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Is 25i NBOMe Neurotoxic?

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People get these syndromes and anxiety from all sorts of drugs, but when you have billions of people on a planet you can certainly find a mega thread of people having xyz symptoms from whatever drug. If you only see the 25i thread because that's what you were looking for, then you may assume it's something specific to that drug, but that's far from reality.

The thing is that your story is pretty common - the anxiety only really sets in after researching thing.

I talked with a guy who had this after a different drug for a long time (did a drug, was fine for a while, then started reading and got obsessive/anxious) and he went on to fully recover with mindfulness (he ended up going to a mindfulness retreat and practicing mindfulness a lot, with results coming slowly but surely).

He researched a lot and had to be convinced over and over that he hadn't done "permanent damage". Then he started worrying he was doing permanent damage to his serotonin with SSRIs. Trust me, your story is common.

What doesn't help is that people freak out over the "synthetic drug" bit, listen to yourself here for example

"25i NBOMe and its super high potency and full agonism displayed on the 5HT2A receptors."

But cannabis is "natural", yet it can cause intense depersonalization and psychosis in some who are predisposed to it or who have a bad experience on it. Same with feeling off for a while after a bad trip. Or drugs aside, feeling off for a while after a traumatic experience or an emotional loss. No super potent full agonism at 5-HT2A required ;)

Yeah true, it's just cannabis is a weak partial agonist at the cannabinoid receptors and it can't actually cause permanent damage. I just get really worried about the high affinity and high efficacy part at the 5HT2a receptors. The scary part about this entire thing is: 1. 25I came out in 2010, only 7 years of human exposure to it. 2. There are a bunch of negative after effects reported after use, development of anxiety disorders/panic disorders etc. 3. 25I is one of the only few full agonists of the 5HT2A receptors and it has a ki value of .04, which makes it 100 times the potency of LSD on these same receptors, which worries me that some sort of conformation change occurred making it harder for my serotonin to bind. (Dr. Nichols told me its impossible to change the conformation of these receptors, since the proteins that make the receptors are elastic like a rubber-band. A ligand can push down on it and alter its conformation but once it is gone, the receptor goes back to its native conformation).

Now, the reassuring parts of this entire situation are: 1. Dr. Nichols told me that 25i can not damage or change the conformation of receptors. If they're internalized or downgraded, more are made to take their spot 2. I posted on reddit and a bunch of other people talked about how they've done way more 25i and feel completely fine (over 200 doses at 1000 ug etc. [Don't know if these people are being completely honest])3. My friends who've also taken the substance said they feel in control of their mental health, although they do deal with bouts of anxiety (One of my friends who did around the same amount as me actually developed epilepsy recently after seizures that hospitalized him and ever since he's been on the keppra medication, he's said he's felt a lot more control of his life and anxiety - Something interesting to note). Do you think that the 25i had any effect on this? He developed seizures a couple of years after his last trip.

I just have to have faith that I didn't inflict any sort of permanent damage.
 
Psilocybin is a partial agonist at 5-HT2A but of course some people can develop all kinds of issues after taking mushrooms.

So for example, mescaline has very low affinity for 5-HT2A, you have to take ~500mg or so, but it can still produce profound effects, and after effects in those vulnerable to them.

Serotonin is by definition a full agonist at 5-HT receptors yet lots of people do great on serotonin releasing agents and they take them all the time for years, not to mention people that chronically take SSRIs and derive great benefit. So once again don't get stuck in the "25i is an ultra potent synthetic full agonist" loop, because people get exactly what you've got going on from all sorts of other drugs, including naturally occurring partial agonists at 5-HT2A and other compounds entirely like THC.

The answer for what you're experiencing is not within your 5-HT2A receptors, it's better conceptualized by issues with how different brain regions and nuclei are communicating with each other. Things will normalize as you learn mindfulness and learn to apply it throughout the day though.

I've personally had a lot of success with antipsychotics for rumination, and they are sedating as well (sleep deprivation will make you feel brain damaged, therefore you ruminate even more and sleep even less, fun times lol)
 
I
I mean, whose word are you going to take? One of the most brilliant scientists in psychedelic work, the guy who invented the NBOMes and has done by far the most research on them of any human?
Sorry to correct you here. Nichols did not invent the NBOMe series and Nicoles himself never claimed that ;) The molecule is from a 2004 PhD thesis from a chemist called Ralf Heim from the FU Berlin. For some reason, he and his professor Sigurd Elz decided not to publish the findings in a journal (which would be in English) but went the way with less impact where you just publish the PhD thesis locally at your university. I did my PhD in this system and when you do this (and not publish in a journal) you either admit that your research did not work or you want to hide it from the public. In addition to this, they simply published the thesis in German without a translation. I can only speculate why they did this. I read the thesis and Ralf thinks that the research was actually successful and they found what they wanted to find.

Somehow Nichols got his hand on the results and published a first paper on the series in 2006.

Sorry :)
 
Hey guys,

I just went to the grocery store and came back. I had awful feelings of derealization my entire time there.. this is getting strange, I'm worried that my brain chemistry has been permanently altered so I'm losing more and more hope..

This sucks, why does derealization occur? I felt like I was in a dream state the entire time. Does anyone know how to deal with this? Psychological trauma can induce this right? Constant rumination? I just hope and pray that it isn't something actually physically wrong inside my brain and my perception center.
 
Also is there any possibility that 25I inserts a halogen into these neurons which damage them farther? Iodine would act as a reactive species and potentially damage it right? Anyone have any information regarding this? I just want to put my mind at ease
 
You're apparently panicking which is running around in circles, putting your mind at ease would be taking a breath and reflecting on this neutrally - taking the repeated assurances in this thread seriously for example instead of relapsing into the same worry that they meant to put at ease. Re-read those earlier posts if you have to, particularly the ones after it was established that there is no receptor damage (which is where the interaction with the neuron is).

- The halogen has nothing to do with it, an atom on it's own does nothing - it is always about the functional shape of a molecule in it's entirety and Nichols has already told you the receptors are not being damaged. Iodine is not reactive like that especially not when covalently bonded in an organic molecule.
- Derealization (well from psychedelics in particular I guess) may happen - suggested by recent LSD brain scans - from a change in how brain regions communicate at a high level. It seems like on psychedelics the brain regions become less isolated and communicate more which can account for various psychedelic effects and the general feeling that everything melts into one. At the same time this may remove us from our feeling of self and normal reality because those are normally *roughly* derived from how our more isolated and distinctly communicating brain regions relate to each other.

This is not proven yet or anything but I have faith in this perspective. This after effect is not as intense for all people or after every psychedelic, or the impact is not always as destabilizing on someone's composure or anxiety... but it should be partially reassuring that it is not the end of the world if for a while your senses and faculties blend into some super-sense. Eventually you should just return to your previous thinking mode, I think living in the world and engaging in it encourages our mind to become compartmentalized and as some people say more ego-oriented.

If this keeps alarming you, that keeps you from recovering and probably also from engaging in the world... I think it is best if you accept things a bit more and try to gain some confidence that you can adapt and it just takes time and effort. Neurotoxicity is not your worry. Panic freezing you is more of a problem, and that panic just feeds on itself. Take it easy and just try to go through it without continuing to get more more more explanations that match your panic rather than that match your derealization and anxiety per se.

You're not bad for panicking, not at all, but just try to use these suggestions ^^^ to calm down.
 
If I were to give you an advice, I would try to go to a new environment for some days. Something like hiking could work well where you are distracted and your mind is occupied with other things. Go out to nature with friends, no drugs, and do something fun.
 
My recommendation to you is to go to a therapist or psychiatrist. I'm worried about you with your obsessive thoughts. You're causing yourself derealization at this point, your anxiety level is so high you can't sleep. You've already admitted it only happened after you started researching. As I said before, anxiety can cause all sorts of issues and mental disturbances in people. You are obsessing and experiencing intrusive thoughts, and the only way you're going to get past this is to address that and stop putting it on the 25i. Reading about 25i is only going to keep making your thoughts more obsessive. Reading our replies seems unlikely to help since you've received a good amount of advice so far but you are repeating the same stuff over and over to us. I mean no offense, I am just worried about you. I think you need to learn how to halt your internal dialogue when you need to, because right now it is hurting you. Therapy is a good way to help to learn how to deal with this. As a last resort, if it keeps getting worse and you can't get a handle on it, antipsychotics can help to disrupt intrusive thought patterns, but you should be able to learn to deal with this on your own. Chances are intrusive/obsessive thoughts are going to happen to you throughout your life, so learning to recognize and dismiss them is going to be very important for you.

You're fine, your brain is not damaged, but you're thinking yourself into a hole. <3
 
Therapist / psychiatrist, possible semi off-label anti-psychotics.. seconded. I was thinking the same sorts of things.. it's just proper care. Seeking help was of the necessary parts for me to get better too. Just make sure you switch to someone else if you feel like you're not with the right type or at a dead end (well due to a mismatch etc), and it should be good.
 
Thanks a lot guys, I appreciate all the input and constant support. It's just so hard. I keep getting intrusive thoughts of all the different stuff that I've picked up online.. The extremely potent nature of 25i on 5HT2a, 100 times the potency of LSD. the 25i blasting my neurons/receptors with its extreme potency as a full agonist. I also get intrusive thoughts of 25I inserting a halogen into the neuron and acting as a reactive species etc. I wish I didn't read all these reports and stuff online. It's really been ingrained in my subconscious mind and the anxiety from thinking I'm potentially damaged is hurting me.

I also don't want to develop seizures anytime in the near future.. I'm just sketched out about the fact that my friend developed epilepsy recently and we both did 25I the same exact amount. Is the development of seizure related disorders common after 25I? I know that people experience them during the trip itself but does this linger over into the future at all due to the strong activation of 5HT2A receptors?

Thanks once again guys. Your input has been really helpful.
 
I don't know why I'm being so skeptical about the entire thing, my mind is coming up with every reason to believe that my brain is damaged
I did not read everything, but in my opinion and also personal experience, this is classic anxiety driven thinking. one tends to obsessively look for physiological causes of the mental health issue because it feels like it's less of one's own fault if it were physiological.
 
Jacktheripper42, I am curious. Where did you find that there is a formation of a reactive halogen species? This seems very unlikely that the body splits the halogen-carbon bond in the brain or somewhere else. The elimination of these chemicals follows a different route.
 
Some guy named mellowparty on shroomery.com
Idk if this is BS or not though:

25I-NBOMe is a phenetylamine and these are known to be neurotoxic as they generate ROS species and also may induce stereoselective DNA attacks (at least thats the deal with other phenethylamines with a secondary amine). But thats not even the problem here. Such a powerfully binding molecule uncovers internalization motifs on the cytoplasmic side of its cognate receptor. Since its a full agonist the internalization (or endocytosis) phenomenon will be significantly expressed. This causes plasma membrane invagination, essentially the cells suck in the 25I-Receptor complex so you end up with a halogenated phenethylamine inside your brian cells (i.e. makes it much easier for the drug to damage your DNA or generate ROS and fuck up neuronal function).








 
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Hi Doctor Nichols,

What is the purpose of the halogen at the end of the NBOMe compound? There is absolutely 0% chance that the halogen gets inside the neuron and acts as a catalyst for reactive species?


0%.

It interacts with a hydrophobic amino acid through weak van der Waals forces.

Sent from my iPad

^ above is a response that I received from Dr. Nichols himself.







 
This is another response I found from another shroomery member:

It does not always lead to receptor degradation. The receptor may be recycled back to the cell surface but as Caine I'm inclined to believe that in response to NBOMe stimulation its ubiquitinated and degraded.

Internalization could be because of receptor phosphorylation and association with beta-arrestin followed by clathrin and adaptors sucking it in. Alternatively the ligand may induce a conformation change that exposes internalisation motifs that again could act through adaptors and clathrin triskelions.

It has been shown that some secondary phenetylamines undergo some sort of fancy intramolecular cyclization and radical generation that results in stereoselective DNA damage and cell death. It is possible that NBOMes do something of that sort.

But what I'm really interested in is what happens to the halogen inside the cell. Does it act as a catalyst for ROS production?


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If Nichols tells you that it will not happen, why do you bother? He knows way better than anyone here or on shroomery. I may have a PhD in Chemistry but my knowledge is nothing compared to him.

Honestly jacktheripper42, find professional help for your mental state. We are not able to help you out of this. A form can only advice you to go in a certain direction but you have to go yourself.
 
Stop reading what people think out loud on the Shroomery, it's just fueling your anxiety pointlessly as if you were scratching an itch that is just getting worse. We really can't respond to every shroomery or other post related to this on the internet.

There are plenty of drugs with halogen groups and apart from some exceptional functional groups that are not relevant here, those halogens don't really do anything in particular except for - as nichols said - interact in certain ways with polar / non-polar pockets and moieties attached to receptors. Which is just what other groups on a drug do too, just slightly different.

Ask yourself: are halogenated 2C-X that kind of toxic? Isn't 25D-NBOMe also very potent and potentially problematic despite having no halogen? Aren't there countless halogens on e.g. benzos? Just forget about the iodine please, it's not doing any harm - you cannot compare organic halides with diatomic halogens like chlorine gas or with loose ionic halogens like the chloride in tablesalt.

Things like internalization should account for perhaps things like the tolerance development, but mostly there are apparently benefits involved with lowering the number of 5-HT2A receptors available or at the worst some uninspired mindset as on anti-psychotics. So no, this is all about psychological sensitivity and most of the toxicity of NBOMe's as far as we know about acute dangers.

So please start taking care of your psyche, this obsessive witch-hunt stuff is reinforcing this whole problem.
 
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Stop reading what people think out loud on the Shroomery, it's just fueling your anxiety pointlessly as if you were scratching an itch that is just getting worse. We really can't respond to every shroomery or other post related to this on the internet.

There are plenty of drugs with halogen groups and apart from some exceptional functional groups that are not relevant here, those halogens don't really do anything in particular except for - as nichols said - interact in certain ways with polar / non-polar pockets and moieties attached to receptors. Which is just what other groups on a drug do too, just slightly different.

Ask yourself: are halogenated 2C-X that kind of toxic? Isn't 25D-NBOMe also very potent and potentially problematic despite having no halogen? Aren't there countless halogens on e.g. benzos? Just forget about the iodine please, it's not doing any harm - you cannot compare organic halides with diatomic halogens like chlorine gas or with loose ionic halogens like the chloride in tablesalt.

Things like internalization should account for perhaps things like the tolerance development, but mostly there are apparently benefits involved with lowering the number of 5-HT2A receptors available or at the worst some uninspired mindset as on anti-psychotics. So no, this is all about psychological sensitivity and most of the toxicity of NBOMe's as far as we know about acute dangers.

So please start taking care of your psyche, this obsessive witch-hunt stuff is reinforcing this whole problem.

I need to get out of this victim mentality. It sucks that I did a bunch of research on this stuff and now random bits from my research pop into my head and bother me. I just really don't want to develop seizures either. My friend developed them recently and we did the same dose with the exception of the fact that he experienced one extra trip on 25I.

There's no chance that NBOMe induces seizures in past users? 5HT2A has to do with epilepsy I'm pretty sure
 
5-HT2A doesn't have much to do with seizures, but lots of people have seizures without ever having touched drugs so it could be a coincidence. Especially if you're using drugs that lower the seizure threshold during use or drugs that lower the threshold on the withdrawal. Which is a lot of drugs.

Anywho, don't worry/catastrophize too much man. Try some mindfulness audios, through the Headspace app. There are also guided mindfulness meditations on YouTube.
 
Ugh, I hate this shit. I keep getting in my own head so easily :/. I constantly think about the importance of serotonin in regulating regular human bodily functions and I keep getting really sad. It feels like I've played this game of life and I've automatically lost because I've taken a substance as risky and dangerous as 25i NBOMe. My libido has been decreasing, losing sleep, anxious, having a hard time being genuinely happy etc. Worst care scenario, if 25i NBOMe did do something to my 5HT2A receptors/neurons would it still be possible to live a happy life free of anxiety and etc? How significant are 5HT2A receptors/neurons in relation to all the other serotonin parts?

I feel like something's missing in my life and that I've ruined the one perception center I was born with. This is really sad, it's almost as if my mind is catastrophizing this entire situation into something as severe as receiving a fatal cancer diagnosis. The thing with this situation is that if my serotonin system did get permanently altered, I'm going to have to live a life with sadness,anxiety, lower libido and a lack of sleep. That sounds like the most hellish reality.. All because of a mistake I made as a 17 year old and being offered a substance "that is just like LSD, only synthetic" according to my one friend. If I knew about the extremely high potency, full agonistic properties, potential for DNA related Halogen damage, I would have never taken it.


I'm such an idiot for ever taking it. Every morning I wake up, I wish I could go back and never task the NBOMe. I hope this is just all a result of me psyching myself out and not any physical damage.

 
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