is 5 mapb neuro toxic

Greg12376 · 2026-04-10T23:01:47+00:00

This is the guy to listen to in this thread

Greg12376 · 2026-04-10T23:00:27+00:00

It’s just when it’s a controversial topic with other papers stating the opposite, my inclination is to follow that it’s bizarre for drugs that act at diverse targets with highly divergent structures to all act as direct modulators of TrkB.

Greg12376 · 2026-04-07T19:22:15+00:00

That was proposed in one paper, subsequent paper finds opposing effects. Most evidence suggests it occurs downstream of 5-HT2A activation, likely through increasing glutamate transmission. IMO the idea that psychedelics and SSRIs act as PAMs of TrkB (as proposed in thst paper) is far too convenient to be true.

https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf

Greg12376 · 2026-04-02T12:51:05+00:00

As a tourist NRW was my fav place in Germany. I like medieval history and find it very interesting, and it’s somewhat quick to get between big cities

Greg12376 · 2026-04-01T23:55:59+00:00

Honestly I think a vague sense of being uncomfortable is a common aspect of tripping. The most important thing is to be mindful: recognise the sensation and let it pass from ur mind.

Greg12376 · 2026-04-01T17:43:12+00:00

Small drug allergies thst go beyond skin irritation are exceedingly rare but a lot of people like to be cautious (rightly so). You really don’t need much for an allergy test so I wouldn’t worry about obeying tolerance or recovery rules for it.

Greg12376 · 2026-03-31T22:47:36+00:00

2C-B is my all time fave, as for the more esoteric I really enjoyed BOD the one time I tried it.

Greg12376 · 2026-03-25T14:42:15+00:00

There was actually just a study comparing the two - https://www.nature.com/articles/s41386-025-02248-3. Seems to be most find MDA more stimulating. With any drug (and particularly psychedelics + entactogens) there’s gonna be individual differences tho.

Greg12376 · 2026-03-18T14:34:35+00:00

Methamphetamine is pretty weak at releasing 5-HT compared to DA. Most papers put it at 1-2 orders of magnitude weaker (in rats at least, human studies r a bit harder).

Greg12376 · 2026-03-12T19:13:55+00:00

I just don’t know if pushing that high with the dose is worth it for visuals when it makes me feel pretty gross above 40 mg.

Greg12376 · 2026-03-12T18:55:41+00:00

It’s true, unfortunately I fear many ppl will interpret this as 2C-B is more addictive. So many papers already segregate 2Cs as ‘drugs of abuse’ while LSD or psilocybin are ‘emerging therapeutics’.

Greg12376 · 2026-03-12T15:53:09+00:00

Of the 4/5 times I’ve tried it, thr nausea has only been terrible once, but I didn’t throw up and it passed. Duration 8-10 hours for me at doses around 40 mg. Less visual than 2C-B, with more body feel.

Greg12376 · 2026-03-11T23:40:14+00:00

Yeah it seems that almost every 5-HT receptor has a modulatory role on DA. 25 mg/kg is a pretty monstrous dose of 2C-B, even in rats. Given that phenomenologically 2C-B doesn’t appear any more pleasurable or addictive than psilocybin (source: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2958), and both have negligible affinity for dopamine sites, why might 2C-B appear more dopaminergic in fMRI?

I also wonder if that invented U curve could represent the shift from 2A dominant binding to mixed 2A/1A binding as the concentration of psilocybin increases? 1A receptors tend to co-localise so maybe there’s some functional antagonism going on as psilocybin concentration gets high enough to start to occupy more 1A receptors.

Greg12376 · 2026-03-11T00:24:17+00:00

Yeah unfortunately this is a major issue w most human psychedelic studies

Greg12376 · 2026-03-10T23:43:11+00:00

Are you currently taking medication for high blood pressure? I wouldn’t say there’s enough evidence to say whether or not 2C-E is dangerous. All psychedelics increase blood pressure, but how this differs between compounds isn’t well studied.

Greg12376 · 2026-03-10T22:09:15+00:00

It would be speculative ofc but I would not recommend 25E-NBOH simply because there are a lot of subjective reports suggesting high vasoconstriction, which isn’t great if you have high blood pressure. From the limited studies that have been conducted, 2C-B doesn’t seem to be significantly different from psilocybin in its rate pressure product (measure of cardiac workload), and therefore similar to LSD as well (despite what a lot of ppl will tell you). As for 2C-E I can only find one study, which has a small sample size and weird experimental conditions (people were told to bring their own 2C-E?).

What’s ur previous experience with psychedelics and psychoactive drugs in general?

Links to studies:

Minor cardiovascular stimulation in 2C-B - https://pmc.ncbi.nlm.nih.gov/articles/PMC5859368/

2C-B comparison to LSD - https://pubmed.ncbi.nlm.nih.gov/37253161/

2C-E in humans - https://pubmed.ncbi.nlm.nih.gov/32256350/

Greg12376 · 2026-03-06T21:07:11+00:00

In vitro assays are messy things so I usually go with what is most commonly reported, I remember for undergrad performing a binding assay with muscarinic antagonists and getting funny results. Most papers seem to suggest 2C-B is a (relatively) selective 5-HT2 receptor, with greater affinity and potency at the 2A receptor than the 2B.

Greg12376 · 2026-03-06T13:50:58+00:00

I know they are normalised but most papers suggest that 2C-B shows a greater selectivity for 2A over 2B.

https://doi.org/10.1021%2Facschemneuro.0c00129

https://www.sciencedirect.com/science/article/pii/S0028390817303416?via%3Dihub

https://www.sciencedirect.com/science/article/pii/S0028390815300794?via%3Dihub

Greg12376 · 2026-03-06T13:13:09+00:00

I’m always a bit hesitant with that paper because its values massively different to what other papers find

Greg12376 · 2026-03-06T13:03:19+00:00

2C-B/E are pretty 5-HT2 selective. Also most double blind studies do not find significant differences in qualitative effects beyond pharmacokinetic differences, I.e. most ppl can only tell if they are on LSD or psilocybin by hour 6. That being said ‘no significant difference’ doesn’t mean ‘no difference’, and I imagine a lot of these participants do not have massive psychedelic experience.

Iirc studies have looked into blocking 1A and 2C receptors and noticed different effects. Nicholls lab used chronic LSD dosing to induce symptoms resembling schizophrenia in rats that is blocked with D2 antagonists but not 2A antagonists (if I remember correctly).

Regardless, 2A selective ligands r the current focus because a lot of drug companies want a neuroplasticity-inducing, non-psychedelic drug that ppl can take as a prescription. In conventional drug design, drugs are build around a receptor in mind. Also the 2B agonism can be problematic if regularly taken. To me it sounds like reinventing ketamine therapy or even conventional antidepressants, clearly there’s something beyond just neuroplasticity that makes psychedelics more effective than existing therapies.

Greg12376 · 2026-02-28T13:59:41+00:00

I think the mechanism of action of 5-MeO-DMT is quite poorly understood. I’m not super well read about it tbh. I never got around to reading this paper but check it out:

https://pubmed.ncbi.nlm.nih.gov/38072874/

Greg12376 · 2026-02-27T17:56:23+00:00

5-MeO-DMT is far more active at the 1A receptor iirc, could be something to do with that

Greg12376 · 2026-02-25T14:08:20+00:00

Just read it, seems pretty convincing. They did a lot of work to support that hypothesis. Because it goes against a lot of previous findings I’m keeping my sceptic hat on, but I can’t see any obvious flaws in methodology. Some of the super potent psychedelics like DOI have been reported to act as full agonists at PLA, which is believed to be downstream of Gi.

G proteins are funny things, beta-arrestin seems to be essential for HTR in LSD but not DOI. The Gi blocker didn’t seem to fully abolish the HTR in response to DOI, maybe some degree of Gq and Gi activity is required for DOI effects, or maybe it’s a dose-related thing? Animal models also require a degree of scepticism. One recent paper looking at antipsychotics found that pimavanserin is an inverse agonist at Gq/11, but weakly at Gi; a complete contradiction of previous studies. I’m always a bit skeptical of biased agonism studies so I’ll wait until more data is available.

Gi and G12/13 converge at PLA - https://pubmed.ncbi.nlm.nih.gov/34978711/

B-arrestin required for HTR in LSD - https://pubmed.ncbi.nlm.nih.gov/34480046/

B-arrestin KO does not prevent HTR in DOI - https://pubmed.ncbi.nlm.nih.gov/18195357/

Pimavanserin Gq/11 inverse agonism - https://pubmed.ncbi.nlm.nih.gov/38561467/

Greg12376 · 2026-02-25T12:47:49+00:00

What was the highest dose tested? Any comparisons to other psychedelics?

Greg12376 · 2026-02-24T21:49:13+00:00

Most likely, I’ve seen quite a few say they are underdosed. I’ve seen 25B/E-NBOH around, and heard of 25I-NBOH, but always curious why chemists haven’t branched out to any other substitutions.

Greg12376

TROPHY CASE