Update on Addiction 2022: Mouse Cocaine Addict Studies

Recent experiments on mice are giving us interesting information on addiction, and suggesting that l-dopa may be able to control/mitigate addiction. This lecture about how dopamine works in addiction using a mouse model (poor mice) blew me away. The mice fell into two categories: maintenance users and vulnerable addict rats. The study of the dopamine postulates a reason for the difference.

20th Annual Drug Conference Washington State from 2019

Notes from lecture 3: Paul Phillips PhD
Dopamine Neurotransmission in Substance Use Disorders: from Preclinical studies

For a long time there were no agreed upon animal models: rats don’t steal money from other rats to buy drugs. However, rats do get addicted and this can be studied.

There are features in rats, rat behavior and rat brains that might translate to humans.

1. Basic discoveries about dopamine neurotransmission in substance use disorders is discussed.
A neurotransmitter study checking every ten minutes in brain examines two areas: dorsal and ventral striatum. Dopamine is increased in the area between cells from the administration of substances “first time use” in animal models: cocaine, alcohol, methadone, cannabinoids, nicotine, amphetamine, morphine. This is the first clue re addictive drugs, whether there is an increase in dopamine intraneuronally. The endpoint is that direct effect on dopamine receptors, which has a different brain mechanism for each drug. Cocaine blocks the receptor that reuptakes the drug into the neuron. Methamphetamines and amphetamines reverse the reuptake pump, makes the receptor spit it out. Gaba neurons act to inhibit dopamine neurons, normally mu receptors on the gaba interneurons and the opioids block those. Ethanol has another mechanism of action. It changes inhibitory activity, lowering the inhibition of the gaba interneurons. Nicotine REALLY messes with multiple receptors and multiple cells, but main effect is increase of dopamine in the striatum.
Increased dopamine in human brain relates to the feeling of being high: brain PET scans show amphetamine and dopamine bound less, reduction in the binding. Subjects were substance abusers. Subjective questioning of how high they felt correlated with the amount of dopamine released on the PET scan. Methylphenidate was used in that study. Canada study: cocaine increases dopamine in human brain by PET scan.
Addiction does lead to changes in the brain, on both PET scans and functional MRIs.
PET scans measuring dopamine binding in the brain show that the baseline in brains of substance abusers differs from non-abusers. The levels of dopamine receptors is lower in the substance overuses and there is lower binding than controls: heroin, alcohol, meth, cocaine (and obesity and ADHD…..). (This has been known for opioid overuse and chronic use for a while: the brain cells withdraw receptors, so the same dose does not reduce pain because there are less receptors. The change in receptors appears to vary in different subjects. Recovery is very slow.)
The role of dopamine has been confusing. It is known that it is involved in the cue evoking cocaine “craving”, but is also involved with — satiety. This has been confusing and contradictory — what does dopamine do but also the dynamic structural signaling.

2. The animal studies demonstrate that the dopamine signals are phasic.
Rat studies measure changes in dopamine minute to minute electrochemistry for sub-second dopamine detection in vivo, which means we can measure changes in dopamine in real time. There is an identified output signature for dopamine levels, measure in 8.5 millisecond, ten measures per second.
The rats were voluntarily taking cocaine. The cocaine was available in a liquid with a light that would come on when it was available, for two hours daily. The animal presses a lever when the light cue is on and gets an infusion of drug. With the ten measures per second, the first and smaller dopamine response in the brain is before the lever is pressed. That is, there is a rise in dopamine BEFORE the rat presses the lever. If stimulated dopamine, the animal would go press the lever. Then there is a larger reward dopamine signal when the drug hits.
Dopamine is the chicken and the egg: signal to USE and signal that has ARRIVED.

3. Changes that take place with drug use
There is a signal change over time that correlation with features of addiction.
The mice had an implanted brain electrode, tinier than human hair, 7 microns, biocompatability — don’t make the brain attack it as a foreign object so rat brain keeps working. The study involves tyrosine hydroxylase, a precursor of dopamine. A food pellet response of the tyrosine remains the same at 1, 2, 6 months so can monitor substance abuse brain changes. These are cocaine addicted rats. They get cocaine via a nose poke of a button when it lights up. Pellets, not iv (they learn that faster). There are 2 ports to nose poke: active and inactive. The signal that cocaine is available and the pellet is active: a light comes on for 20s and then drug arrives. Can take again after 20sec. The rats titrate cocaine use: not continuous. They pace cocaine use, wait for it to wear off. Over time, drug use 1 hour access daily… slow increase, relatively stable.
When the access is bumped up to 6 hours access daily… rats do increase use — first of 6 hours, escalation of drug use faster — in humans development of tolerance.
With 1 hour cocaine availability, the dopamine response to the cocaine in the rat brain is lower by the 2nd and 3rd week, slowly decreases, then with 6 hours of access the loss of dopamine is very robust, happens faster, dopamine signal gets smaller every time.
Rats long access: were there individual differences? Yes, metric, nonescalated vs escalated groups so like humans. 60 escalated 40 didn’t and stayed stable. So essentially I named these “Vulnerable addict rats” and “Maintenance rats”.
Which group most motivated to take cocaine? The study ups the price of cocaine for rats, how many times are you willing to receive the drug? The escalating animals made more responses, “worked harder” for the drug. The escalator brains, Vulnerable Addict Rats, had just about a complete loss of dopamine signal by three weeks.
The nonescalators had more stable dopamine responses, retained some dopamine brain function.
The greater the loss of dopamine, the more the animal escalates the drug use.
The Vulnerable Addict rats would use cocaine to the exclusion of food, water, sex and sleep and died early.
This is a feedback loop. The rats get a success signal when the drug is taken — but over time don’t get the success signal because dopamine receptors are gone — so take more. In the Vulnerable Addict escalators, the dopamine signal of anticipation goes down in response to the cue, the drug effect takes a little longer but the pharmacological response to drug actually remains.
They tried giving l-dopa, a parkinson’s drug and if treat, the rats get a restoration of the dopamine cue — pharmacological response didn’t change — how does this affect behavior? A daily shot of l-dopa and the animals on the l-dopa have less escalation. (wow!) The l-dopa didn’t affect the nonescalators/maintenance rats. When they remove the l-dopa in the vulnerable addict rats, the animals jump to higher use and so the brain changes are happening even when it is masked by the l-dopa but does not stop the brain changes.
They ask the question: can you reverse escalation? With the the l-dopa, they use less.
Dopamine signaling to take drugs (the anticipation cue when the light goes on) decreases in animals that escalate drug taking, but does not change in animals with stable drug taking.
Restoring dopamine signaling with l-dopa can prevent or reverse escalated drug taking.
This dopamine signaling….

4. Mechanisms — drug cue elicits dopamine.
So this is about triggers. This is a paired drug cue: the light signals that the drug is available. If a non-contingent drug given to animal, the light still elicits drug seeking. Using a naive animal: pair reward with cue, over time the cue will increase dopamine.
(hmm. Facebook. blogging. Instagram. “You have mail”. )
The initial addiction has a short access time. One hour out of 24. When this is changed to long access, some animals escalate vs non escalation — as take more and more drug, the response to the drug taking cue gets larger in the escalators/Vulnerable Addicts. Presentation of cue — by investigator vs animal:
If elicits drug seeking than the dopamine response gets larger to the cue over time.
If the cue is given but other choices of liquid, then the dopamine response gets smaller in some rats — so terminating drug seeking. The Vulnerable Addict Rats had a larger and larger dopamine craving cue spike, the longer they were off the drug. The the increase in the cue drives craving and decrease drives seeking — so both bad.
The conclusion in the rats is that craving for drug, related to cues, is dependent to length of time off drug. The longer the rats were off the drug, the larger the dopamine spike when the cue light comes on. The measure of cue behavior gets worse …. 60 day study in rats, this is not physiological withdrawal, is prolonged way beyond the withdrawal.
1. noncontingent
wait a day or wait a month
work harder to get drug, harder a month out
reaction to drug cue presentation, enhanced over time
at start of drug small signal to drug cue
long access then cue gets bigger
same a day after stop drug
but huge in a month after no drug — huge dopamine response

(my thought was then swearing. how do we treat this?)
In chronic drug use the cue signal shrinks which reinforces drug use AND stopping increases the cue response which ALSO reinforces.

5. Implications for treatment
treating rats
They discuss a virus with promotor that affects dopamine cells, light activated ion channel, cells release dopamine when light stimulated
only activates release of dopamine, to understand mechanisms.
For the self administered nose cue …. In the nonescalator maintenence rats, dopamine cue response stays fairly robust, stimulate those cells and no change.
In the escalator/vulnerable addict rats… if do a virus stimulation of dopamine in the brain, more dopamine to cue boosted, so they use less cocaine and look like the non-escalators.
5th cue less dopamine than 1st cue: if put dopamine back then maintains the drug seeking.

What underlies the decrease in dopamine release?
When the animals use cocaine, dynorphin goes up (kappa antagonist).
They injected a kappa receptor blocker — animal no longer escalate (not in humans at this time, don’t understand well enough) treating animals that are escalating, so the bad addict/vulnerable rats.
Most animals don’t escalate — but pretty serious amounts of drug cocaine so not abstinent.

For future
Dopamine diametric changes: dopamine may reduce consumption but might increase craving, so it is difficult to treat.
l-dopa — treatment — some studies, looking for abstinence, does NOT produce abstinence. Does not make abstinence worse. Says that promise seen relates to the status of the subject — helps with people who are still using (some) but doesn’t help increase or prolong abstinence. So could reduce harm but not abstinent….politically unpopular. Happier with turning alcoholic into a social alcohol user, but that idea is less popular/politically ok with cocaine/opioids (and especially meth).

They are studying mouse nosepokes for alcohol — reduced intake when the rats are on l-dopa.

There is a functional agonist for kappa receptors == buprenorphine, might have effects on drug consumption, speculation across different drugs.

Dynorphin is a stress related peptide, so does that signaling produce escalation of drug taking? So other stress drugs — like corisol, CRF, plan for more studies.

Question: Stress related hormones– babies in stress in utero and in stressful childhood have less dopamine receptors and need more dopamine for pleasure, susceptibility to drug addiction (ACE scores) so is still really early studying neurotransmitters.

Dr. Question: why do people do better with agonist therapy than abstinence in opioids vs other drugs? Answer: we don’t know….. yet.

further information:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920543/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC80880/
https://archives.drugabuse.gov/news-events/nida-notes/2017/03/impacts-drugs-neurotransmission
https://nida.nih.gov/

abuse, enabler style

I am raised by a family of triangulating enablers and enablees.

The enablers are my mother and two uncles. They are very very smart. Let me qualify that: they are very very smart intellectually. Emotionally, not so much.

The two uncles have PhDs and are professors. They marry wives that are lessor in their view. One tells my mother that he wants a woman who is not as bright as he is. I don’t know if she is less bright, but she is a hella better athlete. I also have the impression that she had a time where she drank too much.

The other uncle marries a woman who tends to be a hypochondriac. He takes her to India, where she gets polio while pregnant. She is then a sick hypochondriac, which is very difficult. The ill can control their families by planning things and then getting sick at the last moment. On the other hand, chronic fatigue and fibromyalgia are very real and we are on the edge of figuring them out. That uncle divorces his wife and I instantly like both of them better. They stop being a weird unit and are suddenly individuals.

My mother tells me, when I am in college, “I wondered if your father was an alcoholic when I married him.” I want to hit her. She won’t leave him, she won’t stop enabling him, they scream at each other at 2 am often. Now I wonder about that and conclude that either screaming at someone was something she needed or she was an alchoholic too.

After my mother dies, I ask my uncle, what about his parents? After all, the three of them learned enabling somewhere and it pretty much has to be at home.

My uncle tells me his parents had a PERFECT marriage and that my grandmother LOVED being the wife of a physician and professor.

Um, so, then, why did she pay my tuition to medical school, uncle?

And I think about my mother’s stories. Once, she says, your Uncle Jim bet his friend Dick that Dick was too chicken to shoot a cigarette out of Jim’s mother’s mouth. Ooooo. With a rubber band shooter. Yes, my grandmother. Bob took the bet and succeeded. My grandmother roared with anger and the two boys ran like hell and hid.

And someone in the family tells me: your grandfather helped your grandmother control her temper.

There it is. The enabler/enablee.

The enablers die first. My grandfather of cancer at 79, my mother of cancer at 62. The cousins are all angry at me because I won’t follow the family rules and triangulate in a satisfactory manner, and I don’t care any more. I am ignoring them. I got my father’s banjo back and I am done. The two cousins I own land with jointly are not the worst triangulators.

I have to remind myself: for them, this is love. For some people, controlling or being controlled is what functions as love and intimacy. Fighting and tears when person A talks to person C about person B and person C then lets person B know, that is how they feel close. It is not only families, but communities. Clay Shirky’s description of a group being it’s own worst enemy describes the same patterns: identify an enemy inside or outside the group and then everyone comes together against the enemy. The enemy says the wrong thing, doesn’t worship the right god/desses, wears different clothes, looks different. And the group feels safer once the scapegoat has been killed, the guy has been burned. It would be nice if we could burn a ritual guy instead of torching each other.

The real anger is in the enabler. They control it by having the enablee express it. Then it is not “theirs”. They can feel superior to the enablee who is out of control. Sadly, the problem is only fixed temporarily and they will need their anger expressed again and again and again.

The cycle can be broken. It is a lot of work.

Blessings.

______________________________________________

mad skills

What are your mad skills?

My maddest baddest skill, shared with my younger sister, is reading hidden emotions. Children of alcoholics and addicts learn that one young. Or die. Or start drinking/drugging to numb young.

Our culture is bloody weird. Emotions are stuffed like turkeys until people are near bursting. I swear that half my clinic time was letting people talk about emotions and then saying, well, those seem like pretty reasonable feelings in view of the insanity going on in your family. There would be a silence while the person thought about the horrible terrible feelings being reasonable and then I would say, “You said you want an antidepressant. Do you want to discuss that?”

Often people put it off. Once the feelings are OUT and present and looked at instead of stuffed/contained/terrifying, the person would say, “I don’t know. I don’t know if I need it.”

“Do you want to schedule to come back in two weeks?”

Sometimes yes, sometimes no. If they wanted to start an antidepressant, I would caution that the recommendation was to stay on it for six months minimum if tolerated. Also, if they were starting it in June, I would say, “Don’t stop it in January. Wait until the sun is back. Here that can be July 4th. At least wait until spring.”

The plants are all thinking about spring now. My magnolia would like three more days of sun and then it will burst into bloom. The plums are budding and close to exploding. My camellia is usually first, but I trimmed it at the wrong time of year and so it is not blooming. It looks healthy, though. It is sort of sulking for a season. I would like to sulk for a season too.

Why is our culture, the US, so terrified of emotion? We think everything should be about logic. Emotions are both hormonally and electrically mediated through nerves and blood and they are INFORMATION about our environment and each other. We should let emotions roll through us like waves, and not worry about them so much. I think of myself as an ocean. The emotions are the weather. They roll through. Ok, big storm. Then rain, and lightening. Then low clouds and some fog. Then sun and a beautiful day to sail with a light breeze. But the deeper currents change slowly and the weather is not really that important. I reside in the depths.

The furor over rising prices seems ridiculous to me. The roaring twenties has begun already in housing and buying stuff on Amazon. I have bought two things from Amazon in the last two years. I like to buy local. One order was for my future daughter in law’s wish list. I think people are buying so that they do not have to feel. It is cultural mania. Everyone is rushing around trying to make money instead of grieving. Yesterday I thought, if this keeps up, we WILL have a depression like 1929.

Don’t do it. Don’t buy stuff to avoid the stuff inside. Sit still twice a day, for at least five minutes, and just listen. Try to listen to the depths.

adult doll house

When mom leaves in the car with the kids, dad gets trashed on beer and destroys the living room. Yes, there is an enormous black panther in the background. Will it eat dad? Maybe it will wait until some of the alcohol wears off. He won’t taste as good drunk.

_______________________________

For the Ragtag Daily Prompt: Tiger.

Adverse Childhood Experiences 13: unsense

As a child in an alcoholic/addict household where you can not trust adults, who do you trust?

You either trust yourself or you buy in the alcohol story.

If you buy in, you have a high probability of either becoming an addict or marrying one, depending if you prefer the enabler or the enablee role.

If you trust yourself, you develop certain senses. You pay attention to people’s emotions. You pay attention to what people FEEL, what people DO and not what people SAY. You do not care what they say: what matters is what they do. My sister said she used to walk my parent’s house during high school and try to feel the mood. Did she need to hide?

The enabler role is trying to control the other person. There are amazing variations on this. I cared for a person whose sister would not take care of herself. Every time the sister is hospitalized, the person goes and cleans tons of garbage and rotted food from the apartment.

“Stop doing that,” I say, “You are enabling her. Call Adult Protective Services to go look at it instead.”

It can be very difficult to stop and can take years. People can change.

I have noticed that the enabler role is lethal. The enablers seem to die before the enablee. Certainly in my immediate family and with many patients too.

Enablee is the person controlled. Alcohol, drugs, gambling, anger, emotions. It is very very interesting to watch. I have read parts of my mother’s diaries. She was the enabler, with my father as the enablee. However, the diaries document them fighting in the middle of the night when he is drunk. And I remember high school, putting the pillow over my ears, because they were screaming at each other.

But wait. Why would she argue with her drunk husband? Why would anyone argue with a drunk person? You have to wait until they are sober.

And slowly I realize that my mother too was an alcoholic. I remember her drinking. Best cover for an alcoholic is a worse alcoholic, right? It’s fairly horrid. But it explains some stories and my food insecurity. They would not get up in the morning to feed me. My mother told stories of me trying to feed myself: cheerios and laundry soap. If my father was hung over, ok, but, why wouldn’t my mother get up? I think they were both hung over. That or else she really did not want a child. Especially a nine month old with opinions while she was trying to get over tuberculosis. She never got to hold me after birth until 9 months. And then I did not want her. I wanted her mother.

Trusting yourself, life can be a bit complicated. You sense the emotions others are hiding. Being a physician allows me to ask about the hidden things, very gently. Sometimes they come out right away. Sometimes it takes months. Sometimes years and sometimes never. My sister and I discussed going to parties and thinking, oh, that person is the child of an addict/alcoholic. This person is in pain. This person is quite happy but hiding stuff.

I told a counselor I do not know how to turn it off. She replies, “Why do you think I am a counselor?”

I don’t see auras. I feel things: like a cloud. Like a tiger, like a bear, like a whale, singing.

I think I will go with the whale.

Covid-19: aftermath

I am thinking about the roaring twenties a lot. I think people went a little nuts, not because of the war, but because they had difficulty being emotionally honest about the influenza pandemic. I think we humans will do it again to forget the deaths, to go into denial, to refuse to grieve.

Yes, that is my prediction.

Be very quiet, I am hunting wabbits.

Be careful in our future roaring twenties. Money will flow like honey and people will go nuts. Hold fast, hunker down, don’t go out without your macintosh, wear clean underwear. Remember what your mother told you, remember what your father tells you. Because that was followed by the Depression and that is one risk.

I don’t know if it will start this spring or next spring. Ok, I AM hoping that my son and future daughter-in-law can get married in early May, since they’ve put it off for two years. But. The 1918-19 influenza was really three years, not two. It tailed off. Half the people in the world got it. In Samoa, half the adults died, or was it 70%? They had little exposure to infection but a ship brought it. They KNEW they were high risk, but a sailor didn’t know he was sick yet.

Why a roaring twenties? Because we want to forget this pandemic, as the last one was forgotten. Our history books say that the Roaring Twenties was about the end of World War I. We teach lots about that. We barely mention the influenza world pandemic. I am reading a book about the 1918-19 influenza pandemic published in 2018. The author says that it is only now, 100 years later, that we are starting to really tell the stories of that pandemic. She gathers stories from all over the world, including stores of different infection control strategies in two cities. One guessed right and one guessed wrong, and in the wrong one, way more people died.

I read about that 1918-19 pandemic after influenza nearly killed me in 2003. I was 42, healthy, a physician, a mother, an athlete. I had NO risk factors except stress. Now it looks like it was a PANS reaction, but at the time, neither my doctor nor I could figure out why I was short of breath and tachycardic walking across a room for two months. Fatigue, chest pain, tachycardia, shortness of breath. Hmmm, what does that sound like? My partners thought I was faking and I was so sick that I could barely communicate. The stresses were my mother dying of ovarian cancer in May 2000 and my marriage being pretty on the rocks and me working way too hard. My psychiatrist said I should take time off. I said, I can’t. He said, you’d better. Then I got flu. “See?” he said. The body decides, not the conscious brain. He was correct, damn him.

The book I read in 2004 looked dry and medical from the outside. It had pages and pages of footnotes. It had photographs of Los Angeles. They knew the influenza was coming towards them like a wave and they tried to get ready. Bodies under sheets were stacked five deep in the hallways of the hospitals. It hit that fast. People, usually age 20-50, turned blue and fell over dead. WHY? It was the immune response. The 20-50 year olds had a better immune response than the 50 and older and their lungs would swell until there was no airspace left. Even then, that pandemic death rate was only 1-2 % in the US. But it was so fast and spread so quickly that everything was disrupted because it was the workers that were deathly ill and at home and there was no one to work.

People wore masks in public, except for the mask refusers, but not in their homes. So entire families would get ill. I don’t think they had figured out viral loads yet. If you are the last one standing, and you are trying to take care of a spouse and six children, you were high risk from viral load and exhaustion.

The Roaring Twenties WAS a way to grieve, it’s just a dysfunctional one. The stages of grief: denial, bargaining, anger, grief and acceptance. My sister said that acting out and revenge ought to be added as stages of grief. She died of breast cancer after fighting it for 8 years. Roaring is denial and bargaining and acting out and revenge, all at once. Everyone grieves differently, remember that. There is not an order to the stages of grief and you don’t do them once. You do them over and over and over.

I am a Cheerful Charlie, right?

War is one way to forget/deny/act out. Let’s not do that. Let’s not have a civil war of forgetfulness and denial.

Let us remember clearly and lean on each other.

Playing for change: lean on me

I think this fits the Ragtag Daily Prompt: inflammable.

My sister’s blog: https://e2grundoon.blogspot.com/2009/01/chemo-not-in-vain.html . She died on March 29, 2012. The start of the blog is here: https://e2grundoon.blogspot.com/2002/02/ .

Blessings.

______________

I got Cheerful Charlie from Pogo comics: read the Albert Alligator section. https://comicstrips.fandom.com/wiki/List_of_Pogo_characters
More recently, Downton Abby used Cheerful Charlie. https://downtonabbey.fandom.com/wiki/The_Cheerful_Charlies

small child

You work at healing
For years

You dive in the swamp
Of your psyche
Turn over the mud
Tunnel through it
Breath it
See lilies arise
From the muck

The Beloved is a deer
Dainty hooves
In the swamp

At last you come
To bedrock

So you rest
Bedrock
You think

Until you notice
A chink in the rock
You look away
You avoid it

At last you look
It isn’t going away

The Beloved is a bittern
In the reeds

Fluid leaks
From the chink

Foul black bilious
Acidic
Burning holes in the slanted rock
Again you look away
But not for long

You step forward
Touch the rock

I am present you say
Who is there?

The stream of foul black
Increases
Pours from a widening crack

Beloved is a tiger
Paw against the rock

You see the acid burning
Her paw
But she does not run
She stands guard

Who are you?
You whisper

The rock crumbles

There is a child

Go away” says the child
Ancient

No you say
Beloved and I
Stay present

The black is swirling around you
It’s hard to keep your footing
Beloved, an orca
Steadies you, swimming

No one stays says the child

We stay present you say

I was born I loved I was abandoned When I was afraid

We are present now you say
Swimming by the Beloved
Hand on black fin

I was abandoned When I grieved

We are here now you say

I was abandoned In my despair

We are here you say

You say
You fought
Out of love
You argued
Out of love
You gave
Out of love
Please child
Let us cradle you

The child is silent

The tide is slowing
The rock has crumbled away
A trickle of clear water bubbles

You will stay? says the child

We stay you say

Beloved is a whale
Singing in space
Singing to the stars

Am I lovable? says the child

You and Beloved
Earth and sky
Wind and trees
Moon and stars
Answer yes

Am I loved?

Yes
Yes

8/27/2007

mask up

Care for your family and friends and community. Mask up and do the best you can not to get nor give Covid-19 this season. The winter is dark but the sun will start returning to us soon. Like the seeds in the ground and the trees with no leaves, we can get through this dark season caring for each other.

adaptive theory of PANS/PANDAS

This is my working theory on PANS/PANDAS. Pediatric autoimmune neuropsychiatric syndrome/Pediatric autoimmune neuropsychiatric disorders associated with Strep A.

Four or more antibodies. The antibodies can take different patterns in different people.

  1. Antibodies to dopamine 1 and dopamine 2 receptors.

The antibodies are like keys fitting in a lock. The key may fit in the lock and BLOCK or fit in the lock and OPEN IT. So, there are a very large number of patterns that could arise from this, especially when we remember the rat neuron with 300 different receptors for serotonin in one neuron. Think of the possibilities here.

If this antibody BLOCKS, an ANTAGONIST, it will cause slowing/brain fog/depression/and I don’t know what all.

If this antibody is an AGONIST and the key turns, it apparently can cause mania, ADHD, OCD, oppositional defiance, clinginess, separation anxiety, anxiety, etc.

We do not know what causes psychiatric disorders. Now we have a category called neuropsychiatric, where it is caused by an antibody. Or antibodies. What percentage of psychiatric disorders are caused by this? I am betting high rather than low.

  1. Antibodies to tubulin.

If the antibody is an ANTAGONIST, blocking, then slow or fast twitch muscles won’t function correctly. It could block both. I think if it blocks both, that is the severe lie in bed chronic fatigue. I have trouble with my fast twitch muscles but my slow twitch ones work just fine.

If the antibody is an AGONIST, you get some super athletes. I know a number of people that I would suspect fall into this category. I can name five off the top of my head, friends.

  1. Antibodies to lysoganglioside.

This one worries me. Lysogangliosides lyse ganglions. These antibodies are used in soap making, among other things. They break down fatty cell walls.

When I have a high antibody level, I have trouble eating any carbohydrates. As I improve, I have trouble mostly with sucrose, fructose and gluten but not lactose. Also, when I eat gluten, I get acidic. When you get acidic, your body tries to compensate by slowing your breathing to hold on to CO2, because you need to balance the acid H+ with a base, OH-. So: triple whammy. Acidic I automatically breathe slower, which is not helpful when I am already hypoxic and tachycardic.

I have not figured out whether my antibody is an agonist or antagonist.

An agonist would lyse more ganglions. This could be bad for the brain and for peripheral nerves. Neuropathy and dementia.

An antagonist would stop ganglion lysing. Um, in theory, cancer. Lysogangliosides are supposed to clear out bad cells.My guess is that I have an antagonist because of the family history. At least, on my mother’s and sister’s side. My father smoked two packs of Camels for 55 years and did not get cancer: tough bugger, right? Or did he have an Agonist? This line of thinking makes me very highly motivated to eat in whatever way the antibodies want me to. I do not understand why gluten would trigger this and why the gluten effect in me lasts longer than the fructose and sucrose effect. Gluten intolerance and other gut problems are on the rise and this would certainly explain that. This is the cause of at least some fibromyalgia patterns. Not only does eating gluten screw up my breathing, but it makes any muscle that I have used recently hurt like hell. I ate some meatballs without reading the stupid package back in April. Two hours of chest wall muscle pain and honestly, heart pain. I dug the package out and duh: bread crumbs. Gol dang it, I hate it when I am stupid. However, it hurts like hell but at it’s worst I had normal cardiac enzymes and no heart attack. Weird.

Ok, but WAIT, you said ADAPTIVE. How can this nightmare be adaptive?

Sure, adaptive. Remember the back up system for when we are starving? We switch from metabolizing glucose to metabolizing protein and fats, our own if necessary. We go from glycogen metabolism to protein/fat metabolism which produces ketones.

This is the crisis shit hits the fan emotionally and in plagues system.

So, can be caused by stress or infection or a combination.

Why why why?

Because if the stress gets too high or the infection gets too bad, our body switches gears and runs a back up system. I’ve thought of chronic fatigue as some sort of switch the body throws for years, because it’s the hypercrazy work too hard workaholic Type A people who get it. Type B people do not get it or don’t notice or don’t care. Type B people just say, wow, I’m tired, I think I will rest. The Type A people flip out and say “Put me back like I was!!!!” and then they go to 47 doctors and refuse to do anything the doctors say and do internet research and see any kind of quack you can imagine and they are the most exhausting patients.

Why the psychiatric stuff? Ok, take mania. If there is plague or you are in a really dangerous abusive situation, mania suddenly makes sense. Overnight you are different and what’s more, it scares the hell out of everyone. You are shunned. You are alone. You may get thrown out of a job, family, friend group or all of the above. This would tend to protect you against both plague and the really dangerous abusive situation. Whether you like it or not.

And how clever of the brain/body. Here is a back up system. It changes at least four systems, so you are now a different person. You freak your employer, friends and family out. AND you are sick as shit and they won’t listen. You have to get out and go elsewhere for help or hide in your castle or house or whatever. You can’t move or you have super muscles. And every single person has a different pattern.

I look at the long haul covid. The most common symptoms are psychiatric, shortness of breath and fatigue. Sound familiar?

Now, will someone PLEASE fund my NIH west?

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Guidelines for treating PANS/PANDAS: https://www.pandasppn.org/jcap2017/

werewolf

Time out word warning, in this poem. This poem is about discrimination. Substitute practically anything for werewolf…. disabled, bipolar, depressed, autistic, substance abuser. I am sick of discrimination. For human, substitute “normal”.

You know I’ve been a werewolf my whole life

Started in the womb
triggered by antibodies
to tuberculosis

And I am tired

of people telling me

I’m a werewolf.

Ok? I fucking know that.
I have known it since Kindergarten
where I arrived full of joy
ready to sing

and was shunned

we didn’t have a television

but I knew that wasn’t really it
I was different
I am different

and fuck you humans
different is ok.

I am a werewolf
and I am fucking proud
of all I have accomplished
in the teeth of humans hating me
and trying to shut me down
and shunning me
and reporting me
and doing everything short of shooting me
with real guns

I’ve been told to sit down
shut up
stop arguing
be nice
be good
go away
die
don’t read my writeups
don’t C! my work
don’t talk to me
stop making waves
been fired
been reported
been shunned
been alone

and fuck you humans

get ready
because I am middle aged now
for a werewolf
and I am ready

to be one all the timee

damn the torpedoes
full speed ahead
fuck you humans
for how you’ve treated me

I’ve turned the other cheek
for sixty years

and now
I
will
fight