Levodopa-Induced Euphoria and Addictions ... - Cure Parkinson's

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Levodopa-Induced Euphoria and Addictions in Parkinson’s. It's of concern for people with neuropsychiatric fluctuations between ON and OFF.

ElliotGreen profile image
22 Replies

I'm referencing a 2017 research article.

Some people have more significant neuropsychiatric fluctuations between ON and OFF levodopa drug treatment states. These people seem to be more at risk for triggered addictive behavior and drug abuse.

The conclusion of the abstract is "The psychostimulant effects of dopamine treatment during on‐drug euphoria, rather than avoidance of off‐drug dysphoria, appear to drive both behavioral addictions and abuse of medication."

Popular article on the subject:

neurologyadvisor.com/topics...

Scientific article:

onlinelibrary.wiley.com/doi...

(Let me know if you have trouble accessing scientific article and you would like to see it.)

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ElliotGreen
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park_bear profile image
park_bear

Thank you for providing links and a copy of the abstract. So often I have to go hunting for these things.

From the text of the study:

"In the present study, we focused on neuro-psychiatric fluctuations characterized by variations of mood, motivation, and anxiety between off-drug and on-drug states. In the off-state, patients typically experience a variable combination of apathy, anxiety, and depressed mood, known as hypodopaminergic behavior, a state we called off-drug dysphoria. In contrast, euphoria, hyperactivity and impulsivity characterize on-drug hyperdopaminergic behavior, which we baptized on-drug euphoria."

It makes sense that PWPs subject to this would be vulnerable to addiction.

GymBag profile image
GymBag in reply topark_bear

I remember when My mother was dying of cancer and my sister was so concerned that the morphine mom was taking would lead to addiction that she hid her medicine . We had to get more and keep her away from it. Mom was dead in 6 weeks .

AM I addicted to PD medication ? probably. SO what.

park_bear profile image
park_bear in reply toGymBag

Your comment highlights how frequently the term "addiction" is misunderstood. Most PWPs need medication in order to function well. No different than asthmatics or diabetics or cancer patients who need painkillers to alleviate pain. This is not addiction. In the matter at hand the authors of this study define addiction as: " intake of dopaminergic drugs ... superior to the dosage required to control motor symptoms, despite the possibility of severely destructive social behavior". In other words, addiction is taking more than you need to control symptoms and is usually accompanied by destructive behavior.

GymBag profile image
GymBag in reply topark_bear

ooooooooh

thanks

pvw2 profile image
pvw2 in reply topark_bear

We could truly say that a bipolar personality is addicted to the dopamine their brain already produces when they don't want to take their medicine to counter it. They don't like to get pulled down from the dopamine high. That is a common problem for many people with a bipolar personality.

pvw2 profile image
pvw2 in reply toGymBag

Essentially you are addicted to PD medication before you start taking it because you are missing many dopamine producing neurons, but there is an upper limit to how much L/C you can tolerate. Everyone is addicted to food and water. The type 1 diabetic is addicted to insulin. Neurons overproducing dopamine causes a manic state in bipolar personalities. However, I've never heard of a person with PD being able to reach that point with L/C dosage. Other symptoms show up first and puts a limit on the dosage.

MarionP profile image
MarionP in reply topvw2

Just like everyone is addicted to food, water, essential nutrients, etc.

A problematic addiction such as this one alleged has to be distinguished and labelled as differently (though perhaps sometimes in degree, but still distinguished even then) from what is really more of a dependency because the brain receptors and mechanisms and anabolic/catabolic feedback loops and negative feedback loops (often both at once on the same particular long reaction step and sequence).

In other words, such "addictions" are natural and functional, such as internally produced opiates that your own brain manufactures...called endorphins...(ever heard of "positive addictions?" rather than dysfunctional. It's the dysfunctional ones, which may be distinctions of degree and also difference in other cases, that is the problem. The rest are just natural functions.

pvw2 profile image
pvw2 in reply toMarionP

Quote:

Key Difference – Dopamine vs Endorphins

Dopamine and Endorphin are chemical substances involved in the signal transmission within the nervous system. Both are known as neurotransmitters. The key difference between Dopamine and Endorphin is that Dopamine is a small molecule neurotransmitter which is mainly responsible for movements and feeling of pleasure while the Endorphin is a larger molecule of neuropeptide with the main function of pain relief.

differencebetween.com/diffe...

MarionP profile image
MarionP in reply topvw2

Yes I'm sure you know best. I'll bet you change lanes without looking, or only think there is really a vehicle there if it's one you find to your liking.

ElliotGreen profile image
ElliotGreen in reply topvw2

Thank you for engaging with this material.

I personally don't think it's very helpful to equate our desire for food and water with addiction, because it's missing something of what addiction is, and it's lessening this particular problem. More directly, I don't think it's useful to equate a harmful desire for excessive amounts of levodopa pills with our normal desire for water.

Here is my understanding: With Parkinson's disease, there is not a global deficiency of dopamine. There is a local deficiency of dopamine in the substantia nigra and the striatum. When we supplement the dopamine precursor levodopa, we raise the overall dopamine levels in the brain, everywhere.

Dopamine is used elsewhere in the brain as a neurotransmitter used for rewards and pleasure. It is implicated in every addiction. With Parkinson's disease, we are dosing directly with that. This isn't a problem for some people, but it is a problem for others. The paper I cited tries to assess who it is more likely to be a problem for.

Some people take excessive amounts of levodopa medication because it TEMPORARILY FEELS GOOD, even though it is hurting their mobility rather than helping. FURTHERMORE, some people engage in OTHER addictive behaviors when they are on levodopa medication.

Here's another article, from the Lancet:

sciencedirect.com/science/a...

TITLE: Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry?

ABSTRACT: Dopamine replacement therapy (DRT) is the most effective treatment for Parkinson's disease (PD); it provides substantial benefit for most patients, extends independence, and increases survival. A few patients with PD, however, take increasing quantities of medication far beyond those required to treat their motor disabilities. These patients demand rapid drug escalation and continue to request more DRT despite the emergence of increasingly severe drug-induced motor complications and harmful behavioural consequences. In this article we detail the features of compulsive DRT-seeking and intake in PD, in relation to theories of compulsive drug use.

pvw2 profile image
pvw2 in reply toElliotGreen

If someone takes enough L/C to get continuous dyskinesia and still keeps increasing the L/C dosage, I would call that a true addiction. I'm not referring to people temporarily getting dyskinesia for a short period of time because of uneven dosage.

MarionP profile image
MarionP in reply toElliotGreen

ummm...not helpful. Hmmm. Well, it's not quite just a "desire." Try going without food and water for a while. I'll bet after a bit everything that follows is exactly a symptom of addiction, until you get some more.

Keep re-defining terms though so that they suit you. Maybe they will be helpful then. Maybe you then will not have to discover like scientists have since the early 1980s and on up to now that the brain is wired to require, by addictive craving mechanism, exactly those things that it cannot do without. Like, oh I don't know, food. Maybe you will create the next form of addiction science and addiction medicine as a scientific subset of biology (as it currently is established, not "believed") and get to re-define the term. Then it will be "helpful" to more than one of us. Waiting with eager anticipation.

ElliotGreen profile image
ElliotGreen in reply toMarionP

Yes, of course, the reward system was evolved so that we act in ways which meet our needs. This includes desires ("gosh I'm a little thirsty") as well as very strong desires ("I literally haven't eaten in a week! I'm starving!")

Eating an appropriate amount of food is not addiction.

Overeating can be an addiction. It's not just the strong felt need for food, it's a strong felt need for food when there isn't actually a need for more food.

Taking an appropriate amount of levodopa for therapeutic effect is not levodopa addiction.

Taking excessive amounts of levodopa, well beyond therapeutic effect -- when it causes all sorts of problems -- is levodopa addiction.

The people in these cases feel like it's a life or death matter. They feel like they need those levodopa pills in the same way that starving person feels like they need food.

To quote the scientists , it's a "reward systems gone awry".

MarionP profile image
MarionP in reply toElliotGreen

There you go, partway at least. But if the underlying mechanism is the same for normal and abnormal, assigning a difference is an artifact of social convention, not physics or science, just politics, and THAT'S "unhelpful,", except for social policy, which is variable, not factual...meanwhile the experience of the individual is exactly the same, addiction as defined by the pros, going back long, this is not new, this was going on in the late 70s and just developed ever since from there. These things are axiomatic in the relevant fields, all long history, nothing new. Addiction is the mechanism, only persistent dysfunction persistently resistant to reversal at the mechanism level that makes for "disorder." Social goofing around with terms is not knowledge, not factual, not current and not helpful. Amateur blithering is not helpful. But reinventing the wheel IS pleasantly distracting pastime. And even at that, it is mainly wasteful and harmful to anyone suffering and sent off on some goofy tangent for having trusted it at face value, especially if the disease is shortening their lifetime for want of a truly useful direction..., to them it is not mere pleasant time killing to have their limited directionality lured by such inviting misinformation. Better to think it over a bit first.

MarionP profile image
MarionP in reply toElliotGreen

Not awry. The scientists know that the mechanism is exactly the same fir 'nomal' as well as 'abnormal'. So what you added you must be making up on your own, for rhetoric perhaps. You are off just a tad, go learn about it.

ElliotGreen profile image
ElliotGreen in reply toMarionP

Please read the following account of levodopa addiction.

outthinkingparkinsons.com/a...

It points to an extremely serious and challenging condition that befalls SOME persons with Parkinson's.

Figuratively, we may say we ALL are "addicted" to dopamine. But what Gary went through is something else: the true pain of a real and serious addiction. He was stuck feeling and believing like he desperately needed something, and that something was hurting him! Badly!

Listen, I have a Masters degree in the sociology of science. I'm well aware of the concept (and process) of "social construction". But I find it both amusing and frustrating that you are accusing me of fiddling with the meaning of addiction when you are pushing a less conventional one. You say the mechanism is "exactly the same", but the truth is that it is the same in some ways, but different in others.

What is your goal here? Why are you arguing with me?

I'm posting here because I'm trying to relieve suffering and increase well-being. I'm trying to help us individually and collectively figure things out, so that we may live better (and happier) lives and make more informed decisions.

MarionP profile image
MarionP in reply toElliotGreen

Sounded more like impromptu pontificating to me. Read your words again. Your pontificating indicates your view unqalifiely applies to all rather than one and sets back actual work in addiction treatment if taken literally. When you run someone over, it is no good saying I meant well just wanted to help to the victim most quickly so I drove into them.

MarionP profile image
MarionP in reply toGymBag

So what? Yes, exactly. :)

No functional difference or significance for you in this case, until it affects your life negatively. So it's an emotional distinction only by whoever has a need to deform things until they get credit for appearing to be right. That's the problem with social or casual hijacking of terms to arbitrarily suit oneself and expanding them into meaninglessness. Pretty soon they are, well, meaningless. People who don't know but don't know they don't know. "People who think they know everything are very irritating to those of us who do."

pvw2 profile image
pvw2 in reply toMarionP

How about defining addiction as a desire that overrides a person's best judgement and leads to destructive behavior; a desire that leads to poor decision making.

MarionP profile image
MarionP in reply topvw2

It's already been established beyond social convention, in science, psychology, medicine and chemistry. Established as an actual mechanism of neurology, physiology and neurochemistry, as well as learning at the cellular level. Why would we want to start over at "a is for apple?"

ElliotGreen profile image
ElliotGreen in reply topvw2

pvw2, that definition seems pretty good to me.

GymBag profile image
GymBag in reply toElliotGreen

An argument over one word

Pick something else you both disagree on, maybe philosophy, religion, politics , sardines and have a real go at it. I bet it would be amazing.

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