> 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.

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/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.

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.

Except none of the stuff you antropomorphize possess human intelligence.

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.

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.

Totally. Between bread and alcohol, yeast has basically managed to domesticate humans. Maybe our experiences differ so much that we can't strike up a conversion, but that's no reason to discount intelligence.

Indeed, it's a reasonable argument that fungi evolved these molecules specifically to affect animal's brains. After all, we can see specific behaviors that help spores spread, like the zombie ants.

I think marijuana or poppies have less plausible explanations for how they would have evolved specifically to mess with animal's minds.

THC and opiates in poppies basically are animal neurotransmitters, so I disagree. Their original function was probably to discourage animals from eating the plant. Animals seems to have a reflex by which any drastic changes to brain function induce vomiting of and aversion to any food the animal just ate.

Could herbalists just be God's AlphaFold?

I don't really buy this theory. Taking mushrooms is more likely to make me want to curl up in bed rather than run around. And would it really last long enough to get an animal outside of it's normal range? Not in my opinion.

For me, psilocybin catalyzed such pivotal decisions as moving out of my parents' house, getting married, and changing careers. It seems plausible that it would be relevant to the founder effect (https://www.genome.gov/genetics-glossary/Founder-Effect) in other animals.

Sometimes we need a little shove to start doing new things that end up being advantageous. There's no reason to believe that we're unique in that way. If that shove is advantageous enough to be worth returning for a second shove, well now you've got the seed of a cross-kingdom relationship.

But that is outside of the timeframe you'd be spreading spores. Deciding to move out in a month isn't doing anything for the mushroom.

Well in that particular case, moving out meant I could dedicate a whole closet to cultivating them. But I don't think that cultivation is a necessary step, merely returning for more is enough to start the kind of relationship where adaptations which allow for one party to help the other are selected for.

> 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.

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/

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/

They deter insects.

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.

Yes, thank you, that is what I was trying to express.

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.

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.