4 ms·

I have always been fascinated in the fact that psychedelics, and, indeed, any plant-based molecule that can mimic a neurotransmitter, exists. Us and plants are

by SamBam 3y ago

I have always been fascinated in the fact that psychedelics, and, indeed, any plant-based molecule that can mimic a neurotransmitter, exists. Us and plants aren't creating the same molecule because we share a common ancestor. There are far too many other plants that don't create cannabinoids or opiates or whatever, and far too many other animals that don't create them, for this to be at all likely. It had to have evolved multiple times. It's not any kind of symbiotic relationship. Our ancestors didn't cause opiates to evolve by selectively eating and spreading their seeds. So it's a coincidental convergent evolution. But these are really complex molecules doing quite different things. Both cannabinoids and opiates evolved in plants to defend them from viruses and fungi. I don't know what other neurotransmitter-mimics are for, but they're not being used for plant nerves. I'm sure people know the answers to this, and I could read a book about it.

deleted 3y ago
[deleted]
__MatrixMan__ 3y ago
> I'm sure people know the answers to this I don't think they do. AFAIK most of your assertions above are unknowns. My theory, at least re: psilocybin and the like, is that a parasitic fungus developed neurotransmitter agonists as a way of manipulating its host. The complete cocktail that was needed to make the target species behave in a way that completed the fungus' lifecycle may be lost to time, but certain components of it still exist in the gene pool. And if you're going to have millions of spores (rather than the two or three offspring that, say, humans have) you can afford to set them up with a wider array of gene expression profiles. So you've got these fungi just trying stuff to see what works--now armed with neurotransmitter agonists as part of that "stuff". Later on you've got other organisms eating those mushrooms and behaving strangely. If you're a fungal spore, and you're in an animal's digestive tract, "strangely" is probably how you want it to be behaving. You're going to end up in a different place or with different nutrients or in some other situation which is abnormal for your host--you end up with greater habitat diversity. How specifically that host-behavior-strangeness would lead to a lifecycle that would reinforce the inclusion of psychedelics to the point where P. Cubensis is reliably psychedelic, rather than just the occasional mutant, I have no idea, but when you've got billions of years to play with, it's not hard to accept that some pretty weird animal-fungus interactions came up here and there.
- timschmidt 3y ago
  Many psychoactive molecules are also structurally very similar to other hormones, and molecules produced for other aspects of biological function. Take a look at NN-DMT and Melatonin: https://en.wikipedia.org/wiki/N,N-Dimethyltryptamine https://en.wikipedia.org/wiki/N,N-Dimethyltryptamine https://en.wikipedia.org/wiki/Melatonin https://en.wikipedia.org/wiki/Melatonin Just a slight mutation, or even biological synthesis under non-ideal conditions could easily result in synthesizing one or the other via the same pathway.
- danielbln 3y ago
  It's equally likely that alkaloids like psilocybin are insect or bird repellents or mere metabolic byproducts, and that the fact they sort of slot into the 5-HT2A receptor in the brains of some species, wreaking havoc on various processing systems there, is a mere coincidence.
- Aerbil313 3y ago
  Except none of the stuff you antropomorphize possess human intelligence.
  - __MatrixMan__ 3y ago
    Are you sure? There is a lot of complexity in a million years of mixing spores and mycelial karyotypes. I haven't done the math but it seems like it could easily rival a human brain.
    - kjkjadksj 3y ago
      Humans always assume intelligence requires a brain. I think sugar cane are quite intelligent on the other hand. They have came up with a means to coopt another species for breeding: us humans, who have in turn created this cult of the sugar cane where it is now the most cultivated crop on the planet for probably the forseeable future. What an amazingly efficient way to proliferate your lineage. You don’t need to evolve these costly and highly derived structures like brains or articulated thumbs yourself, let the dumb human break their back harvesting you and spreading your lineage around the world.
timschmidt 3y ago
> Us and plants aren't creating the same molecule because we share a common ancestor. That is, in fact, exactly the reason. You are of course correct that synthesis of many biological molecules has evolved countless times over the eons, but chirality of certain critical molecules, amino acids, ribosomes, all evolved exceedingly early. Once the cellular machinery is synthesizing these things, synthesis of similar molecules, one, two, three mutations away become likely across swaths of related organisms, however distant. In short, we're all playing with the same lego bricks, and there are only so many different models possible to build with the set.
- SamBam 3y ago
  Yes, sure, we're all playing with amino acids in order to create proteins that can then synthesize complex things. This doesn't mean that it's easy to create the pathways that create these complex things. The synthesis of opium, for instance, requires two specialized cell types, complex organelles, and hundreds of different proteins, all told requiring thousands of different genes [1]. This is all for the purpose of creating one single highly-complex molecule. This isn't something you get at easily by "playing with the same Lego blocks." The question is, if it's not a coincidence that both poppies and a small subset of animals both go through all this work to create two versions of this extremely-specific molecule, then what's the reason? Sure, in the end the reason will be "it's advantageous for both species," but it's still pretty mind-blowing, and I think we're still missing a bunch of steps. 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877807/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877807/
  - timschmidt 3y ago
    Perhaps plants and animals are not so far removed from each other as you think. At the cellular level they are far more similar to each other than to any bacterium. And as to why they manufacture similar molecules, i would suspect reason #1 to be that they derive similar utility. Plants and animals both perform chemical signalling between cells. Both use ion channels. Similarities go on and on. And when we're talking about molecules with only a few dozen constituent atoms, there really is a very finite set of possible combinations which are not toxic and structurally suited to perform some task in the biochemical mechanistic computational environment of the cell. Also, this is not a refutation of your point, just interesting, but complete opioid synthesis has been engineered into yeast by at least two different teams at his point: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924617/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924617/
Anotheroneagain 3y ago
They deter insects.
dekhn 3y ago
I would state this as "chemical space is so large it's surprising that an evolutionarily distance biosynthetic pathway would, through evolution, actually find and optimize molecules that were remarkably effective modulators of an extremely distantly related organism." (I'm not ascribing intent or desire to evolution here, when I say "find and optimize"). But like many things in biology, if you view it through a billion-year evolutionary lens, it's not completely surprising. I doubt anybody could come up with a general rule or law that explained this well, and anything I did would just speculative arm-waving, of which this site has enough.
- SamBam 3y ago
  Yes, thank you, that is what I was trying to express.
kjkjadksj 3y ago
If a substance is abundant in the environment, you don’t need to spend your energy and reduce fitness in other areas to produce it on your own. Many species as a result might need things like certain amino acids found in their food that they don’t produce on their own, instead taking advantage of what is there. That logic shouldn’t really stop at nutrients or amino acids. There is no doubt an advantage to seeking out environmental compounds that act as neurotransmitters, saving you from having to spend energy generating those compounds internally.
- SamBam 3y ago
  Right, but the point is that certain plants and mammals do produce these independently. Humans don't require smoking weed to get enough cannabinoids into their system to get their brain to actually work. Likewise poppies aren't stealing humans' opiates to defend against fungi. Both sets of species are each doing a whole bunch of work to create these very specific, very complex molecules, and using them for different purposes.

by SamBam 3y ago

deleted 3y ago

[deleted]

__MatrixMan__ 3y ago

> I'm sure people know the answers to this I don't think they do. AFAIK most of your assertions above are unknowns. My theory, at least re: psilocybin and the like, is that a parasitic fungus developed neurotransmitter agonists as a way of manipulating its host. The complete cocktail that was needed to make the target species behave in a way that completed the fungus' lifecycle may be lost to time, but certain components of it still exist in the gene pool. And if you're going to have millions of spores (rather than the two or three offspring that, say, humans have) you can afford to set them up with a wider array of gene expression profiles. So you've got these fungi just trying stuff to see what works--now armed with neurotransmitter agonists as part of that "stuff". Later on you've got other organisms eating those mushrooms and behaving strangely. If you're a fungal spore, and you're in an animal's digestive tract, "strangely" is probably how you want it to be behaving. You're going to end up in a different place or with different nutrients or in some other situation which is abnormal for your host--you end up with greater habitat diversity. How specifically that host-behavior-strangeness would lead to a lifecycle that would reinforce the inclusion of psychedelics to the point where P. Cubensis is reliably psychedelic, rather than just the occasional mutant, I have no idea, but when you've got billions of years to play with, it's not hard to accept that some pretty weird animal-fungus interactions came up here and there.

timschmidt 3y ago
Many psychoactive molecules are also structurally very similar to other hormones, and molecules produced for other aspects of biological function. Take a look at NN-DMT and Melatonin: https://en.wikipedia.org/wiki/N,N-Dimethyltryptamine https://en.wikipedia.org/wiki/N,N-Dimethyltryptamine https://en.wikipedia.org/wiki/Melatonin https://en.wikipedia.org/wiki/Melatonin Just a slight mutation, or even biological synthesis under non-ideal conditions could easily result in synthesizing one or the other via the same pathway.
danielbln 3y ago
It's equally likely that alkaloids like psilocybin are insect or bird repellents or mere metabolic byproducts, and that the fact they sort of slot into the 5-HT2A receptor in the brains of some species, wreaking havoc on various processing systems there, is a mere coincidence.
Aerbil313 3y ago
Except none of the stuff you antropomorphize possess human intelligence.
- __MatrixMan__ 3y ago
  Are you sure? There is a lot of complexity in a million years of mixing spores and mycelial karyotypes. I haven't done the math but it seems like it could easily rival a human brain.
  - kjkjadksj 3y ago
    Humans always assume intelligence requires a brain. I think sugar cane are quite intelligent on the other hand. They have came up with a means to coopt another species for breeding: us humans, who have in turn created this cult of the sugar cane where it is now the most cultivated crop on the planet for probably the forseeable future. What an amazingly efficient way to proliferate your lineage. You don’t need to evolve these costly and highly derived structures like brains or articulated thumbs yourself, let the dumb human break their back harvesting you and spreading your lineage around the world.

timschmidt 3y ago

> Us and plants aren't creating the same molecule because we share a common ancestor. That is, in fact, exactly the reason. You are of course correct that synthesis of many biological molecules has evolved countless times over the eons, but chirality of certain critical molecules, amino acids, ribosomes, all evolved exceedingly early. Once the cellular machinery is synthesizing these things, synthesis of similar molecules, one, two, three mutations away become likely across swaths of related organisms, however distant. In short, we're all playing with the same lego bricks, and there are only so many different models possible to build with the set.

SamBam 3y ago
Yes, sure, we're all playing with amino acids in order to create proteins that can then synthesize complex things. This doesn't mean that it's easy to create the pathways that create these complex things. The synthesis of opium, for instance, requires two specialized cell types, complex organelles, and hundreds of different proteins, all told requiring thousands of different genes [1]. This is all for the purpose of creating one single highly-complex molecule. This isn't something you get at easily by "playing with the same Lego blocks." The question is, if it's not a coincidence that both poppies and a small subset of animals both go through all this work to create two versions of this extremely-specific molecule, then what's the reason? Sure, in the end the reason will be "it's advantageous for both species," but it's still pretty mind-blowing, and I think we're still missing a bunch of steps. 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877807/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877807/
- timschmidt 3y ago
  Perhaps plants and animals are not so far removed from each other as you think. At the cellular level they are far more similar to each other than to any bacterium. And as to why they manufacture similar molecules, i would suspect reason #1 to be that they derive similar utility. Plants and animals both perform chemical signalling between cells. Both use ion channels. Similarities go on and on. And when we're talking about molecules with only a few dozen constituent atoms, there really is a very finite set of possible combinations which are not toxic and structurally suited to perform some task in the biochemical mechanistic computational environment of the cell. Also, this is not a refutation of your point, just interesting, but complete opioid synthesis has been engineered into yeast by at least two different teams at his point: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924617/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924617/

Anotheroneagain 3y ago

They deter insects.

dekhn 3y ago

I would state this as "chemical space is so large it's surprising that an evolutionarily distance biosynthetic pathway would, through evolution, actually find and optimize molecules that were remarkably effective modulators of an extremely distantly related organism." (I'm not ascribing intent or desire to evolution here, when I say "find and optimize"). But like many things in biology, if you view it through a billion-year evolutionary lens, it's not completely surprising. I doubt anybody could come up with a general rule or law that explained this well, and anything I did would just speculative arm-waving, of which this site has enough.

SamBam 3y ago
Yes, thank you, that is what I was trying to express.

kjkjadksj 3y ago

If a substance is abundant in the environment, you don’t need to spend your energy and reduce fitness in other areas to produce it on your own. Many species as a result might need things like certain amino acids found in their food that they don’t produce on their own, instead taking advantage of what is there. That logic shouldn’t really stop at nutrients or amino acids. There is no doubt an advantage to seeking out environmental compounds that act as neurotransmitters, saving you from having to spend energy generating those compounds internally.

SamBam 3y ago
Right, but the point is that certain plants and mammals do produce these independently. Humans don't require smoking weed to get enough cannabinoids into their system to get their brain to actually work. Likewise poppies aren't stealing humans' opiates to defend against fungi. Both sets of species are each doing a whole bunch of work to create these very specific, very complex molecules, and using them for different purposes.