390 replies to this topic

[John250]

On August 8 I am going off all amphetamines. Do you think this would be a good addition to restore my dopamine system or could it further inhibit it and cause further problems? Also in the studies I don’t see dosing anywhere for humans?

[jacobjerondin]

Has anyone bought teamtlr's 9-me-bc lately? Is it still good?

[Hyperflux]

How does 9-MBC interact with amphetamines when used on conjunction? I can see a potential issue arise due to its strong (although reversible) MAOI properties. Are you supposed to use 9-MBC solo to get off of dopaminergic substances and to regenerate neurons? Earlier logs in this thread have people use their ADHD meds together and they ended up with reduced tolerance.

[John250]

How does 9-MBC interact with amphetamines when used on conjunction? I can see a potential issue arise due to its strong (although reversible) MAOI properties. Are you supposed to use 9-MBC solo to get off of dopaminergic substances and to regenerate neurons? Earlier logs in this thread have people use their ADHD meds together and they ended up with reduced tolerance.

I used it only for a few days while still on amphetamines and didn’t notice anything

[jacobjerondin]

I used it only for a few days while still on amphetamines and didn’t notice anything

What dosage? I think that the amphetamines would kind of overpower any effects the 9-me-bc would have beyond the MAOi action. I'd very interested to hear how it goes for you now since you're off them. Please give us a report if you still have some

[John250]

What dosage? I think that the amphetamines would kind of overpower any effects the 9-me-bc would have beyond the MAOi action. I'd very interested to hear how it goes for you now since you're off them. Please give us a report if you still have some

Well not off completely lol
https://www.longecit...th/#entry855963

I was using 15mg. I’m going to give it another run soon at 30mg and see how it goes

[jacobjerondin]

You gotta taper down man haha, going off cold turkey is def not the move. Trying out just Vyvanse for now is prob a great idea, and try and reduce the dosage if you can.

 

And 30mg should be a great dose, please do that and let us know how it goes!!

Edited by jacobjerondin, 21 August 2018 - 02:23 AM.

[Hyperflux]

Is there any issues with using this long-term, any potential dependence or withdrawals? I've found 15-30mg to completely obliterate Vyvanse withdrawals and frankly replace it altogether.  I'm wondering if a 6-12 week cycle might be warranted but I've read about tolerance.

[John250]

Is there any issues with using this long-term, any potential dependence or withdrawals? I've found 15-30mg to completely obliterate Vyvanse withdrawals and frankly replace it altogether. I'm wondering if a 6-12 week cycle might be warranted but I've read about tolerance.

Man I wish I got The same results. I’m going to continue to use it off and on long-term just because of all the positive effects It has on preventing amphetamine neurotoxicity

Edited by John250, 26 August 2018 - 06:46 PM.

[Hyperflux]

I've been using this @15-30mg for a couple weeks and there's definite tolerance to the dopaminergic headspace. I'll still keep taking it for its benefits on the dopaminergic system but I think I'll stop around the 4-6 week mark. I think my ideal dose is 20mg orally, higher doses can produce anxiety and too much MAO inhibition.

[John250]

Any updates on the dna damage from UV? With this be avoided by putting on sunblock before going out in the sun? And doesn’t 9-me-bc have a relatively long half life so the time you take it to avoid UV exposure shouldn’t matter.

[theCLK]

Tried some this morning - having a nice day so far!

 

Anyone else still using this ?

Edited by theCLK, 24 December 2018 - 04:32 PM.

[John250]

Tried some this morning - having a nice day so far!

Anyone else still using this ?

What was your dose? Do you take any other stimulants?

[theCLK]

No other stims

 

Was using 20mg and then 15mg. Nice effects lasted about 2 hours tops. Seems like if was going to go this route would probably use Syrian Rue or Baniseteropsis Caapi? Not crazy about the DNA UV damage issue as I have VDR Taq and need sunshine from the sun..

[John250]

No other stims

Was using 20mg and then 15mg. Nice effects lasted about 2 hours tops. Seems like if was going to go this route would probably use Syrian Rue or Baniseteropsis Caapi? Not crazy about the DNA UV damage issue as I have VDR Taq and need sunshine from the sun..

Yah the dna part is a bit worrisome. I wish they actually had studies showing the amount needed to cause it though both the amount of UV damage and 9-Me-Bc.

[BioHacker=Life]

Tried some this morning - having a nice day so far!

 

Anyone else still using this ?

 

I am it's probably the best dopamine nootropic out there I've used next to deprenyl. Just pricey so I take it more as needed these days but damn the mood and focus boost is outstanding. Perhaps it's somewhat addictive because I would take it everyday if it was cheaper.

[BasicBiO]

Still using it and it's become a staple for me. No addiction/tolerance noted at all and I cycle on and off it frequently. Just gives me a nice sustained boost in motivation and positive mental energy.

 

Would appreciate PM's of additional sources, if that's ok by forum rules. Team TLR is not responding to inquiries other than to send out auto replies.

[BioHacker=Life]

Still using it and it's become a staple for me. No addiction/tolerance noted at all and I cycle on and off it frequently. Just gives me a nice sustained boost in motivation and positive mental energy.

 

Would appreciate PM's of additional sources, if that's ok by forum rules. Team TLR is not responding to inquiries other than to send out auto replies.

 

Not surprised I tried ordering from them and got ripped off over $200 bucks. AVOID at all costs.

 

Hydrapharm is legit.

[Infinite1]

I wanted to verify if we've been able to definitively determine whether this compound qualifies as a reversible or irreversible MAOI A/B. I've read through and it looks as though there was suggestion that it would be considered reversible, however still seemed a bit speculative in context. I suppose given it should follow in suite with those others in the same class, however reassurance is appreciated!

https://www.ncbi.nlm...pubmed/8990278/

[nickthird]

1. I am confused as to what u guys mean by brain damage from stimulants. Do you mean just tolerance or what? I am asking for myself.

 

2. Is this useful for those without this damage?

[Infinite1]

1. I am confused as to what u guys mean by brain damage from stimulants. Do you mean just tolerance or what? I am asking for myself.

 

2. Is this useful for those without this damage?

 

It should have action regardless the history of the organism. Those that may find it more beneficial are those with a deficit within the same architecture; however can be an agent for optimization for anyone. For example, chronic inflammation regardless of the source can profoundly attenuate dopaminergic tone, with perhaps downregulation of TH being a key node. In this case 9-me-bc would be the ideal agent.  

 

In the aforementioned "damage" is more accurately maladaption. What is considered optimal is really context dependent, and relation to a given goal. That said, most certainly there are discrete pathologies where this might offer alleviation or abolishment given the neuroregenerative properties. 

[Swim15]

Interested in starting this after several years of Adderall use culminating in some mild anhedonia brought on and/or exacerbated by some chronic autoimmune inflammation that is now under control.

Has anyone used this in injectible form? Gonna grab some and make up an injection that I’ll probably stack with sublingual NSI-189

[graatch]

Someone on reddit cited our 1992 paper "Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants: New Vistas In Parkinson's Disease Therapy" in combination with "Pavlos (2017) Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme" and this 2011 book regarding this beta-carboline series in general to claim that 9-me-bc certainly will undergo endogenous conversion to the fearsomely neurotoxic 2,9-Me-BC. Unfortunately I'm having trouble evuluating for myself the truth of the idea due to presently insufficient understanding of the NNMT enzyme in question. Perhaps others can chime in on what they think of that? I have attached the papers and the book.

 

 

 

Just a heads up if you're looking to to try 9-me-bc:

9-me-bc converts to the potent neurotoxin 2,9-dimethyl-bc via SAM dependent methyl transferases. Nicotinamide-N-methyl-transferase (NNMT), the enzyme that methylates nicotinamide, is one of the SAM dependent enzymes responsible for this process. NNMT is found in the brain so it can trap 2,9-me-bc+ after activation. Researchers have found the 9-N methylation step to be rate limiting, and 2-N methylation occurs easily after 9-N methylation. So 2-me-bc would be less likely than 9-me-bc to convert to 2,9-dimethyl-me-bc.

SAMe supplementation increases NNMT so should definitely be avoided when taking 9-me-bc. Methyl donors will also probably increase NNMT activity since SA can be synthesized de novo.

Nicotinamide may be beneficial to take when on 9-me-bc IOT compete for NNMT active sites. However, nicotinamide may also up regulate NNMT activity in the long run. Nicotine and caffeine are NNMT inhibitors but may also up regulate NNMT in the long run. Nicotine and caffeine consumption have been inversely correlated to PD.

​

"Indeed, it is plausible to consider 2,9-Me2BCs as MPP+-like toxic factors that could be generated within the brain over time by SAM-dependent N-methyl- transferases

When incubations containing NH, [3H]S.AM and guinea pig brain were extracted and analyzed by reversed phase HPLC, the radiochromatograms consistently demonstrated the presence of two tritiated products with retention times identical to 2-MeNH and 2,9-Me2NH, respectively (Fig. 4A). In no experiment was there evidence for a tritiated product with the retention time of 9[indole]-N-methyl-norharman (9-MeNH; arrow). Importantly, similar brain incubations with two other BC substrates -- HA and HI--and [3H]SAM showed the corresponding formation of tritiated compounds at the precise retention times of their respective 2-MeBC and 2,9- Me2BC products, and the absence of components agreeing with 9-MeHA or 9-MeH122.

These experiments suggest for the first time that mammalian brain has the enzymatic capability to biosynthesize 2,9-Me2BCs of appreciable neurotoxicity from simple 'endogenous' BCs such as NH and HA.

If N-methylated BCs, and particularly the 2,9- dimethylated derivatives, are to be seriously considered as endogenous toxins that are trapped by bioactivation (quaternization) of BCs within brain, the SAM- dependent N-methyltransferase(s) necessary for their formation ought to be demonstrable in brain tissue

since 9-MeBC product was not detectable in the normethyl BC incubations, 2[fl]-methylation was necessary to confer sufficient nucleophilicity upon the 9[indole]-nitrogen-- i.e., sequential N-methylation of a BC was required to yield the 2,9-MezBCs via one or more N-methyl- transferases.

Parenthetically, in regard to biosynthesis, it is relevant to note studies linking 'excess' SAM- dependent biological methylation with parkinsonian behavior in rats5. "

Collins et al. (1991) Indole-N-methylated β-carbolinium ions as potential brain-bioactivated neurotoxins

Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants: New Vistas In Parkinson's Disease Therapy

 

Pavlos (2017) Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme

 

 

Attached Files

•  Indole-N-methylated-beta-carbolinium ions as potential brain-bioactivated neurotoxins.pdf   637.12KB   5 downloads
•  (book) Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants.pdf   2.77MB   6 downloads
•  Pavlos (2017) Nicotinamide N-methyltransferase - more than a vitamin B3 clearance enzyme.pdf   657.54KB   3 downloads

Edited by graatch, 26 May 2020 - 10:24 PM.

[graatch]

(I'm unsure about the idea that NNMT and/or PNMT (which has some small presence in neurons) will indeed manage to convert 9-me-bc to 2,9-dimethyl-BC.) There are people here who know a lot about nicotinamide and related compounds; and thus the enzymatic pathways like Nicotinamide N-methyltransferase aka NNMT (and homeostatic responses, if any) which respond to the presence of nicotinamide and related compounds; I especially would like their look at this notion.

Edited by graatch, 27 May 2020 - 12:57 AM.

[Rorororo]

(I'm unsure about the idea that NNMT and/or PNMT (which has some small presence in neurons) will indeed manage to convert 9-me-bc to 2,9-dimethyl-BC.) There are people here who know a lot about nicotinamide and related compounds; and thus the enzymatic pathways like Nicotinamide N-methyltransferase aka NNMT (and homeostatic responses, if any) which respond to the presence of nicotinamide and related compounds; I especially would like their look at this notion.

 

 

I would too. I am curious and I might take it upon myself to look for a way to mitigate the risk.  

[Rorororo]

(I'm unsure about the idea that NNMT and/or PNMT (which has some small presence in neurons) will indeed manage to convert 9-me-bc to 2,9-dimethyl-BC.) There are people here who know a lot about nicotinamide and related compounds; and thus the enzymatic pathways like Nicotinamide N-methyltransferase aka NNMT (and homeostatic responses, if any) which respond to the presence of nicotinamide and related compounds; I especially would like their look at this notion.

 

I read some literature, I have a clue on how to prevent the conversion. But, I will wait a couple of days to see if someone with more experiences chimes in. I don't want to divert the topic. 

Edited by Rorororo, 27 May 2020 - 03:18 AM.

[Ames]

Right so  Harmane (a metabolite of Syrian Rue) is according to wiki is
" a methylated derivative of β-carboline with the molecular formula C₁₂H₁₀N₂."
9 ME-BC according to wiki is ...
" a methylated derivative of β-carboline with the molecular formula C₁₂H₁₀N₂."

So what you are saying is that even though they both have the Exact same molecular formula and are both methylated,  one (harmane which happens to be cheap as chips and natural ) is "neurotoxic" and the other (patented and pricey as heck) is "neuroprotective" ...hmmmm...ok yeah its possible I guess even though I dont understand how.
 

Personally I haven't experienced anything "neurotoxic" (admittedly I microdose) and I  get all the dopamine stim and alertness effects from Syrian Rue. 

I wonder if there is anyone on this thread that has tried both and can give us a comparative review?
 

 

I'd have to dig back into the research to again find it, but the reason I never took syrian rue / harmala extract (though perhaps not the only good reason not to) was because  I found research that linked its use to Parkinson's symptoms.

 

Which makes me nervous in regard to 9-me-BC.

 

The benefit claim seems to rely on the implication that it threads a fine needle of potential neurotoxicity.

 

Do we know for sure that there are no long term risks?

 

What is the risk of chemically related contaminants that could be neurotoxic?

 

Can 9-me-BC degrade into a neurotoxic substance?

Edited by Ames, 23 August 2020 - 03:38 PM.

[Keizo]

Very interesting thread! 

[...]

 

Then I tried 9-mbc. All I can say is Holy Crap! The benefits are so wide ranged and far sweeping I'm really not sure where to start. I have been taking it for about 2-3 weeks.

 

#1) I now take 20mg of adderall a day. And damn does it work well. I went from 50 to 20 in 1 week. and that was after I had to drive for 21 hours straight. Usually my tolerance skyrockets after all-nighters.  I've never reduced my dose that drastically.  I take 30mg 9-mbc along with my nsi-189(20-30mg)  2x/day. Memantine never came close to this kind of reduction in tolerance.  

 

#2) I noticed an immediate improvement of general coordination. I have always been clumsy to the extreme, probably due to my attention span. Suddenly I was able to multitask with my hands without thinking about it. By about day 3 my tremor disappeared. I have noticed much more 'body awareness' lately. When I close my eyes I no longer feel unstable. When I sing I can feel the vibration and can sense when I am on key(very rarely lol). I get tingles and goose bumps when I listen to music or see something cool. These things are all new to me. I am kind of shocked at the improvement

 

#3) Mood. Damn man. I have been dismally anhedonic, depressed, anxious and exhausted for most of my adult life. Satiety... I suddenly felt full somehow, or satisfied. My craving for nicotine and other substances has faded to background noise. Now I dont feel 100% better just by taking this stuff. I can still have a really shitty day. But I do feel REAL potential for a wider range of emotion. I feel at times like Im a teenager again and everything seems new or novel. I now have the option to feel like shit or focus on something positive instead. Before It didn't seem to matter... 

 

I am pretty sure there is a strong synergy between the 9-mbc and the nsi-189. I skipped the nsi for a few days and it was possibly a bit less intense, but its hard to say for sure.  

 

On a weird note, I tried giving the 9-mbc to my mom who has no problems with addiction and doesnt take stimulants. I thought it would make her feel great. For some reason she didn't seem to notice much aside from increased sweating. I gave her pretty high doses too(150mg a day for 3 days). But to be honest she never seems to notice supplements I give her. My brother who has a similar history as mine had a nearly identical response. We will both be taking this stuff for the forseeable future, if finances allow.

 

[...]

For me several pharmaceuticals whose presumed (main) mechanism relates to neurotrophic factors (most notably Selank and Cerebrolysin, which I have lots of experience with) tend to enhance the effects of caffeine, dexamphetamine and so on. However the only drug that on it's own has produced those "enhanced coordination" effects for me is Cerebrolysin - in fact that's the most obvious immediate effect it has. This will sound really trivial but when I'm cooking everything works super smoothly, I close the oven hatch without thinking and it all works fine. (Overall the effects Cere has are very wide, thinking and executing my thinking is just much smoother and better.) For Cere I think this must be thru a plethora of mechanisms. For example the slight anti-tension/anti-anxiety effect it has (not sure about what exact mechanism that is, maybe several, anything from GABA receptor modulation, influencing enzymes relating to learned fear, to perhaps even dopaminergic effects, or perhaps some mysterious neurotrophic unique mechanism) probably helps with making the muscle coordination smooth and less spastic (I'm a really tense person, without having any sort of anxiety diagnosis, I think I'm just super-charged in the acetylcholine department since birth if we go by the flawed but sort of useful Braverman personality types https://www.bravermantest.com/ ). Other immediate effects of Cerebrolysin I get are a period of a few days where music sounds much better. And I also notice a clear difference in simply feeling more youthful, noticing colors around me, etc, this is most obvious for the first few days on starting a cycle (presumably due the contrast, rather than diminishing effects).

 

I wouldn't doubt there's strong synergy between NSI-189 and various vaguely speaking stimulating compunds, as NSI-189 (I have not tried) seems vaguely similar to above mentioned compounds I have tried.

 

For me I purposefully avoid combining Cerebrolysin with my prescription d-amphetamine (even tho I only take the equivalent of ~9mg dexamphetamine sulphate (30mg vyvanse)). Because the effects in my estimation are either too strong (near unpleasant) when I had previously combined it with low MPH or d-amph, or even caffeine, or it just seemed like it was way too much of a good thing (probably unsustainable) at other times. Since it seems no one knows how these kinds of synergies work I'd be very careful. However! I suspect it might be (if one has to combine already powerful agents like amphetamines) more sane to combine neurotrophic compunds with some low doses of well-known stimulants. Rather than doing these dopaminergic/MAOI cocktails. Bombarding the "same" system from different angles might cause more desensitization than going thru some novel mechanism that probably is directly unrelated to the stimulant drug. Seems pretty common sense to me.

 

Also I think that the dopamine system seems unique. It seems more flexible than other systems. In my opinion it's not "in the cards" to be able to keep it optimized for psychological well-being, so much as practical usefulness, if that makes sense. And I would advise anyone to be very weary of not being fooled by the surface level experience. This is why I'm such a fan of Cerebrolysin, because it's very subtle in many ways yet so powerful. And also why I continue taking my rather low dose of lisdexamphetamine 90% of days (between the rare Cerebrolysin cycles), because I know it works even tho it's not necessarily super obvious immediately any longer (and the more obvious effects have certainly faded, but over time it still does as great a job as ever improving my overall performance in many ways that can be quantified).

I don't want to overstate any great danger with amphetamines and similar drugs, but due to how powerful they are it's quite easy to think that it's possible to chase a blissful state forever (and yeah if one has a problem with depression, ADHD etc, a super low dose of d-amph could certainly seem amazing! when I first took 2.5mg IR d-amph I almost fell asleep on the spot and I've never felt so relaxed in my life).

I think some racetams (piracetam, phenylpiracetam) share some of this property (on a surface level) in that they can produce very obvious immediate effects (that I think are useless) like making one feel "enhanced" but it seems to me more of a psychological delusion in most cases. With that said I think prescription stims and in particular d-amphetamine is an amazing drug that certainly can have long-lasting amazing effects, but I think it wise to not assume that should extend to feeling "great". Albeit no doubt I think I've gotten some mild anti-depressant effects for these 12(?) months or so I've been taking my 20-30mg vyvanse (maybe it's an indirect effect at this point, of me being more functional and stable).

 

 

I just wanted to write this because me (and I think a few others) have experienced in particular that "youthful" effect when taking Cerebrolysin. And the synergy/interaction with caffeine etc. In fact for me when I've taken cere for a few weeks my tolerance to stimulants is much lower for weeks at least. Maybe cere is my secret recipe for never needing a dose increase for my scripts, quite possible. 

 

Finally I just want to say that, on the note of the dopamine system being in my pleb opinion unique... I'm not a great believer in "become whoever you want, your dreams are the limit" etc, but since I've lived for near 29 years now so many times have I felt like shit and sometimes those feelings were obliterated in an instant  thru social interaction, affirmations, recognition, social mirroring, etc. And when it comes to "ruining ones brain thru drug abuse" I think that is way easier to do on drugs that lean towards serotonin type effects. SSRI withdrawals anyone? The most useless drugs in psychiatry, yet they produce with startling regularity rather obvious withdrawals. So if ones problems seem related to dopamine (whatever that means), then I think there's way more hope, because the drugs that act on those pathways are 1. way more powerful than anything else used in psychiatry 2. very rarely produce problematic withdrawals 

I think the biggest danger with prescription stims is that people take unnecessarily large doses because they are so obviously effective. 

[Keizo]

Interested in starting this after several years of Adderall use culminating in some mild anhedonia brought on and/or exacerbated by some chronic autoimmune inflammation that is now under control.

Has anyone used this in injectible form? Gonna grab some and make up an injection that I’ll probably stack with sublingual NSI-189

 

It should have action regardless the history of the organism. Those that may find it more beneficial are those with a deficit within the same architecture; however can be an agent for optimization for anyone. For example, chronic inflammation regardless of the source can profoundly attenuate dopaminergic tone, with perhaps downregulation of TH being a key node. In this case 9-me-bc would be the ideal agent.  

 

In the aforementioned "damage" is more accurately maladaption. What is considered optimal is really context dependent, and relation to a given goal. That said, most certainly there are discrete pathologies where this might offer alleviation or abolishment given the neuroregenerative properties. 

 

1. I am confused as to what u guys mean by brain damage from stimulants. Do you mean just tolerance or what? I am asking for myself.

 

2. Is this useful for those without this damage?

The main problem I've encountered when taking prescription dexamphetamine or methylphenidate is that it gets very hard to tell what the drug does after some time. Especially the times where I've just gone at it non stop with no Cerebrolysin in between, etc. Now for me like I said 30mg vyvanse I can probably take indefinitely, it seems.

 

So if you quit adderall let's say, after taking it for 1 year or 20 years, then you got "problems with anhedonia" that you notice rather immediately and they persist. Just an example. Well... how do you know what is the cause? Do people even remember how they felt 1 year ago? 6 months ago? 10 years ago? I'm not sure. AFAIK humans are pretty good at being able to tell significant differences (30%+ change) that happen rather quickly. E.g. quit caffeine and you get tired upon quitting. But after that it starts getting more blurry.

 

Also due to the mechanism of in particular amphetamines this might become even more blurry. I think there's probably lots of stuff that's more or less unconscious that will be altered in anyone taking amphetamines no matter the dose, and especially the more immediate the release is. What I mean is basically seeking a certain type of mental state without even knowing why you would want that, but it seems plausible to me it could be related to the amphetamines, and the experience of having taken a small dose of prescribed amphetamine for a period might very well alter ones image of what is normal. I could well imagine amphetamine causes blindness to ones normal state of being, or increases the "dislike" for the normal state of being, and combine that with humans in general having mediocre recollection of their mental states anyway...... Not hard for me to imagine that a lot of what is termed "problems after I quit X stimulant" is an altered perception of reality. And what I'm saying isn't even necessarily unique to amphetamines, it could just be a natural bias along the lines of "It used to be therefore my normal should be closer to how it used to be" which I think is perfectly reasonable that it exists for anyone. Along with several other such cognitive biases that everyone probably have.

 

Now of course what really matters is how to improve people's lives, and what can be explained like I did here probably has some sort of physical/chemical/electrical equivalent in the brain.

[gintrux]

Is anyone interested in this stepholidine group synthesis? It could help with amotivation, anhedonia, apathy. In one study it increased D1, D2 receptors by 40% https://www.longecit...ia-amotivation/