Parkinson's Disease: Placebos may be effective for pain, but can they work on a really serious illness?

Parkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's ability to move, talk, and to do many other things that use big or small muscles in the body. It results from the brain having too little of the chemical that's necessary for sending commands to the rest of the body to move.

In one study [3], a placebo for a standard Parkinson's treatment resulted in an increase in physical agility in some of the Parkinson's patients that was comparable in magnitude to a therapeutic dose of the standard treatment. Treatments and placebos for Parkinson's both stimulate the production of a neuro-transmitter dopamine in a part of the brain that has a direct effect on motor performance. It's called the striatum (in green): 3D image of striatum Here's a simplified view of what's happening:

The image below shows one of the key pathways of the human brain that involve dopamine, the key brain chemical that is lacking Parkinson's Disease, and which is stimulated by placebo treatments for PD. Both the traditional medicines for PD and placebos for PD stimulate the production of dopamine. Both types of medicine stimulate dopamine release in the striatum, and use the dopamine-dependent reward pathway.

dopamine in normal vs PD brain

Five caveats

Placebos have successfully improved physical agility in Parkinson's patients [3] [27], but placebos are not a cure-all (for any illness). Here are the caveats:

1. If the patient knows it's a placebo rather than the 'real' thing, it won't have an effect. A placebo only 'works' if the person believes it's the 'real' medication, because it's the belief that triggers a beneficial change in the chemistry of the brain, because the anticipation of benefit is essential. [31] Parkinson's is one of many diseases in which the chemistry of the brain has a strong effect on full-body health.

2. Even if believed, the placebo usually works only if it mimics a treatment that had 'worked' for that patient previously, because a medicine that works conditions the body to respond favorably to that medicine. Placebos piggy-back on that conditioning. [4] [27]

3. People who are not able to respond to a placebo for a given illness are often not able to respond to the 'active' treament as well.

4. The effect of a placebo treatment often isn't as long-lasting as the 'real' treatment it replaces, and often is not as potent. (On the other hand, neither does it --usually-- have the negative side effects of the 'real' treatment.) As an example, a placebo injection of morphine is equivalent in effect to about 1mg of actual morphine [15].

5. Even when all the other conditions are met, placebo still may never work for some diseases (such as Alzheimer's), and particularly may not work for advanced cases of diseases that respond to placebos in their early stages (just as is true with many 'active' medications).

Dopamine has often been called the 'pleasure molecule', because one its the main functions in the brain is to stimulate expectation of something pleasurable, or in this case, expectation of improvement in health. The 3 big players in this 'magic' that the brain plays on itself are the Anterior Cingulate Cortex (ACC), the OrbitoFrontal Cortex (OFC), and the nucleus accumbens (NucAc):

Here is an example of a Parkinson's brain before placebo and one after that shows how a subtle change on a brain scan can correlate to a noticeable increase in ease movement for a Parkinson's patient [3]:


As an example of how densely packed the mental functions of the brain are, here are 2 essential Parkinson's placebo-response functions occurring within the tiny space of the striatum mentioned above.

There is more on experience vs. expectation in the placebo response in the second article of this series.

In sum, though there is a lot that's still unknown, it appears that placebos which help (but not cure) Parkinson's Disease do so because they mimic something that has helped the patient previously. The expectation of benefit from the treatment sets off a cascade of chemical changes in the brain that produce a needed neurotransmitter in a part of the brain (the striatum) that favorably affects their ability to move. This is the same part of the brain to which the traditional medicine stimulates needed dopamine.


3. de la Fuente-Fernandez R, Stoessl AJ: The placebo effect in Parkinson's disease. Trends in Neuroscience 2002; 25(6):302-306
15. Petrovic P et. al.: Placebo and opioid analgesia -- imaging a shared neuronal network. Science 2002; 295(5560): 1737-1740
17. Wager TD et. al.: Placebo-induced changes in fMRI in the anticipation and experience of pain. Science 2004; 303(5661): 1162
27. de la Fuente-Fernandez et. al.: Placebo mechanisms and reward circuitry; clues from Parkinson's disease. Biological Psychiatry, in press as of Mar 2004
31. de la Fuente-Fernandez R, Stossel J: The Biochemical Bases for reward: Implications for the Placebo Effect. Evaluation and the Health Professions, Dec 2002, 25(4) 387-398
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