Thread by @paraicodonnell

When you have a neurological illness, you see a lot of lists like these. They can be alarming at first, so it’s important to inform yourself. That way you can be properly terrified.

Here are some fun things you may not know about neuropharmacology.

https://twitter.com/dawnhfoster/status/1143224288171974657

Until the 1930s, we didn’t really have any medicines to treat diseases of the nervous system. That was because no one really knew how the nervous system worked.

When we did begin to develop treatments, it was mainly by accident.

Since the 1870s, scientists at BASF and elsewhere had been synthesising derivatives of phenothiazine and testing them as treatments for diseases like malaria.

The results were mixed, but they did happen upon derivatives like promethazine.

Researchers at what is now Sanofi were trying to develop treatments for worms. Instead, they accidentally produced the first antihistamine.

Also, the particular sedative properties of promethazine turned out to be beneficial to patients with Parkinson's disease.

Other derivatives of phenothiazine, like chlorpromazine, ended up becoming the first generation of antipsychotics. By way of an interesting sidelight, it was later discovered that sustained treatment with chlorpromazine can itself give rise to parkinsonism.

See, the thing was, until the late 1940s, all neurologists knew about the diseases they were treating was what they could figure out by cutting up dead brains.

Which wasn't nothing, to be fair.

Multiple sclerosis, for instance, was so named by the pioneering French neurologist Jean-Martin Charcot, who made post-mortem observations of 'sclérose en plaques' (disseminated plaque-like lesions) and was the first to correlate them with clinical findings.

But as for the mechanisms of these diseases – how they arose, progressed and gave rise to symptoms – no one had much of a clue. You just gave stuff to patients to see what happened. Because fuck it, it was worth a shot, right?

This was true until the 1930s and 1940s, when we started to figure out how neurotransmitters like dopamine and serotonin might be involved. Now, this was definitely a big deal. For the first time, a patient's response to a brain medicine could be objectively measured.

For the first time, too, patients with schizophrenia could be effectively treated. The barbaric carceral regimes that had been central to psychiatric treatment began to be dismantled.

However, we still only knew this one thing, still only had this one therapeutic target, and we got kind of carried away. We went crazy over amphetamines, for instance, and then previously healthy patients started presenting with schizophrenia. I mean, who knew, right?

But things are different now, right? I mean, we know so much more, and everything is so closely regulated. Well, yes and no.

I take a drug called fampridine to help me walk. It works by blocking potassium channels in cell membranes, which can improve conductivity in demyelinated nerve cells.

Until quite recently, we didn't even know that mechanism existed. Knowing things helps, obviously.

However, I also take a drug called modafinil to help me maintain alertness. Here are some of its potential side effects, which @DawnHFoster's earlier tweet reminded me of.

Now, modafinil was originally marketed as a treatment for narcolepsy. It's prescribed for multiple sclerosis on what's known as an off-label basis. On an off-off-label basis, it's also routinely chugged by tens of thousands of tech industry dudebros who want to be 'enhanced'.

And it's great, don't get me wrong. Modafinil is fantastic. It's like being on a serene and highly refined form of speed. It's kept me productive for years.

Here's the thing, though.

No one knows how it works.

It's therapeutic mechanism of action, to quote the literature, remains unknown.

Is this starting to sound familiar?

There are two reasons why that list of potential side effects is long and scary.

First, modafinil is centrally active, which means it acts on the central nervous system. The main component of the central nervous system is the brain.

Your brain, obviously, controls all of you. Walking, breathing, swallowing, regulating blood pressure, rage, bliss, thinking about cake, all that good stuff.

You put novel organic compounds in there, basically anything could happen. It probably won't, but could.

The second reason is this. Hundreds of thousands of random punters all over the world, many of them perfectly healthy, are horsing this stuff into them.

Sometimes bad shit happens to them. I mean, some of them are tech bros with cyborg complexes, and they deserve it. But still.

Did the drug cause the bad shit to happen.

Meh. I mean, maybe?

But it's still someone's job to write all this stuff down. And therefore: scary lists of side effects.

NB: I'm not suggesting that the lists are nonsense, or that you shouldn't read them carefully.

However, while clinical trials are generally well designed and regulated, they're focused on therapeutic endpoints and side effect data tends to be captured incidentally.

In conclusion, then, it's a better time than ever before to have a neurological illness, but that's not saying much.

Brains are still vastly complicated and medicine still proceeds, quite literally, by trial and error.

Thanks for coming, everyone. Grab a muffin and a handout.

‘Its’, for Christ’s sake. So much for cognitive fucking enhancement.