Astral Codex Ten

Nutt

5 min read

Nutt

Article

Nutt is a recurring person in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 31, 2021 and June 15, 2021. The archive places it in contexts such as “see Nutt and Feetam, What One Hand Giveth, The Other Taketh Away: Some Unpredicted Effects Of Enantiomers In Psychopharmacology”; “Nutt and Carhart-Harris’s paper on serotonin receptors”; “I think Carhart-Harris, Nutt, and maybe George think that this “active coping” isn’t necessarily physical action per se”. It most often appears alongside 5-HT1A, 5-HT2A, active inference.

Metadata

  • Category: People
  • Mention count: 2
  • Issue count: 2
  • First seen: March 31, 2021
  • Last seen: June 15, 2021

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Oh, The Places You'll Go When Trying To Figure Out The Right Dose Of Escitalopram
March 31, 2021 · Original source
Sanchez, Reines, and Montgomery are so excited by this that they are willing to give Lexapro its own new class of medications, calling it not just an SSRI but additionally an ASRI (allosteric serotonin reuptake inhibitor). They claim they are taking this term from somewhere else but I cannot find it in any of their sources and I think Sanchez might have made it up in an earlier paper. There's some interesting stereochemistry here where the s-enantiomer binds this site, the r-enantiomer prevents it from binding, and so the purely sinister escitalopram is more than twice as effective as the racemic mixture. For more on this, see Nutt and Feetam, What One Hand Giveth, The Other Taketh Away: Some Unpredicted Effects Of Enantiomers In Psychopharmacology. I hope the three of you who understand stereochemistry appreciate that title as much as it deserves.
Inline links: What One Hand Giveth, The Other Taketh Away: Some Unpredicted Effects Of Enantiomers In Psychopharmacology
Carhart-Harris On Serotonin
June 15, 2021 · Original source
George at CerebraLab has a new review of Nutt and Carhart-Harris's paper on serotonin receptors (I previously reviewed it here). Two points stood out that I had previously missed:
Inline links: new review, Nutt and Carhart-Harris's paper on serotonin receptors, here
George's take on Carhart-Harris & Nutt is that this is influenced by the balance of 5-HT1A vs. 5-HT2A receptors - two different kinds of serotonin receptor. 5-HT1A is (to vastly oversimplify) the main target of antidepressants. The more strongly it's stimulated, the more likely you are to resolve prediction error by adjusting your predictions - the equivalent of stepping into a freezing shower, but then acclimating so that it feels okay. Suppose you're depressed/anxious/upset because your boss keeps yelling at you. With enough 5-HT1A activation, you're better able to - on a neurological level - adjust your world-model to include a prediction that your boss will yell at you. Then when your boss does yell at you, there's less prediction error and less suffering. This is good insofar as you're suffering less, but bad insofar as you've adjusted to stop caring about a bad thing or thinking of it as something that needs solving - though it's more complicated than this, since suffering less can make you less depressed and being less depressed can put you in a more solution-oriented frame of mind.
5-HT2A receptors are (to vastly oversimplify) the main target of psychedelics. The more strongly it's stimulated, the more active your inference gets. George argues that this means psychedelics are more likely to get you to try to solve your problems. But is this really true? The average person on shrooms doesn't spend their trip contacting HR and reporting their abusive boss, they spend it staring at a flower marveling at how delicate the petals are or something. What problem is this solving? I think Carhart-Harris, Nutt, and maybe George think that this "active coping" isn't necessarily physical action per se, it's rejiggering your world model on a deeper level so that it's more creative and risky in generating strategies. It's a bias towards thinking of problems as solveable. This could potentially fit with the thing where people who do too much LSD become yogis or transhumanists or whatever; they're biased towards believing *all* problems are solveable, even the tough ones like suffering and mortality.