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Coluracetam (INN) (code name BCI-540; formerly MKC-231) is a nootropic agent of the racetam family. It was initially developed and tested by the Mitsubishi Tanabe Pharma Corporation for Alzheimer's disease. After the drug failed to reach endpoints in its clinical trials it was in-licensed by BrainCells Inc for investigations into major depressive disorder (MDD), which was preceded by being awarded a "Qualifying Therapeutic Discovery Program Grant" by the state of California. Findings from phase IIa clinical trials have suggested that it would be a potential medication for comorbidMDD with generalized anxiety disorder (GAD). BrainCells Inc is currently[when?] out-licensing the drug for this purpose.[full citation needed] It may also have potential use in prevention and treatment of ischemic retinopathy andretinal and optic nerve injury.[medical citation needed]
Coluracetam has been shown to reverse the loss of choline acetyltransferase production in the medial septal nucleus of rats exposed to phencyclidine (PCP), and is considered a potential therapeutic drug for schizophrenia.
Coluracetam is a new and unique member of the racetam class of synthetic nootropics. Originally developed as a potential treatment for Alzheimer’s disease and later considered as a treatment for depression and anxiety, coluracetam has become a popular nootropic known for improving mood, increasing motivation, and enhancing vision.
Coluracetam was first synthesized in 2005 by Japan’s Mitsubishi Tanabe Pharma Corporation as an Alzheimer’s disease treatment. After disappointing clinical trials, coluracetam was licensed to US biotechnology firm BrainCells Inc., which started testing the compound as a treatment for depression and anxiety. Though initial test results were positive and suggested that further study of coluracetam would be worthwhile, development was discontinued and BrainCells, Inc. closed in 2014. Coluracetam has been available for licensing since 2012.
Coluracetam acts primarily as a choline uptake enhancer that selectively affects memory function. It specifically enhances high-affinity choline uptake, increasing levels of the neurotransmitter acetylcholine by providing more of the choline from which it is made. Since acetylcholine is the neurotransmitter most closely associated with memory and cognition, it is believed that this function is the primary source of coluracetam’s nootropic capabilities.
Coluracetam is particularly potent and requires a much smaller dose than other racetam class nootropics. It’s fast-acting, reaching high levels in plasma within 30 minutes of ingestion, but within three hours levels are in decline.
Coluracetam is unregulated in the US and is sold as a dietary supplement, but its legal status varies from country to country. In Canada and the UK, it cannot be legally sold except by prescription, but it can be legally imported and possessed.
Coluracetam has been shown to improve cognitive function and memory in rats, and in theory, similar results may translate to humans.
In a 2010 animal study, coluracetam improved artificially-induced memory deficits without producing any significant side effects. The positive results were still apparent three days after the last dose, even though the serum concentration of coluracetam was negligible.
Some users say coluracetam dramatically improves short-term memory and free recall, increases memorization and recall abilities and enhances reading comprehension, and increases thought and learning speed and information retention.
The Phase 2a clinical trial of coluracetam suggested that it may be effective for treatment-resistant patients with both depression and anxiety.
The six-week placebo-controlled study, which was one of the few coluracetam tests involving humans, determined that a dosage of 240 mg (split into three daily doses of 80 mg) was useful in treating major depressive disorder (MDD) with co-morbid generalized anxiety disorder (GAD).
At the end of the test period, the overall treatment group and the placebo group scored similarly on scales for depression and anxiety, but there was a measurable improvement in the subset of treatment group participants who had both MDD and GAD, and who had previously failed an average of two antidepressants.
User reports on coluracetam’s effect on anxiety and depression vary considerably, with some saying it alleviates both and is a potent and reliable mood booster, while others say it can actually trigger depression and anxiety.
Coluracetam’s effect on vision is frequently reported by users, who say it enhances color vision, shape recognition, and optical vividness. Some users describe the effect as “HD vision”while others say it makes lights brighter and intensifies contrast.
Though enhanced vision is one of the most commonly reported benefits of coluracetam, there is no conclusive scientific evidence to explain or confirm this effect.
Like most racetam compounds, coluracetam works mainly by increasing levels of the neurotransmitter acetylcholine, which is strongly associated with learning, memory, and cognition.
The means by which coluracetam modulates acetylcholine levels is unique, however; while racetams typically trigger acetylcholine production by stimulating the appropriate receptors, coluracetam does so by enhancing high-affinity choline uptake, or HACU. The HACU system determines the rate at which choline is drawn into neurons for conversion into acetylcholine.
By increasing the rate at which choline is drawn into nerve cells, coluracetam promotes the production of acetylcholine and causes brain levels of this crucial neurotransmitter to rise. It has also been shown to create an increase in the high-affinity choline transporter molecule CHT1, which leads to the rapid availability of choline for uptake.
Together these actions lead to higher levels of acetylcholine, which are associated with enhanced cognition and memory.
Most of the research on coluracetam was done on animals rather than humans, so there are no universally accepted dosing guidelines. The active dosage range is generally described as 5–20 mg, though users report a wide range of doses taken both orally and sublingually.
Many users note that tolerance may develop quickly, but there is no research data on that aspect of coluracetam.
As is true with all nootropics, it’s generally best to begin dosing at the lower end of the range to determine your reaction to the substance and increase as necessary.
None of the animal or human studies on coluracetam documented any side effects.
The lack of adverse side effects was considered one of the most notable aspects of the animal study in which coluracetam was shown to offset artificially induced memory deficits in rats.
The most commonly reported side effect associated with racetam class nootropics is headache, which can often be eliminated by taking additional choline.
Coluracetam users have also reported intermittent nausea and daytime sleepiness as negative side effects, both of which were lessened by reducing dosage.
Like most racetams, coluracetam stacks well with a choline source, such as alpha GPC, for added memory and cognitive benefits.
The recommended doses for supplemental choline is 300–600 mg daily if you’re stacking with alpha GPC and 250–750 mg daily
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