Are nootropics drugs, too?

Brain

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Many people are convinced of the existence of a miracle pill that gives the brain the power of Eddie from the movie «Limitless». Google leads to a group of drugs called «nootropics». We explain what they are, whether there are substances that can give us superhuman abilities to memorize information - and if not, how pharmacology can be useful for the mind.

Our memory and consciousness is a set of connections between neurons, and these connections can be stable and unstable, permanent and temporary. One type of such connections is long-term potentialization, when frequent stimulation of a neuron that «receives» an impulse increases the strength of its response.

At the biochemical level, this is manifested in the fact that receptors for signaling substances (neurotransmitters) on the surface of the «receiving» neuron have increased density and ionic conductance. However, this is only one of the few described mechanisms of memory.

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This mechanism was discovered relatively recently, but since the middle of the twentieth century, scientists have been trying to invent substances (or schemes for their reception) that would increase people's ability to memorize, or activate the brain 100%.

Usually amphetamine derivatives and other psychostimulants were used for this purpose: it was believed that after increasing vigilance and reaction, the transfer of information from short-term memory to long-term memory would also improve. As it turned out, this is not quite true: information learned under psychostimulants is retained in memory only for a short time.

In practice, it looks like this - the student learned something, brought it to the exam and almost immediately forgot it.

Fun fact: medicines that inhibit memorization have been known since antiquity. An example is Atropa belladonna — the plant from which atropine was first isolated. In addition, the first antipsychotics (chlorpromazine) and antihistamines (antegran), which were known from the 1940s-1950s, also made memorization much more difficult.

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Piracetam and the emergence of nootropics
This changed in the 1960s when Romanian chemist Corneliu E. Giurgea invented piracetam and introduced the term «nootropic» into the classification of drugs.

According to Corneliu Giurgea, a nootropic drug should have the following features:
  • Improvement of memory and learning processes;
  • Protection against adverse factors (electrical seizures, shock, hypoxia) and the effects of chemicals (e.g. barbiturates or cholinolytics like scopolamine) that negatively affect memory processes;
  • Enhancement of cortical and subcortical functions;
  • Absence of effects inherent in other groups of drugs (stimulation, sedation);
  • Extremely low toxicity.
Strangely enough, most of these properties apply to piracetam. But this is not accurate: according to current data, piracetam only protects against hypoxia and electric shock.

«Nootropic» properties and ability to accelerate recovery in ischemic stroke piracetam is shown only in meta-analyses of clinical trials. In fact, this is another violence against statistics, when primary patient data are not available for analysis and the data are «adjusted» to the desired result.

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Basically, piracetam (especially in the amounts that students use) does more harm than good: it reduces blood clotting factor levels by 30-40%.

Pseudostimulant Phenylpiracetam
You all know such a «pharmacy stimulant» as Phenylpiracetam. Many suggestible people have even compared its effect with classic psychostimulants, describing its «very strong psychostimulant» property, but this is a lie.

Indeed, phenylpiracetam is a nootropic: it indirectly increases the density of NMDA-receptors and thus accelerates the formation of long-term potentialization.

But the «aggression» is due to the fact that it directly acts on nicotinic cholinoreceptors: their activation promotes the release of catecholamines (mainly norepinephrine) from the adrenal glands into the blood.

One pity: the drug was withdrawn from production in early 2018 due to patent disputes between the inventors and the manufacturing company. The essence of the claims was that the company refused to develop new dosage forms of phenylpiracetam. Although there are rumors that the creators have several tested supernootropics in stock, which are waiting for their time to enter the market.

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Memantine is also worth mentioning - many people consider it a nootropic because it is prescribed to elderly people in the severe stages of Alzheimer's disease. Its effect on a healthy brain is negligible.

And if we take into account the fact that by structure it is a «little brother» of midantane (and binds to dopamine receptors almost better than to NMDA), then users of high doses instead of improving the ability to remember may get liver damage and psychosis with hallucinations.

Other interesting substances
And now it's time to move a little away from what's available in pharmacies, towards things you can, at your own risk, order online. I'll warn you right away: many of the substances that will be described below have only been tested on a narrow sample of unofficial volunteers. Effects are subjective, harm is unknown, and dosages are by eye.
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Luzindole — is an antagonist of melatonin receptors: a person does not want to sleep, his brain simply loses the feeling of need for sleep. Naturally, during this period of wakefulness (2-3 days) a person can learn quite a large amount of information without much harm. In addition, the user will not experience withdrawal syndrome after and hyperactivity during the period of action, because the synaptic pool of neurotransmitters in this case is depleted much more slowly than when using psychostimulants.

Also worth mentioning in the list of experimental drugs is a promising group of «hypermnesthetics», or rather, two of its representatives - PRL-8 and IDRA-21. I would not recommend the first of them: the mechanism of action is unknown, there is no data on toxicity in constant use and, most dangerous of all, it is not proven that it protects the ability to remember from unfavorable factors, i.e. it does not remove the negative effect of scopolamine on memory.

IDRA-21 - protects against amnesia caused by scopolamine, has a clear and understandable mechanism of action. But in overdose it turns into a neurotoxic substance causing neuron death from impaired calcium metabolism (so-called excitotoxicity).

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If you still like to drink and often expose your brain to extremely wide-ranging adverse effects (such as ethanol metabolites or stress), LM22A-4 may help. To date, it is the only inducer of BDNF synthesis, which protects nerve cells from the direct impact of neurotoxic substances and whose efficacy has been experimentally tested.

But the next substance, although it has a positive effect on neurogenesis, but in doses of 0.5-3 mg it has a devastating effect on the psyche and perception of reality. It is DOI, aka 2,5-dimethoxy-4-iodoamphetamine. In the course of research, scientists found out that this substance promotes the formation of so-called «dendritic spines» - preparations for the synapse, the basis of communication between neurons. Unfortunately, there are no known doses of the substance that would increase synaptic plasticity without producing hallucinogenic effects.


As a conclusion, we can add that the miracle pill for the brain is a myth, and if a person is just a fool, he will not be helped by all the power of modern pharmacology.
 

Frit Buchner

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Cranston

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Phenibut surely is phychoactive and can be habit forming too.
Fasoracetam is phsychoactive, too.
High doses of Niacin (Vitamine B3) is interesting, too. There is one form that creates funny flushes in the face :)
 

cascade

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Cranston

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What was your experience with fasoracetam? I may have noticed some enhanced active recall, but other than that (which I'm not sure was real in itself) I noticed no overt psychoactivity. Tried dosages ranging from 5mg-1g, & tried in combination with a cycle of aniracetam & coluracetam -- no results to write about.
cascadeFasoracetam is said to be a GABA-B antagonist. So the idea was to reduce GABA-B* tolerance.
One may think that the effect of Fasoracetam should be uncomfortable like a GABA-B withdrawal, but they are not.
Probably there is much more going on with Fasoracetam.


*Examples of GABA-B agonists: GHB, Baclofen, Phenibut and of course, albeit only partly: Alcohol.
 

jetes

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I'm looking for a source for phenibut. Doesn't seem to offered on the usual marketplaces
 

cascade

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Cranston

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I always buy from https://nootropicsource.com/. They have F-phenibut too which personally I find indistinguishable from regular phenibut besides the roughly 5-fold increase in potency. I always go with the fluorinated because it seems like more bang for your buck and you don't have to consume such massive amounts of a chemical by weight. Many people find the two very different qualitatively, however, and there seems to be a general public preference more for the unsubstituted phenibut.

Definitely keep dosing to 2x per week max, the WDs with this one are not pretty. Take a scroll through r/quittingphenibut if you don't wanna take my word for it.
cascadeIf you convert the Phenibut HCL with Baking Soda into some other, non acid form, it's noticable stronger.
 

Cranston

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Do you know if the freebase is a solid powder and if it's deliquescent?
cascadeIt's white powder with doesn't solve well in water (in contrast to the HCL-Form).
Not sure if it is a freebase. There is a reaction with the baking sode where quite amout of CO2 is going out.
 

BlueDex

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I tried a whole lot of cognitive enhancers and some have permanently enhanced most parts of cognition, but not much help with ADHD. The only ones that help with ADHD are stimulants, wakefulness enhancers, and selegiline. D,L-Deprenyl might help more. When I take Modafinil, Armodafinil, Prolintane, Methiopropamine (MPA), Ethiopropamine (EPA), Flodafinil (Flmodafinil), Hydrafinil (Fluorenol), 3-FA, and more, I remember more and focus more. Exercise and good eating habits help too. I ate a lot of fish and sometimes crabs and stuff growing up and went fishing with dad and brother. Fish has Omega 3's. 2-methyl-2-butanol is a good alternative to ethanol because it doesn't have a hangover. Also, I like Kratom.
 

BlueDex

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I enjoyed Weed sometimes and Weed with Modafinil and Energy drinks. Usually alcohol. I want to combine Weed and Alcohol (Ethanol). I tried 2-methyl-2-butanol. Weed and 2-methyl-2-butanol. I also enjoyed Phenylpiracetam Hydrazide. I want to try Thiopropamine (TPA), Methiopropamine (MPA), Ethiopropamine (EPA), 3-FA (3-Fluoroamphetamine, and maybe Adderall, Ritalin, Modafinil, Sunosi, Armodafinil, Concerta, and Khat for ADHD. Also beer colored Crystal Speed! (Ethylamphetamine) Also, Kratom, Prolintane, 4F-MPH (4-Fluoromethylphenidate), A-PVP, a-PHP, Propylhexedrine HCl, and more.

Always stack stimulants with 7,8-Dihydroxyflavone (Tropoflavin)!
 
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