Pilots & heroin & voting & endorphins & 2-way streets
Bihari thinks naltrexone works by increasing endorphins, I think excess endorphins are often the problem, and the antagonist can sometimes be helpful.—Ray Peat
When pilots test for a license to fly airplanes they have to demonstrate that they can do instrument navigation. Instrument navigation is used when a pilot can’t see the environment he’s flying in, either because it’s nighttime or it’s cloudy.
To do instrument navigation he has to learn to shut off his sensory perception, especially that streaming into the eyes because the sensory field is incomplete for flying safely. Under those circumstances shutting off the senses & trusting only the instruments is not easy to do. There is always risk of confusion & inadvertently reverting to the senses, even when they are sensing incorrectly. In the dark the senses may tell a pilot he’s going down when he’s really going up, or that he’s going up when he’s really going down. This is thought to be the reason John Kennedy Jr. crashed his Piper Saratoga into the Atlantic Ocean at night on July 16, 1999.
This is similar to the problem at the center of how the terms “down-regulation” and “up-regulation” obscure the biological facts of how drugs and medications cause changes in physiological adaptation in the body over time.
This post will explain how miscommunication about this adaptation persists because the language is taken as more relevant and real than understanding the developmental processes at work biologically. But without an accurate physiological understanding, medical therapies cannot work as intended. And their failure is attributed to unknown causes, when the reality could be easily known.
When it comes to understanding up-regulation & down-regulation as concepts it occurs to English speakers that “up” probably means “more” & “down” probably means “less,” as it would if you were talking about height or altitude or temperature as heat units.
But an A/C thermostat is an inverse case: when you turn the temperature on a thermostat on an air-conditioner up, you are setting it to cool less, & the opposite with turning it down. Heat is the opposite.
So when the terms “up-regulation” and “down-regulation” are used to describe how a hormone-neurotransmitter system in the body works physiologically you’d want to make sure which of those terms is describing more of that tissue response system or less of it.
When a person begins to take an opioid for the first time the drug is effective at small doses because the opioid responsive tissues are naïve. It doesn’t take much of the drug to work. The opioid naïve system begins to adapt to opioid dosing after 1 week, when a higher dose is needed for the same level of pain relief.
And since “up-regulation” sounds like it would mean “more” of something, the assumption by doctors has been that biological up-regulation of the opioid responsive tissues means more opioid receptors. The reasoning is that more receptors in this system means more pain relief. But this is just like the confusion school children sometimes have when they first learn addition of negative numbers: growth in amount is reversed.
If receptors aren’t real, then you’d have to contextualize the function of a tissue before you could impute its structure. In systems of only up-down, bigger-smaller, more-less critical information is left out. You can't get off two-way streets unless there's a crossroad. It’s the work of an organicist view of science & politics to demand those cross-roads: a contextual account of what gives those scales any meaning.
The tragedy of getting this wrong is that it isn’t hard to understand that if an opioid addict can quit and de-adapt his opioid tissues then the most dangerous condition is returning to drug use and overdosing accidentally because the accustomed dose has overwhelmed the opioid system. That is, it takes less of that drug to have the same effect after de-adaptation, meaning, the responsive tissue is less dense, not more. The drug works in smaller doses because there is less tissue to satisfy.
The opioid de-adaptation constitutes greater tissue sensitivity by a reduction in the stimulation and use of it. The language of sensitizing and de-sensitizing would probably communicate this adaptive development much better than up-regulation and down-regulation. And doctors might think about this accurately if they talked about it that way.
Hardly anyone sees that the understanding of this is muddled by the language of using up and down to describe greater & lesser cellular response. The Wikipedia entry, Upregulation and Downregulation says it like this,
“The more receptors a cell has that are tuned to the message, the more the cell will respond to it.”
This is a radio metaphor, apparently, and it is true that more receiving antennae would mean more opportunity to have a radio transmission be known. The antenna system would be more sensitive. And in the case of nerve tissue the more nerves there are the more sensitive the skin is to response to touch or pain. The lips & soles of the feet are more sensitive than the skin on the buttocks.
So it wouldn’t be surprising that skin that is blocked from stimulation, say by being covered with clothing through long winter months, will be oversensitive to wind & sun exposure in the spring. Going to show that it is the function of the tissue that determines its structure & not the language used to communicate that knowing that is critical to understanding life.
This is not a negligible problem. Opioids are the second most common class of drugs involved in hospital medication errors after cardiac drugs. People suffer lethal consequences from treating medicine like a storyboard. The political upshot is that the authority that medicine takes up in the system is not only not natural, but it is unjustified and this misunderstanding demonstrates why.
It has been part of the mythology of distance running for about 40 years that the stress of it brings on euphoria by “boosting endorphins.” It probably isn’t the endorphins that brings on the euphoria of endurance sports. It’s probably the adrenaline that is secreted when glycogen runs out & the body uses its own tissue for fuel. The endorphin boost does suppress pain in the face of inescapable stress, such as a runner deciding to finish a race with injuries. But it’s an addled euphoria that blocks the stress just to survive until the injury can be treated, the runner can eat, or the race is over. Some die trying. There’s a reason it’s called an endurance sport. Since ultra-distance running became more popular in the past 20 years met-enkephalin tattoos & having the toenails removed are just part of the culture of suffering as “proof of concept.”
Sometimes drugs can be used to advantage in spite of the bad metaphors they’re built on. Contrave is the brand name of a weight loss drug approved in the US in 2014. It is a drug combination where one of the drugs is Naltrexone, an opioid system blocker. The other is bupropion, a norepinephrine & dopamine reuptake inhibitor. Naltrexone, like Naloxone, is an opioid system blocker. And similar in kind, but not in extent to rescue treatment of a heroin overdose, low-dose Naltrexone can revive the vitality of a person who has sensations of fatigue that are not caused by under-calorization or under availability of sugar or CO2. There is terrific social stress in the world of an over-fat person. It wouldn’t be surprising if that stress caused a slowing down of the whole system to mitigate the pain, slow emotional response, slow GI movement, low thyroid function, slow metabolism. If there were a loss of sensitivity of the endorphin system then it would be a kind of nodding off from a hostile environment. Low-dose Naltrexone can correct that.
In politics, the same problem with language hides the realities of the bad uses of power & the way it harms people and their culture. It’s one thing to want to vote for the candidate of your choice. It’s another thing to vote for one candidate because you can’t stomach voting for his opponent. Many voters report that they aren’t voting for anyone, but that they are casting a vote against the other party’s candidate. And though the media still report the horserace as polls in terms of support, it isn’t clear that the votes are support for the political system, or a desperate attempt to prevent the system from collapsing as quickly as it might if they didn’t vote at all.
Most of modern politics since the 17th century has assumed that human beings don’t intelligently seek a better state, but only that they are feverishly trying to escape a worse condition without the state. It’s a pathetic “it could be worse” threat against picturing & seeking robust life, happiness, fun. Without those life is just better or worse drudgery, it’s not half human.
If people go out for a beer on Friday night is it because they are seeking the social web of contact? Or is it because they find being alone unpleasant? Fear of missing out is just a stick. Satisfying & enriching social contact is a carrot. But prima facie they might look nearly exactly the same. The difference matters to the meaning of the motion. And the words we use to describe those matter.
When people say that the health care system is really an illness maintenance system they aren’t wrong. A pandemic has revealed the system for what it really is in health, in its politics, economically. But there is opportunity in the collapse of the hallucination. As education built on bad caricatures collapses, an opening for empirical links between function & structure in politics as well as biology has a chance.
Celise Schneider©
Photo credit: Aida Imamovic