Founder of Health Rising and Phoenix Rising
Researchers are beginning to dig down into why the placebo effect happens and why it is stronger in some people than others. A placebo response refers to a sometimes rather dramatic improvement but usually transient effect on a person's symptoms when they believe they're getting an effective treatment. The placebo response appears to be strongest in pain conditions. It appears that about 30% of the population can generate a significant placebo response.
One study found, to the author's surprise, that the placebo effect was reduced in chronic fatigue syndrome. (They thought it would be higher.) My experience, particularly in the first fifteen years of this illness, with the placebo effect was that I rarely had one. I didn't react positively to treatment options that I was excited about (or negatively). I didn't react at all.
A recent study examining the genetic roots of the placebo effect may suggest why some people with ME/CFS or FM have trouble achieving a placebo response.
Early studies indicated that the placebo response increases the levels of endogenous opioids in the brain. We know that the opioid system is not working particularly well in FM. We know that while opioids can help that many patients don't benefit.
View attachment 378As the opioid system emerged as a major underlying biochemical mechanism involved in placebo analgesia, the role of mu opioid receptors in placebo analgesia was further confirmed in neuroimaging studies
The placebo response also relies on many of the brain areas associated with ME/CFS and/or FM (anterior cingulate, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, the brainstem periaqueductal gray matter, and the spinal cord)
The reward system and dopamine is another important player in the placebo effect. You must be able to anticipate reward in order to lock the placebo effect in. Dopamine plays a key role in activating the reward system. A recent basal ganglia study in ME/CFS, however, found reduced activation of the reward pathways in ME/CFS. The implication was that reduced dopamine was responsible. The authors suggested that not only had inflammation knocked the dopamine system out, but that the weakened dopamine system had left the brain vulnerable to low levels of inflammation.
Polymorphisms in the COMT gene - implicated in both ME/CFS and FM - play a role in how strong the placebo effect is as well. One COMT polymorphism has been linked to increased pain levels in fibromyalgia. Alterations in the COMT gene may also play a role in ME/CFS.To test whether neural correlates of reward were also associated with anticipation of placebo responses, Scott et al. used a pain model that looked at both opioid and dopamine receptor activation in brain regions associated with reward [mce-anchor26]. They showed that both pathways were activated in anticipation of the placebo response and that higher levels of dopamine receptor activation were seen in individuals with higher placebo responses.
Conversely, they found that in individuals who reported an increase in pain (i.e., placebo nonresponders or, more accurately, negative placebo or nocebo responders), dopaminergic and opioid signaling was reduced.
All three factors that appear to be strongly linked to the strength of the placebo effect appear to be disturbed in ME/CFS and/or FM. The opioid system is operating strangely in FM, dopamine and the reward system appears to be underactive in ME/CFS and the COMT gene has been implicated in both disorders. Serotonin, another possibly important factor in FM particularly, may be involved as well.
These factors could explain why one meta-analysis found lower than expected rates of placebo response in ME/CFS patients - particularly with regard to behavioral studies.
The authors of the article speculated that drugs may be able to enhance or inhibit the placebo response at some point. They also proposed that some drugs may be inhibiting it.
The PollWhile studies have not as yet been conducted to identify genes and drugs that modify placebo response, hypothetically there may even be situations in which one might opt to intentionally use a drug to modify the placebo response. For instance, purposefully using a drug to inhibit the placebo response in clinical trials could minimize the placebo response and allow for a more accurate measurement of the drug effect..
The placebo response is associated with reduced symptoms and increased feelings of health and well-being when taking a treatment which is the treatment is not producing. The placeboo response can be a bit hard to parse. For me treatment effectiveness tends to fade or more likely I usually get worse over time. I don't beleive that's the placebo response at work but it's not really clear