More Nootropics: Racetams and Glycinergics

A large amount of somewhat poorly researched compounds

This week brings about a large amount of updates in the nootropic category. The glycinergics, the racetams, and some various herbs.

The glycinergics are those molecules that can bind to what is known as the 'glycine binding site' of a particular subset of stimulatory receptors (NMDA), and it seems that by stimulating this binding site the overall signalling is increased. There is also a depressant receptor known as the glycincergic receptor which can also respond to these molecules, so they serve a neuromodulatory role of sorts.

The glycinergics updated this week include:

  • Glycine as the most basic glycinergic (glycinergic being named after it), but supplemental doses are impractically high.

  • D-Serine as a more potent derivative, which appears to actually be useful in supplemental dosages that are feasible (2g or so).

  • Sarcosine which is inherently a weak glycinergic, but sort of works as a glycine reuptake inhibitor and increases levels of both glycine and D-serine.

The molecules have potential benefits for cognitive states characterized by NMDA underactivity (schizophrenia, depression, and cognitive decline) and although they are not well studied in healthy controls they may possess nootropic properties. Glycine is unlikely to be a good supplemental intervention, whereas D-serine and sarcosine are better options.

The racetams updated this week (previously we only had Piracetam and Noopept) include:

  • Oxiracetam, a structurally similar and slightly more potent derivative of piracetam.

  • Pramiracetam, a very understudied cognitive enhancer, possibly increases the choline transporter and promotes acetylcholine formation.

  • Coluracetam, a potent choline transport promoter only in models of cognitive decline (not likely capable of doing so in healthy controls).

  • Phenylpiracetam a phenylated derivative of piracetam. Also understudied, but appears to be stimulatory and has been used by athletes to increase cold-resistant.

  • Nefiracetam, a relatively potent cognitive enhancer similar to Aniracetam in structure and actions and working mostly through augmenting acetylcholine signalling.

  • Sunifiram is not actually a racetam compound (although derived from piracetam) that also appears to be similar to nefiracetam.

This list is mostly complete, aside from notable exceptions (aniracetam is not yet completed due to the large body of evidence needing to be covered, and levetiracetam has not yet been investigated), and while oxiracetam and nefiracetam seem to have enough evidence to support their safety and usage in humans the other compounds are not studied enough to draw conclusions.

Finally, some other random herbs have been added:

  • Eucommia ulmoides (Rubber Bark Tree) currently cannot be recommended, as its leads (fat metabolism and augmenting steroid signalling) are quite understudied. It does hold promise as a fat burner, but perhaps the most interesting bit is its augmentation of testosterone and estrogen signalling, which is said to be solely due to caprylic acid (ie. the main fatty acid of Coconut Oil).

  • Emblica officinalis (Indian Gooseberry) is a longevity and cognition promoting berry from Ayurveda medicine, and while it seems to currently be seen as a basic antioxidant compound that can prevent the rate of cognitive decline, it has also been associated with improvements in cognition (in young and otherwise healthy rodents) and the potency of this berry in increasing lifespan in fruitflies seems to exceed other supplements (83% increase in average lifespan). Pending future research, this berry could be a very promising health booster and longevity agent.

  • Scutellaria baicalensis (Skullcap) has some surprisingly potent molecules in it, and oral ingestion of low levels of this plant to rodents (no human evidence currently) seem to have neuroprotective and neurogenesis capabilities, with one compound (Oroxylin A) being effective in isolation at promoting memory formation in young rats at a very low dose possibly found in the herb (about 24mg for a human). Other molecules seem to be agonists at the benzodiazepine binding site and may induce anxiolysis, but since they have a limit on how much they can signal through they currently are not associated with sedation nor addiction.

We've been heavily researching the brain, and more is to come in the upcoming weeks.

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