Is there proof of the physiological cascade in the Placebo effect?

Question

This is a very contentious subject betwen fans of alt-med and fans of allopathy.

When Alt-med makes claims to cure and/or treat conditions the overwhelming response from fans of allopathy is they would either have got better anyway or they got better because they beleived they would as a result of the placebo effect.

The assumption is that the patients are deluded and/or stupid.

Alt-med studies are often criticised as being unscientific by the same group.

One glaring inconsistency I have noticed is the same people who claim reasearch, they disagree with, is unscientific are unable to produce any evidence of the placebo effect.

What is the physiological process? What is the Cascade?

Can anyone prove this and show randomised controlled trials which are of the quality always demanded by the fans of allopathy?

Why should one group unable to produce "scientific" evidence be dismissed and another group which produces no evidence at all be taken seriously?

Answer 1

The placebo effect doesn't assume that the people are deluded or stupid, it is just a testament to the power of suggestion. It is the same as how some foods make us feel certain ways. Like porridge in the morning makes us feel cozy. Or coffee. Its psychological more than physiological effect.

A quick search on pub med will reveal much discussion on this topic, but most of these articles are only available if you have a subscription. Like from a university. Most altmed student don't have access to them, as their studies are not connected to a university. The subscriptions are incredibly expensive so the smaller alternative institutes cannot afford them.

This said, here are some articles on the topic. And there are many many more.

I realize most of the ones I have referenced are reviews, but you can look up the original articles they discuss for yourself. This is a good one and I think is what you are after.

Conventional medicine provides plenty of evidence. That is why it is conventionally used. Look up some common medicines and their mechanisms, whilst you are there. At the cellular level we can prove why most medications work. Of course there are some exceptions. But the overwhelming majority is proved, and clear mechanisms outlined.

I think a problem conventional medicine has is that no mechanism has been outlined for alternative methods. For example, when using metformin, we can say that this molecule acts on this receptor and does this. For alternative medicine, there is no such thing.

This is the abstract of some studies. Which explains the chemical effect of the placebo.

Title: Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses.

Source: Archives of general psychiatry [0003-990X] Scott yr.2008 vol.65 iss.2 pg.220 -31

CONTEXT: Placebo and nocebo effects, the therapeutic and adverse effects, respectively, of inert substances or sham procedures, represent serious confounds in the evaluation of therapeutic interventions. They are also an example of cognitive processes, particularly expectations, capable of influencing physiology. OBJECTIVE: To examine the contribution of 2 different neurotransmitters, the endogenous opioid and the dopaminergic (DA) systems, to the development of placebo and nocebo effects. DESIGN AND SETTING: Using a within-subject design, subjects twice underwent a 20-minute standardized pain challenge, in the absence and presence of a placebo with expected analgesic properties. Studies were conducted in a university hospital setting. PARTICIPANTS: Twenty healthy men and women aged 20 to 30 years recruited by advertisement. MAIN OUTCOME MEASURES: Activation of DA and opioid neurotransmission by a pain stressor with and without placebo (changes in the binding potential of carbon 11 [11C]-labeled raclopride and [11C] carfentanil with positron emission tomography) and ratings of pain, affective state, and anticipation and perception of analgesia. RESULTS: Placebo-induced activation of opioid neurotransmission was detected in the anterior cingulate, orbitofrontal and insular cortices, nucleus accumbens, amygdala, and periaqueductal gray matter. Dopaminergic activation was observed in the ventral basal ganglia, including the nucleus accumbens. Regional DA and opioid activity were associated with the anticipated and subjectively perceived effectiveness of the placebo and reductions in continuous pain ratings. High placebo responses were associated with greater DA and opioid activity in the nucleus accumbens. Nocebo responses were associated with a deactivation of DA and opioid release. Nucleus accumbens DA release accounted for 25% of the variance in placebo analgesic effects. CONCLUSIONS: Placebo and nocebo effects are associated with opposite responses of DA and endogenous opioid neurotransmission in a distributed network of regions. The brain areas involved in these phenomena form part of the circuit typically implicated in reward responses and motivated behavior.

Source: Archives of general psychiatry [0003-990X] Scott yr.2008 vol.65 iss.2 pg.220 -31

Title: Placebo effects on human mu-opioid activity during pain.

Source: Proceedings of the National Academy of Sciences of the United States of America [0027-8424] Wager yr.2007 vol.104 iss.26 pg.11056 -61

Placebo-induced expectancies have been shown to decrease pain in a manner reversible by opioid antagonists, but little is known about the central brain mechanisms of opioid release during placebo treatment. This study examined placebo effects in pain by using positron-emission tomography with [(11)C]carfentanil, which measures regional mu-opioid receptor availability in vivo. Noxious thermal stimulation was applied at the same temperature for placebo and control conditions. Placebo treatment affected endogenous opioid activity in a number of predicted mu-opioid receptor-rich regions that play central roles in pain and affect, including periaqueductal gray and nearby dorsal raphe and nucleus cuneiformis, amygdala, orbitofrontal cortex, insula, rostral anterior cingulate, and lateral prefrontal cortex. These regions appeared to be subdivided into two sets, one showing placebo-induced opioid activation specific to noxious heat and the other showing placebo-induced opioid reduction during warm stimulation in anticipation of pain. These findings suggest that a mechanism of placebo analgesia is the potentiation of endogenous opioid responses to noxious stimuli. Opioid activity in many of these regions was correlated with placebo effects in reported pain. Connectivity analyses on individual differences in endogenous opioid system activity revealed that placebo treatment increased functional connectivity between the periaqueductal gray and rostral anterior cingulate, as hypothesized a priori, and also increased connectivity among a number of limbic and prefrontal regions, suggesting increased functional integration of opioid responses. Overall, the results suggest that endogenous opioid release in core affective brain regions is an integral part of the mechanism whereby expectancies regulate affective and nociceptive circuits.

Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, Stohler CS.

Free Full Text

Placebo effects mediated by endogenous opioid activity on mu-opioid receptors.

J Neurosci. 2005 Aug 24;25(34):7754-62.

PMID: 16120776 [PubMed - indexed for MEDLINE]

Reductions in pain ratings when administered a placebo with expected analgesic properties have been described and hypothesized to be mediated by the pain-suppressive endogenous opioid system. Using molecular imaging techniques, we directly examined the activity of the endogenous opioid system on mu-opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of mu-opioid receptor-mediated neurotransmission was observed in both higher-order and sub-cortical brain regions, which included the pregenual and subgenual rostral anterior cingulate, the dorsolateral prefrontal cortex, the insular cortex, and the nucleus accumbens. Regional activations were paralleled by lower ratings of pain intensity, reductions in its sensory and affective qualities, and in the negative emotional state of the volunteers. These data demonstrate that cognitive factors (e.g., expectation of pain relief) are capable of modulating physical and emotional states through the site-specific activation of mu-opioid receptor signaling in the human brain.

1: Brain Behav Immun. 2006 Jan;20(1):15-26. Epub 2005 Oct 20.Click here to read Links

    Belief or Need? Accounting for individual variations in the neurochemistry of the placebo effect.

    Zubieta JK, Yau WY, Scott DJ, Stohler CS.

The activation of pain-suppressive, endogenous opioid neurotransmission after administration of a placebo with expectation of analgesia has been directly demonstrated in humans using molecular imaging techniques in recent work. Regional effects were described in the dorsolateral prefrontal cortex, pregenual anterior cingulate, anterior insula, and nucleus accumbens. However, it was also observed that the magnitude of these responses was subject to substantial individual and regional variation. The present study was undertaken to examine the contribution of various factors to the observed variability in the neurochemical responses to placebo administration. Multiple regression analyses were conducted on data from 19 healthy males to study to what degree expectations of analgesia and various elements of the experience of pain itself, in the absence of placebo, were associated with the individual and brain regional variability in endogenous opioid neurochemical responses to placebo. A model that included affective qualities of pain, the volume of algesic stimulus required to maintain pain over the experimental period within a moderate range, and the internal affective state of the volunteers contributed to 40-68% of the variance in the regional neurochemical responses to placebo. These initial data suggests that in the case of endogenous opioid mediated placebo analgesic responses, the individual experience of pain, in particular its affective elements, the internal affective state of the individuals during pain and a measure of sustained pain sensitivity are important factors contributing to the formation of a placebo effect. Further examination of individual variations in placebo responding will need to take into account the underlying process for which relief is required.

1: Rev Neurosci. 2007;18(3-4):173-90.Links

    Placebo analgesia: findings from brain imaging studies and emerging hypotheses.

    Kong J, Kaptchuk TJ, Polich G, Kirsch I, Gollub RL

Thats ok, hope they are useful.

Answer 2

woah, all i know is that a significant percentage of people feel better after taking a sugar pill...

Answer 3

Well, the power of belief is not only well documented, it has made millions for many authors. One such author, managed to cure my depression with his book, "The Feeling Good Handbook". David Burns is a psychiatrist who realized that antidepressants were ineffective at curing depression and sought to make cognitive behavior therapy easy to understand in a comprehensive study guide. By using the power of thought control, I changed my entire belief system and cured my depression ON MY OWN, with no help from doctors (excluding the author, of course), drugs, or therapists. I had been ill for years, seen many doctors, tried many drugs, and was institutionalized... all to no benefit. Along comes Dr. Burns, and with a little positive thinking, I'm 100% cured. I've used those techniques to cure other ailments as well. My diabetes is gone, my fibromyalgia is practically gone, and diseases like colds and flu disappear in hours, not days. Why? Because I believe I can cure them myself.

Answer 4

There is actually scientific evidence the placebo effect occurs, and a decent ammount.  One of my teachers (and friends) is a PhD in the subject, and he's told me tons about it.  As far as the technicalities of the placebo effect go (I may be phrasing this wrong) it's efficacy varies depending on the condition (ie. w/viral it works by activating the immune system, and theres a whole branch of science that shows the physiology of that, whereas with pain it can also work, but I have no idea how it applies to other conditions).  Overall though, I believe (but I'll have to check this on friday) that the complete physiology of the placebo effect is not completely understood.  I actually think a large majority of it lies within the energetic realm, which medical science does not believe exists, hence I doubt other than being certain of it's existence the physiology of it's process will remain somewhat of an enigma.

My own "golden standard" for testing for the placebo effect is to give people therapies they are skeptical of, and tell them I don't think they will work, and then if it works say that the placebo effect did not result in a cure.

I also know that with many drugs which are tested, in their actual results they tend to find their efficacy is equal or lower than expected placebo rates, but they only submit the trials conducted which are doctored to show favorable results.  There was a huge scandal about this with some of the major anti depressants recently, which I'm pretty sure you've heard of.

Lastly, I spent ages and ages trying to find this study everyone kept on referring to, but I finally did!  I'm just going  to quote something instead of rewriting it

"Most medical, surgical procedures and drug usage are not backed by studies - only by anecdotal evidence. According to the US Government's Office of Technology Assessment (Congress of the United States, Office of Technology Assessment: Assessing the efficacy and safety of medical technologies.Washington, DC: US Government Printing Office, 1978), only 10-20% of all medical procedures and off-label drug usage are backed by clinical studies.

Strong anecdotal evidence among informed professionals is actually quite reliable - at least as reliable as clinical testing.

Many clinical tests come to diametrically opposed conclusions. You could say that the problem was discovered through anecdotal evidence - and merely confirmed through a peer reviewed study.

http://www.i-sis.org.uk/peerReviewUnderT...

The problem isn't with the use of anecdotal evidence. It's with the double standard applied by the establishment (medical and regulatory) that holds complementary medicine to an absurdly higher standard, allowing medical doctors to do pretty much whatever they want. If informed anecdotal evidence is allowable for 85% of all medical procedure and drug usage, why is alternative health held to an impossible 0% standard? "

Hope you like this answer!