The psychedelic phenethylamine 25C-NBF, a selective 5-HT2A agonist, shows psychoplastogenic properties and rapid antidepressant effects in male rodents (2025)

https://doi.org/10.1038/s41380-025-03341-1

Thus, this study aims to investigate the pharmacological profile, safety and therapeutic potential of novel N-(2-fluorobenzyl) phenethylamine analogs (NBFs) of the 2C-X series—25C-NBF, 25B-NBF, and 25I-NBF. NBFs displayed high affinity and selectivity for the 5-HT2A receptor and demonstrated bias factors (defined in our study as the preference for Gq over β-arrestin pathways at 5-HT2A receptor) similar to that of 5-HT.

46 Upvotes

91% Upvoted

u/OpiatedSadness Aug 28 '26

So how does this differ from the 25I and 25B NBOMe’s. Is the safety profile there because from what I know those psychedelics can be neurotoxic and even deadly. I personally experienced a OD on 25i

4

u/drippysoap Aug 29 '26

How much did you take? I’ve only had an amazing time on them

4

u/Jakey-poo Aug 29 '26

Thats the hard part. Back some 11 years ago when bitters sold as tabs were going around you had no idea the dose.

2

u/OpiatedSadness Aug 30 '26 edited Aug 30 '26

2 tabs, but before the OD started kicking in, I had the most insane visuals off any tabs I’ve ever tried it was awesome. Luckily I didn’t have to go to hospital but my entire body was in extreme pain ( probably amplified because I was tripping ) and I felt like I was having micro seizures

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u/Kalki_X Aug 28 '26 edited Aug 29 '26

Personally, I think these highly selective (and potent) compounds are excellent for research purposes, but not really appropriate for "recreational" use.

It might be different for the non-hallucinogenic psychedelics which are very popular atm ... but hopefully some researchers are exploring the psychoactivity of 5-HT4, 5, 6 and 7. The HT2A tunnel vision needs illumination — Shulgin knew this:

After the emergence of the 5-HT2 paradigm the full-flavor concept appeared mainly outside of the mainstream of neuroscience (Shulgin & Shulgin, 1991) (Goldsmith, 2007) (Doyle, 2011)(Coyle et al., 2012) (Ray, 2012). A concept of complex action was advanced by (Shulgin & Shulgin, 1991):

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u/ebolaRETURNS Aug 29 '26

There appears to be greater selectivity for 5ht2a among other 5ht2 subtypes for the NBF series, and to a lesser extent NBOHs. Whether this translates to greater safety is unclear: it was a surprise that nBOMes were significantly more toxic than DOxs, the latter mostly being broad-spectrum 5ht2 agonists.

3

u/Sandgrease Aug 29 '26

The NBOMes aren't really that bad, people just ended up taking way too much. 25i nbome reminded me A LOT of DOi, maybe a little more vasoconstrictive than I'd like but neither felt like I was gonna have a cardiovascular event.

3

u/ebolaRETURNS Aug 29 '26 edited Aug 30 '26

The NBOMes aren't really that bad, people just ended up taking way too much.

'Way' too much can be as low as 3 mg if you're idiosyncratically susceptible, which could be 3 pieces of blotter. That's worlds away from the safety profile of LSD.

I personally did fine with both 25I and 25C, but I was measuring the pure compound myself.

neither felt like I was gonna have a cardiovascular event.

The life-threatening type adverse events instead seem to involve renal failure, rhabdomyolysis, and global inflammatory responses that are not well understood.

2

u/Sandgrease Aug 29 '26

That's what I mean. People were taking random tabs and holding them under their tongue. Of course it was gonna end bad. I did it too and got lucky (possible heart damage?)

I love Phenethylamines but the side effects ramp up quick. I was there back in the 00s and 10s trying all kinds of things, but the people that got hurt only have themselves to blame for just taking random things.

I've tried 30+ psychedelics over my 25 year experimentation run, and yea I took random tabs (took a 5 strip of DOi once, basically changed my neurochemistry forever going forward) but that was my fault, not the chemical's ya know.

I took 25i and foolishly added MDMA to the mix, one of the few times I thought I was gonna die in a wave of bliss and cardiovascular constriction.

Again, these substances can be used safely if you know about volumetric dosing, own a mg scale and pace yourself. Just eating unknown things bc your friend said it is good, can get ya burned.

1

u/LtHughMann Aug 29 '26

A big part of what makes them dangerous is their potency, which isn't really an issue in a controlled setting since they account for it in dosage

u/Fickle_Cellist Aug 29 '26

Wild that they don't mention previous work like https://doi.org/10.1021/cn400216u which is arguably the closest prior knowledge

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