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Golden Thinker ® – Encyclopedia of Substances – Coluracetam

What is Coluracetam?

Coluracetam (BCI-540 or MKC-231) belongs to the racetam family of nootropic drugs. The compound was originally developed as a potential treatment for Alzheimer’s disease. However, in recent years, much of the neuroscience literature has focussed on the potential anti-depressant effects of the drug. There are also many reports that Coluracetam many provide long-lasting cognitive enhancements and anti-anxiety effects.

Coluracetam is a fat-soluble molecule which is one of the more powerful of the racetam group of nootropics. As with many racetams, coluracetam’s main target of modulation is the cholinergic system. However, the compound exerts a unique effect. Instead of aiding in receptor acceptance of acetylcholine, coluracetam actually boosts the conversion of choline into acetylcholine.

Acetylcholine is sometimes referred to as the ‘learning neurotransmitter’ of the brain. Coluracetam increase acetylcholine synthesis through the high affinity choline uptake process. This mechanism increases the pool of acetylcholine available in the brain.

Coluracetam also appears to improve the function a major class of glutamatergic receptors, called AMPA receptors. These receptors play a vital role in the excitatory signalling system of the brain, and have known roles in plasticity, alertness and cognition.

This unique combination of increased acetylcholine and elevated AMPA receptor function has some powerful brain-boosting effects. Notably, coluracetam appears to improve mood without interacting the serotonin system.

The serotonergic system is often targeted by classical antidepressants. However, since serotonin is expressed all over the body, modulating serotonin levels to treat depression can have some undesirable consequences elsewhere.

Brain Benefits and Mode of Action
May Improve Cognition and Alertness

Coluracetam has been shown to improve cognition and memory in animal models.

In one study, researchers found that an 8-day administration of coluracetam reversed damage that had been experimentally induced in the cholinergic system. The study also found that learning and memory deficits which were associated with this damage were reversed too. Further research demonstrated that coluracetam was able to reverse acetylcholine deficits in mice. This reversal was accompanied with improvements in working-memory.

Since Alzheimer’s disease is characterised by a reduction of acetylcholine, many scientists suggest Coluracetam may provide an effective treatment. Coluracetam can increase levels of acetylcholine in the hippocampus, a brain region strongly involved in memory. This mechanism may aid in the recovery of cognitive and memory function

Mode of action: Coluracetam can provide support the acetylcholine synthesising enzyme ChAT by helping to increase the production of acetylcholine directly. This enzyme is known to be dysfunctional in a variety of psychiatric disorders, such as schizophrenia. Acetylcholine and the cholinergic system and vital in working memory, cognition, learning and mental focus. Increasing the function of this system is likely produce many cognitive benefits.

A study using human-derived stem cells suggested that coluracetam may stimulate the growth of new neurons, a process known as neurogenesis. Researchers from this group suggested that stimulating neurogenesis may also play a part in the cognitive enhancements induced by coluracetam.

May Boost Mood and Fights Depression

Coluracetam interacts with a major subclass of glutamatergic receptors called AMPA receptors. Modulation of these receptions can alter excitatory activity in the brain.

One of the hallmarks of depression, especially cases which are difficult to treat, is dysfunction to the glutamatergic system.

One human study investigated 101 patients with depression which had be untreatable with at least two types of classical anti-depressant drugs (for example, serotonin reuptake inhibitors). In this study, patients were administered 80mg of coluracetam three times per day. The researchers found that Coluracetam supplementation significantly improved depression symptoms and improved the patient’s perception of their quality of life.

The researchers suggest that coluracetam ability to modulate excitatory activity and reduce glutamate induced excitotoxicity may underlie these effects. Further neuroscience review articles have cited coluracetam as a potentially exciting new therapy for depression.

How to Use

Coluracetam is a compound which isn’t found in any foods and our bodies cannot produce it. Hence, the only way to yield the benefits of this molecule is through supplementation.

Coluracetam is typically sold in powder or capsule form and can be taken orally. Doses can also be taken sublingually (under the tongue) for faster and more efficient absorption.

Since coluracetam is a particularly powerful agent, it’s advisable to start with the lowest effect dose. If you find you need to increase the dose to feel the benefits, this should be done so gradually and should not exceed 80mg.

Coluracetam is non-toxic and considered safe and well-tolerated.

There are only a few rare side effects associated with the compound, such as anxiety, headache, fatigue and nausea. These side effects are rare and usually only occur when there is not a large enough precursor pool of choline to be used for acetylcholine synthesis. This is why we recommend start the synthesis-increase coluracetam with a choline level enhancer such as citicoline.

Coluracetam can interact with some drugs, especially those that interact with the NMDA receptor. This includes cough suppressants and anaesthetics. Other substances which interact with the cholinergic system, such as glaucoma medication and nicotine, may also interact with the effects of coluracetam. Coluracetam can counteract the effects of anti-cholinergic drugs (such as some Benadryl, some antipsychotics and Parkinson’s medications).

As with any supplement, if you’re on medication or have an underlying health condition, it is sensible that you speak to your doctor before starting any supplement regime.

Stacks well with
  • Coluracetam is a fat-soluble molecule, so it’s best stacked with a healthy fat such as coconut or MCT oil.
  • Coluracetam should also be stacked with a choline supplement such as citicoline. Citicoline increases the pool of available choline for synthesis. The stack can create powerful effects by increasing available choline (citicoline) and the ability to synthesise it into acetylcholine (coluracetam).
Recommended Dose: 5-80mg per day

We recommend between 5-80mg of coluracetam per day.

The safe upper limit for coluracetam is 80mg per day. However, we recommend staying with 35mg per day as the consequences of higher doses have not yet been fully examined in humans.

It’s optimal to split these doses into a morning or afternoon dose. For example, a 20mg dose of 10mg in the morning and a further 10mg in the afternoon.

As previously mentioned, you should start at the lower end of the dosing scale. Beginning of the lowest effective dose will decrease the likelihood of experience any negative side effects.

Classification: Cognition, Energy, Mood

We’ve classified coluracetam as a robust cognitive and energy enhancer. This is because a variety of studies have shown that coluracetam can exert important increases in acetylcholine and improve function of the cholinergic system. This system is vital for memory, learning, focus and alertness.

We also suggest coluracetam may significantly boost mood without interfering with the serotonin system. This is because coluracetam has the ability to regulate AMPA receptor function and stabilise excitatory activity within the brain.

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  2. Brauser D. “Neurogenesis-Stimulating Compounds Show Promise in the Treatment of Major Depression” Medscape Medical News September 21, 2009
  3. Bessho T., Takashina K., Eguchi J., Komatsu T., Saito K. “MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats.” Journal of Neural Transmission (Vienna). 2008 Jul;115(7):1019-25.
  4. Machado-Vieira, R., Henter, I. D., & Zarate, C. A., Jr (2017). New targets for rapid antidepressant action. Progress in neurobiology, 152, 21–37. https://doi.org/10.1016/j.pneurobio.2015.12.001
  5. Murai S., Saito H., Abe E., Masuda Y., Odashima J., Itoh T. “MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.” Journal of Neural Transmission General Section. 1994;98(1):1-13.
  6. Philippe Taupin (2009) Nootropic agents stimulate neurogenesis, Expert Opinion on Therapeutic Patents, 19:5, 727-730, DOI: 10.1517/13543770902721303
  7. Ray B., Bailey J.A., Simon J.R., Lahiri D.K. “High-affinity choline uptake (HACU) and choline acetyltransferase (ChAT) activity in neuronal cultures for mechanistic and drug discovery studies.” Current Protocols in Neuroscience. 2012 Jul;Chapter 7:Unit 7.23.
  8. Takashina K., Bessho T., Mori R., Eguchi J., Saito K. “MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats.” Journal of Neural Transmission (Vienna). 2008 Jul;115(7):1027-35.
  9. Talih, F., & Ajaltouni, J. (2015). Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases. Innovations in clinical neuroscience, 12(11-12), 21–25.
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