• N&PD Moderators: Skorpio | thegreenhand

Pre-084

To get an even more unambiguous result, you should have taken heroin and cocaine along with it.
 
Caffeine and Kratom are my baseline. Without this measurement, my assessment would be of no value at all. 6 hours later, no perceivable effects, whatsoever, fwiw. Just the normal post meal lull.
 
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Snorting is painful.

It's not very active on its own. Up to 10mg showed not many effects. I feel a bit more alert and clear headed, but no recreational high to speak of.

Few minutes later: I'm totally not a morning person at all, however I feel somewhat awake and stimulated and am multitasking a few things at once. So there's definitely something going on. No euphoria to speak of though.

I'll try other ROAs and mixing it with some other stuff!

I could've told you that. Sigma1R agonists on their own tend to have essentially zero behavioral or biochemical effects, but this has to do with their likely role as molecular chaperones. Interestingly enough, Sigma1R agonists have been shown to mediate, to at least some extent, BDNF trafficking and release;

https://www.ncbi.nlm.nih.gov/pubmed/28188803

Though this is almost undoubtedly responsible for the cognitive enhancement and antidepressant effects seen with Sigma1R agonists, BDNF release on it's own tends to have negligible effect on markers of neuroplasticity in vitro. You normally need to pair a BDNF releasing agent with some other form of cortical activation, and from there you'll start seeing increases in the complexity of dendritic arbors, increased dendritic spines, etc. Because the Sigma1R pharmacophore is so simple (you essentially only need a molecule with a lipophillic end and an amino nitrogen which can carry a positive charge), the receptor itself is incredibly promiscuous and will often bind drugs that have other pharmacologic targets. What seems to be happening in the case of a drug like ketamine is you have a combined increase in cortical activity via inhibition of GABA-ergic interneurons via NMDA blockade, which causes glutamate release at the same time as the Sigma1R is facilitating BDNF secretion.

I'd be curious to know if you could simply combine a Sigma1R agonist with some sort of mentally stimulating activity and get therapeutic effects that way.
 
does anyone else have experience with this by now. thinking of getting 250mg...
 
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