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Nootropics which psychedelic would induce the most neuroplasticity?

neuroplasticity is a bit of a fake term, a catch all, panacea word that is seriously abused by researchers, reporters, and psychonauts.

when I try to direct people to study nature, I am trying to get them to dig into and beyond the veils that accumulate in popular culture like the term "neuroplasticity" which people use freely and never grasp the meaning of.

it is abused in marketing, law making, and in experimental science as well.

Instead of you coming up with an explanation for "neuroplasticity" that is an apology for all the people abusing the term, you can abandon the word.
Focus instead upon what is really detected in experiments, and, or what is really happening in the lives we live. you can see in yourself and others increases and decreases in vigor, clarity, flexibility, etc.

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Most people have the view that nerve tendrils like branching rootlets grow making new connections during neuroplastic activities, but this is only the case in developmental biology, i.e. for humans it happens in the first 3 months of foetal existence, after that hardly at all except in growth and healing from severe damage, or in experimentally growing brain organoids which more closely resemble tumors than functional brain tissue.

The changes in nerve tissue involving protein that happens every second of every minute of every day while awake or dreaming in adult humans, involves the microscopic formation of protein spines connecting branched axons and dendrites of cortical neurons - this interlinks neurons that fire together in the same fraction of a second - thus forming memory, enabling us to recognize what we encounter.

Even if you ask neuroscientists about "neuroplasticity", you will get more hand waving and confusion, because usually they cannot say what they mean other than - yes, protein was formed among nerve tissue, and we can see radio-labelled protein in this part of the tissue when the animal learned something.
 
I haven't seen any mention of DMT in this thread. Supposedly DMT is good for neuroplasticity via it's moderate activation of the sigma receptors.

Hopefully somebody better educated than me can elaborate.
 
There is something about Nature that is neuroplastic.
I think that walking barefoot on actual earth would be the most neuroplastic thing possible. Also drinking water from a freshwater source, water that has been structured in a coherent manner.

...after talking with my friend's daughter I am trying to formulate exactly what neuroplasticity is and what helps or hinders. Still real fuzzy.
Perhaps in simple terms, it's neurogenesis v the opposite.

Neurogenesis involves notably BDNF, GDNF, NGF, 5-HT2a alongside inhibitory things like GABA & adenosine (but also inhibitory hormones notably progesterone, pregnenolone, allopregnanolone; see images below).

The opposite of neurogenesis is excitatory things which promote excitotoxicity (ie neurotoxicity) eg cortisol, adrenaline, glutamate.

2026-06-20-0o7-Kleki.png

image.png
 
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Supposedly DMT is good for neuroplasticity via it's moderate activation of the sigma receptors.

Nice! I didn't know that sigma receptors did that kinda stuff.
These findings support a role for sigma-1 in the modulation of BDNF levels... Treatment with sigma-1 agonists might provide benefit...by increasing BDNF levels from endogenous sources. (source)
 
Nice! I didn't know that sigma receptors did that kinda stuff.
It's theorized that the sigma receptors are why some people respond to certain SSRIs better than others as some SSRIs hit the sigma receptors hard while others only minimally.

My personal speculation is that sigma might be why DMT produces rapid antidepressant effects in some people - though many of the same people respond well to psilocybin which is weaker at the sigma receptors so 5ht2a activation is probably still the main effect. As well as whatever downstream effects activation of these receptors has.

DXM also hits the sigma receptors, though I would assume it's nmda antagonism and SNRI effects are the main reason it's being used as an antidepressant nowadays.

The sigma receptors fascinate my casual armchair scientist mind though. I believe it is an area that deserves a lot more study.
 
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I think that walking barefoot on actual earth would be the most neuroplastic thing possible. Also drinking water from a freshwater source, water that has been structured in a coherent manner.
Funny enough I walk through one of our state parks 2 miles away from my house to get natural spring water from an aquifer. Cleanest water comes from when the Earth filters it. Been doing that at least 20 years.

And even better recently one of my friends new girlfriends told me walking barefoot in grass is the fastest way to ground oneself. Been doing that too every morning in my meadow walk.

Lately been forest bathing. I have a mountain near my house, takes 40 minutes to climb straight up, then I just sit and let the forest ground me.

These are my non drug ways of doing a few things. But I notice no matter what I do at some point life comes back in and something aggravates me again.
 
The sigma receptors fascinate my casual armchair scientist mind though. I believe it is an area that deserves a lot more study.
Amantadine is also a sigma agonist. The wikipedia page for amantadine has plenty of info on the downstream effects of sigma-1 activation. Amantadine feels like a psychostimulant, almost a cross between amphetamine and ketamine/DXM. I imagine that amantadine + pro-5HT2a item (eg agmatine, citral, terpinolene) would be interesting.
 
i think weed would introduce neuroplasticity
From what I've gathered weed has a mixture of effects wrt neuroplasticity. In small and non-chronic amounts it seems to stimulate some neuroplasticity (maybe this is just the novelty factor rather than a pharmacological effect) whereas larger and chronic amounts seem to reduce neuroplasticity - it is more neuroprotective, or encouraging stasis.

Anecdotally from what I've seen in how it affects myself and people around me, this checks out. One effect of overconsumption of cannabis is getting stuck in certain modes, less flexibility, less learning, whereas initial and light use can be really expanding. It's definitely complex though, there are definitely some really high-functioning chronic users who seem to maintain a lot of growth, positive change and learning. Not sure if it's their approach to how they use it, nuances in how they respond to it, or what. All this stuff is really complex and we don't know much about it yet.
 
From what I've gathered weed has a mixture of effects wrt neuroplasticity. In small and non-chronic amounts it seems to...

The key 'issue' here is what exactly is the weed you're referring to(?) Eg is it:
  • THC-dominant
  • CBD-dominant
  • THCV-dominant
  • CBG-dominant
  • CB×-dominant
Then there's the question of terpenoid content. These all have unique psychoactive properties, including pro-neuroplasticity. Some interact with 5-HT2A directly, others promote neuroplasticity via BDNF / NGF.
 
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