We've had numerous conversations in this forum about the placebo effect, and particularly as it relates to PD. I came across this article by Erik Vance and thought it was pretty interesting. As an example, here is a quote from one paragraph in the article:

Some practitioners dismiss the placebo effect as irrelevant. Others blame it on neurosis. But scientists are increasingly recognizing the placebo response as an authentic neurochemical reaction in the brain. In the past decade, imaging studies have opened up the possibility that scientists will soon understand the mysterious phenomenon and even harness it in clinical practice — unleashing the power of, well, nothing. The new evidence has established that placebos trigger the brain’s “internal pharmacy” — in essence, a warehouse perpetually stocked to deliver active drugs to itself. In addition to improving Parkinson’s symptoms, that same inner pharmacy can affect conditions like pain, depression, irritable bowel syndrome, anxiety, schizophrenia and more. As the placebo effect emerges from a long history in the shadows, the new question is: How can we use this age-old brain trick to our advantage? or as long as medicine has existed, the placebo effect has been quietly playing a role in treatment.

http://www.erikvance.com/why-nothing-works/

While I totally believe in the placebo, I'll play devil's advocate and offer this explanation of why patients were able to move around/the PET scans showed dopamine "flooding their brain": is it possible that dopamine really was flooding their brain, but it was dopamine from medicine they had taken previously in the day which was just then making it into their brain? Sometimes our drugs take an hour or more to take effect, other times, 30 minutes. It would be helpful if they could trace the actual drug molecules you ingested to see how long it took for a dose to go from mouth to stomach to small intestine to bloodstream to brain.

Either way, the concept of our brains having their own internal perpetual pharmacy, stocked with whatever we might need, is really cool How do we harness that!!

Either way, the concept of our brains having their own internal perpetual pharmacy, stocked with whatever we might need, is really cool How do we harness that!!

Summary

Based on the observation that the placebo effect in Parkinson's disease was mediated by the release of endogenous dopamine in both the dorsal and ventral striatum, in 2002 we formally proposed the placebo-reward hypothesis. This hypothesis establishes a link between the placebo effect and reward mechanisms, and predicts that the activation of the ventral striatum should be present in any placebo response, in any medical condition. In keeping with this prediction, functional neuroimaging studies have shown placebo-induced activation of the reward circuitry in Parkinson's disease, depression, and pain. In fact, recent evidence suggests that the release of dopamine in the ventral striatum likely triggers the activation of the endogenous opioid system in placebo analgesia. The placebo-reward hypothesis also supports the notion that the expectation of clinical benefit plays a major role in the placebo effect. Probability and trust, two key factors involved in shaping expectations, must therefore be essential to the development of placebo responses. The ventral loop of the basal ganglia circuitry (anterior cingulate cortex–ventral striatum–ventral pallidum– mediodorsal nucleus of the thalamus –anterior cingulate cortex) is a fundamental component of the neuroanatomy of the placebo effect.


one more explanation.

Placebo Effect Linked to Dopamine-Clearing Enzyme

Patients who carry one particular functional polymorphism of an enzyme responsible for clearing dopamine from the prefrontal cortex region of the brain are more likely to respond to placebo therapy than those with a different variant of the enzyme, as long as the placebo is administered in a caring, positive manner, researchers report. The polymorphism generates a less-active version of the enzyme catechol-O-methyltransferase (COMT), which is less efficient than the native enzyme at mopping up dopamine that has been released from nerve synapses.

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http://www.genengnews.com/gen-news-h...zyme/81247530/

Thanks for the quotes. The bit that that I find particularly interesting is:

"The placebo-reward hypothesis also supports the notion that the expectation of clinical benefit plays a major role in the placebo effect. Probability and trust, two key factors involved in shaping expectations, must therefore be essential to the development of placebo responses."

If the hypothesis is correct, we can engineer placebos to have increased effect.

How?

1. Work with things that may work. I find it difficult to think of a true placebo - an inert substance or action. For instance, water can have an enormous therapeutic effect to the dehydrated. There's a vast array of what I call "therebos" - things that may have true therapeutic value or may be just placebos, things such curcumin, tai chi, this forum.

2. Provide data. People try therebos. Some of these interventions are followed perhaps coincidentally by improved symptoms. Report the results. If I see a therebo has a 10/10 rating, it will lift my expectation, perhaps leading to a virtuous cycle of ever increasing potency.

3. Package. We're all affected by the way a product is packaged.

4. Promote. We need to hear about therebos, especially about the success stories, but not to bias reporting to the extent that trust is lost.

Placebo engineering would, I believe, be a good area for PD organizations, such as MJFF, to work in.

John