I believe most of the TBG circulating is coming from a US-based vendor. I would vouch for the few items (bromantane, TAK-653, and tropisetron) I’ve tried from them, although I haven’t tried their TBG.
There’s quite a few of these non-psychedelic 5-HT2A agonists, although it’s not known whether they also increase cortical spinogenesis. Probably the most famous is the prescription drug lisuride, and quite the effort has been made to understand why it lacks psychedelic effects.
Another example is 4C-D, which I’ve tried a handful of times myself. It doesn’t induce psychedelic effects but it certainly affects mood, in a subtle but positive way.
I feel like there’s a billion drugs and supplements that increase ‘neuroplasticity’ and other buzzwords. If they don’t have a clinically significant effect in a clinical trial, then it’s probably not going to do anything.
Ketamine’s efficacy in depressive disorders has been demonstrated in numerous clinical trials, and I think there’s quite a bit of evidence that this is occurring through neuroplasticity. Although I think the most convincing body of preclinical research suggests this occurs through functional plasticity in the hippocampus, rather than structural plasticity (e.g neurogenesis, spinogenesis, synaptogenesis, etc).
There’s also evidence that the deliriant and muscarinic antagonist scopolamine has efficacy in depression, while the related molecule benzoyltropine has low affinity for muscarinic receptors (unlikely to be deliriant), and like scopolamine increases cortical spinogenesis.
It will be interesting to know what role (if any) cortical spinogenesis and synaptogenesis plays in scopolamine’s putative antidepressant effects. The sustained antidepressant effects of scopolamine and ketamine are believed to require similar hippocampal modulation of a protein which binds methylated DNA sequences, although scopolamine’s acute effects on hippocampal functional plasticity are different than ketamine’s.
Ketamine and scopolamine also both activate mTORC1, so in that regard I wonder if they might have a negative impact on brain longevity. I certainly hope not, as I’ve used quite a bit of ketamine in my life.
I’m aware of a paper showing mTORC1 activation with chronic psychedelic administration, but I can’t remember if this has been shown with acute administration. Psychedelics will also activate the MEK-ERK and PKC axes, both of which are probably anti-longevity.
On the bright side, 5-HT2A receptors are positively coupled to transcription of VEGF, which is one of the most promising pro-longevity proteins. It’s actually been shown that 5-HT2A activation can rejuvenate aged liver in a VEGF-dependent manner.
