On The Edge of Humanity Magazine

Huge thanks to The Edge of Humanity Magazine, for publishing two essays.

The first one on May 9, 2022, that abortion must remain legal for women’s health:

The second today, about behavioral health in a pandemic and war. As caring humans, how could we NOT respond with distress to the suffering and deaths from both Covid-19 and disasters and wars?

I am so delighted to be featured on this platform. I enjoy so many of the artists and writers and poets who are featured there and I am very happy to contribute!

how to use a specialist

I am a rural Family Medicine doctor, board certified and board eligible. I have used the Telemedicine groups in the nearest big University Hospital since 2010.

Initially I started with the Addiction Telemedicine. I accidentally became the only physician in my county prescribing buprenorphine for opioid overuse in 2010. I panicked when I started getting calls. Dr. Merrill from UW had taught the course and gave me his pager number. I acquired 30 patients in three weeks, because the only other provider was suddenly unavailable. Dr. Merrill talked me through that 21 day trial by fire.

I think that I presented at least 20 patients to telemedicine the first year. The telemedicine took an hour and a half. First was a continuing medical education talk on some aspect of “overuse”, aka addiction, and then different doctors would present cases. We had to fill out a form and send it in. It had the gender and year of birth, but was not otherwise supposed to identify the person. TeleAddiction had a panel, consisting of Dr. Merrill (addiction), a psychiatrist, the moderator/pain doctor, and a physiatrist. Physiatrists are the doctor version of a physical therapist. They are the experts in trying to get people the best equipment and function after being blown up in the military or after a terrible car wreck or with multiple sclerosis. There would usually be a fifth guest specialist, often the presenter.

After a while, TeleAddiction got rolled into Telepain and changed days. They added other groups: one for psychiatry, one for HIV and one for hepatitis C. These can all overlap. I mostly attend TelePain and TelePsychiatry.

After a while, I pretty much know what the Telepain specialists are going to advise. So why would I present a patient at that point? Ah, good question. I use Telepain for the weight of authority. I would present a patient when the patient was refusing to follow my recommendations. I would present to Telepain, usually with a very good idea of what the recommendations would be. The team would each speak and fax me a hard copy. I would present this to the patient. Not one physician, and a rural primary care doctor, but five: I was backed up by four specialists. My patients still have a choice. They can negotiate and they always have the right to switch to another doctor. Some do, some don’t.

I am a specialist too. Family Practice is a specialty requiring a three year residency. The general practitioners used to go into practice after one year of internship. My residency was at OHSU in Portland, with rotations through multiple other specialties. We rotated through the high risk obstetrics group, alternating call with the obstetrics residents, which gave me excellent training for doing rural obstetrics and knowing when to call the high risk perinatologist. In my first job I was four hours by fixed wing from the nearest more comprehensive obstetrics, so we really had to think ahead. No helicopter, the distance was too far and over a 9000 foot pass, in all four directions. That was rather exciting as well.

from blue to breathe

I attended a medical conference on line yesterday and today and it made me very blue. At first it just frustrated me, because it is about increasing behavioral health access. Isn’t that a good thing? Yes, but they completely missed the biggest barrier for primary care: TIME.

With the current US medical corporate money extracting insurance non-caring system, primary care is increasingly forced into 20 or 15 or 10 minute visits. I fought my hospital district when they said “See patients for one thing only.” I replied “That is unethical and dangerous: if it is a diabetic with an infected toe, I HAVE to check their kidney function, because antibiotic dose must be adjusted if their kidney function is reduced.” And there are at least two and maybe three problems there: infection, and if the diabetes is out of control that worsens the infection, and then kidney function. And actually I have to be sure anyone going on antibiotics has good kidney function or adjust my dose. I am very very good at this, but it takes time. I can work with complex patients, with veterans, with opiate overuse, with depression: but none of this is a simple template slam dunk. A study more than a decade ago says that the “average” primary care patient had 5 chronic illnesses. My patients don’t want to come in for each one separately and anyhow, if they have kidney problems I have to pay attention when I pick medicines for their high blood pressure. None of it can be separated out. That is why medicine is complicated.

Someone asked why can’t I just post the price of a “simple” visit for a sore throat. But a sore throat can be viral, can be strep A, can be a paralyzed vocal cord, can be a throat abscess, can be vocal cord cancer. I can’t tell ahead of time. I can’t. Early on during covid, a patient called and wanted a Zoom visit for abdominal pain that he said was constipation. I said “No, I can’t do abdominal pain over Zoom safely.” I can’t ASSUME it is constipation. It was appendicitis and he had his appendix out that evening. He called from his hospital bed the next day to thank me for making him come in.

The conference made me blue because they ignored my questions about why they were not advocating for primary care to have more time with patients. They claim to be all about change, but changing the US medical system? Nope. Do not want to talk about that. But I do want to talk about it. You can help by letting Congress know: single payer or medicare for all. That insurance company gets 20 cents of every dollar to profit and wastes tons of money forcing doctors’ offices to call for prior authorization. And if we have single payer, think of all the small businesses that will start because the terror about health insurance will disappear! I think it would reduce everyone’s stress, except the insurance CEOs. And they have earned more than enough, goodbye greed.

I am also tired of specialists telling me that primary care needs to do MORE. When I get told that I am not doing enough about hypertension, bladder leakage, depression and stopping smoking, and then 20 other specialists lecture me. Ok, so one minute per topic to fulfill what all of them think I should do? I want a primary care conference where primary care doctors are celebrated: cases are presented where the specialist says what a brilliant job the primary care doctor did.

I received a consult letter from a cancer doctor a few years ago. He wrote that I had diagnosed the earliest case of chronic leukemia that he had ever seen and that he was impressed and the patient would do fine. That’s the conference that I want to go to: where primary care and specialists talk about that and we inspire more doctors to do primary care.

You can learn more and how to talk to your congressperson here: HealthCare Now: https://www.healthcare-now.org/

or at Physicians for a National Healthcare Program: https://pnhp.org

And put your vote and your money towards healthcare, not health insurance.

speaking up

A friend says he does whatever he wants. He refuses to answer questions about how he makes his money. He doesn’t care if this annoys people. I suspect he may enjoy it.

I have one of those public jobs. Well, had. I have now been disabled from Family Medicine for a year. My lungs are much better than a year ago but they are not normal. And I have now seen 17 specialists and 3 primary care doctors since 2012. The consensus is “We don’t know.” Though many specialists are not willing to say that. What they say instead is, MY testing is NORMAL, go to someone else. My lungs are not normal, but I am on my fourth pulmonologist. I saw a cardiologist this year and the first thing he says is, “It’s your lungs, not your heart.” Well, yeah, I know that.

I miss my patients, but there is something freeing about not working. Ok, more money would be nice, but I am doing ok. Meanwhile, I am thinking about what to do now. I can write full time. Write, make music, travel (on a budget) and sing. And speak up.

Doctors have interesting portrayals on television. We went from Dr. Kildare to Dr. House, working our way through the shows with an emergency room and medical residents. ER drove me nuts. No one EVER dictated a chart so at the end of each show I hyperventilated at the hours of paperwork/computer/dictating they had left. House interests me because it’s always the thing that the patient is hiding or lying about that is the key. “Go search his apartment.” says House. I have figured out cases by getting permission to call family or a group home. More than once.

But a physician is a public figure. I had been here for less than a year when a woman comes up to me in the grocery store and says “What are my lab results?” I look at her blankly. I can’t remember if I really did the snappy comeback that comes to mind: “Take off your clothes and I will see if I remember.” I respond politely and she says, “Oh. I should call the office, right?” “Yes, I try to leave the work there,” I say. If a particularly difficult person was bearing down on me, I would whisper “cry” to my kids. That worked. They would act out on cue and I would be the harassed mother. The person would back off.

I am in a small town. We have three grocery stores. I see patients everywhere, now that it has been 22 years. If I remember every detail, that means they are or were really sick. And we have the layers of relationships: someone might have kids the same age or work with boats or be in chorus with me. Once I take my daughter to a party. The mom introduces me to two other mothers. “She’s my doctor,” says the introducing mom. “Well, me too.” says the second. “And me,” says the third. We all laugh.

Once I am visiting my brother outlaw’s bicycle shop. He has a customer. The customer starts talking to me too. Brother outlaw says, “Do you two know each other?” The customer eyes me. I have my neutral doc face on. “She’s seen me NAKED!” says the customer and I howl with laughter. What a great reply. And my brother outlaw gets it.

Docs have to pay attention to HIPAA. When three women say that I am their doctor, I reply, “Yeah and I left my brain at work, so I can’t remember a thing.” Those three were healthy, so I really do not remember labs or the results of a pap smear. Once I was in cut off shorts and waved at an older woman who was at the ophthalmologist’s. She sniffs and looks away. I get the giggles: I think she did not recognize me. My town is only 10,000 people, so after 22 years I have taken care of many of them. Though sometimes people thank me for taking care of their mother, and after it sounds unfamiliar I ask if they mean Dr. Parkman? Oh. Yes. People get me mixed up with two other small Caucasian woman doctors.

I started the “outfits inappropriate for work” category last year when I was still very sick and short of breath and on oxygen. I did not go out much, partly to avoid covid. My pneumonia was something other than covid and it was my fourth pneumonia and I should not need oxygen. Now I’ve had mild covid and the oxygen is only part time. I sang at my son’s wedding, off oxygen, so I can sing off oxygen for a short time. I danced off oxygen too and did get QUITE short of breath. Since I am no longer a public figure, I can speak out and speak up more. I am thinking about that, particularly with the recent Supreme Court news. I do not agree with what they seem to be planning.

Patient Satisfaction Score

The latest issue of Family Practice Medicine has an article on patient satisfaction scores.

I remember my first patient satisfaction score VIVIDLY.

I am in my first family medicine job in Alamosa, Colorado. I receive a 21 page handout with multiple graphs about my patient satisfaction scores. I am horrified because I score 30% overall. I am more horrified by the score than the information that I will not receive the bonus.

I go to my PA (physician’s assistant). He too has scored 30%. We are clearly complete failures as medical providers.

Then I go to my partner who has been there for over 20 years.

She snorts. “Look at the number of patients.”

“What?” I say. I look.

My score is based on interviews with three patients. Yes, you read that correctly. THREE PEOPLE.

And I have 21 pages of graphs in color based on three people.

I am annoyed and creative. I talk to the Physicians Assistant and we plan. I call the CFO.

“My PA and I think we should resign.”

“What? Why?”

“We scored 30% on the patient satisfaction. We have never scored that low on anything in our lives before. We are failures as medical people. We are going to go work for the post office.”

“NO! It’s not that important! It is only three patients! You are not failures!”

“Three patients?” I ask.

“Yes, just three.”

“And you based a bonus on three patients? And sent me 21 pages of colored graphs based on three patients?”

“Um…”

“I think we should discuss the bonus further….”

I did not get the bonus. It was a total set up and I am not sure that ANYONE got that bonus. Much of the maximum “earning potential” advertised was impossible for any one person to get. You would have to work around the clock. They got out of paying us by having multiple bonuses that each required a lot of extra work…. They were experts in cheating the employed physicians. That became pretty clear and I was 5th senior physician out of 15 in two years, because ten physicians got right out of there. I lasted three years, barely. I knew I would not last when an excellent partner refused her second year of $50,000 in federal rural underserved loan repayment to quit AND stayed in the Valley working in the emergency room. I called the CEO: “Doesn’t this get your attention?”

“She just didn’t fit in.”

“Yes, well, I don’t think anyone will.” I asked my senior partner how she stayed. “You pick your turf and you guard it!” said my partner. I thought, you know, I hope that medicine is not that grim everywhere.

Unfortunately I think that it IS that grim and getting grimmer. Remember that in the end, it is we the people who vote who control the US medical system. If we vote to privatize Medicare, we will destroy it. Right now 1 in 5 doctors and 1 in 4 nurses want to leave medicine. Covid-19 has accelerated the destruction of the US medical non-system, as my fellow Mad as Hell Doctor calls it. We need Medicare for all, a shut down of US health insurance companies, and to have money going to healthcare rather than to paying employees $100,000 or more per year to try to get prior authorizations from over 500 different insurance companies all with different rules, multiple insurance plans and different computer websites. Right now I have specialists in four different local systems. The only person who has read everyone’s clinic notes is ME because it is nearly impossible to get them to communicate with each other. Two of them use the EPIC electronic medical record but consider the patient information “proprietary” and I have to call to get them to release the notes to each other. Is this something that we think helps people’s health? I don’t think so. I have trouble with the system in spite of being a physician and I HATE going to my local healthcare organization. Vote the system down and tell your congresspeople that you too want Medicare For All and single payer.

Physicians for a National Healthcare Program: https://pnhp.org/

Healthcare Now: https://www.healthcare-now.org/

I have had people say, but think of all the people out of work when we shut down insurance companies. Yes AND think of the freedom to start small businesses if we no longer have to fear the huge cost of insurance: Medicare for all!

Covert covid conundrum

I had covid recently AND I have been very lucky with it.

WHAT?

Ok, so when the war started I had been talking to a friend in Europe about visiting. He said nice seasons were May and September, but he and his wife have a kitchen make over planned for September.

“My son is getting married at the end of April, after two year long postponements, and so May doesn’t seem feasible. Maybe next May.”

Then the war starts. And it is affecting gasoline and causing inflation. I call my friend. “Can I come in two weeks?” March to early April.

“Yes. We have other guests a week after that.”

“Ok.” I try to get a British Airways ticket to stop in London to see an old friend from high school. British Airways has a computer attack and three days go by. To heck with it. I buy a ticket to Paris and on to my friend’s country.

I spend an hour on the phone trying to change to a layover in Paris for three days. I manage that. I fly to Paris and then take the train to London. Three wonderful days with my friend in London. I mask on planes, metros and trains. I double mask on the airplane, with my oxygen, and use a ceramic straw to drink liquids.

After three days I take the train back to Paris, the local train to the airport, and fly to my old friend’s. I arrive at midnight and we take the metro.

We do lots of sightseeing and take a memory trip to his parents’ graves and the town we lived in when I was 17 and he was 18.5. I was an exchange student. The language comes back. I can read but listening is more difficult. My brain won’t process it fast enough.

Four days before I am due to fly back, I get an email from AirFrance. I need a negative PCR covid test within 24 hours of flying to return to the US.

Well. I have a mild headache and muscle aches. Probably not covid, BUT. I go online, register in the country for a test and go to the testing site. Positive. I read about covid. The muscle aches of this strain usually happen at day 4-5. I did notice that going from London to Paris to my destination four days earlier, I feel a little off balance. Not bad, not spinning, just slightly weird. So my guess is that I am at day 4 or 5 of covid.

My hosts have both had covid within the last month, so I am not confined to my room. I read the rules for being allowed on the airplane once you HAVE covid. I have to wait 11 days, have a certificate of the test and then the eleven day certificate saying cleared. I isolate for 5 days, spend about 8 hours rescheduling the flight with Air France and Delta, and contact my doctor. My doc wants me to take medicine, but the local medical people where I am say I am not sick enough. I agree with the local people. The headache is gone the next day, I have mild sniffles, and my lungs are fine. Well, at least, they are no worse.

When I am out of isolation, I take a train to another town masked and stay at a hotel for four days. In that country, 80% of the people are vaccinated and 80% have had covid. They are no longer masking, except a few. I am feeling good. I mask when I am around other people and in all public spaces in the hotel.

The trip home is rather more exciting than I would like. At the airport I am informed that I need a doctor clearance ALSO. They say retest. I say “I AM a doctor.” and pull out a copy of my license. I brought it just in case the war spread and I needed to help out. They let me on the plane. In Paris I nearly miss my connection, but am one of the last 8 people on the plane. I am very relieved once we take off.

The silver lining is that at my son’s wedding I am now very unlikely to get covid or give anyone covid and mine was very mild. The Omicron BA2.12.1 that is circulating in Europe is milder than the previous strains AND ten times more contagious or more. So the covid is morphing towards a cold, which is what coronaviruses used to do to us. There are some strains that I read about that are going in a more virulent direction, so I would prefer to have the mild one and be protected from the nasty ones.

Here is the CDC section about strains in the US:

https://covid.cdc.gov/covid-data-tracker/#variant-proportions

I arrive home on April 12 and then am unsurprised to see covid cases starting to rise again in the US. Here is the CDC tracker: https://covid.cdc.gov/covid-data-tracker/#datatracker-home

I am hoping that it’s more and more Omicron BA2.12.1, since it seems to be milder. I am reassured that covid did not make my lungs worse. Within a week I am better from covid and then get what seems like a normal cold. Covid testing negative. I am feeling well for the wedding and reassured that a normal cold does not force me on to continuous oxygen. I am feeling lucky about the version of covid that I have but I am NOT recommending that people get it on purpose, because even with mild covid, some people go on to develop long covid. Here is an article that I got yesterday through the American Academy of Family Practice:

https://www.healio.com/news/infectious-disease/20220425/global-prevalence-of-long-covid-substantial-researchers-say

Long covid is very worrisome and we don’t know what it will look like after a year or more. Many of the present studies are on unimmunized people, from the first year of covid, so the studies of immunized are still evolving. There is hope that there is less risk of long covid with immunization but there is still a risk.

Covid will continue to morph into different strains. We continue to get “colds” or “upper respiratory infections” because the viruses are very very good and fast at changing and avoiding our immune systems. Consider checking the CDC data tracker above regularly to see if your county or your destination has a high covid level and if so, mask back up.

One caveat: my local health department says we have a high level of transmission right now, here:

https://www.jeffersoncountypublichealth.org/1429/COVID-19

while the CDC says low, here:

Remember that all of these sites have to exchange data and update everything. My best guess is that the local has the best numbers, but that is a guess.

Are our immune systems failing because of isolation? No, and here is why.

A friend quotes her son, who says that our immune systems are failing because we have been in isolation. I respond that it’s not isolation: it is stress. Anyone who is not stressed by the addition of war to a pandemic needs to have their head examined. Why does stress mess up our immune systems?

We have two main systemic states: sympathetic and parasympathetic. Sympathetic is the high stress, fight or flight, muscles fired up, gut on hold, and unfortunately we have a pretty sympathetic state culture. Add a pandemic on top of that and then a war and no wonder everyone is flipping out. Parasympathetic is the one we don’t hear about: the happy, relaxed one that likes stupid cat videos and laughter.

Without the sympathetic nervous system, we can survive. Without the parasympathetic, we die.

I have written about how we metabolize cholesterol, depending on whether we are in a sympathetic or parasympathetic state. When we are relaxed, or less stressed, we make more sex hormones and thyroid hormone. That is parasympathetic.

When we are in a crisis, or more stressed, we make more adrenaline and cortisol. That is in the sympathetic nervous system arousal state.

A pain conference I went to at Swedish Hospital took this a step further. They said that chronic pain and PTSD patients are in a high sympathetic nervous system state. The sympathetic nervous system is the fight or flight state. It’s great for emergencies: increases heart rate, dilates air passages in the lungs, dilates pupils, reduces gut mobility, increases blood glucose, and tightens the fascia in the muscles so that you can fight or run. But…. what if you are in a sympathetic nervous system state all the time? Fatigue, decreased sex drive, insomnia and agitated or anxious. And remember the tightened fascia? Muscle pain. The high cortisol level also is not good for the immune system, so we are more likely to get sick. High cortisol also raises blood sugar and the immune system is hyperalert. We are more likely to develop autoimmune disorders.

When we are relaxed, the parasympathetic system is in charge. Digesting food, resting, sexual arousal, salivation, lacrimation, urination, and defecation. So saliva, tears, urine, and bowel movements, not to mention digesting food and interest in sex. And muscles relax.

If the sympathetic nervous system is in overdrive, how do we shut it off? I had an interesting conversation with a person with PTSD , where he said that he finds that all his muscles are tight when he is watching television. He can consciously relax them.

“Do they stay relaxed?” I asked.

“I don’t know.” he replies, “but my normal is the hyperalert state.”

“Maybe the hyperalert state, the sympathetic state, is what you are used to, rather than being your normal.”

He sat and stared at me. A different idea….

So HOW do we switch over from the sympathetic to the parasympathetic state?

Swedish taught a breathing technique.

Twenty minutes. Six breaths per minute, either 5 seconds in and 5 seconds out, or 6 in and 4 out. Your preference. And they said that after 15 minutes, people switch from the sympathetic to the parasympathetic state.

Does this work for everyone? Is it always at 15 minutes? I don’t know yet. But now I am thinking hard about different ways to switch the sympathetic to parasympathetic.

Meditation.
Slow walking outside. No headphones! We need to listen to the birds and wind, watch the trees, really look at nature. All of the new sensory input relaxes us.
Rocking: a rocking chair or glider.
Breathing exercises: 5 seconds in and 5 seconds out. Work up to 20 minutes.
Massage: but not for people who fear being touched. One study of a one hour massage showed cortisol dropping by 50% on average in blood levels. That is huge.
Playing: (one site says especially with children and animals. But it also says we are intelligently designed).
Yoga, tai chi, and chi kung.
Whatever relaxes YOU: knitting, singing, working on cars, carving, puttering, soduku, jigsaw puzzles, word searches, making bean pictures or macaroni pictures, coloring, a purring cat, throwing a ball for a dog…..and I’ll bet the stupid pet photos and videos help too….

My patient took my diagrams and notes written on the exam table paper home. He is thinking about the parasympathetic state: about getting to know it and deliberately exploring it.

More ideas: http://www.wisebrain.org/ParasympatheticNS.pdf

stranded mermaid, cilia and tubulin

I took this photograph last summer at North Beach. I thought she looks like a stranded mermaid, thrown up on shore. I couldn’t move her, she was twice my length. The rock attachment had come too, up from our sea beds.

Happy solstice. Today marks the one year day from when I realized that I was having my fourth round of pneumonia, with hypoxia, agitation, fast twitch muscle dysfuntion and felt sick as could be. I am way better but not well. That is, I still need oxygen to play flute, to sing, to do heavy exercise and to carry anything heavy. Which is WAY better then having to wear oxygen all the time. Today I find a connection between the lungs and the brain, in quanta magazine. This video talks about a new found connection between cilia and the brain. We were taught that cilia and flagella are for locomotion, powered by tubulin. However, this shows that cilia behave like neurons and there is a connection. Since my peculiar illness seems to involve cilia dysfunction in my muscles and lungs, so that I get pneumonia, and the brain, because I am wired when it hits, this is a fascinating connection. If neurons developed from cilia, the dual illness makes a lot more sense. Hooray for quantum mechanics! We use it in medicine every single day.

Happy solstice! Here comes the sun!

Avoid death by fentanyl

Some of the West Point Cadets overdosed on March 12, 2022 are still on ventilators. They took what they thought was cocaine. It was laced with fentanyl and they all nearly died.

Not only that, but two of the bystanders who did not use the drug, but did cardiopulmonary resuscitation, CPR, also succumbed. They stopped breathing because they got a heavy dose of fentanyl giving CPR.

Fentanyl is being laced into ANY illegal drug, and being 50 times stronger than morphine, it can kill you by making you stop breathing. Also, fake pills are made. Do not buy pills on the street. And I don’t care if it is your friend. Remember that when someone is really addicted, the addiction is running the show. They need the drug more than your friendship. People will lie, steal and sell drugs. Protect yourself:

Please read the website at

https://www.cdc.gov/stopoverdose/

If you or a family member uses illegal drugs, please get naloxone to have at home. If the shot is given in time, very soon after the person stops breathing, it can save their life.

Here: https://www.cdc.gov/stopoverdose/naloxone/index.html

If you give someone a dose of naloxone CALL AN AMBULANCE. Because it is short acting and the opioid may take back over. The person may need to be on naloxone iv! You must get them to an emergency room as fast as possible.

Our local Health Department was giving out naloxone shot kits in the last few years for free. Our local police carry naloxone. If you are on prescription opioids, you should be offered a prescription for naloxone and your family should be instructed on how to use it.

And teach your children well. I interviewed my patients for years on the age they started smoking. Most of my patients started at age nine. One woman said age seven. We have to start talking to children about drugs and risk and not smoking anything by third grade. That is the horrific reality.

And Bless the punk band The Offspring for reaching out to opioid overuse people and saying, “Get help. You can do it. Please do not die.”

The Opioid diaries live by the Offspring.

And they too are inimitable.

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/