The "true nature" of the 2C's.

[Bi0hazardOpeth]

For those who feel like their memory has been effected from 2C-I, I found L-Tyrosine that others had recommeneded for those with 2c-i burnout feelings that helps with mental bandwidth a lot. I had this burn out issue pretty bad for about half a year or so after my 8 uses of 2c-i in 5 months. I would forget what I was going to say mid sentence and end up getting more and more frustrated with myself overtime, as I would try to explain something and have it drop out of my mind in the middle of conveying it. This did go away, just like the electric jolts I would get that would send my body into quick spasms here and there. Even when I was alone, with nothing close to any anxiety at all - it was this left over stimulant effect that I felt for 1 and 1/2 years or so.

2C-I cured my ADHD clear as day. I used to take prescribed Ritalin, Concerta, Focaltin (Stims) and Straterra (Non-Stim) at different times for my ADHD: reading and writing. Previously without the stims, I would find myself having to read the same sentence 3x times just to keep track of what I just read - Now, specifically after my 2C-I period, it's like I have permanent increases in Dopamine (What Ritalin increased) and Nor-epinephrine (What Straterra increased). I can sit down and write a 20 page paper in about 40 minutes when it used to take me hours on end. I have a bigger mental bandwidth, I can store many more things in my working memory and hold on to them until I need to write them down or apply them to the thought at hand. It's unprecedented and even beyond the bandwidth of the narrow tunnel vision-focus of Ritalin.

Along with the 1 and 1/2 years of stimulant body load after 2c-i I that finally went away, I still preserved this positive increase in mental bandwidth - and an ability to read and write without getting distracted or getting stuck on parts. Which has allowed me to fluently write out large papers, without stepping back and having to cycle around what I was just thinking to get it on paper. I really do think I have 2c-I to thank for this, it was just waiting to get past the stimulant bodyload/personality effects that came along with it for the first 2 years.

Also 1x or 2x 500mg of L-Tyrosine a day has been incredibly helpful in resolving the concentration side effects I got during the first 2 years, and it still helps today. It is the Amino Acid that produces the precursors for Dopamine and nor-epinephrine and allows the brain to produce more if it needs. Basically after the 6th time of 2c-I, I would feel burnt out, unable to think of words or what I was trying to say around Mid-Day over and over. For almost a year I was ok until a certain point in the day, then I would get burnt out without fail. Taking 500mg of L-Tyrosine 1x or 2x a day, allowed me to have that increased mental bandwidth without getting burnt out half way through the day. It is as if, my brain was draining the dopamine and nor-epinephrine with the increased level of brain activity. L-Tyrosine gives me the bandwidth to use that increased brain activity all day without burnout.

I learned a lot of these resolutions to my side effects on BL, it's truly an important and great place on the web.

-Bi0hazard

 

[azzazza !?]

i would just like to point out that this experience of 'mindless noise' is in no way something.. i was gonna say inhuman, but it actually is inhuman; but lets say 'beyond human'. the negation of what is human is nevertheless always still within the human scope. There is a philosopher who nabbed this into a concept; Levinas' 'Il y a', which is french; word for word it translates to "there is 'itness'". put into context one could say: "there still is itness"; which would mean that the consciousness in question was not negated despite the humanity of it having been done so. This 'itness' is as such the thread remaining and that brings, despite the illusion (cause thats what it is) of negation, knowledge of being; as to what it actually means to say: 'there is'.
i realize it looks like an almost carefree or careless thought when written down like this, but i do realize the experience itself is horrifying and 'endless'. a meeting with the 'Il y a' is always a difficult (to say the least) lesson. A close friend of him, Blanchot, also particularly wrote about it, but he does so in a much more literary fashion; he conceptualized it as 'the second night'. bear in mind that these are difficult authors though

many stories do tell about this as well, though it is more deeply ingrained into context (as any myth is); Orpheus and Eurydice springs to mind; but you'll find it in the Oddysee as well (and so many more obscure ones like Ovids Metamorphoses etc..). though recognizing what is sought after in them tends to be more of an a posteroiri; though again not entirely. another type of works which relate to such experiences are mystical works, in particular medieval christian mystics with an ascetic undertone like John of Ruysbroeck or Catherine of Genoa.

just saying; you're not off the map.

(yet )

 

[kobilica]

I tried l-tyrosine, a bit help, but not much. I am clean from all shit for some days now, gonna make it to the full month. But, it seems I am not so screewed after all, and that social anxiety did not completely developed from only 2cx abuse, it was already there, but not so much. It's not so bad after all, but I still feel anxiety. Guess I will try to just break the barrier, after all, I don't have nothing to lose. Also neurotonin or pregabalin, I doubt they will prescribe it for me, because doctors are stupid fucks.

 

[Bi0hazardOpeth]

A user on another thread, posted a relationship between serotonin and HPPD. I thought it might be useful to post it here as well, and add on related discussions to follow up on my 2c-i adverse after effects - that now are worn off and created many positive mental benefits.

Agonizing of serotonin receptors is one of the many reasons that causes eyes to dilate. HPPD isn't really rewiring of the brain. One theory is that a process in the perception part of the brain called sensory gating is disrupted. Sensory gating is the brain "filtering" out excess or redundant information coming in. For instance people that are Schizophrenic have sensory gating problems which is probably why LSD and other psychedelics mimic Schizophrenia symptoms. Also, since HPPD fades over time it's more likely saturation of the serotonin receptor sites that deal with vision. But, as with most information about the brain and psychedelics this is all theory and rational speculation.

Interesting hypothesis. A lot of my HPPD symptoms from 2c-I was like a very mild - non deadly Serotonin syndrome.

Excessively locked muscles over 2 years
Over active reflexes, that would make me and my motor control very jumpy
Tremors, that would start after 10 minutes of waking up - this is completely absent of any anxiety.
Muscles locking up involuntary, even when going to talk sometimes the muscles wouldn't be released in time and the beginnings of sentences would come out sharp and forceful.

Luckily, the HPPD is finally disappearing with amazing benefits now - I feel like I'm left with a permanent increase in dopamine and norepinephrine - which I can maintain at full rate all day with a L-Tyrosine supplement. I've never had such a extensive working memory, I can hold 10-15 thoughts or responses to someones discussion in my head, and call them in any order I want when replying to people. The increase in mental bandwidth and analysis is similar to the benefits while on 2c-i. It's been a weird and at times scary road, thinking the bad effects were permanent, but now I'm much better off than before taking 2C-I. For my whole life I had to take stimulants to read or write for my ADHD, since my half year of taking 2c-i, 7 times, I have an endogenous mental bandwidth equal to a 35mg dose of ritalin without any of the stimulant side effects. I am more productive and can write better than I ever could on ritalin and I don't feel burnt out like being on ritalin.

I've heard of others say that Mescaline use fixed their ADHD. I wonder if it is something with the phenethylamine family - specifically those that deal with Dopamine and Norepinephrine which are the neurotransmitter pathways that the 2 main types of ADHD medicines target.

 

[Bi0hazardOpeth]

---- These are the symptoms I had for 2 years before it started dying down and getting back to normal. - Medical Definitions

They exacerbated the effects of each other. Overactive reflexes -> Clonus contractions -> with tremors -> (Cogwheel Rigidity) Hypertonia.

1) Clonus / Myoclonus / Spontaneous clonus (from the Greek for "violent, confused motion") is a series of involuntary muscular contractions and relaxations. Unlike the small, spontaneous twitching known as fasciculations (usually caused by lower motor neuron pathology), clonus causes large motions that are usually initiated by a reflex.

2) Hyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies

3) Muscle tremors

4) Hypertonia is a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch.. Rigidity is a state of hypertonia where muscle resistance occurs throughout the entire range of motion and is independent of velocity (whereas spasticity is velocity-dependent). People with rigidity present with stiffness, decreased functional ability and flexibility. There are two main forms of rigidity: leadpipe and **cogwheel**. With leadpipe rigidity, resistance from the muscle(s) remains throughout the entire range of movement and it is not velocity-dependent. When rigidity is present with Parkinson's disease it is often termed as cogwheel. Cogwheel rigidity is a hypertonic state with rachetlike movements, and is believed to be present when rigidity and tremor occur together. Furthermore, the muscle(s) that have rigidity will not return to a fixed position after taken through range of motion

 

[Roger&Me]

Interesting... was the diagnosis of serotonin syndrome confirmed by a physician? The reason I ask is that 2C's are not known to release serotonin (and indeed physically cannot even bind at SERT), and definitely should not cause SS. I think a persisting, non-lethal perturbation of secondary signaling pathways in the cortical pyramidal cells and deep cortical layer glutamatergic pyramidal cells would be a more likely explanation for those symptoms (although that is just speculation on my part). 2C's possess the incorrect stereochemical configuration to bind at SERT, so I don't think that SS is a viable explanation unless its caused by an obscure, as-yet-unknown mechanism.

 

[Bi0hazardOpeth]

Roger&Me,

Thanks for your reply. The Serotonin Syndrome was just a guess, because it accounted for basically all the symptoms I was having. It could easily be something else that has the same expression of symptoms - I just haven't explored many of the other options for a lack where to start.

I think a persisting, non-lethal perturbation of secondary signaling pathways in the cortical pyramidal cells and deep cortical layer glutamatergic pyramidal cells would be a more likely explanation for those symptoms (although that is just speculation on my part)

Would you be kind enough to elaborate more on this, general search terms or links to better understand the possible mechanism you are talking about and it's relation to the symptoms discussed. It would be great to understand it's basis, since it does come back here and there - but no where as bad as before. I changed my post above to say general symptoms rather than implying it is SS.

Thank you for your kind and helpful response,

Bi0hazard

 

[Roger&Me]

Again, just speculation on my part. Psychedelics bind to 5-HT2A receptors that are located on glutamatergic pyramidal cells, and influence those cells to release glutamate through signaling cascades; but since they're only partial agonists, the specific way that they activate the pathways differs from the way serotonin does... theoretically, persistent use of psychedelics could cause a continuing disturbance in the way those pathways function... IMHO almost all of those symptoms sound glutamatergic in nature. It would be interesting to see what effect an NMDA antagonist has on the severity of the symptoms, that would definitely provide some further insight into the nature of the problem. Everything in the brain is linked together in all sorts of ways though... its hard to say anything for sure; but I definitely don't think its SS (not even possible, IMHO).

edit-- 2C-I does seem to be one of the worst phenethylamines when it comes to inducing long-lasting side effects. I think its just because its a pretty good agonist; that iodine at the 4 position is really big and really hydrophobic, so its going to maximize the interaction between the molecule and the hydrophobic region of the receptor. In contrast, 2C-C's relatively benign nature can be attributed to the much smaller chlorine at the 4 position that has less non-polar surface area and thus less receptor interaction.

My advice to all concerning 2C-I is to dose low and infrequently.

 

[MattPsy]

If hydrophobicity at -4 is the key to this then you should see the corresponding effects in the 4-alkyl and 4-alkylthio derivatives, pobably 2 carbons or larger i.e. 2C-E, 2C-T-2 to match iodine's atomic radius. How's the efficacy of 2C-I compare to 2C-E, say? I'd check myself but I'm on my phone so not convenient!

 

[Bi0hazardOpeth]

Thanks for the replies

Could this be why Neurontin (gabapentin) works so well for reversing a lot of those symptoms of locking up muscles, spasms. Part of Neurontin's function is as a glutamate antagonist. Could the reduction of glutamate in certain areas help with the symptoms of such a thing as what you discussed with the glutamatergic pyramidal cells? When the symptoms began (before taking neurontin or when I didn't take it) I would go to open a cabinet in my kitchen and my fingers/hand wouldn't have fully opened/extended to grab the knob by the time I should have been holding it. I used to have really quick reflexes on stuff like this, and taking 400mg of neurontin brings my old agility right back, where I can fly between opening and closing multiple things fast and accurately. Although, the neurontin never really reduced my tremors much. I tried a beta blocker (propranolol), which did remove the tremor (not the locking up - it actually made the Clonus/hypertonia worse) and other side effects, so I stopped that months ago. Luckily the bad storm of symptoms are gone, and I'm incredibly grateful for the amazing mental benefits I have left over - the symptoms described above were horrible and life impeding in ways- but was potentially worth it all.

I'm quite interested in this - what other possible Glutumate suppliments or regiments might help with, if this the case. I understand this is an educated guess on many fronts, and that it's "what might be at play" - but it does fit a lot of the symptoms and basis of how they started.

It all started on my 5th or 6th 2c-i trip. I ate 22mg at 8am, and went back to sleep (first time I tried this on 2c-i), getting ready to wake up tripping. When I woke up it was great, but about 30 minutes into the trip my whole body started shaking with a tremor, I realized that it was a feeling like I hadn't eaten all day - but way more intense, like I needed protein/sugar. After about ?10 minutes? I went and ate peanutbutter on bread and a smoothie with lots of natural sugar. 2-5 minutes later the body trembling stopped and I returned back to an incredible trip - but it seems those persistent negative aftereffects that lasted 2 years started right there at that point. After this trip, for the next 2 weeks I would get completely hungry with no warning, like there was no sensor for getting hungry then, bam - I'm so incredibly starving it was like I hadn't eating most of the day. Same thing with urinating, I would have no warning of it building up, then all of a sudden (a feeling of full bladder). The urination was never an issue, but it would come without much warning.

Dunno if those are related or give you more insight, but I really appreciate what you've added so far as well as our future discussions on the topic.

Thanks in advance...

 

[Roger&Me]

Try an NMDA antagonist like memantine, and see if that helps at all. Might be worth a try.

If hydrophobicity at -4 is the key to this then you should see the corresponding effects in the 4-alkyl and 4-alkylthio derivatives, pobably 2 carbons or larger i.e. 2C-E, 2C-T-2 to match iodine's atomic radius.

You see the same trend, but you have to take certain factors into account when comparing numerical values for Ki or EC50 between 4-halo and 4-alkyl compounds. In 2,4,5-subbed phenethylamines, if the 4 position is an alkyl longer than methyl or an alkoxy longer than methoxy, you get the substituent lying coplanar with the aromatic ring, which causes it to jut into a sterically crowded region of the receptor... so you can't really compare the numerical EC50 of a 4-halo to that of a 4-alkyl (for instance, EC50(2C-I) ~ 25nM; EC50 (2C-E) ~ 45nM... even though -I isn't twice as hydrophobic as -Et). The trend does hold within each group though; for instance, if you arrange the 4-halos in order of decreasing EC50, you'll find it correlates with increasing hydrophobicity at the 4 and you'll find the same trend hold through among the 4-alkyls until you get past a 3 carbon chain (when the steric effect begins completely inhibiting binding at reasonable concentrations). I don't know EC50s for the 4-alkylthios off the top of my head, and I don't really feel like digging through my pdfs right now to look for them D), but take a look at basically any paper dealing with the SAR of psychedelic phenethylamines and you'll definitely see hydrophobicity of the 4-pos mentioned as a key factor in determining activity.

 

[applefritters]

how can you make a blanket statement about the "true nature" of the 2c's when you've only tried two of them? the op is talking out of his ass on this one, until you try all the 2c's you can't really judge all the 2c's can you?

 

[MattPsy]

Yeah 4-alkyls will be coplanar as you say but at least with alkyl > 1 chain length (i.e. Et and larger) the bonds can freely rotate so the extra carbon(s) can orient themselves somewhat in the conformation of least steric hindrance. I doubt both faces (looking "down into" or "up out of" the page) or sides (2 and 5-positions of PEA) of the ligand have equivalent requirements for planarity; indeed, experiments with the "hemi-fly" compounds show this (more important to cyclize the 2-position oxygen into a nice planar benzofuran, not the -5, IIRC), as well as the 5-EtO series of phenethylamines/amphetamines (2-EtO drops potency much more so than 5-EtO).

I expect the electronegativity also plays a key part, maybe in determining functional selectivity (aka signal trafficking) and so qualitative effects since the 4-halo PEAs have quite distinct effects that aren't really replicated in any of the other classes of PEAs, even where the 4-substituent is otherwise of similar properties such as size and hydrophobicity,although this is speculation pure and simple. Also, from what I remember 4-(2,2,2-trifluoroethyl)-2,5-DM-PEA [... or was it the simpler 4-(2-fluoroethyl)? no, i'm not talking about DOET, the DOx compounds seem to be less variable in potency, I guess because the alpha-Me sidechain probably reduces the number of viable binding poses...] is actually quite similar to 2C-B or 2C-I, not 2C-E as you might otherwise suspect. Might be worthwhile making both the (R) and (S) stereoisomers of 4-(1-fluoroethyl)-2,5-DM-PEA because then you could see whether orientation of electronegativity mattered at all.

Actually, functional selectivity at the relevant targets (h5-HT1A, 2A, and 2C) and their relative activation levels really seems to be THE key part in the subjective effects and potency of psychedelics. You don't see this when you just compare Kis, EC50s, and efficacy at h5-HT2A/C. It's especially illuminating to think in these terms since there as so many mismatches in potency based on Ki/EC50/efficacy, even among really similar members of classes, that can't really be explained away as pharmacokinetic or other (MAOI activity, say, like with some of the alkylthios) variances.
I look forward to more papers where there is more than just the usual data like affinity, efficacy, and EC50 of PI hydrolysis by phospholipase C at h5-HT2A/C receptors, for example showing induction of gene activity. c-fos gene transcription induction - the pathway activated by ALL h5-HT2A agonists, regardless of whether they are psychedelic or not - appears to be associated with the classical Gq/11-mediated PLC-beta activation signalling, commonly tested for by measurement of PI hydrolysis, whereas egr-1 and egr-2 gene transcription induction - the pathway activated only by psychedelic 2A agonists - appears to be associated with the Gi/o (well, to be exact, G-beta-gamma) -mediated induction of Src kinase, and possibly others.
I don't recall seeing any studies that used mutated receptors (in the normal active site, where the key interactions currently appear to be made up from residues Asp155, Thr160, Gly238, Ser239, Ser242, Phe339, and Phe340) that also tested with a functional-selectivity-sensitive method. Pity, as it would be highly illuminating I think, showing what residues are most important for psychedelic activity, and so the optimum binding modes .

 

[lolusername]

It seems that the more I get to know 2c-e the more it just seems draining and nasty. Just an observation. 8(

 

[Psyke]

It seems the more I get to know 2c-c the more it just seems friendly and comfy. Just an observation

 

[Thorns Have Roses]

It seems that the more I get to know 2c-e the more it just seems draining and nasty. Just an observation. 8(

If that's the case, think about cutting back your use, you tend to get more out of it with longer breaks between trips. Ya'know, it accentuates the positives of it.

 

[lolusername]

You are right that I should be spacing out my trips more, but I think once I'm done with my current 2c-e stash I won't be getting anymore.

 

[Jesusgreen]

You are right that I should be spacing out my trips more, but I think once I'm done with my current 2c-e stash I won't be getting anymore.

"Still having some left" isn't an excuse to continue abuse, and yes, not spacing trips out is definitely abuse imo. You'll get much more out of what's left out of your stash if you leave it for a good couple months before you decide to trip again so your tolerance can fully return to baseline and you can integrate your experiences better. If it's draining and nasty why are you taking more in the first place?

 

[lolusername]

"Still having some left" isn't an excuse to continue abuse, and yes, not spacing trips out is definitely abuse imo. You'll get much more out of what's left out of your stash if you leave it for a good couple months before you decide to trip again so your tolerance can fully return to baseline and you can integrate your experiences better. If it's draining and nasty why are you taking more in the first place?

Boredom.

 

[Jesusgreen]

Boredom.

Absolute waste of drugs, and as I said, it's abuse, just as if you were using alcohol or other drugs out of boredom. Don't say "I'm abusing drugs and I'm getting bad effects - why??" - don't expect anything good until you use them correctly. Particularly when psychedelics have such quick tolerance build up, and the magic fades quickly just like MDMA (only thankfully with psychedelics, it comes back quickly too if you just take a break)

If you're bored, do something. Get some exercise, read a book, play a game, watch a movie, go out with friends, post here, write something, draw something, make some music, whatever.. If you can't think of anything better to do than something you find "draining and nasty" then you need to rethink your hobbies, there's plenty to do, plus you can then finally enjoy and learn from your trips as you won't be plagued by tolerance. :D