Coluracetam-anti-anxiety and lifts mood

Coluracetam

David Tomen
Author:
David Tomen
11 minute read
Coluracetam has been shown to boost long-term & working memory, relieve depression & anxiety, and enhance color & sound perception

Key Takeaways

  1. Coluracetam is a fat-soluble nootropic, more potent than Piracetam, in the racetam class.
  2. It boosts brain choline conversion to acetylcholine (ACh), improving learning, memory, alertness, and attention.
  3. Coluracetam may act as an ampakine, producing stimulant-like effects without typical stimulant side effects.
  4. It exhibits anxiolytic qualities and has potential in treating depressive disorders without affecting serotonin levels.
  5. Benefits include restoring acetylcholine synthesis, improving memory, relieving severe depression and anxiety, repairing retinal and optic nerve damage, and enhancing mood and cognition.

Coluracetam (BCI-540, or MKC-231) is a fat-soluble nootropic in the racetam-class of compounds. Coluracetam is much more potent than the original racetam, Piracetam.

Coluracetam was patented by Mitsubishi Tanabe Pharma of Japan in 2005. Making it one of the newest racetam-based nootropics.

The patent for Coluracetam was later sold to BrainCells, Inc. in San Diego, California. BrainCells is a small, privately-held biopharmaceutical company specializing in developing compounds for the treatment of major depressive disorder (MDD), treatment resistant depression (TRD), and Alzheimer’s Disease.

Coluracetam is similar in structure to Piracetam. And like all racetam nootropics, has a pyrrolidone nucleus at its core. The latest clinical research indicates potential for treating depressive disorders, and retinal and optic nerve damage.

Coluracetam is a very strong choline targeting supplement. It boosts your brain’s choline conversion to acetylcholine (ACh) through the high affinity choline uptake (HACU) process. Which increases alertness, attention to detail and memory.

Some research, and personal experience shows Coluracetam may affect AMPA receptors. Making it a potential ampakine nootropic. Which could explain the stimulant-like effects without the side effects of traditional stimulants.

Coluracetam also shows some anxiolytic (anti-anxiety) qualities helping improve mood and quieting anxiety.

Coluracetam helps:

  • Brain Optimization: Coluracetam is a choline uptake enhancer which boosts the effects of choline in your brain. It increases the production of acetylcholine (ACh) through HACU. Resulting in better learning and memory.[i]
  • Neurotransmitters: Coluracetam reduces glutamate toxicity in your brain.[ii] Which boosts neural signaling by increasing the effectiveness of glutamate. Resulting in better focus and concentration.
  • Mood & Anti-anxiety: Coluracetam is effective in treating anxiety and depression. Even in people suffering from major depression and who do not respond to SSRI’s.

Overview

Coluracetam is in the racetam-family of nootropic compounds. It is a fat-soluble nootropic. The racetam-class of nootropics share a pyrrolidone nucleus at their core.

Coluracetam is a High Affinity Choline Uptake Enhancer

Coluracetam chemical structure
Coluracetam

Coluracetam is unique among the racetams in the way it targets choline in the brain. It boosts your brain’s choline conversion to acetylcholine (ACh) through the high affinity choline uptake (HACU) process.

Pramiracetam is the only other racetam that has a similar mechanism of action. By influencing the HACU process.

Coluracetam is one of the newest synthetic nootropic compounds. It is known for improving long-term memory and mood. And for enhancing sounds and color.

Coluracetam is considered to be much more potent than Piracetam. And suggested doses are much smaller – often in the 3 – 10 mg range.

Coluracetam helps increase attention span, alertness and boosts long-term memory.

Coluracetam acts like an ampakine nootropic although this hasn’t been verified in clinical trials. Ampakines tend to have a stimulant effect. But do not produce the same stimulant side effects as Ritalin or coffee.

Coluracetam enhances color vision

Coluracetam vs. Piracetam: What’s the Difference?

Piracetam, the original racetam that started the nootropic movement, is a cyclic derivative of GABA. It affects the neurotransmitter acetylcholine (ACh) by helping ACh receptors accept, or be more sensitive to acetylcholine.

Coluracetam also boosts acetylcholine in the brain. But through a different mechanism of action. Rather than making the ACh receptors more sensitive to ACh, it actually increases the synthesis of acetylcholine from choline. By affecting the high affinity choline uptake (HACU) process.

How does Coluracetam Work in the Brain?

Coluracetam boosts brain health and function in several ways. But two in particular stand out.

  1. Coluracetam boosts your brain’s choline uptake by targeting and working with the high affinity choline uptake (HACU) process in the brain’s neurons.

Acetylcholine (ACh) is made up of choline and acetate. These must be available to the neuron terminal at all times. So that ACh can be synthesized whenever it is needed.

Free choline circulating in the blood crosses the blood-brain barrier. And is taken up by cholinergic neuron terminals. It gets taken into the neuron by the high affinity choline uptake (HACU) system.[iii]

The synthesis of ACh takes place in the synaptic cleft. The space between neurons as it travels into the neuron. In animal experiments, Coluracetam has been shown to reverse decreased hippocampal acetylcholine induced by a reduction in high affinity choline uptake.

The HACU system is temperature-, energy-, and sodium-dependent. This system is the primary means by which choline needed for the synthesis of ACh is transported into the neuron. And is the rate-limiting step in the production of this critical neurotransmitter.[iv]

Coluracetam improves memory & brain fogWhen this system breaks down or doesn’t work as efficiently as it was designed, you experience problems with memory, learning, and brain fog.

Coluracetam effects this process (ameliorates working memory deficits) and helps it work more efficiently. In fact, it seems to boost the HACU process. Even in damaged neurons.

Increased acetylcholine in neurons helps improve memory, boosts cognition and provides better decision-making capabilities.

  1. Coluracetam also seems to improve AMPA potentiation. AMPA receptors are affected by glutamate. Which works in the brain and central nervous system to improve alertness and cognition.

Coluracetam works with both AMPA potentiation and choline uptake enhancement. This combination seems to help improve mood disorders without affecting serotonin levels.

Serotonin Selective Reuptake Inhibitors (SSRIs) is the current preferred mainstream medical method for dealing with mood disorders and depression. They come with a list of detrimental side effects. And don’t work for every depressed patient.

Researchers reported that Coluracetam was beneficial in treating major clinical depression and anxiety disorder.[v] Without affecting serotonin levels in the brain. And without the side effects that go with disrupting serotonin.

How things go bad:

As we get older, our brain chemistry and energy metabolism changes.Coluracetam is anti-anxiety and lifts mood

↓ Brain cell membranes degenerate

Recall, reaction time and mood diminish

↓ Conversion of choline to acetylcholine breaks down

↓ Acetylcholine levels decline

All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more.

So Coluracetam can help mood disorders and age-related cognitive decline. But it works as well for the student looking to do better in school. By boosting acetylcholine and controlling glutamate in the brain.

Coluracetam benefits

Research from a very limited number of studies have shown that Coluracetam will:

  • Restore the synthesis of acetylcholine
  • Restore long-term memory
  • Improve working memory
  • Relieve symptoms of severe depression
  • Treat symptoms of generalized anxiety disorder
  • Increase choline uptake even in damaged neurons
  • Repair retinal and optic nerve damage

The benefits from supplementing with Coluracetam seem to be long-lasting. Even after supplementation has stopped.

How does Coluracetam feel?

Even with very small doses of Coluracetam you should experience a decrease in anxiety and improved mood. Overall energy levels should go up.

Unlike the effect commonly produced by stimulants, Coluracetam offers a more relaxed, calm and free-minded kind of thought-processing.

Coluracetam acts quickly to boost long-term and working memory and word-recall. And many nootropic-users report that colors are crisper, or enhanced. Sound and audio seems to wash through you.

Some even report that Coluracetam enhances meditation. There is an extremely pleasant sense of being at peace with the world.

Coluracetam enhances music and vision

Coluracetam Clinical Research

Coluracetam was first discovered the late 1990’s. And because it’s so new, very few clinical trials have been done with humans. Most of the clinical research available to us has been done on animals.

BrainCells, Inc., who acquired the patent from the company that first developed Coluracetam, have begun human trials. Here we have two examples of the clinical research done in the last 15 years on animals.

Coluracetam Provides Long-lasting Cognitive Improvement

Researchers in Japan worked with rats whose memory was chemically impaired. In this study, rats were dosed with Coluracetam (MKC-231) for 8 days.

The team studied the effects on the high affinity choline uptake (HACU) system of the rats after 8-days of repeated administration of Coluracetam treatment.

They reported an increase of HACU activity along with a boost in cognition. And concluded that Coluracetamcould induce long-lasting pro-cognitive effects by changing the choline transporter regulation system”.[vi]

Coluracetam Improves Working Memory

A study at Iwate Medical University in Japan was done on mice with working memory deficits.  In this study, scientists found that Coluracetam improved working memory at all doses tested.

They found it significantly reversed an acetylcholine deficit. And concluded that Coluracetam improved memory deficits by boosting high affinity choline uptake (HACU), and the release of acetylcholine.[vii]

Coluracetam Dosage

Recommended Coluracetam dosage is 20 – 80 mg per day. So 20 mg would be taken in two 10 mg doses. One Coluracetam dose in the morning, and one in the early afternoon.

Higher doses of Coluracetam are based on clinical trials mostly done on animals. When first adding Coluracetam to your stack, most neurohackers start out with a much smaller dose. And see how you react to it.

Coluracetam dosed sublinguallyColuracetam is typically sold in powder form. Smaller doses are often taken sublingually for faster and better absorption.

Since Coluracetam is a fat-soluble nootropic, you should take it with a meal containing healthy fats. Or with a tablespoon of unrefined coconut oil.

My preferred healthy fat is a tablespoon of the new organic, non-GMO Performance Lab® MCT Oil.

Coluracetam Side Effects

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

Many first-time users of Coluracetam report fatigue which is often the result of starting with too high a dose.

Remember, Coluracetam works by enhancing choline uptake in your brain. Choline is a precursor to the production of acetylcholine. If not enough choline is available in your system, you’ll feel the side effects.

Side effects are rare but can include anxiety, fatigue, headaches, nervousness and nausea. Again, side effects are often a result of unusually high doses of the nootropic.

Headaches from using Coluracetam typically happen when you forget to combine it with a good choline supplement. Headaches are often a symptom of a choline deficit in your brain.

Where to buy Coluracetam

Coluracetam is usually sold in powder form. A couple of companies offer it in a liquid base making it easier to dose and take sublingually.

The best place to buy Coluracetam is: Science.bio – Coluracetam who sell Coluracetam as a “research” compound. It is sold to be used in an academic laboratory research setting. They go on to state “nothing we sell is intended for nor is it manufactured for diagnostic or therapeutic purposes in humans.”

Nootropics Expert Recommendation

Coluracetam 20 – 80 mg per day

Nootropics Expert Tested and ApprovedI recommend using Coluracetam as a nootropic supplement.

Your body does not make Coluracetam on its own. So to get its benefits you must take it as a supplement.

Coluracetam is unique among racetams because it is a high affinity choline uptake (HACU) enhancer.

Coluracetam is especially helpful for restoring long-term memory, boosting cognition and better decision-making. All benefits associated with improved choline uptake into neurons. And the improved synthesis of acetylcholine.

Coluracetam also has a strong, albeit brief history of treating major depression. For the healthy neurohacker you’ll get the benefit of a sense of contentment and peace.

And as an added bonus, the extra choline activity affects optic nerves. So you may experience enhanced colors and sound.

The positive effects of Coluracetam appear to be at least semi-permanent. The benefits continue even after it leaves your system.

You should use Coluracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost acetylcholine synthesis, so demands the presence of more choline in your brain.

Clinical trials say you can safely boost daily intake of Coluracetam to 200 mg for major depressive disorder if needed. But we suggest starting with 20 mg per day. And increasing your doses only after you see how it works in your system.

And Coluracetam is a fat-soluble nootropic so for proper absorption into cells must be taken with a healthy fat like unrefined coconut oil, or extra virgin olive oil. My preferred healthy fat is a tablespoon of the new organic, non-GMO Performance Lab® MCT Oil.

The best place to buy Coluracetam is Science.bio – Coluracetam

NOTE: Science.bio states on their FAQ page, “Our products are manufactured and sold to be used in an academic laboratory research setting. Nothing we sell is intended for nor is it manufactured for diagnostic or therapeutic purposes in humans.” This statement is required because the FDA has not  classified nor approved Coluracetam as a “dietary supplement” in the USA.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] 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. (source)

[ii] Akaike A., Maeda T., Kaneko S., Tamura Y. “Protective effect of MKC-231, a novel high affinity choline uptake enhancer, on glutamate cytotoxicity in cultured cortical neurons.” Japanese Journal of Pharmacology. 1998 Feb;76(2):219-22. (source)

[iii] 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. (source)

[iv] “Uptake of Choline, a Precursor of Acetylcholine” Williams Collegewilliams.edu Retrieved May 3, 2016 (source)

[v] Brauser D. “Neurogenesis-Stimulating Compounds Show Promise in the Treatment of Major Depression” Medscape Medical News September 21, 2009 (source)

[vi] 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. (source)

[vii] 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. (source)

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Join The Discussion - 63 comments

Christian
September 28, 2023

Hi David.

From my understanding of your reviews of Pramiracetam and Coluracetam, it seems Pramiracetam sensitized acetylcholine receptors and Coluracetam does not (although they both increase choline to acetylcholine conversion). Am I understanding correctly? I’m just a bit confused since in your Coluracetam review, you mention headaches being a potential side effect due to choline deficit in the brain. I know a deficit in acetylcholine can cause headaches, but does this mean that even if you have enough acetylcholine in your brain, a lack of regular choline can cause headaches as well (due to Coluracetam turning it into acetylcholine)?

    David Tomen
    October 1, 2023

    Christian, Coluracetam boosts your brain’s choline conversion to acetylcholine (ACh) through the high affinity choline uptake (HACU) process. That is assuming you have enough choline present to make that conversion. Which is the reason why I recommend using CDP-Choline or Alpha GPC with Coluracetam. You will likely get more benefit from this racetam by using a choline supplement. It is the same with Pramiracetam.

spudchick
September 4, 2023

Thanks for this article. I had a fantastic experience with coluracetam (from Pure Nootropics), particularly after a bad case of COVID apparently broke my brain for a while–I doubled up on dosage for a few weeks and it really helped with repair. It helped me with recall, processing speed and motivation as well as mood and anxiety, no side effects–really just a perfect fit for me after trying several other racetams with varying pros and cons. But it has become very hard to find, Pure Noots has been out of stock for over a year now. Wonder if you (with industry contacts maybe?) can find out more about why that is. Has Brain Cells Inc. sold the patent or something? I’ve gotten some in powder form from NutriVitaShop but it’s much more expensive due to scarcity and trying to make capsules with a consistent dosage is challenging.

This feels like a really valuable product that could be helping a lot of people with cognitive issues from illness, menopause, age etc. It gets overlooked by racetam enthusiasts who are usually taking a lot to get recreational or “limitless” effects but Coluracetam feels like it’s more about healing than hacking. And I really hope it’s not being held up by people trying to either compete with it or jack up the prices.

    David Tomen
    September 4, 2023

    Most in this community has a favorite racetam and uses them for the benefits they provide. Not many are looking for “limitless” effects because we learned long ago that it does not exist.

    The racetams are harder to find because of supply chain problems that started with the pandemic. And the FDA forced some sites to shut down because of health claims they were making which is not allowed here the good ol’ USA.

    The only other reliable supplier of Coluracetam who has it in stack is Science.bio and this is my affiliate link to their product: https://nootropicsexpert.com/go/science-bio-coluracetam/

      spudchick
      September 5, 2023

      Thank you, appreciate this link and plan to stock up right away. Yes, I believe it’s all about finding the perfect fit for your chemistry. Coluracetam is an every day maintenance and repair hero for me, but I do use some others when I have a lot of intricate work to knock out.

      Re: ‘limitless’, I was referring more to the broader attitudes I see on the web regarding racetams.
      Grateful to find your site yesterday. Thanks again for the link.

        David Tomen
        September 6, 2023

        I think you will find that Nootropics Expert is unlike any other website out there. We take a common sense approach to fixing or optimizing the brain around here. 🙂

Bebop
June 27, 2023

David, if you take Coluracetam does it even make sense to also take Noopept? I’ve taken Noopept with Alpha GPC and the word recall was evident – which is why that benefit of Coluracetam caught my eye. Do the effects of Coluracetam make Noopept unnecessary?

    David Tomen
    June 29, 2023

    Good question. But two very different compounds. Noopept stimulates dopamine receptors (D2 and D3) and acetylcholine nicotinic receptors. And Noopept also seems to modulate some serotonin receptors. And Noopept boosts the level of cycloprolylglycine (CPG), a dipeptide consisting of proline and glycine which acts as a modulator of acetylcholine transmission.

    Coluracetam on the other hand boosts the high affinity choline uptake (HACU) process which increases your brain’s choline conversion to acetylcholine.

    The effects compliment each other. So, as long as you are using CDP-Choline along with both you should enjoy the benefits of both. Look at the >benefits” section and the “how does _____ feel?” section of each review to see what I mean.

Anthony Smith
June 30, 2022

Hello David,

A few years ago, when I went back to college, I experimented with an Oxiracetam/Aniracetam stack that yielded significant benefits for memory and focus. I have also experimented with Pramiracetam because it’s more potent than Oxiracetam. The powder has a very pungent taste. Yuck!

Through more reading and research, I have recently learned about Coluracetam; I’m curious to know your thoughts on using Coluracetam instead of Pramiracetam if the key benefit sought is laser focus?

Best,

Anthony

    David Tomen
    July 1, 2022

    Anthony, see this article: https://nootropicsexpert.com/the-top-7-racetams-which-one-is-best/. Pramiracetam is likely the best choice for what you are looking for.

    Hacu
    March 30, 2023

    Pramiracetam has been shown to significantly increase HACU in the hippocampus, does coluracetam have exactly the same mechanism of action of HACU? Or are there any differences, such as is it more effective in other parts of the brain, or is the effect exactly the same?

      David Tomen
      March 31, 2023

      Hacu, both racetams convert choline to acetylcholine (ACh) through the high affinity choline uptake (HACU) process. But clinical studies haven’t detailed exactly which region of the brain Coluracetam affects. See my racetam article for a quick comparison: https://nootropicsexpert.com/the-top-7-racetams-which-one-is-best/. That article also links through to my full review on each racetam.

ken
June 23, 2022

Hi David,

It is good to combine with Noopept? or after a month of taking coluracetam next will be Noopept? which is better of two for students?

Thanks

    David Tomen
    June 24, 2022

    Ken, you could combine Noopept with Coluracetam. Just make sure you are using CDP-Choline each time you take it.

    Noopept is probably a better study nootropic than Coluracetam.

      Ken
      July 10, 2022

      Thank you for your response sir David

      I like with coluracetam it has a long lasting effect. How about noopept? It has a long lasting effect after long term of dosage? (Sample 3 months dosing of noopept)

      Thanks

        David Tomen
        July 10, 2022

        Ken, Noopept needs to be taken twice per day to stay in your system all day long. It will only provide its benefit the days you take it.

        Ken
        July 11, 2022

        Hi David

        Thank you for your fast response I will combined the two as you suggest to reap the benefits especially the long lasting effect of coluracetam

Aleksander
April 20, 2022

Hi David! I would like to know your opinion. Our Europe coluracetam vendor says two interesting things:

1) Every racetam that affect LTP need proper levels of ACH and glutamate to work. It’s important to me because I feel tired after nearly all racetams (although I add 600mg CDP + 500mg B5 + all cofactors possible) would L-Glutamine work in this direction? Or do you recommend something else for glutamate levels? Gaba is my dominant neurotransmitter so I assume glutamate might be lower.

2) They say coluracetam lasts 72h.

Thank you!

    David Tomen
    April 22, 2022

    Aleksander, glutamate attaches to receptors which opens ion channels allowing neurotransmitters to pass through the neuron wall. You can increase glutamate by supplementing with L-Glutamine.

    The recommended dosage for CDP-Choline is 300 mg. Recommended dose of Vitamin B5 is 5 mg per day. Try reducing those and see if it still makes you feel fatigued.

    If it does then the racetams are likely the wrong supplement for you.

Chris Darakjian
February 17, 2022

Hi David, I have been taking 20mg of Coluracetam for the past week, and yesterday I took 50mg of “coq10 phytosome” from science.bio. I have been having random headaches that are very short lived in random places around my head. Someone suggested that I take a vasodilator (so I took some ALA, Pine Bark, and magnesium l-threonate). But I’m not sure what is going on at the neurochemistry side of things, as I wasn’t expecting the coq10 to cross the blood-brain barrier and potentially interact with coluracetam, perhaps by supplying more ATP through bolstering mitochondria. Can you please give me your thoughts?

    David Tomen
    February 18, 2022

    Chris, headaches when using any of the racetams is called a “racetam-headache” and it is unique to the racetams. Because they affect how your brain uses acetylcholine.

    If you are deficient in acetylcholine while using Oxiracetam you’ll get a headache. This is why you need to take 300 mg CDP-Choline each time you use Oxiracetam. Your brain is telling you it needs more acetylcholine.

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