Year: 2024

Categories
Biohacking Chronic Disease

Day 1283 and nAChRs

Never one to take things laying down, I started a crazy “n of 1” experiment today. My family doctor prioritizes keeping up on literature. We’d chat about anti-inflammatory research in reputable journals.

But I am on week seven of Covid symptoms simply not clearing. I’ve been coughing when under stress or exertion, my seasonal allergies exacerbated the issue, my reconditioning of my cardiovascular system wasn’t going great and I was exhausted.

At a visit with my osteopath who helps with my chronic autoimmune issues in my spine (I’ve been diagnosed with ankylosing spondylitis) I mentioned my ribs felt tender and constricted from Covid coughing.

She asked me if I was familiar with the research coming out about Nicotinic acetylcholine receptors and Covid-19 treatments. She’s casual like that.

Now I am a child of the internet so I’m passingly familiar with Gwen’s work documenting scientific literature on nicotine but I had not ever thought I’d try it myself.

In a joking “don’t try this at home” way my osteopath said she’d seen folks use nicotine patches for a week to shorten their Covid symptoms to some success.

Now for some caveats. In any type of crazy self treatment it’s important to consider your risks and consult a professional. Don’t do anything without your doctor’s input. Every medicinal treatment has risk and side effects.

I am using going to use a 7mg slow release nicotine patch (of the type made for smoking cessation) for the next 3-5 days to see if it impacts my over-stayed their welcome Covid symptoms. I started my experiment at 9am Saturday July 6th.

I am treating this as a “kitchen table” science experiment in which I am clearly an N of 1 from which you can only take anecdotal evidence. But maybe one data point becomes many and with the network effects of social media maybe we push forward other experiments.

Here is what I know so far thanks to searches from perplexity AI but I encountered some of the papers through mutuals on Twitter, some on forums, others I’d discussed with physicians, some were just raw dogging Google Scholar.

The AI synopsis I’m sharing isn’t meant to be conclusive just to give interested parties a starting place to see why I believe this is an experiment I’m comfortable running on myself.

Nicotinic acetylcholine receptors (nAChRs) have been proposed as potential therapeutic targets for COVID-19. Research suggests that the SARS-CoV-2 spike protein may interact with nAChRs, potentially influencing the disease’s pathophysiology[1].

Nicotine and other nAChR agonists could modulate inflammation and the immune response, offering therapeutic benefits[2][3].

Sources
[1] Simulations support the interaction of the SARS-CoV-2 spike protein
[2] Disorders of the Cholinergic System in COVID-19 Era—A Review of
[3] SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine …

Given that I’m working with inflammation as my primary issue which is not modulated even without Covid, I was obviously quite curious to learn about this cholinergic system and potential for up regulation. I’d seen discussions as early as 2020 about the curious fact that smokers had experienced some protection from Covid infections.

This all clicked in my head as being testable on my own without significant risk. Gwern had significantly reduced my concern about nicotine usage where previously as a child of the drug wars I’d put smoking nicotine in basically the same category of dangers as injecting heroin. It is not.

It seems it is possible we’ve got an explanation for why smokers didn’t catch covid at the rates you’d expect and they did better with the infections. We may even have things to learn from it to improve treatments.

Nicotine agonists could potentially be used to prevent inflammation in COVID-19 patients by modulating the immune response. Nicotine, a cholinergic agonist, has been shown to inhibit the release of pro-inflammatory cytokines, which could help mitigate the cytokine storm associated with severe COVID-19[1][2][3].

The cholinergic anti-inflammatory pathway, activated by nicotine, suppresses maladaptive inflammatory responses, suggesting that nicotine or similar agonists might offer therapeutic benefits in managing COVID-19-induced inflammation[3][4][5].

Sources via PerplexityAI.
[1] Nicotine and Covid
[2] Can nicotine alleviate the dysregulated inflammation in COVID-19? L
[3] Medicinal nicotine in COVID-19 acute respiratory distress syndrome
[4] Nicotine and the nicotinic cholinergic system in COVID‐19 – PMC
[5] Cytokine Release Syndrome (CRS) and Nicotine in COVID-19

Stopping a maladaptive inflammatory response is one of my top goals. If I can test it out with a cheap over the counter substance well I’m interested.

Andre Watson the CEO of Ligandal (not an investor just a fan) an AI discovery platform for precision targeting of therapies suggested a method of action for nicotine’s effect.

Nicotine and quercetin were some of the earliest predicted compounds to reduce the binding affinity of the spike protein to ACE2 — which in turn, we described the MOA of here: biorxiv.org/
TL;DR is that reducing the affinity may increase neutralizing immune response.

I do want to reinforce that I am aware nicotine is addictive. I’ve had to take drugs that form chemical dependencies in the past. I’ve used Prednisone in the less controlled phases of my spinal condition and tittering off that steroid is a nightmare. But it can be done. It is doable with a plan, careful monitoring, and supervision.

All evidence suggests this experiment isn’t long enough for me to develop a dependency let alone an addiction. I am thankfully free from any genetic predisposition to addiction in my family.

I plan to do a B3 Niacin flush at the end which is meant to help tittering. I will also be monitoring my heart rate as Nicotine has a tendency to raise your BPM so if I don’t like what I see I’ll lower dosage or stop usage.

With all that said, let’s see if it helps me out. I’ll post because it is in my nature.

Categories
Community Media

Day 1281 and Independence Day

On day 915, which was last year’s 4th of July I wrote about the aspirational America as an idea. It involved blowing shit up. It seems like each Independence Day I find a way to praise Roland Emmerich’s fine science fiction film.

I haven’t watched it yet today but hopefully I’ll at least put on a few clips to enjoy fighter pilots, aliens, inspirational Presidential speeches and fireworks.

The backdrop of drama in the media about Joe Biden is in some ways an ideal way to recall the fractious American community. A continent held together not by ethnicity or religion but by entirely abstract ideals is going to constantly tested.

The theory of print capitalism posits that capital sprung from the solidarity of nationalism presented for the first time in mass media. The common cause of one’s countryman makes it easier to levy for taxes for conflict.

We are far beyond print in our media now. It’s almost cheap to call out media climate “totalizing” an it undersells the experience. Social media makes the experience of Americanness so fluid it ranges from aesthetic choice to the anarcho-tyranny of ailing power.

And yet we try to do better as the general temperament of the nations. America is a place where the founding mythos is that anyone from anywhere can become one of us.

The nationalism of belonging in America has nothing to do with meeting a check box of criteria. Though we are trying to make it more so with bureaucracy. The ideal is that free country sets the condition so anyone succeed. Liberty is a hard fought thing. You can celebrate it in a manner that’s pleasing here. Namely fireworks.

Happy 4th of July everyone. I’m as committed to the American project. The frontier is in our souls and we search it out together in freedom.

Categories
Chronic Disease

Day 1282 and Summertime Sadness

Montana has blessedly been free of excess heat and fire season doesn’t seem to have arrived. But it was a wet spring and I fear we have a long summer ahead of me. I live in one of the best possible places to spend a summer and I still find it challenging m.

I was looking back at pictures from this time last year and I was not in the best health. I’ve never been a summer person and I have to accept some aspect of its misery is likely to forever plague me.

Other people have season affect disorder in the winter. I guess my people are a winter people. I can’t wait for snow to return.

Maybe I’m not alone in finding summertime unbearable. Lana Del Ray croons through summer’s emotional ghosts. Crime gets worse when it’s hotter.

I’m sure my mood is affected by the lingering Covid (does it count as long when you feel shitty 7 weeks later?) as well as the general unease in American politics. I’ll do what I can to shake it. But I’ll never understand anyone’s affection the season.

Categories
Media Politics

Day 1280 and Campaign Season

I am very much beginning to wish I had not watched the presidential debates. I want to say it’s been amusing to watch the different flavors of panic, but it makes me feel a bit gross.

Schadenfreude feels like a cousin to envy. It’s a dirty vice you shouldn’t be swift to cultivate in yourself even if it’s a very human response. I’d prefer to cultivate what virtues I can embody even if imperfectly.

I don’t want to lose my head just because everyone else seems to be doing so but it’s hard not pay attention to the politics when it’s the 4th of July week. I know I can’t do anything about national politics so I continue locally and on issues where we can have clear impact like housing and regulatory reform.

It’s possible that having more hands on experience with on community boards and with local permitting made the more tangible aspects of “Yes In My Neighborhood” campaigns clear to me.

I would prefer to be active in my contributions and focus on solutions. Am I angry and afraid when I see national politics and grand geopolitical news? Of course. If I thought about it too much I’d remember that everyone involved is human just like me. Then I’d worry even more. So I’ll try to focus on moving what I can.

Categories
Emotional Work Media

Day 1279 and Not The Whole Story

I have recently been prioritizing correcting mistaken impressions of the world. As the rationalist set say, I like to update my heuristics.

It’s just not all that uncommon to believe wrong things and for the wrong reasons. We find out with alarming about retracted studies, updates to long held beliefs about culture or politics, or simply something galling about reality. And so sometimes we have to adjust our priors. We never have the whole story.

I recently found myself comparing myself to another person only to get quickly reminded of a set of circumstances that made our situations basically incomparable. I simply didn’t have the whole picture.

My mother loved a hippie bumper sticker about the folly of sincere youthful knowledge.

Quick ask your teenage for advice while they still know everything

The best part of middle age is discovering just how little you know. It can feel paralyzing at times. I’m sure you can imagine how “I don’t know the whole story” can be interpreted in many ways. I hope to be on the sunny side of learning.

Two men sit on a bus. On the dark side facing a dark mountain we see scared sad man with a “I don’t know the whole story” thought bubble. On the bright side of the bus with a wide vista a man thinks “I don’t know the whole story!”
Categories
Culture Startups

Day 1278 and Follow On

I’d like to think I’ve got a talent for understanding how hype and momentum are built.

I learned this skill set by doing. I picked it up simply by being a cool kid working in the trenches of the business of style.

How does hype turn into capital? Well it’s complicated. Consider two significant trends from my youth. Was Indie Sleeze a real cultural moment or manufactured? Did we get taken in by the HypeBeast? Ask Glenn Youngkin in his Caryle Group era about his Supreme investment. Get Gavin McInnes and James Jebbia to go a couple rounds about their relative wealth. and come back to me. Still unsure? Ask Barbara Kruger about the clusterfuck of uncool jokers.

The original culture and the commodification of the culture is a spectrum and the Tommy Hilfiger Event Horizon is infinite. Who makes culture, who money and who only brings money can be challenging to calculate.

The thing about cool, it’s sine qua non, is that it grapples at every stage of its existence with its own validity. Cool thrives as a grounding process to what’s actually happening in reality.

Cool is a relational experience between someone or something authentically popular amongst a group that relates well with each other.

And that relational power is validated by some wider need in the world for their belief, innovation, art, product or philosophy. Sometimes this can be quite irrational surely but consensus is hard to come by. One of the classic essays in validation of cool is geeks, mops and sociopaths in subculture evolution.

The validation of something “cool” eventually reaches a point of opportunistic acceptance by those merely into a thing for the capital. Sometimes it’s social and sometimes literal currency.

These so called “sociopaths” who follow the momentum often do not realize that they are just in it to capitalize on cool. I don’t want to suggest anyone in a thing for money or cachet is a sociopath just that incentives for status are significant drivers for people.

Often we need the people in it for the money. It’s wonderful that angel investing exists and momentum investors have perfectly rational incentives. Sometimes you will even see significant self awareness about this. If you put resources into a community and don’t cause trouble you are often welcome.

Now you can refer to this type in startup investing as dumb money. The follow-on capital that is riding on the work of others who authentically believed before a thing was cool is a necessary part of the ecosystem.

I don’t at all mind when someone is a follower. You can be “a cringe follower late adopter” or whatever terminology we are now using to describe laggards in the adoption curve.


 Everett Rogers in his book Diffusion of Innovations

Unless you are a pain in the ass, actively predatory, or making your contribution more trouble than it’s worth, you should go ahead and lend your support if you can take the risk.

Don’t take it personally when hipsters sneer. They may have been earlier than you but it’s fine to back winners. Just don’t expect the founders to give you special dispensation for getting on board when it was safe to do so. It’s right that the alpha premium applies. I personally love it when not only am I right but I got paid more for the privilege.

Categories
Community Politics

Day 1277 and Don’t Lose Your Head

Everyone has their entertainment and mine is makes me a little bit of a stereotype. I hate podcasts but do most of my chores while listening to Bloomberg’s Odd Lots podcast.

I was catching up today with an interview with equities analyst Tom Lee. My attention got caught and stuck on his description of Bitcoin.

“Yes, Bitcoin is unlike other asset classes because there is a cooperative value. You know, the people who contribute to the network benefit from it. And that’s different than any other asset class.”

From Odd Lots: Why Tom Lee Thinks We Could See S&P 15,000 by 2030, Jun 24, 2024

Now I don’t think this is unique to Bitcoin. Cooperative value can be found in everything from nationalist politics to luxury handbag resale pricing. But I do this it’s important to have cooperative values be baked into a network for it accrue value.

We’ve traditionally mitigated concerns about market cooperation through clear property rights and legal protections. We’d backed up those claims with things as abstract as a monarch. We’ve evolved to it to the slightly more concrete full faith of the United States and Byzantine bodies of securities law. Fiduciary duty and all that.

But as we become less inclined to trust that the buck does in fact stop “anywhere” we are looking for ways to mitigate that risk. How to operate in a world without trust? You develop trustless protocols. Humans have plenty of intuitions about trust and many these intuitions struggle without a clear person with authority to act.

So I ask if we are heading into a “headless” age?

As distrust in institutional power struggles we are seeking out new ways to continue the business of life and civilization even if a high trust society is in question.

We’ve got networks like Bitcoin that work without a head. We have new corporate structures like decentralized autonomous organization (DAOs) that can operate strictly based on cooperative rules, and indeed now entire memetic cultures (like e/-cc) which hold power while being headless.

Lest you think this is some frontier tech idea that doesn’t apply to you we’ve headless content moderation systems & headless retail platforms. Huge swathes of financial tech is living above the API.

You could even argue that we’ve got headless political parties as the Democrats and Republicans both struggle with defacto heads nobody particular trusts. I don’t know if we can live in a headless democracy. Deciding who is a citizen is a very different matter than deciding who is a shareholder.

Categories
Politics Preparedness

Day 1276 and Not Just A River in Egypt

I’m pretty comfortable with being embarrassed. I get stuff wrong and I have to come to terms with it even as my ego complains bitterly. The ego protects itself with denial but that doesn’t mean its conclusions are correct.

Being impartial about your reality is hard. Denial is such a normal part of catastrophic events the CDC even has handy public health explainers. I hope post pandemic everyone can enjoy the irony of that.

Taking an impartial view when approaching a problem is hard. If it’s an especially destructive situation (as most forms of crisis tend to be) wanting to put off action is a common coping mechanism. We do it as individuals and we do it within the meta-organisms that form the cultural and political systems we live within.

My suspicion is that some of our current political problems are a result of denialism. Seeing things as they are is impossible for some people. Avoidance, rationalization and minimization is practically a skill set.

I’d hope in a crisis I would attempt to solve a problem with whatever meager tools and skills I had at my disposal. I’ve done my best to take action on a few slow moving problems. And yet impartiality only arises when I can accept reality. And I wouldn’t blame anyone who finding the reality completely unacceptable.

Categories
Politics

Day 1275 and Old Goat

I miss living in a world where nothing happens. I suspect well-off Americans took for granted the artificial smoothing of conflicts & markets that our global dominance granted. That era seems to be over. And blame must be apportioned.

Like many people, I watched the presidential debate last night between former President Trump and President Joe Biden. I had low expectations. It would seem they weren’t low enough.

You expect the lies from politicians. You expect spin from media commentators.

But nothing prepared me for the scapegoating of an old man clearly struggling. The entire chattering class, sensing weakness in Biden, seems to have decided to turn en mass.

A screenshot of headlines declaring Biden’s performance was a disaster.

Americans have many sins, not the least of which is tolerating a political establishment that is unable or unwilling to be held accountable.

Making a sacrifice of Biden when the hour is so late has the flavor of a desperate prayer. Placing those failures onto one symbol is powerful. Biden being subject to the ancient ritual in Leviticus was perhaps inevitable. The poor old goat deserved better than being made to carry the iniquities of us all.

Categories
Emotional Work

Day 1274 and Anger is Secondary

I am in a pocket of emotions today that I’m working through by writing. I’ve been told that anger is what’s called a secondary emotion.

Some metaphors that are helpful to understanding what is meant by a “secondary emotion” are thinking of anger as a boiling cauldron or a volcano. What you see isn’t the whole picture. It is the steam coming off something deeper. If you prefer cooler (literally) metaphor, the Gottman Institute calls it the Anger Iceberg.

The Anger Iceberg via Choosing Therapy from the Gottman Institute.

I am unsure what mix of feelings are making up my roiling cauldron. I’m struggling to feel them as chilly like an iceberg. The heat of it feels closer to my current experience than something frozen. But you get the picture. Looking underneath is important.

And underneath the anger disappointment, hurt, and frustration are all emotions I can “touch” as I explore ny feelings. But it’s underneath a roiling boiling mess that is only clear in glimpses.

I imagine I’m not the only one who struggles to see where the primary emotions. The optimism I have temperamentally abuts against a shared reality that feels angry.

I intend to watch a debate between two unpopular geriatric candidates for President of the United States of America. Of course being angry about that is secondary to a host of other more salient emotions. We must reach. It is crucial to reach those emotions if we desire to change as a nation.