Nootropics - Smart Drugs (Cognitive Enhancers)

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Nootropics (/noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks) are drugs, supplements, and other substances that may improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals.[1].


The word nootropic was coined in 1972 by a Romanian psychologist and chemist, Corneliu E. Giurgea, from the Greek words νοῦς (nous), or "mind", and τρέπειν (trepein), meaning to bend or turn.


While many substances are purported to improve cognition, research is at a preliminary stage as of 2018, and the effects of the majority of these agents are not fully determined.




Racetams, such as piracetam, oxiracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter.] The racetams have poorly understood mechanisms, although piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.




Piracetam is the proto-typical racetam drug: Mechanism of Action of Piracetam:


Piracetam influences neuronal and vascular functions and influences cognitive function without acting as a sedative or stimulant [P1].


Piracetam is a positive allosteric modulator of the AMPA receptor, although this action is very weak and its clinical effects may not necessarily be mediated by this action.[P2] It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability. Piracetam has been found to increase blood flow and oxygen consumption in parts of the brain, but this may be a side effect of increased brain activity rather than a primary effect or mechanism of action for the drug.


Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors, which are implicated in memory processes. Furthermore, piracetam may have an effect on NMDA glutamate receptors, which are involved with learning and memory processes.It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains.
 

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AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the AMPA receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system.[A1]


AMPAR PAMs have cognition- and memory-enhancing and antidepressant-like effects in preclinical models, and have potential medical applications in the treatment of cognitive impairment (e.g., cognitive symptoms in schizophrenia, mild cognitive impairment), dementia (e.g., Alzheimer's disease), depression, and for other indications. They can broadly be divided into low-impact and high-impact potentiators, with high-impact potentiators able to produce comparatively more robust increases in AMPAR activation. However, high-impact AMPAR PAMs can cause motor coordination disruptions, convulsions, and neurotoxicity at sufficiently high doses, similarly to orthosteric AMPAR activators (i.e., active/glutamate site agonists).


The AMPAR is one of the most highly expressed receptors in the brain, and is responsible for the majority of fast excitatory amino acid neurotransmission in the central nervous system (CNS). Low doses of AMPAR activators may nonetheless be useful, and AMPAR PAMs, which, unlike agonists, show selectivity for AMPAR subpopulations of different subunit compositions, may hold greater potential for medical applications.


Pharmacology
AMPAR PAMs bind to one or more allosteric sites on the AMPAR complex and potentiate the receptor. Unlike orthosteric (active/glutamate) site AMPAR activators, otherwise known as AMPAR agonists, AMPAR PAMs only potentiate AMPAR signaling in the presence of glutamate and hence do not activate the receptor directly/themselves. Moreover, whereas AMPAR agonists activate all AMPARs, AMPAR PAMs can show selectivity for specific subpopulations of AMPARs. This is because the AMPAR is composed of different combinations of various subunits, and the allosteric sites differ depending on the different subunit combinations.


AMPAR PAMs can be broadly grouped into two types based on their binding site and impact on AMPAR activation: low-impact (type I) and high-impact (type II).


Low-impact AMPAR PAMs have the following criteria:


Have little or no effect on the half-width of the field excitatory postsynaptic potential (fEPSP); and
Do not substantially bind to the cyclothiazide site on the AMPAR complex; and
Do not induce the expression of brain-derived neurotrophic factor (BDNF)


While high-impact AMPAR PAMs have the following criteria:


Substantially alter/increase the half-width of the fEPSP; and/or
Substantially bind to the cyclothiazide site on the AMPAR complex; and
Induce the expression of BDNF (brain-derived neurotrophic factor)
 

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Racetams
(From Wikipedia, the free encyclopedia)


[2-Pyrrolidone]


Racetams are a class of drugs that share a pyrrolidone nucleus.


Some, such as piracetam, are considered nootropics.
Some such as aniracetam, oxiracetam and phenylpiracetam are also nootropics.
Others such as levetiracetam and seletracetam are anticonvulsants.


Mechanism of Action
There is no universally accepted mechanism of action for racetams. Racetams generally show negligible affinity for common central nervous system receptors, but modulation of central neurotransmitters, including acetylcholine and glutamate, has been reported. Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam demonstrates nanomolar interactions. Modification of membrane-located mechanisms of central signal transduction is another hypothesis.[P-1]


Like some ampakines, some racetams such as piracetam and aniracetam are positive allosteric modulators of the AMPA receptor.


Racetams are understood to work by activating glutamate receptors that are colocalized with cholinergic receptors, thus increasing the frequency of activation of the latter.


Racetams are posited to enhance memory through interaction with cholinergic and glutamate receptors in the central nervous system.


Methylphenylpiracetam is a positive allosteric modulator of the sigma-1 receptor.


Cofactors
In studies with aged rats, marked improvement has been observed in cognitive tasks in experimental groups given piracetam. Performance was further increased with piracetam combined with cholines. Evidence in studies with rats has indicated that the potency of piracetam is increased when administered with choline.

Racetams generally show negligible affinity for common central nervous system receptors, but modulation of central neurotransmitters, including acetylcholine and glutamate, has been reported. Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam demonstrates nanomolar interactions. Modification of membrane-located mechanisms of central signal transduction is another hypothesis. Like some ampakines, some racetams such as piracetam and aniracetam are positive allosteric modulators of the AMPA receptor. Racetams are understood to work by activating glutamate receptors that are colocalized with cholinergic receptors, thus increasing the frequency of activation of the latter. Racetams are posited to enhance memory through interaction with cholinergic and glutamate receptors in the central nervous system. Methylphenylpiracetam is a positive allosteric modulator of the sigma-1 receptor.
 

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Sensory effects of Piracetam
Acuity enhancement
Auditory enhancement
Colour enhancement
Mindfulness
Tactile enhancement


Cognitive effects of Piracetam
Anxiety suppression or Anxiety
Dream potentiation
Focus enhancement
Irritability
Memory enhancement
Motivation enhancement
Thought connectivity
Wakefulness


Source: https://psychonautwiki.org/wiki/Piracetam#cite_note-1
 

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Motivation enhancement is defined as an increased desire to perform tasks and accomplish goals in a productive manner.[1][2][3] This includes tasks and goals that would normally be considered too monotonous or overwhelming to fully commit oneself to.


A number of factors (which often, but not always, co-occur) reflect or contribute to task motivation: namely, wanting to complete a task, enjoying it or being interested in it.[3] Motivation may also be supported by closely related factors, such as positive mood, alertness, energy, and the absence of anxiety. Although motivation is a state, there are trait-like differences in the motivational states that people typically bring to tasks, just as there are differences in cognitive ability.[2]


Motivation enhancement is often accompanied by other coinciding effects such as stimulation and thought acceleration in a manner which further increases one's productivity. It is most commonly induced under the influence of moderate dosages of stimulant and nootropic compounds, such as amphetamine,[2] methylphenidate (Ritalin) ,[2] nicotine, and modafinil.


However, it may also occur to a much lesser extent under the influence of certain opioids, and GABAergic depressants (eg. Xanax, Valium, and other Benzodiazepines)


Psychoactive substances within the Psychonaut Wiki psychoactive substance index which may cause this effect include:


2-Aminoindane
5-Hydroxytryptophan
A-PVP
AL-LAD
Adrafinil
Alpha-GPC
Amphetamine
Aniracetam
Armodafinil
Bromantane
Caffeine
Cocaine
Coluracetam
Creatine
Cyclazodone
Desoxypipradrol
Dichloropane
Ephenidine
Ephylone
Ethylphenidate
F-Phenibut
Hexedrone
Isopropylphenidate
Kratom
LSD
Lisdexamfetamine
MDA
MDMA
MDPV
 

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Pharmacology
Alpha-GPC breaks down into two key components, choline and glycerophosphate.


Choline and its metabolites are needed for three main physiological purposes: structural integrity and signaling roles for cell membranes as well as cholinergic neurotransmission (acetylcholine synthesis). This process essentially allows acetylcholine to accumulate at higher levels than it otherwise would. As acetylcholine is involved in the function of memory and other essential cognitive functions, this could potentially account for its nootropic effects.


Glycerophosphate, the other component, can also help with the production of cellular membranes, but this remains largely unstudied and is not well understood by the scientific literature.


Subjective effects
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.


Physical effects
Bodily control enhancement
Stimulation - The stimulation which alpha-GPC presents can be considered as primarily subtle and similar to that of caffeine.
Stamina enhancement
Headaches
Teeth grinding
Body odor alteration - This can be caused in some populations, especially those suffering from trimethylaminuria. Choline (a byproduct of alpha-GPC) is a precursor to trimethylamine, which those with trimethylaminuria are not able to easily break down, oftening resulting in smelling similar to fish.


Cognitive effects
Wakefulness - In comparison to citicoline, alpha-GPC manifests itself primarily in a physically stimulating manner over a mental stimulation.
Dream potentiation
Focus enhancement
Mindfulness
Memory enhancement
Motivation enhancement



Source: https://psychonautwiki.org/wiki/Alpha_GPC
 

AlphaMethylPhenyl

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Yeah nootropics work in that manner^

I can say for sure that MDMA/MDA has no utility in cognition. Cocaine isn't feasible either. Beyond being cardiotoxic, regular users get too spun to actually think, and it doesn't last nearly long enough.
 
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