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Would 4-bmc and 4-cmc be as neurotoxic as their amphetamine counterparts?

Toz

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So I've seen these (4-bromomethcathinone and 4-chloromethcathinone) pop up for sale lately on some RC vendor sites and it has me a bit worried. They seem eerily similiar to the infamous PCA and less so PBA. Could anyone shed some light on whether they would still be as neurotoxic and if so, why or why not.
 
Well as of now, there is such little information out there regarding these halogenated cathinones. This means that anyone's conclusion will be speculative at best. My opinion is to not touch them with a 10 ft pole. Purely because of the similarity between cathinones and amphetamines, especially regarding the phenyl ring characteristics, I would just assume toxic. And assumptions other than that can lead to very bad things, if my assumption ( of them being toxic) turns out to be true. So, I say they have a good chance of toxicity and to stay away.
 
It's interesting to speculate since AFAIK recent studies have shown Mephedrone to be non-neurotoxic after all (though I'm pretty sure it still down-regulates your serotonin transporter system so you can't really use it with any sort of regularity if you don't want negative effects) - though it's pretty cardiotoxic, while I'm fairly certain 4-Methylamphetamine and 4-Methylmethamphetamine are both known neurotoxins.

That said though I thought one of the other worries was that certain halogenated structures can break down into some nasty toxic metabolites which in themselves may be neurotoxic or toxic in other ways - fluoroamphs not having this aspect makes sense.

That said, I've tried 4-BMC/Brephedrone and it's not worth the time or money even if it's non-neurotoxic, and certainly not if it is. It's not very potent or fun, seems mostly to be a kind of selective SRI/SRA with only a tiny bit of stimulation, and potentiated other drugs but not something you'd take on its own. I imagine 4-CMC should be similar.
 
By the way please remind us (me), which is worse, pIA or pCA?

Not worth it anyway seems a very fair assessment that I keep returning to as well with some of these iffy research chemicals. I guess you need some perspective after having taken a step back to make a call like that? Cause I don't really understand the kind of fixation or ignorance that makes people go for their 'novelty fix' or 'whatever gets you off fix'.

When I first saw 4-BMC become available I tried doing some lobbying to get rid of the availability, but people get hung up on the fact that its mode of toxicity is probably not acutely painful or lethal, if it is anything like 4-MA... and anyway, with some people it would take a lot to get them to abandon their pile-sized supply.
 
SAR suggests that the beta-ketone substitution inhibits activity as an MAOI, at least to some extent, and also tends to reduce selectivity for SERT, reducing the likelihood of serotonergic neurotoxicity. So all else considered, they should be less neurotoxic than their amphetamine homologues, but given how neurotoxic some of these amphetamines are, I wouldn't put any of these proposed cathinones in myself without additional academic study confirming a lack of neurotoxicity.

ebola
 
A quick Google search discovered that, somewhat strangely, this paper claims that brephedrone is used in the clinical treatment of psychological disorders! So I had to investigate. Sure enough, brephedrone was trialled as an antidepressant:

https://ewsd.wiv-isp.be/Publication...ephedrone/Foley2003_methcathinone-analogs.pdf

It was tested in rats; their brains were not examined, but hopefully if it had been extremely damaging to the rats' psyches the researchers would have noticed; to be fair, this is a weak definition of safety.

Caution is warranted whenever using the term neurotoxicity, of course, because some authors like to refer to any change in brain structure as neurotoxicity, under which definitions even using the Internet is neurotoxic:

http://www.psychologytoday.com/blog...atters-too-much-screen-time-damages-the-brain

Ultimately it really does seem that we are going to need more specific terms and ideas than "neurotoxicity". It seems likely that with sufficiently precise imaging equipment, virtually any stimulus or sequence of stimuli will eventually produce changes in brain structure! It's ridiculous and insane to declare that everything is neurotoxic on this basis. The current attempt to classify drugs as "neurotoxic" or "non-neurotoxic" may be a wild goose chase.

By the way please remind us (me), which is worse, pIA or pCA?

pCA. See http://www.sciencedirect.com/science/article/pii/009130579190601W
 
Does it state what phase 4-BMC (if it has gone that far) is in?

I wonder if it would feel unique in comparison to your typical SSRI in terms of its SRI activity. Also, does it really have no effect on dopamine?
 
SAR suggests that the beta-ketone substitution inhibits activity as an MAOI, at least to some extent, and also tends to reduce selectivity for SERT, reducing the likelihood of serotonergic neurotoxicity. So all else considered, they should be less neurotoxic than their amphetamine homologues, but given how neurotoxic some of these amphetamines are, I wouldn't put any of these proposed cathinones in myself without additional academic study confirming a lack of neurotoxicity.

ebola

This was what I thought. Thanks for all the answers guys. It seems these 2 drugs are catching on the RC market here in Sweden and people seem to be using them so far without problems. I will stay far away from them and I was hoping for some good argument as to why other people should too. However I've found no papers or anything else to specifically say they are as bad as their amphetamine counterparts so I will give it a rest for now and people can go for whatever gets them off if that's what they only care about.

Ultimately it really does seem that we are going to need more specific terms and ideas than "neurotoxicity". It seems likely that with sufficiently precise imaging equipment, virtually any stimulus or sequence of stimuli will eventually produce changes in brain structure! It's ridiculous and insane to declare that everything is neurotoxic on this basis. The current attempt to classify drugs as "neurotoxic" or "non-neurotoxic" may be a wild goose chase.



pCA. See http://www.sciencedirect.com/science/article/pii/009130579190601W

When I used the term neurotoxic I meant harmful in the same way as PCA or the likes. Something that alters brain chemistry to a level which complicates your day to day life afterward for an extended period of time.
 
When I used the term neurotoxic I meant harmful in the same way as PCA or the likes. Something that alters brain chemistry to a level which complicates your day to day life afterward for an extended period of time.

From the user's perspective I think that is a great operational definition.

If you're a neuron you might define it a bit differently, but I think around here we're usually interested in the user's perspective.
 
I'd say comparing PMMA and 4-MMC, no....

Still though I wouldn't mind some real info before taking the plunge. However considering 4-BMC is not much more than an antidepressant which doesn't share the similarities with 4-BA, I'd say that the chloro would be most worth my while but even then, it may be on the light side for me. As most accounts say, with the cathinones/amphetamines, you'd need a lightweight group at the 4 position.

So that brings me to the next idea; double and triple bonded 4-subbed Cathinones. 4-VMC & 4-YMC should be absolute winners in my book. Hell, you could even start playing with deuterated compounds (3D-4-MMC anyone?!). Food for thought though, 4-TFM-MC; would it be too bulky or does that change with the trifluoro's? They seem to vary from family to family but in this instance I'd say it'd be along the lines of 4-BMC (i.e. not worth my time of day).
 
It's interesting to speculate since AFAIK recent studies have shown Mephedrone to be non-neurotoxic after all...

Do you have a source/link? I dont think so. Yes there was a study ,the results shown that through VMAT 2 binding it was only little to non neurotoxic to dopamine neurons. There was no info about the toxity to the serotonin system. I think it is significant neurotoxic for your serotonin system.
And from what i expierenced with meph (excessive usage), ive had long term problems who were (also) related with the damage of my serotonin system. It took me quite a few years to recover, I was completly BURNED OUT. Felt like i was only half alive, sometimes like a zombie. No energy ,burned out. It was horrible! Depressions, Affective Disorder as well.
I took sometimes Stimulants (which was really retarded in this situation) that my life at least was not everyday worthless.
 
Well, it was all too beautiful to be true. And 50 mg/kg in mice isn't really that high of a dose in human (~4mg/kg for a 60kg human). I heard a lot of people saying that mephedrone in a binge felt more toxic to them than plain amphetamine in a binge.
 
Another vote for "probably", but I don't think that the research is firm enough to make very good inference via SAR (the mechanism of PCA's neurotoxicity is as of yet unidentified, but known to be mediated via SERT).

ebola
 
I think with repeated dosing 4-MMC, 4-CMC, and 4-BMC are all neurotoxic. The duration of interaction of p-CA with SERT seems to play an important role in the degree of neurotoxicity, 3-chloroamphetamine which is metabolised via para-hydroxylation is less neurotoxic than PCA unless one blocks para-hydroxylation. Considering that cathinones are additionally metabolised via ketone reduction and are more short-lived than amphetamines, I would say that a single dose of 4-CMC is less toxic than a single dose of PCA.
 
Im glad I waited for some info before going ahead and ordering 4-CMC.

A big thank you to the chem nerds for helping keep us safe.
 
While I don't intend to try 4-BMC or 4-CMC - the fact that 4-Chloroamphetamine has been used as an antidepressant in humans without adverse effects and toxicity was caused by a metabolite in rat cells, not by the main compound itself, makes me wonder if metabolism in humans might be different enough for that given metabolite not to form?

Also it seems not to be related to MAO inhibition at all like with methedrone / PMMA.

--

Edit: Here is a disturbing report of a member who suffered probably permanent neurotoxicity from some chemical that could well have been 4-bromomethcathinone. But we don't know in the end.

Back when mephedrone was still legal and I was younger and careless, I had a weird experience from combining maybe 40mg 4-mmc of unknown purity (from a vendor that also sold methedrone) with an unknown (ranging somewhere above 100 and below 250mg) amount of dextromethorphan. Was a long-lasting, gradually building experience that got quite intensive, a little "out of it" but very socially stimulating, euphoric, lowering inhibitions and feeling toward others - so, and lacking regular - high dose experiences of mephedrone, MDMA or anything comparable, the effects read like they could have been just from the mmc or maybe a bit amplified by the dxm.

But well - the next day I woke up feeling .. different. And really not that unlike a light version of what the report above describes. This increased upon the day, in the late afternoon I walked along a street in the city I've lived in and knew very well, yet I felt like I was an alien in an alien landscape. I do not remember much more in detail, but it shocked me - and everything, even the fear and all, felt like they were not my emotions. They were there and I felt them, but like I was an emotionless being sitting behind a screen watching life's movie.

Thankfully I recovered fully after a few days, and in that time I have used DXM in low dose range almost daily too ... I'll never really know what it was, but both 4-mmc and DXM are powerful serotonergics and I guess this was too much at once. Maybe even the NMDA antagonism of DXM / its metabolite actually saved me from further damage...
Also from the day after 4,4'-dimethylaminorex (as well as from discontinuing SSRIs, to some extent) I know how serotonin depletion feels. Nothing one intends to feel, but by far not comparable.

After that I thought mephedrone just wasn't for me - but since I've got to know 3-mmc (and today I do more effort to be sure what I take) which feels completely different, much clearer and I actually enjoy it from time to time... So I think differently now about that incident.
 
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But well - the next day I woke up feeling .. different. And really not that unlike a light version of what the report above describes. This increased upon the day, in the late afternoon I walked along a street in the city I've lived in and knew very well, yet I felt like I was an alien in an alien landscape. I do not remember much more in detail, but it shocked me - and everything, even the fear and all, felt like they were not my emotions. They were there and I felt them, but like I was an emotionless being sitting behind a screen watching life's movie.

Thankfully I recovered fully after a few days, and in that time I have used DXM in low dose range almost daily too ... I'll never really know what it was, but both 4-mmc and DXM are powerful serotonergics and I guess this was too much at once. Maybe even the NMDA antagonism of DXM / its metabolite actually saved me from further damage...
Also from the day after 4,4'-dimethylaminorex (as well as from discontinuing SSRIs, to some extent) I know how serotonin depletion feels. Nothing one intends to feel, but by far not comparable.

What you experienced was depersonalisation/derealisation and it happened mostly due to DXM/DXO, not mephedrone (if it was actually mephedrone at all). I've been experiencing depresonalisation and derealisation since I quit benzodiazepines, that's almost one year now and that's what it is. I feel dissociated from myself and everyone and everything around me, it's a very weird feeling, but it's much worse that I can't feel normal around people, even those that I've known for some time now. I'm switching between being my old spontaneous self and a silent depressed weirdo. I feel lonely but at the same time my emotions are so weird when I'm with other people that I feel completely isolated and I can't be part of the group. This is actually quite difficult to put into words, this is something that people who haven't experienced it have a very hard time understanding or even believing it could be happening.
 
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