Thread by @alexhaagaard

One of my favourite examples of this was when my former allergist told me to stop taking the Benadryl that was newly regulating my sleep architecture.

https://twitter.com/alexhaagaard/status/1414635006501195778

Now, this man is an unmitigated jackass who smirked when I asked if my narcolepsy could be linked to my MCAS and laughed when I described symptoms of exercise-induced anaphylaxis (despite having authored one of the most-cited papers on EIA)

His reasoning was: "Benadryl will make you fall asleep but it won't give you good quality sleep and studies have found that long-term use leads to cognitive decline"

Both of those things are true. Benadryl won't afford you normal sleep architecture - if you're a person whose sleep architecture isn't already fucked up by dysregulated histamine signalling in the hypothalamus.

And there are concerns about the anticholinergic action of Benadryl, which was indeed found to contribute to cognitive decline - in a couple studies of older patients, who tend to have constitutively decreased cholinergic tone, using Benadryl during the day, in hospital settings.

But funny thing. Decreasing cholinergic signalling during sleep is actually essential for memory consolidation.

And elevated cholinergic tone is associated with a few things. One of those is increased REM activity during sleep.

You know, the diagnostic hallmark of narcolepsy.

A few other things associated with cholinergic tone are:

Muscle fatiguability, spasticity and fasciculations.
Increased gastric motility.
Disordered mood.
Cataplexy (another hallmark of narcolepsy, albeit a connection studied only in dogs).

Myofascial trigger points have been found to contain elevated levels of acetylcholine.

Which makes logical sense, because acetylcholine release at the neuromuscular junctions mediates muscle contraction.

But there's incredibly little clinical research on what happens if you've got too much cholinergic signalling going on.

The vast majority is focused on decreased cholinergic signalling, which is implicated in conditions like myasthenia gravis and Alzheimer's.

What little info there is about excessive cholinergic signalling is focused on organophosphate poisoning, the classic symptoms of which are...familiar

Which is not to say I think every chronically ill person with these symptoms has OP poisoning.

I think it's more likely that a lot more folks than we realize have some version of the extremely understudied congenital acetylcholinesterase deficiency (or related neuromyotonias).

(Fun fact, congenital endplate acetylcholinesterase deficiency is classically treated with ephedrine which is...another highly stigmatized medication we can obtain from plants)

pubmed.ncbi.nlm.nih.gov/16009904/

So anyway I was taking Benadryl and it was working in ways that were nothing short of miraculous for me, and this fucking jackass told me to discontinue it because he had no knowledge or curiosity about the actual molecular underpinnings of the condition in which he's an "expert"

All he was invested in was "I know more than you, the patient, and your self-treatments are fundamentally dangerous"

Anyway, further fun fact, I've been taking maral root for two years which is the sketchiest plant medicine I've tried because I had no real idea how it worked, only that it's used traditionally to treat muscle fatigue in Eastern Europe and Russia and I had a hunch.

And it was another freaking miracle. Since I was a kid, I haven't been able to walk (or wheel) more than a block without experiencing intense muscle fasciculations. I couldn't wheel up a hill without my shoulders locking up painfully.

And then suddenly...I could.

And anyway, I got to reading more about acetylcholine a couple weeks ago when I was lying in bed unable to move because my neck was seized up because I had to discontinue my mast cell meds because of my latest jackass doctor.

And I found out about the whole "trigger points contain Ach" thing.

So eventually I searched "induces acetylcholinesterase" on Google Scholar.

(Acetylcholinesterase is the enzyme that breaks down and thus deactivates acetylcholine.)

The top result was a study showing that ecdysterone, the primary active ingredient in maral root, induces acetylcholinesterase.

I doubled my dose of it that night.

europepmc.org/article/med/61…