The neurotoxicity of psychoactive phenethylamines “2C series”

[redtailedhawk]

Would anybody be willing to comment on the following study/article?

Published: 21 February 2020
The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines
Masato Asanuma, Ikuko Miyazaki & Masahiko Funada

Conclusion
The 2,5-dimethoxy-substitution of “2C series” induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons.

The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines - Forensic Toxicology

Purpose The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines “2C series” in monoaminergic neurons. Methods After the exposure to “2C series”, 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7)...

link.springer.com

 

[deficiT]

Hmmm, I am not savvy enough to comment anything other than that I'm interested and would like to follow along.

I will note that the study was conducted primarily on the 2C-Tx compounds, and only included 2c-i and 2c-c. Notably absent was 2c-b, which is weird because it's the most commonly used one.

And it said they administered a "single dose over 24 hours"... But they didn't explain anything about what the dosage was like, or how what they used would compare to the actual human dosage, and I feel like it sounds like they could've just dumped a pile of the stuff on some cells and they died, due to it just being a lot of the stuff.

 

[Neuropharmacist]

In my opinion, dumping 250 uM of 2C-psychedelics on top of those weird cell lines is not a recipe for victory.

 

[cdin]

really wish they examined 2c-b

 

[Xorkoth]

I'd be really surprised if the 2C-Xs in general turned out to be neurotoxic. They certainly don't feel like it, though of course how something feels isn't necessarily indicative of toxicity. What is the proposed mechanism of neurotoxicity? Most of them are just agonists of serotonin, similar to classical psychedelics. A notable exception is 2C-T-7, which is reported an MAOI and has caused deaths (mostly when combined with MDMA though, which makes sense since MDMA is extremely dangerous to combine with an MAOI due to the risk of serotonin syndrome).

 

[nepalnt21]

speculation: you'd think dr. shulgin would have shown signs decades ago of neurotoxicity if this were a substantial concern, mirite?

 

[Skorpio]

speculation: you'd think dr. shulgin would have shown signs decades ago of neurotoxicity if this were a substantial concern, mirite?

Just arguing for arguments sake, neurotoxicity is often not visible. For example look at long term alcoholics. They often can perform in public quite well.

However the doses used in this study are quite high and likely don't represent dosages reached with recreational use of the 2Cx compounds.

 

[Skorpio]

The doses used in this study are seemingly quite high.

To try and quantify this, we could do some guess-timation: They give the neuronal densities of the samples used (3.1 × 10^4 cells/cm^2 for B65 cells, 1.0 ×10^5 cells/cm^2 for CATH.a cells). Perhaps, then, one could calculate the number of cells/ug 2C-x, and follow on with some back-of-the-envelope maths to determine whether the dose reflects those used by your average 2C-x user.

Each well of the 96-well culture plates used in this study have a diameter of 7mm (roughly, they are semi-conical) and a height of 11.5mm, therefore the surface area of each well is about 8cm^2. The cells were plated, as opposed to being in suspension (making calculations far simpler). Therefore, the number of cells per well is 248000 (8cm^2 * 3.1x10^4 cells/cm^2).

The highest concentration of 2C-x given was 250uM, converting 250umol/L to grams (given that the volume of the well is approximately equal to a 0.00043L) gives us roughly 2.32x10^-5g per well, or 9.35x10^-11g/cell. Multiplying this ratio by the number of neurons in the human brain (recent approximates state around 86 billion), then we get the equivalent of 8 GRAMS OF 2C-X. So, if my maths works out (and realising that the translational value between these experiments and what happens in the human brain is limited), then someone would need to ingest over 8 grams of the 2C-x's to experience the sorts of neurotoxicity seen here, VERY roughly speaking.

So, in short, if you really enjoy 2C-x's, I think you'll be okay.

Good maths, just want to add that you are probably getting a conservative estimate as your 8 grams figure would only apply to direct cranial injection.

With first pass metabolism and limited amounts crossing the blood brain barrier the equivalent dose would be effectively higher.

 

[nepalnt21]

how would one go about injecting multiple grams of 2c-t-7 directly into their cerebrum? asking for a friend