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Racetams (non-Keppra): relevant studies

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Piracetam

 



First and formost: many thanks and credits go to @Syntheso for bringing up the relevance of Racetams, specifically his mentions on Piracetam. I will adress these mentions before reviewing anything else.

Syntheso, alas the study you mentioned, has shown to been a fake, conducted by a fraud. However, it did bring to light an important mechanism by which Piracetam functions, namely calcium modulation. This has been confirmed by legit studies, such as the following:

 

The results suggest that piracetam and GVS-111 suppression of voltage-activated calcium and potassium currents of the neuronal membrane may regulate (both up and down) Ca2+ influx into neurons.

source
 
For a substantial overview of Piracetam's MOA (Mechanism of Action), this [PDF] is a suggested read.
Here's one of the many relevant pieces of information from that file:
 

Micromolar amounts of piracetam enhance the efficacy, but not the potency of AMPA-induced calcium influx in cerebellar granule cells, an effect which persists in the presence of the voltage sensitive L-type calcium channel blocker nifedipine. The AMPA receptor-associated ion channel is not permeable to Ca2+ , but it has been shown that the AMPA and kainate receptor activation causes an increase in intracellular free (Ca2’) by calcium influx, which is partly sensitive to the L-type calcium channel blocker verapamil (40% reduction in calcium influx)
180 pg/ml (1.3 mM) by verapamil channel blockade).

Hmm.. this is what I understand from it: Piracetam enhances calcium influx, even in the presence of a CCB.

From wiki:

 It is hypothesized to act on ion channels orion carriers, thus leading to non-specific increased neuron excitability, while explaining its lack of agonistic or inhibitory effect on synaptic action (quite unlike most neurotransmitters), and its low toxicity.

Note that this statement was derived from the aforementioned PDF.

Alas, so far the evidence seems to portray that Piracetam would causes worsening of symptoms. Nonetheless, it is true that there are many (a lot!) studies available on Piracetam. This is why this statement is subject to alteration. For now, it seems to me to be the most logical conclusion. As always, note that I am not a scientist, I'm just trying to make sense of all this, like you. I could very well be wrong.

Syntheso, despite the evidence showing against Piracetam's potential therapeutic benefit in HPPD, you've still contributed greatly, for even ruling out treatment potential is critical. Moreover, Piracetam is only a member of the racetam family, and you've initiated further research into its each and every kindred substance.

Ok.. wait. I've found some more evidence regarding Piracetams anticonvulsant actions. The same PDF noted that Piracetam intensifies anticonvulsant effect of anti-epileptics. So I skimmed through the references on that claim, and behold:

 

Investigated the anti-epileptic efficacy of carbamazepine (60 mg/kg, orally 3/day) and piracetam (30 mg/kg) on a model of chronic limbic epilepsy (CLE) using 49 male Sprague Dawley rats. Results confirm the present authors' (1985) earlier findings that carbamazepine has an anti-epileptic effect in this model of CLE. Piracetam alone had no anti-epileptic effect.

source: Piracetam potentiates the antiepileptic action of carbamazepine in chronic experimental limbic epilepsy.

 

Results indicate that neither Oxiracetam nor Piracetam diminished the effectiveness of the anti-epileptic agents tested, with the exception of Phenobarbitone.

source: Synergistic effects of oxiracetam and piracetam in combination with antiepileptic drugs

 

Piracetam did not diminish anticonvulsant action of any of the anti-epileptics. Piracetam potentiated the anticonvulsant effects of carbamazepine (and to a lesser extent that of Clonazepam).

Readcube source

 

These findings suggest that the treatment potential should remain open for investigation. Furthermore, the potential of Piracetam to assist in mitigation of common co-morbid symptoms should not be underestimated. Its nootropic effect it putative. It's anxiolytic potential is of lesser popular knowledge:
 

In the social interaction test of anxiety Piracetam (100 mg/kg) had an anxiolytic profile very similar to that seen after 5 days of administration of chlordiazepoxide (5 mg/kg). Piracetam (50–300 mg/kg) produced no signs of sedation and it was therefore suggested that it might be a non-sedative anxiolytic drug. Piracetam (100 mg/kg) produced significantly higher cortical concentrations of 5-hydroxytryptamine and lower concentrations of 5-hydroxyindoleacetic acid, indicating a reduced 5-HT turnover. There were no drug-induced changes in noradrenaline or dopamine in any brain region.

source

 

These findings suggest that Piracetam's MOA (which is still debatable) might involve 5-HT mediated action, and thus provides significant further implications in treating HPPD (for those who believe 5-HT is involved).

Some more anxiolytic evidence:
 

The present study indicates that Piracetam has significant anxiolytic activity in rodents following subchronic, but not acute administration, when tested against several paradigms of experimental anxiety.

source

 

In contrast, the conflict situation tests revealed pronounced anxiolytic activity of piracetam at elevated doses. The nootropic and anxiolytic effects of piracetam do not coexist, and are significantly shifted relative to one another on the dose scale, being probably realized via different mechanisms.

source

 

The latter statement is congruent with the fact that Piracetam has a U-shaped curve dose dependant effect. More info on the optimal dosage of Piracetam (4.8 grams daily) can be found in this Longecity thread. I suggest that anyone who's interested in Piracetam at all, should definitely read it.

 

I'll continue later.

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Coluracetam.


You might come across a post I made in over-excitement, which got be banned for a week. I hadn't read the forum rules, and figured it would be alright to request to buy the stuff, seeing as others make such requests on that forum all the time. But hey whatever, I made a mistake and I literally can't apologize for it. Oh well, such is life. I've requested a custom synthesis lab to have a look and make me an offer instead.

 


Just a heads up: all experiences quoted below come from the thread above. Just thought I'd spare you some time skimming for other possible sources. Furthermore, after all this work, I found someone had already summed up a lot of experiences at this page.

 Blue highlights show undesired effects, red shows desired effects, green shows questionable effects in regard to favorability.

Anecdotal effects on vision and other senses

"I could almost TASTE and EAT the colors, so to speak" Sounds like that could help with DR.

"Informal review: this is a very active substance. Indeed, there are changes in visual perception of color. I have tried oxi, ani, pi and prami -racetam without any color enhancement that I could perceive consistently above placebo status. However initial test of this mystery substance that came in the mail to me has got me saying "whoa" even just looking around my room. Driving around outside with these fall colors on the trees is an absolute pleasure." source

 

"I am pretty sure I noticed an enhanced verbal fluidity and more "high def vision" like I do when on Piracetam" source

"
The visual enhancement and extra clarity+swiftness of mind reminds me a lot of lions mane, both which for me just keep growing with each dose. it happens slower on lions mane though. My vision, mostly outdoors, now pretty much always appears in high definition HDR with a bit of...an indescribable magic/fantasy/artistic look to things mostly outside(I suppose almost exactly the same as a low low dose of a psychedelicno distortions just a very similar if not better extreme enhancement of vision that also makes things, mostly nature, have that indescribable awesome looking feel). I get this effect even when it's been a while(24hrs+) since I've dosed and it seems to build with every doseThe fantasy/awesome look to everything is a lot like aniracetam(of which the effect also builds for me but coluracetam's has already surpassed the visual enhancement I get from aniracetam, and I don't believe aniracetam's visual enhancement lasted after most of the other effects left). The visual effect also started out very similar to piracetam's visual enhancement of very bold colors and detail enhancement(this effect grew very very slow for me but eventually got very obvious, not sure how long it lasted after I stopped taking it, since that was awhile ago). I went to two concerts and the music and lights, while awesome anyway, were incredible... it was like a low-medium dose of MDMA or other serotonin+dopamine releasers except without the euphoria and mostly in those respects." source

 


"I noticed a change in vision, colors do seem more saturated , cognition became more lucid, uplifted feeling, I feel lucid and calm. working memory is bettersource

"I haven't dosed in 4 days and the visual enhancement is still there, just not as obvious as when on it. pretty coool..lion's mane's visual enhancements lasted a while after the last dose too." source

I'll do some extensive research on Lion's Mane Mushroom later, as it seems to have visual effects as well. Note that @bpl4269 has also found mitigation of symptoms when using Lion's Mane, among others.

"I noticed memory seemed to stick better, and color changes were very noticeableThe color effect still persistAlso seemed to make me quicker in speech." source

"I felt more clear and lucid and decided to meditateA 1 hour session was no problemI was to the point where I couldn't feel my physical body but my energy body started vibrating which is the early sign of the energy body moving out the physical body"
"It also definitely enhances meditation which I have mentioned." source


"I have bad eyesight and i think the coluracetam has improved my eye sightMy eyes have not been straining to see anymoreI was kill all my friends in MW2 (Modern Warfare 2; a FPS game for those who don't know) because I see them when they were just tiny specks on the screenI gave some to my dad to take before bed and he was able to sleep much better. He has sleep apnea and he said it helped him breathe better and the effects lasted several days with out repeat dosesource

"What I do notice is some kind of serenity while on coluracetam, coupled with easier memory recall of hard-to-remember info"

source

"I too initially noticed color pronouncement, but like others have mentioned, it seems like overall visual enhancement/acuityThe expectation effect appears to be intruding here, so I'd just encourage everyone to not focus too hard on anything that's been reported and try to be receptive to your own experiences.
Feelings of contentment, peace, and increased ease around others and life in general is noticeableSometimes I have some situational social anxieties, but they essentially disappear with 30mg. I was in a cellphone store for two hours waiting to receive a phone upgrade, and yet I was okay with this. My internal dialogue was forgiving of the employees for their slowness, and I enjoyed talking to the people there more so than I normally would have. This effect might also be heightened due to me being more content, and thus more likable, thus leading to friendlier/deeper conversations that dig beneath the superficial layers I commonly experience when interacting with strangers (especially strangers who want your money). Anyway, this might be valuable to people with OCD-like head running thought patterns
Coluracetam may have taken the edge off adderall a bit, but more significantly, it greatly increased my sense of taste, perhaps even making things tastier, not unlike cannabis can do. I also experienced tracerswhere lights would "paint" the space where they had been moments before in my visual fieldSometimes the tracers even became detached from the light source itself which seems especially odd now that I think about it. (note: Well fark, this sucks. One possible explanation is the combination of Amphetamines. Consider that MDMA is also an Amphetamine.. I don't know, but IMO I think the Amphetamines caused this effect. You should know that I'm largely biased about Amphetamines. Lastly, he does not report having this effect when combined with Cannabis)" source

 

"
2nd day taking this: 10mg/day


Good:
Visual enhancement 
Improved sociability
* Improved patience
* Better right brain activation - I can image stream fiction more easily. (note: Whatever that means.. I think he's referring to visualizing skill)

Somewhat Negative:
* It was a little too much in the foreground.  The perception changing is a bit distracting.
* Mood changes and day resets (when earlier in the day seems like a different day) were more frequent.  Nothing radical but just felt like switching between moods was a bit too easy.  This effect is a bit like Lion's Mane.
Night vision is better but the intensity of lighted vs non-lighted areas is a bit disconcerning.

source

"The effects I noticed were really quite nice, and this was only after one dose! I noticed increased sociability, mildly increased abstract reasoning skillsmassive mental relaxation and a profound effect of visual acuity and appreciation of natural and intricate forms. At one point I was enraptured by a passing cloud for a few minutes, just absolutely lost in its beauty and complexity." source
(note: Hmm... The reported effects sometimes seem to mimic those of classic hallucinogens/psychedelics. No absurdly weird things reported so far, aside from that Amph combo)

"The strongest effect seems to be anxiolytic. I can see why this was being developed to treat depression and anxiety; I take this, and I am a lot more calm and relaxed. Also, like piracetam, it makes being happy easier, and makes music better. I’m not sure if my vision is any different; the question is too subjective, too prone to the placebo effect, for me to answer with any confidence. That said, I’m not 100% certain that my vision is unchanged, unlike piracetam, which I am convinced has no effect on my vision." source

"The vision effect is still growing to the point it's on par with how psychedelics enhance vision(obviously without the distortions haha). I have had no negative thoughts at all, which is somewhat odd, I'm not a depressed person, but when you are tapering off benzos... you tend to get negative thoughts now and then and slightly depressed at random, but it seems to have stopped both of those from happening.source

"I have also noticed to be more into my self (note:DP implication?), more present in that sense of word.. but I should measure Colu effect more precisely, its still a lot anecdotal here.. As I am taking it with noopept, I sometime notice myself staring on landscape fascinated how beautiful it is (probably vision effects, which I think have antidepression qualities)." source

"The visual enhancement is pretty intense at times like Golden has mentioned similiar to Psychedelics but there are no tracers or anything moving just everything looks really bright and sometimes certain scenes look more like a high def painting or an enhanced picture like some of the Photo programs they have that enhance the quality of pictures making the scenes look somewhat fake to a certain degree due to the enhancement.
'm really happy about the improvements in Social Situations because I've struggled for a very long time with this issue and this seems to help in confidence and ability to say what I want without studderingAt other times though I feel somewhat anxious which is strange. Its like the drug doesn't feel like it has anti anxiety effects until after I realize how confident I was." source

 

"I was able to make some music again which was awesome, since my skill at that started going downhill after being on benzos. And yeah joelski28 I agree with your descriptions of the visual effect, heres some HDR pics (note: click source to see the pics.. they're mushrooms. ha-ha!) I took a while ago that remind me of it. Overall I really really like coluracetam and it feels like its building up my brain in a positive way, hard to describe really, but similar to lions mane if anyone hass noticed the effects from that they are pretty similarsource

"Tried 1000mg nefiracetam + 2000mg piracetam + 20mg coluracetam. The high definition vision is apparently enhanced GREATLY by nefiracetamSo is the calmness, but I expected that(intense calmness has always been the main effect of nefiracetam for me). It's definitely like HDR photography, in that the dynamic range of dark and light colors is increased. It's finally surpassed the max visual enhancement I got from aniracetam by a rather large amountSimply looking in the mirror I look as if I am looking at myself through the lens of a professional photographer..with perfect lighting and shadows haha. If you can't tell, I'm more the creative type, so things like enhanced perception and creativity stand out more for me. I'm going to attempt coluracetam with a psychedelic...I'll let you know how that goes." Note: Well.. I'm VERY curious to read how that goes. source

Here's his update on the experience with the (unspecified) psychedelic:

"coluracetam + psychedelic = saturated colors to the point they seem like you can feel them in your head... or taste them or such. extremely crisp vision and 3d perception>>>Less distortions than usual<<<, but more visual enhancements, if that makes sense. It was pretty much an additive effect on most levels. Sound felt like I was in a sea of the music surrounding me for what felt like miles. It certainly enhanced the perceptual elements of the psychedelic to the point it felt extremely amazing, more so than usual...ha." source

So that was the first stable anecdotal evidence that Coluracetam has great potential in treating HPPD!!!

Here's another report of that individual:

"I noticed it's very hard to have unwanted negative feelings, like aniracetam, it just seems to remove the possibility of falling into that pit. Of course if something happened like a pet died, I would be able to cry easily. It's like they (note: say what? who?)rationalize negative thought a bit more. Visual effect seems to only grow or increase when outside studying intense geometry and textures of the world, while when inside for most of the day it appears to slow down or even lower it's visual enhancement (note: this doesn't mean it is causing him vision deficits, he's merely stating the enhancement is less, but still there). I think possibly, since I wear glasses, but got them in highschool I will always be extra WOW'd when looking at many things with them on, so maybe it's helping my brain adjust to the better sense of sight when its being utilized." source


"I had visual quality problems as wellaniracetam is the most colorful racetam with prami the neon colored effects at grocery stores stayed for about a month. what helped enhance this more realistically was:

  • iboga (Note: I tried this myself... I strongly recommend you do NOT use Iboga. My vision was substantially worse for a month or so, before returning to HPPD-baseline. There has been one report of HPPD clearing up after an Iboga session, but it was merely a single sentence mentioning it. Iboga is an entheogen, and as such, with HPPD it is highly recommended to NOT partake in such activities.)
  • DHA/EPA
  • methyl-b12
  • lions mane (note: this seems to be coming up a lot)

another thing to try for visual enchancement is nicergoline (note: I will look into this later)  + hydergine the trick would be to actually get the fatty acids in there and the neuroinflammation out of there to build better visual cortex. (note: well sound all fancy, but no scientific sources. If that was the case, taking an NSAID would improve symptoms, no?)" source


"I've noticed a reduction in social anxietyColors appear to be more saturating and interestingConcentration and quickness of thought are also noticeably improved. During lectures this week, I've had less intrusion of unwanted thoughts (note: I myself have suffered greatly with intrusive thoughts since acquiring HPPD, thus I find this a highly significant effect) and daydreaming and have been able to really focus on comprehending what is being taught." source

"Interestingly the visual enhancement is still here strong after 2 days of no coluracetam and then added on a total of 200mg benedryl(aka DPH, to try to get back to sleep) and its still here clear as ever, just thought that was interesting." source


This post has lots of good stuff too mention, and is basically all summed up, so I figured it be pointless to add that here. One comment was: "semi-extreme visual enhancement/embellishment when in aesthetically interesting places(nature, music event w/ lights and such, fireworks)" I really suggest you take a look, sounds freaking wonderful to me.

 

 

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Thanks for the comprehensive summary! I'm looking very much forward to hear about your trial with coluracetam :-) 

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Here's a little update on what I've found so far with your help, @StateOfRegret:

Coluracetam:

  • Acute adverse effects on peripheral carbohydrate metabolism is pharmacologically negligible.
  • Researchers indicate it could be a novel therapeutic drug for the treatment of schizophrenia
  • Might be useful in cocaine-withdrawal, especially the physiological symptoms (my own conclusion.. there was a study with cocaine involved)
  • Basically through every research article it is said that Coluracetam is far more superior to AChEI's
  • "Coluracetam might act persistently to repair disturbances of cholinergic function in the hippocampus"
  • 90% of Coluracetam remains unchanged in the body, the rest (presumably) converts to a racemic metabolite known as M-MKC-231, which has no effect on HACU. (or so I understood it.. my word is not law) EDIT: Turns out I misunderstood the 90% statement.. had something to do with brain levels to radioactivity ratio, which I can't make any sense out of.

Also, whilst reading through the studies, it was stated that ACh release is inhibited by Serotonin in the hippocampus and neocortex. I'll have to look further into this, but if this effect extends to other areas, it might be indicative to why SSRI's can aggravate HPPD.

Some personal notes:
From what I have found, Coluracetam appears to be an extremely safe substance. Moreover it is highly unlikely to interact with any non-cholinergic medications.
However, given the aforementioned serotonin-acetylcholine link, concurrent use of serotonergic drugs might interact with Coluracetam (yet not necessarily in a dangerous way). As for my personal concerns; I have none now.

This is just what I have gathered so far.. I only just woke up. I'll do more thorough reading of the articles when my brain presents itself with a window of better cognitive opportunity.

Thanks again, StateOfRegret!

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A crucial factor nonetheless :)

How to obtain Coluracetam?
There's currently a vendor (Ceretropic.com), although it's not exactly a reputable source. More reliable sources that will have it soon are New Star Nootropics and Vantage.cc.
The other option is to synthesize it, either yourself or to have a custom synthesis lab do it for you.

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Found a lab in the states called thermo fisher. Will see what the story is come Monday morning. I'm not buying crap and I'm not buying from china but what troubles me is that the tracks left by BCI540 stop cold after the clinical trial. Brain Cells inc has licensed the drug to a company but I can't find any info plus if this compound is their formula that's means to say, if they own it, how could anyone else synthesize and produce it?

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I tried custom synthesis already.. apparently they don't like to sell unique unregulated compounds to individuals without a business license.
And yes, that bothers me as well, as there is no sane reason why such an interesting compound should be abandoned.

I don't know jack squat about the law.. But just search for patents and check pubchem, etc. I'm sure you'll be able to find the synthesis, although it might take you some days of reading before you finally find what you're looking for. Plus it's from 2005 or something, and it's not like you're trying to synthesis Viagra and sell it on the open market.

There was a group buy being organized, but everybody more or less gave up because they thought NSN would be having Coluracetam 2 months ago.

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Yeah let me know if I messed up or forgot something, I was pretty tired nearing the end haha.
Cheers!

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Will probably read it later, I have ~3 hour ride in public transport (bus+train) ahead of me (going home from visiting parents).

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