanding how exactly it works.

Is it a purely psychological effect, that you feel better because of the attention the doctors gave you, or are there other aspects to it?

Does the placebo effect just change your perception of your condition, so you subjectively feel better although nothing changed about your condition, or does it have real, measurable physical effects?

Answer 1

Some very interesting results along those lines were produced by an asthma study done in 2011:

Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma

In a double-blind, crossover pilot study, we randomly assigned 46 patients with asthma to active treatment with an albuterol inhaler, a placebo inhaler, sham acupuncture, or no intervention. Using a block design, we administered one each of these four interventions in random order during four sequential visits (3 to 7 days apart); this procedure was repeated in two more blocks of visits (for a total of 12 visits by each patient). At each visit, spirometry was performed repeatedly over a period of 2 hours. Maximum forced expiratory volume in 1 second (FEV1) was measured, and patients' self-reported improvement ratings were recorded.

(emphasis mine)

So after treatment, each patient was given a spirometry test to determine if there was any objective improvement in their lung capactity. They were also asked to report their subjective impression of whether the treatment helped their asthma symptoms.

Here are the spirometry test results:

The active albuterol treatment group was the only one that showed significant improvement in actual lung capacity after treatment, the placebo and sham acupuncture groups performed the same as those who got no treatment at all.

Ah, but what about the patient's subjective impression?

All treatment groups felt like their asthma symptoms had significantly improved even though the spirometry test showed no such improvement!

So while placebo treatments might make patients feel better about their symptoms, this study suggests that the placebo effect causes no actual objective improvement, and is, therefore, purely psychological.

(I can imagine scenarios where this could lead to real harm, like a patient leaving their inhaler at home because they believed they were in better shape than they actually were.)

Answer 2

There are several aspects of this phenomenon, and I don't think it could be summed up easily even if it were better understood.

Tellingly, placebo has most effect on non-specific symptoms. The easiest category is that which relates to perception, such as pain and nausea. These are entirely mental representations of sensorineural input; constructions that exist because we somehow benefit from the averse reaction to whatever we think might have caused it (i.e. we feel pain because it motivates us to run when animals are eating us, and we are nauseated so that we may refrain from eating the typically harmful stuff we associate with the onset of nausea). These are brain utilities and we shouldn't be surprised that we can ignore listening to them just as we can filter out things that happen right in front of our eyes when we're focusing on something else (*).

It's a bit trickier when it comes to things that can be measured objectively, but even in that group, there are symptoms that stand out as extra easy to explain away. Fever falls into this category, as well as, say, a swelling. When a placebo treatment brings your fever down measurably, we know that something more is going on than simply a selective perception. But it doesn't have to be that much more. Fevers and swellings are prompted by infectious disease, but the foreign antigen isn't the direct cause of these symptoms, but rather, it is your body's way of dealing with the issue. You want that fever (well...), because that's your body adjusting itself to optimally cure you. So it's really not that big a deal that you can reduce a fever by means of placebo; sure, if you can trick yourself that you're not infected (or at least, that it's being taken care of), it makes sense that your body's response would be more relaxed, but you'd probably be worse off for it.

It must be acknowledged, however, that there are effects that seem to be purely driven by placebo, where it is not immediately obvious what the mechanisms behind it are. How do we explain entirely physical manifestations, such as how, say, warts disappear apparently entirely due to placebo? Or have a look at this neat effect, where the nocebo effect (which surely must be but a different application of the same phenomenon) provokes a rash:

Another interesting one that demonstrates both the placebo and nocebo effect in one study is a study done by Japanese researches on 57 high school aged boys. They selected these boys based on the fact that when exposed to Lacquer trees, these boys would get a severe rash, much like is common with poison ivy. They then blindfolded the boys and proceeded to brush one of their arms with the Lacquer tree leaves and the other with an innocuous leaf that would have no effect. They told them however that the arm brushed with the laquer tree was brushed by the harmless leaf and the one brushed by the harmless leaf they were told was brushed by the Lacquer tree leaf. What followed was a rash developed on most of the boys arms that were brushed by the harmless leaf and the other arm that was actually brushed by the Lacquer leaf that should have caused a rash was completely fine in nearly every case.

_(source)

What's going on here is probably that our bodies are being conditioned to release certain endorphins and chemical substances, leading up to this result. I don't think anybody can account for exactly what is going on in every single case of placebo effect, but I don't doubt these effects are all psychogenic, although their manifestations might be very indirect outcomes, far removed from their provoking agent.

Answer 3

How do you define "psychological"? A placebo definitely has an effect on the firing of neurons in the brain. On the other hand, psychological processes are the firing of neurons. So it is up to you to decide if you are calling a change in neuron firing patterns "psychological" or "physiological" effect.

I can't access the study which proved that, but here is a good popular science article which references it. From the article:

he gave college students electrical shocks while they were stuck in an fMRI machine. Half of the people were then supplied with a fake pain-relieving cream. Even though the cream had no analgesic properties - it was just a hand moisturizer - people given the pretend cream said the shocks were significantly less painful. The placebo effect eased their suffering. Wager then imaged the specific parts of the brain that controlled this psychological process. He discovered that the placebo effect depended on the prefrontal cortex, the center of "rational," conscious thought. When people were told that they'd just received a pain-relieving cream, their frontal lobes responded by inhibiting the activity of the emotional brain areas (like the insula) that normally respond to pain. Because people expected to experience less pain, they ended up experiencing less pain.

Seeing that it is the brain which "decides" whether the incoming nerve signals are pain or not, and that it reacts to placebo as to actual pain medication, I'll say the effect is at least neurologically well anchored.

Answer 4

Here is a short YouTube video (3 min). It only concentrates on some aspects of placebos, not so much on how they work, and whether the effect is just an illusion, which is the most interesting aspect of placebos, I guess.

Since some placebos had an effect on the volume of the lung, you can't say it's just an illusionary effect.

Answer 5

I am not sure why most think placebo effect is only psychological. It is easily reversible by opioid antagonists like naloxone: the placebo response could be blocked by naloxone if it was induced by strong expectation cues, whereas if the expectation cues were reduced, it was insensitive to naloxone. In the same study, if the placebo response was obtained after exposure to opioid drugs, it was naloxone reversible, whereas if it was obtained after exposure to non-opioid drugs, it was naloxone insensitive. These data indicate that opioid and non-opioid mechanisms come into play under different circumstances. http://www.jneurosci.org/content/25/45/10390

The placebo effect isn't restricted to only pain relief. A 2001 study on placebo effect and Parkinson's Disease concluded:the placebo effect in PD is mediated by an increase in the synaptic levels of dopamine in the striatum. They found a strong positive response from placebos that increased dopamine levels that mitigated the symptoms of Parkinson's. http://science.sciencemag.org/content/293/5532/1164.full

And a 2011 Nature paper reported that: the endocannabinoid system has a pivotal role in placebo analgesia in some circumstances when the opioid system is not involved. http://www.nature.com/nm/journal/v17/n10/full/nm.2435.html

And don't think placebo effects are restricted to alleviating only pain or depression. The fascinating field of psychoneuroimmunology studies how our thoughts affect our response to infections and immune related illnesses. http://www.apa.org/monitor/dec01/anewtake.aspx

The author of the above study reported: ... it's not the cytokines produced in the blood by macrophages that tell the brain you're sick. They're too big to get past the blood-brain barrier. Instead, the message moves from the bloodstream to the vagus nerve, which delivers it to the brain. "If I cut your vagus," said Maier, who has done such in rats, "your brain doesn't know you're sick."

The psychoneuro response is even the basis for the Nocebo: it is the phenomenon in which inert substances or mere suggestions of substances actually bring about negative effects in a patient or research participant. For some, being informed of a pill or procedure’s potential side effects is enough to bring on real-life symptoms. Like the placebo effect, it is still poorly understood and thought to be brought about by a combination of Pavlovian conditioning and a reaction to expectations. http://www.smithsonianmag.com/science-nature/what-is-the-nocebo-effect-5451823/

A systematic review concluded that contrary to the rhyme you cited as a child, words can hurt you and even cause you to die: https://www.aerzteblatt.de/pdf.asp?id=127210

The nocebo effect has been credited for 'voodoo death'. https://www.psychologytoday.com/blog/owning-pink/201308/the-nocebo-effect-negative-thoughts-can-harm-your-health

Any clinical scientist will tell you that the placebo effect is far more than a psychological effect.