Why PD is so susceptible to the placebo effect
 

Here's What Placebos Can Heal—And What They Can't

Is PD psychogenic?

Animals don't get PD naturally. Substances given to lab animals often cure the brain lesions and symptoms resembling PD deliberately caused by experimenters. When given to human subjects, though, they are no better than a placebo.

Unlike Alzheimer's there is no proven pathology that shows up in diagnostic tests as a cause of idiopathic PD. Alzheimer's does not respond well to the placebo effect.

Every individual with PD differs from others in their symptoms.

If PD can be thwarted by the mind, perhaps it can be caused by it.

The Parkinson's Recovery Project – Information about the cause and treatment of Parkinson's disease project claims it has healed people by changing their beliefs. "They made a significant mental adjustment: deciding that they are indeed safe from clear and present danger even if they let their guard down."

I have speculated that fatal illnesses are sometimes a respectable form of suicide for those with religious or moral opposition to suicide. PD is not as rapidly fatal so perhaps it is less drastic and more of a way to quit engaging with life. Movement, smell, swallowing, defecating, ED, and other affected bodily functions all represent a withdrawal from interfacing with the physical world.

Depression, common in PD, is a clue that the PWP is psychologically ready to withdraw from life. Hallucinations represent a disdain for sensory reality.

Perhaps trying to treat PD with drugs is too downstream from the source of the condition to truly cure it.

The mind is an amazing thing.

I remember reading about one study. Double blind steady, 70% got the drug; 30% placebo. Everyone was told they had gotten the new expensive drug.

Two of the patients getting the placebo were killed in car accidents. Post mortem they made an interesting discovery that they had new brain growth. Since they believed in the study they did great and had physical improvements.

I've mentioned studies where to get the best benefit you have to exercise and diet. Once again as long as you believed in the medication and did exercise and diet you did great.

So biggest thing I found. My dog. Just getting out side, two mile walk for forty minutes a day. It really helps keep depression in check. I seem more motivated. I like going to Rock Steady Boxing. I feel better... all that from a sweet golden retriever who helps me walk around the block and feel more independent.

The National Geographic article is quite interesting. Last week, I was reading the book that it is related to “Suggestible You: The Curious Power of Your Brain to Deceive, Transform and Heal” by Erik Vance. The first few chapters are all about the placebo effect, and how some conditions, such as Parkinson’s Disease, are particularly prone to it.

Contrary to GerryW's post, it does not suggest that PD is psychogenic. Instead, it explores placebos, and suggests the placebo effect is real.

It also talks about a particular COMT genetic variation, which supposedly is common amongst large numbers of people who respond to placebos in trials related to PD and some other conditions.

Of particular interest to PD is the case of a PwP who saw dramatic improvements (that have persisted) after receiving sham surgery as part of a placebo control group in a clinical trial that failed.

I haven't participated enough in this group, so I can't post links.

**

The book is quite thought provoking.

Hi Gerry,

Hope you're ok and thanks for this post.

As some will have twigged this and psychological stress as a causative factor and paradoxical kinesia are my area of interest. It strikes me that these effects must have access to the raw materials ie dopamine (or something else) an amputee can't grow a limb back.
Maybe in some cases a fluctuation in other neurotransmitters 'inhibits' dopamine, switching off production rather than destroying it.
Possibly serotonin as it's starting to look like a master neurotrans.

I'll stop now, looking at my previous posts Im sounding like a stuck record !!!

Best wishes for the festive season to all in Parkinsonia

Nigel

Nigel & Gerry,

As a new member, I can't post external links...but here's a brief post that I wrote summarizing my thoughts on the part of the Vance book that discusses placebos and PD.

Unfortunately, I can't include the reference links that are included where I originally posted this.

---

Parkinson’s Disease – The Placebo Effect, Genetics and the Placebome

While traveling back home on a long cross country flight, I got a chance to read a fascinating book, “Suggestible You: The Curious Power of Your Brain to Deceive, Transform and Heal” by Erik Vance. The first few chapters are all about the placebo effect, and how some conditions, such as Parkinson’s Disease, are particularly prone to it.

In a nutshell, the placebo effect is the big challenge in phase 3 of a clinical trial for a new drug or treatment. In these so-called double blind studies, there is one group that receives the treatment and another group that receives a fake treatment known as the placebo. The patients, and those evaluating the patients do not know who is receiving the real treatment or the placebo until the end of the study. For a treatment to be deemed effective, the patients who received the treatment need to fare better than the placebo group in a statistically significant way. In other words, the treatment being tested has to prove that it’s better than nothing…a challenge that is surprisingly difficult to meet.

A big part of the problem in trials related to Parkinson’s Disease is that there are significant numbers of individuals that see improvement during these tests as part of the placebo group. The author uses the example of an individual (Mike Pauletich) whose neurologist witnessed dramatic improvement in his PD symptoms while taking part in the placebo group for a clinical surgery trial that, in its end result, failed to show effectiveness. Yet, Mike, who received a fake placebo treatment saw improvements that persist to this day.

In many cases, placebo groups to do as well or better than the treatment groups. This phenomenon, the PD placebo effect, is thought to occur because of the reward/release of dopamine associated with the hope and expectation that the treatment will work. This boost of dopamine eases PD symptoms.

This may also explain why some PwP attribute improvements to different unproven vitamin and supplement regimens. I’ve previously divulged my dirty little secret that I take at least 15 different vitamins and supplements. I know that I’m wasting money, but I seem to be doing quite well, so what if one of these is making a difference? Or, what if I am amplifying the placebo effect times 15?

Drug companies consider the placebo effect to be a nuisance. The fact that some people see improvement without treatment doesn’t just rule out that individual as a potential customer, it makes it harder to prove effectiveness for the treatment. Improvements in the placebo group are dismissed as spontaneous temporary remission, wishful thinking, or more often, it is thought that maybe this individual didn’t really have the disease or condition…that it was all in their head to begin with.

However, with PD, we know that there is an actual biochemical effect in the brain as part of the placebo effect, and dopamine is involved.

The above is somewhat old news in PD research, but here’s where it gets more interesting, with newer theories discussed in Erik Vance’s book…

COMT is an enzyme that is responsible for breaking down dopamine after it has been used (normally the brain will just keep making more). People with a particular genetic variation (about 25% of the population), produce a COMT enzyme that is far less effective in breaking down dopamine. These people tend to have more active dopamine in their system, and there are studies that associate common personality traits with these individuals, based upon how environment and experiences have shaped them.

In clinical trials for a number of conditions, individuals with this genetic variation comprise most of the group that responds positively to the placebo. Harvard researcher Dr. Kathryn Hall has published several reports on this subject. She has coined the term placebome to refer to the study of genomic effects on placebo response.

And this is where it gets personal…

I recognize this COMT genetic variation all too well. I had the 23andme DNA test done a couple years ago, since it is free if you have PD. One oddity that stood out to me was COMT V158M rs4680 met/met (A/A). A couple of the services that analyze the raw DNA data flagged this and told me that this built-in COMT inhibitor meant that I had high levels of dopamine and was very unlikely to have PD. Lucky me.

So, here’s a thought: If we accept that this COMT variation enhances the placebo effect, is it also logical to theorize that these individuals are likely to see a more significant benefit from exercise, or any other actions that enhance dopamine levels?

We all know that PD progresses very slowly for some people compared to others. Maybe it’s because of exercise. Maybe it’s because of nutrition. Maybe it’s a particular vitamin or supplement. Maybe it’s the number of placebos we take and my newly discovered theory of placebo amplification. Or maybe it’s genetic…not PD itself, but how our body reacts to PD. And just maybe this COMT variation is a factor.

If it is, then relatively speaking, perhaps I’m one of the lucky ones whose PD will progress slowly.

I’m not taking any chances. Genetically, thanks to this COMT genetic variant, I am susceptible to the placebo effect. And because of that, I will continue taking my current placebos and looking for new placebos. I suppose that’s why my Motion Disorder Specialist neurologist hasn’t tried to dissuade me from my supplement routine…even if it is a placebo effect, it seems to be working.

And I guess that’s the bottom line…for now I’m doing well. Maybe it’s the exercise. Maybe it’s the supplements and vitamins. Maybe it’s a placebo effect, or the placebo amplification effect. Maybe it’s genetic, with this COMT gene, or maybe some other gene? Does it really matter?

The only thing I’m certain of after reading this book is that exercise is real. Strength improvements are real. Improved balance is real. Faster movement is real. Increased stamina is real.

If you’re interested in exploring this subject more, see:

*** I am a new member, so sorry, I can't post the reference links that I included in the original version of this article ***

parkinsons is azn existential problem
 

I am hypersensitive to the sense of conviction in myself and others (or lack of it).
I learned in practicing homeopathy that "knowing" I had the "right" remedy was the single most important element in helping my client and I've been witness to miracles and breakthroughs... but, the interesting thing about having a sense of conviction is it can (also) collapse one into two dimensional thinking (either you are with me or against me mode) which ultimately holds the inclusive nature of truth hostage-

Do placebo controlled trials take into account the impact of the doctor as well as the patients?

How our brains are biologically tuned to be influenced by confident people

Thank you so much my friend, fascinating stuff !

I picked up on the point that you were deemed highly unlikely to get PD. There are cases where diagnosed Px's are exhibiting classic Parkinsonian symptoms and yet a Datscan shows normal levels which is possibly related.

Thanks Parkinson Fit: a very interesting post.

Here's one of the references that you wanted to make [1].

Interestingly, I'm rs4680 AA too.

I wonder if that explains part of my Parkinson's experience, whereby I wake up in the morning feeling good. Sometimes, I go hours without taking medication, but still function OK.

I see the placebo effect as a friend, not an enemy. We should engineer placebos to have the maximum effect. I feel that a distinction should be made between a true placebo, which really is physiologically inert, and what I call a "therebo" (from THERapy or placEBO), something that may have a direct therapeutic effect, but we're not sure. By this definition I would call your 15 supplements therebos.

Reference:

[1] "Genetics and the Placebo Effect: the Placebome"
Kathryn T. Hall, PhD, MPH Joseph Loscalzo, MD and Ted J. Kaptchuk
Trends Mol Med, 2016, May
Genetics and the Placebo Effect: the Placebome

John

Hi Moondaughter,

I don't believe in homeopathy. However, I do acknowledge that there is so much that I don't understand, that I am basically ignorant, but try to keep a somewhat open mind.

In a clinical trial, the underlying concept is double blind. Neither the patient or treating physicians have knowledge whether the treatment is real or placebo. Typically, in this type of scenario, both doctor and patient want to believe. Of course, treating physicians develop suspicions based upon preliminary results that may go on and affect future results.

The bottom line in clinical trials is that people responding to placebos is inconvenient and expensive, because the company paying for the trial is trying to get their drug approved so that they can charge exorbitant sums for it...er, I mean so that suffering patients can experience relief.

Your question is about confidence of the person delivering the treatment, is that significant? Individually, yes...the more confidence the practitioner has, the more the patient believes it will work. I don't think that aspect has received a clinical study of its own, but the author of this book voices that opinion, and I share it.

To be very frank, as I started reading this book, my first thought was never to discuss it.

Why?

You use homeopathy. I don't believe in it. But if you treat somebody and it works because they believe, and the placebo effect is real, what difference does it make what I believe as an external 3rd party? If I discourage you, then I am harming people that you could potentially help.

If 25% of people are genetically predisposed (and that is a big if) to have a positive reaction to a treatment they believe will help them, then as long as no one is exploited or taken advantage of in the process (and no endangered species sacrificed)...that's a positive outcome.

Here's where it gets weirder...

People who are more acceptable to the placebo effect are likely to have experienced positive results from alternative treatments in the past, therefore they are more likely to seek your assistance with alternative treatment. Thus increasing your success rate.

I'll be the first to admit, this could all be a crock of excrement. But at some level it resonates with me. I have so many potential placebos in my personal PD regimen of supplements and nutrition that I have no right to question your homeopathic treatments.

In fact, even though I don't believe in homeopathy, I would encourage you not to be deterred by skeptics. If this theory is true, 25% of people are hard wired skeptics and will not respond.

Understand that I'm simplifying a bit, as the genetic switch I'm referring to applies to only certain conditions such as PD. Other conditions may have different genetic placebo switches, if any. The author notes that chronic pain and IBS are in a similar category to PD, while Alzheimer's appears resistant to placebos.

Or, all of this may be a crock of excrement. The funny thing is that while my initial reaction to this line of thought was to question my placebos, ultimately it is leading me to embrace them more fully, as there is so much that I know that I do not understand.

I would also emphasize that when I talk about the PD placebo effect...the effect is generally not a 100% cure...although I wouldn't rule out that possibility. Usually it would refer to reduced symptoms and/or slower progression.

- Brett

Hi Nigel,

I cannot ignore this possibility. All told I have had 4 neurologists diagnose me with PD, yet none will refer me for a Datscan as they are too expensive and don't provide sufficient additional insight. Because of turnover at a major university hospital, I recently was assigned a new MDS, and I have not discussed Dascan with her.



- Brett

Hi John,

I know that morning feeling. Some dismiss it as the sleep effect/sleep benefit. But I'd like to understand it better also. It's hard to explain, but I do have some superman type mornings. If only I knew how to replicate them.

Therabo is a good concept...the author suggests that the marketing material for many prescription drugs is to encourage additional positive placebo response...additive to the effect of the drug. This is, in essence, your therabo concept.

I believe that, for me, exercise is the biggest therabo. It is additive on so many different levels, and I have embraced it with a religious type fervor.

The supplements as a whole, same category, but less fervor.

As I said to moondaughter, my initial reaction was to never discuss the concepts in this book.

But if the placebo effect has a real biochemical action, and it seems to, then I do think we can use it and manipulate it to our benefit. Minor therapies can become therabos.

- Brett

This idea haunts me to the core...suicide/resignation is subconscious as well as conscious choice... parkinsons is such a perverse contradiction ...existing in the fight/flight mode(till death do you part) but needing to surrender ones own concepts of safety tofind new ways of accessing the very juice/ the vital force that sustains life!!

I dropped in my mothers womb at 6 months gestation....so to keep me alive she took a neurooendicrine interruptor- DES (Diethyl Stiburol) and layed still in bed for 3 months....later I presentwith early onset pd.. I don't know the reason why i dropped but perhaps what iismore important is t hat the love of my mother saved me giving me tthe amazing giift of life in this time and place.....still... but begs the question in bioethics in medicine of quantity verses qualiity of life....when does one prolong life verses letting nature take its course in its wisdom. And now at 90 years old my mother exists with heavy opiod addicition to ease her coonstant pain of many decades...but, she also r esponds when I send her long distance healing, whhich is a tremendous gift for both of us... Managing nature can be a slippery slope.....and not without comprimises . I hate the idea of being a burden to o thers yet I am a caregiver foor my husband who suffered a stroke....and somewhere have lost a part of myself iinn that process... Thing is ..when there are deeply ingrained patterns, ancestral and otherwise we arebeing a sked to reach deep....way back into decisions that twere made by someone else..(its' not a sacrifice when we make the choice) sigh....bad and selfish as this sounds...does some part of me in my subconscious resent her choice to save my life -I certainly don't chose that position consciously. Thinking about it further my mother may have resented me though she denies it vehemently which just confuses me after having a dream where sshe told me I was keeeping her from doing what she wanted to do...not to mention that she left me with a babysitter at 2 weeks old for two weeks to take a break (she says she waited so I would have a good start...... wheres the maternal instinct in that???)

Thanks for listening...........

Rectify
 

When I follow my feelings surrounding my birth, my mother, her pain what comes up are issues around hope for the future. We have a plum tree in our yqrd...it seems to tolerate all manner of neglect. in essence...its got a will to live. It took years before the blossoms turned to tiny fruit ....but, sturdy as the tree is the fruit is more fragile, more susceptible to the elements...wind , deer, water oor lack of , but perhaps most importantly care.

My ancestors were cherry tree planters - I've heard it said that the energy of the cherry tree is hope for the future...perhaps hope is our cure..and ours is a struggle between learning the humility that comes w ith surrender to developing the strength and discipline to overcome resignation. Understanding the nuance between the two I leave to you..

Lately I've been watching the TV series "Rectiify" - chock full of relevant prose and metaphor to my experience of pd. One of the most poignant moments is when Daniel talks about finding his will to fight for himself - as he struggles between surrender and resignation....between having his will utterly broken by cooerced confession and 20 years of solitary confinement for a crime he did not commit just wanting a window to freedom into this world - withh booth feet on the ground...

[QUOTE=moondaughter;1231422]This idea haunts me to the core...suicide/resignation is subconscious as well as conscious choice... parkinsons is such a perverse contradiction ...existing in the fight/flight mode(till death do you part) but needing to surrender ones own concepts of safety tofind new ways of accessing the very juice/ the vital force that sustains life"

...... a perpetual crisis of faith...maybe thats why "the cure" for pd seemsso elusive yet possible (and a rational explanation for susceptibilityy to placebo effect)l and imppossible at once ...it is an exercise taking me between resignation (my body) and surrender (heart and mind)-every day.

what gives you hope? science? drugs? for me its ~love..that is my religion but love demands risk (and discipline) sometimes....thats the hard part when what is at stake is ones own safety....

[QUOTE=moondaughter;1231474]
Hi Moondaughter,

I'm grateful to you for sharing such personal thoughts. Over the last 7 yrs, on three occasions I'v had, whilst sat endlessly awake, in the dark, as my family slept, what I call my 'dark eureka' moments.
I liken it to trying for hours to solve an algebra equation, then suddenly the answer's there ! 2x.... the sense of relief, peace and a feeling that you knew the answer all long is immense.
Only the question isn't algebra, it's how to end the suffering and the answer is not to be here any more.
But I'm aware of what is happening, luckily and I shuffle to my wife and children's rooms and watch them sleeping. That simple act infuses me with such love that I know I can take it and I will win. And with my final breath I'll smile and whisper " see Mr P, you couldn't break me !"

Somebody once told me don't let it define you.... For me this is counter productive, acceptance works better for me. "yes I'v got Parkinson's,I'll give nor expect any quarter"

The 'only' definite, 100% correlation I'v found between being well and not isn't
the amount, timing or type of dopamine replacing meds I'm taking it's how my mental state is. And yes I'v considered correct drugs=better mood=less parki
and my conclusion is better mood=less parki irrespective of the drugs..

When I first came to this forum I was just starting a program of increases under the care of a Parki specialist. Im now on double the amount of agonist and 150mg stalevo 4x daily and feel no real difference ! The reason is because Im living under the constant threat of my wife's cancer returning (told it will )
and the threat of bankrupt..

I mention this because placebo's,exercise and sleep all have a positive effect on mood via the other neurotransmitters..... again suggesting we should be looking beyond dopamine, after all 60y since levodopa and nothing better...

IT DON'T MEAN NOWT


When dark tragedies bring you down,
and black clouds turn sunlight into shade.
When expression is reduced to a frown,
and your zest for life begins to fade.
When you question “for what reason “.
and then wonder what it's all for.
When winter becomes your season
and you just can't take any more.
Imagine a list of all that has you cowed,
turn it to ash and let it to heaven float,
smile at the world and then say aloud,
“you know what, it don't mean nowt”.

Dear Niggs,

T h a n k y o u friend .

I'm so sorry that you and your wife are haunted by such an insidious threat-nothing like a shadow of death to bring the world into sharp focus.

I'mm wondering...how old are your kids? Will you be able to keep your home after bankruptcy? Are you not responsive to levadopa? I think it is such a good thing that your mood which you can initiate through exercise etc can override any drug effect? How do the agonists help you to function better? My very brief encounter with a non therapeutic dose of liquid deprenyl citrate was that it really really landed me in adrenalineville and I only realized it when talking to friends on the phone I became aware of my own narcissism and realized it was the drug talking and I didn't like it...in fact it scared the @#$%%&& out of me - its those eureka moments of grace I feel humbled and my ego overrides those enough as it is w/o adding adrenaline to the mix. Perhaps though we need a strong ego to carry heavy burdens...I mean,doesn't it seem like.the hero archetypes embody a healthy expression of uniqueness, individuality , and self-esteem (all prerequisites for courage)?

I feel this is such an important thread as it asks a question few endeavor to answer..conveniently overlook-thanks again so much for sharing a look into your world through your heart. Its posts like yours that truly matter to me.

Dylan Thomas, 1914 - 1953

Do not go gentle into that good night,
Old age should burn and rave at close of day;
Rage, rage against the dying of the light.

Though wise men at their end know dark is right,
Because their words had forked no lightning they
Do not go gentle into that good night.

Good men, the last wave by, crying how bright
Their frail deeds might have danced in a green bay,
Rage, rage against the dying of the light.

Wild men who caught and sang the sun in flight,
And learn, too late, they grieved it on its way,
Do not go gentle into that good night.

Grave men, near death, who see with blinding sight
Blind eyes could blaze like meteors and be gay,
Rage, rage against the dying of the light.


With kind regards,
MD

A kindred spirit, I love poetry and post regularly on 'creative corner' this piece is one of my favourites.

MD, my daughter is 18y and has just started reading History and English at University. My son is 14y and still lives at home. I was a contact lens Optician/specialist and had a small modest practice. It was nothing special but gave us a reasonable living. After 5y of battling I had to volunteer to hand in my registration as I felt it was only a matter of time before a client accused me of something . Since then my beautiful dedicated ladies have valiantly tried to keep it going while I try to sell, such loyalty ! but alas it's now in tatters and I still have not managed to sell it. I desperately hope to void the bankrupts court as I would lose the house and would struggle to get a mortgage.
2 y ago my wife had oral cancer due to an auto-immune condition, she survived technically but was butchered and suffered terribly during treatment.
We've been told because it's auto-immune it will return in 4y or 40y nobody knows, she is a woman of immense courage and inner strength and remains to me as beautiful as the day I met her.

I am dopa responsive and know I get benefit that comes from dopamine increases but stress is devastating to me. I know stress makes us all worse but it's the degree to which it incapacitates me that makes me wonder. I can go from being briefly almost normal to being like a statue.
Another thing that makes me wonder about other neurotransmitters is I cannot tolerate anti-depressants whether 1st gen fluoxatine (prozac) or newer citalopram. Even St.Johns wort and 5-HTP make me very ill with what seems like panic attacks or serotonin syndrome. (fluctuating bp,pulse,tingling,restlessness/agitation)
Scandanavian Pet.scan research announced a short while ago that contrary to current medical thought folk with diagnosed anxiety ie social phobia not depression had elevated not depleted levels of serotonin. Which could be why I can't tolerate anti-D's they're just piling on the bad stuff. Taking it further I wonder if serotonin acts as a master n.transmitter and as it rises it inhibits dopamine sooooo when stressed serotonin rises and dopamine falls, as I chill the reverse happens. It's all speculation on my part but wonder if I need serotonin reducing drugs as much as dopa elevating.

With regard to ropinirole (known as rock n roll here) it's taken me 6y to properly tolerate this drug and each titration takes min 6 weeks to settle Iv bumped up from 8 - 16mg and I'm still not sure how much it brings to the party. it and stalevo may be very proficient were it not for stress induced anxiety.

One final word on supplements, st johns wort and 5-htp work as anti-depressants and cdp choline/citicholine works as an agonist. How do I know ? because when Iv tried them the side effects/tolerance problems are exactly the same as the prescription only equivalents.

Wishing you love n mercy

Nigel

sativa,iindica, CBD??
 

>"sooooo when stressed serotonin rises and dopamine falls, as I chill the reverse happens" - Niggs

Nigel, as I was meditating on your message what came up was the question of whether you have tried different strains of medical marijuana....found this in a conversation:

"The anti-depressant and intoxicating effects of cannabis are due to its chemical similarity to natural substances in the brain known as ‘endo-cannabinoids,’ which are released under conditions of high stress or pain . These receptors could have a direct effect on the cells producing serotonin.

Some study conducted of rats tend to demonstrate that low doses of Cannabis will raise the level of serotonin in the brain (not the production)

However, the same study show that too much Cannabis will have a dramatic and opposite effect, lowering the soerotonin levels much lower than the control group"-

Cannabis and Serotonin

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I really empathize with your stress issue remembering giving birth to my second son-he had the cord wrapped around his neck and the stress was worse than the pain....thank the heavens you have some venues for relief! Perhaps a higher dosage of 5htp or st johns wort might also effect a lowering of seratonin if you took more rather than less tho it would be counterintuitive given your sensitivity.

Kind regards,
MD