What is Coluracetam?
Coluracetam is a member of the racetam family of nootropics. Also known as MKC-231 and BCI-540, this compound was first studied back in the 1990’s as a potential therapeutic treatment for Alzheimer’s disease.
In 2010 it was researched as a potential treatment for those suffering from depression and anxiety by BrainCells Inc. The promise of this compound was such that California awarded BrainCells Inc a Qualifying Therapeutic Discovery Program Grant.
Despite promising results, this research was never published and BrainCells Inc. went out of business in 2014. This was the last company to study Coluracetam.
Today Coluracetam is commonly used as a nootropic for the purposes of boosting memory, enhancing learning, and helping promote a positive mood.
There is even some anecdotal evidence that it may help improve your vision and eye health, and some limited scientific evidence that it may hold promise as a therapeutic agent for Schizophrenia.
How Does it Work?
As a member of the racetam family, MKC-231 impacts the levels of the neurotransmitter acetylcholine (ACh) in the brain.
If you have taken a racetam nootropic before you are likely well versed in the numerous roles played by ACh. For those that aren’t so familiar, ACh is involved in memory formation, logical thinking, focus, and numerous other cognitive functions.
High-affinity choline uptake (HACU) is known to be the rate-limiting step of ACh synthesis. Coluracetam exerts many of its benefits through increasing HACU, and thus improving cholinergic hypofunction. This boost in choline facilitates the synthesis and release of ACh in the central nervous system. These effects were seen in both in vivo studies on rats and in vitro studies. (3,4)
One study dove deep to discover how exactly this drug was increasing HACU. What they found was that Coluracetam increases the numbers of cloned high-affinity choline transporters at the synaptic membrane. (4)
This drug may even provide benefits lasting longer than the period of time during which you take the drug thanks to its effects on the choline transporter regulation system. (2)
In a human study on depression that was never published, it was discovered that Coluracetam helps with the neurogenesis, helping new neurons to differentiate and survive. (8)
Another study on mice found that Coluracetam decreases glutamate toxicity. This may protect the NMDA receptors, which are critical for controlling memory and synaptic plasticity. (6)
Positive Effects and Benefits
Depression and Anxiety
In the only human study yet carried out, it was found that Coluracetam may help some patients who suffer from both depression and anxiety. (8)
In a Phase IIa clinical trial that was never published, 101 patients with both major depressive disorder (MDD) and anxiety underwent a six-week, randomized, double-blind, and placebo-controlled study to determine if BCI-540 helped to relieve these symptoms.
It was found that treatment with this compound resulted in a significant improvement for patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD). These benefits occurred without impacting serotonin levels as do the most common type of antidepressants on the market today, selective serotonin reuptake inhibitors (SSRIs).
Another study found a positive effect of this nootropic on anxiety. Rats were treated with either BCI-540 or the classical anxiolytic (anxiety fighting drug) diazepam and then subjected to tests to measure their anxiety response. The rats treated with BCI-540 improved by 20%, compared to only 12% by those treated with the classic anxiety medication. (9)
Memory and Learning
Numerous animal studies conducted over the last two decades have found evidence to support the use of Coluracetam for improving memory and learning. (1,2,3,4,7).
The first of these studies was published in 1994 and found that MKC-231 ameliorated deficits in working memory and reversed hippocampal ACh depletion in mice treated with AF64A, a model commonly used in the 1990’s to mimic the progressive degeneration of cholinergic neurotransmission found in Alzheimer’s patients. (1,11)
Following this study, many other animal models of ACh depletion found similar promising results (2,3,4,7).
In a series of three experiments on rats also treated with AF64A, it was found that treatment with MKC-231 increased high-affinity choline uptake (HACU) and ACh synthesis and release into the hippocampus. (2,3,4) These results were found in both in vitro and in vivo studies.
Improvement in cognition was excitingly found even after the drug had fully left the brain.
As still no human studies have been conducted, we must heavily rely on user experiences as well as our own to deduce how this drug impacts the memory and learning in humans.
In one animal study on Schizophrenia, it was found that Coluracetam may help to reverse the damage to ChAT that is characteristic of this disease (5).
ChAT is an enzyme critical to the production of ACh. If this same benefit is found in humans, Coluracetam may hold promise as a therapeutic drug for the treatment
Patents for this drug claim that it promotes neurogenesis, or the growth or new nerve cells. It is not yet fully understood how it does so, however it may be related to the boost of ACh in the hippocampus. (10)
May Help Vision
While there have yet to be any studies on this topic, many users report improved eyesight and more vivid colors when using this nootropic. One possible explanation could be the boost in neurogenesis. If this is the case, it may be able to help those who are currently suffering from macular degeneration, which can lead to diseases such as cataracts and glaucoma. This is highly speculative at this point.
Possible Side Effects
As there has only been one short-term human study conducted on this nootropic, we cannot definitively say what side effects are possible. That said, from the studies conducted on animals as well as the one human study, Coluracetam appears to be well tolerated.
In the one human trial Coluracetam was found to have side effects similar to that of the placebo group. This was at 80 mg orally one or three times daily. (8) Additionally, in one of the rat studies it was found that memory impairment was improved without any side effects.
As so little research has been conducted, one of the best ways to deduce the possible side effects is to comb through user reports. According to posts in Reddit and Longecity, those who have taken this nootropic have experienced depression, mental fatigue, suicidal thoughts, nausea, and some other one-off side effects.
In order to reduce the risk of side effects, be sure that you are taking in plenty of choline. You can do this either by eating foods rich in choline or by taking choline supplements. Some of the best sources of choline in food include:
- Brussel sprouts
As for choline supplementation, a good source are CDP-Choline supplements.
Dosage, Half-Life, and How to Take MKC-231
In the one human trial on depression, the group of patients who took 80 mg orally three times daily were the ones who saw results, not the once daily group. (8) This effect was witnessed at four weeks in. As results weren’t witnessed for four weeks, it may be best to take this supplement daily for at a minimum of four weeks to experience the benefits for mood.
Many users report beneficial effects at much lower doses. One user on Longecity reported, “5-6 mg orally was better for motivation, energy, concentration, and improvements on working memory than anything I had tried.”
Typically, recommended dosage starts at 3 mg and tops out at 30 mg. Coluracetam is normally sold as a powder than can be either taken orally or sublingually, however you will also find liquid suspensions intended for sublingual use. Sublingual application of this compound is common in order to avoid breakdown during digestion. If you do choose to take it this way, allow it to sit under the tongue before swallowing to increase the amount that is absorbed.
Coluracetam is a fat-soluble compound. In order to absorb it well, you should take it with food that contains fat, such as nuts.
This supplement has a half-life of about three hours.
When adding this supplement to your stack, it is advisable to start low and work up. If you experience side effects you can skip days or lower your dose to see how you respond.
Thanks to the boost in choline uptake when taking this supplement, it is best to stack it with a quality source of choline, such as CDP Choline or Alpha GPC.
Another option is to stack it with Centrophenoxine, another nootropic that helps to boost the level of choline available in your body.
Coluracetam vs. Noopept
You may be wondering, which is better, Coluracetam or Noopept?
While Noopept is not a racetam, it behaves very similarly to them. When comparing these two compounds, Noopept is less expensive and acts more as a mild cognitive and psychostimulatory boost. Coluracetam, on the other hand, improves memory, mood, and possibly vision.
They work in very different ways, with Noopept increasing nerve factor growth and brain-derived neurotrophic factor while Coluracetam boosts ACh through increasing HACU.
User Experiences and Reviews
Because the research into Coluracetam is still in its infancy, delving into user reviews can be helpful to see what you may experience.
Benefits that users have found include:
- Improved motivation
- Increased energy and stamina
- Heightened concentration
- Improved working memory
- Reduces anxiety
- Better mood
- Depression relief
- Increased alertness and lucidity
- Improved vision, taste, smell, and sound
- Stimulatory effects
- Increased sociability
Some of the side effects that users have attributed to this supplement include:
- Mood alterations (depression)
- Facial flushing
- “Strange tingly numbness” in hands and arms
- Brain fog
- Lack of energy
“The effect is extremely subtle when taken orally, but highly effective. It brightens mood and relaxation, in my own experience, but it is also so easy to measure out and take the proper dosage of this liquid form.”
-Christopher, Pure Nootropics, after purchasing the Pure Nootropics Coluracetam liquid oral suspension
“I’ve used it for months at a time, and it gets better the longer you use it. At around 5 or 6 weeks, with a standard 15mg or 20mg dose, I get a huge mood-lift and an increased sociability that I haven’t found in anything else I’ve tried. The motivation is also something else.”
-Clingingtothestars, Reddit on long-term Coluracetam experiences
“Coluracetam does seem to share some of the typical general effects a user can expect to experience upon consumption of the other Racetams...greater visual acuity, increased focus and attention, increased mental work capacity...However, it seems to impart a strong antidepressant effect.”
-Heraclitean, Longecity after two weeks of mainly 10 mg per day dosage
Where to Buy
As a member of the racetam family, it is currently legal to both buy and sell Coluracetam in the majority of countries, including the United States, Canada, and Australia. In the UK racetams are prescription drugs, however there is not a penalty for importing them or having them in your possession.
In order to ensure that you’re obtaining the highest quality supplement, it is best to purchase this and other nootropics through reputable online vendors, such as Pure Nootropics and Nootropics Depot.
Users report Coluracetam to be an effective nootropic with few side effects. While this supplement has not been as thoroughly studied as many of the other nootropics on the market today, the research that has been done is very promising in regards to memory, learning, depression, anxiety, and Schizophrenia.
While this is one of the lesser known nootropics, it has rapidly become a favorite among many nootropics users. Since it is a choline uptake enhancer, it is important to be sure you are consuming foods high in choline or that you add a choline supplement to your stack in order to get the most benefit and avoid side effects.
- MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice https://www.ncbi.nlm.nih.gov/pubmed/7710736
- MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats. https://www.ncbi.nlm.nih.gov/m/pubmed/18461272/
- MKC-231, a choline-uptake enhancer: (2) Effect on synthesis and release of acetylcholine in in AF64A-treated rats. https://link.springer.com/article/10.1007%2Fs00702-008-0048-1
- MKC-231, a choline-uptake enhancer: (3) mode of action of MKC-231 in the enhancement of high-affinity choline uptake https://link.springer.com/article/10.1007%2Fs00702-008-0049-0
- Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats. https://www.semanticscholar.org/paper/Subsequent-exposure-to-the-choline-uptake-enhancer-Shirayama-Yamamoto/6120d5234ec029f7c74c1bb6e46792f2f411b105
- Protective effect of MKC-231, a novel high affinity choline uptake enhancer, on glutamate cytotoxicity in cultured cortical neurons. 1998 https://www.semanticscholar.org/paper/Protective-effect-of-MKC-231%2C-a-novel-high-affinity-Akaike-Maeda/dd028556c6d67595f7443cb8e1c88032c7542949
- Effect of the novel high affinity choline uptake enhancer MKC-231 on deficits of water maze learning in rats. https://www.semanticscholar.org/paper/Effect-of-the-novel-high-affinity-choline-uptake-on-Bessho-Takashina/3eb13f55dfc09d600a4c335ff71c802a5d000f59
- BrainCells Inc. Announces Results from Exploratory Phase 2a Trial of CBI-540 in Depression with Anxiety https://www.evaluategroup.com/Universal/View.aspx?type=Story&id=216319
- 4-acylaminopyridine derivative mediated neurogenesis https://patents.google.com/patent/US20090088449
- Small molecules that promote neurogenesis in vitro https://www.ncbi.nlm.nih.gov/pubmed/18991809
- Modeling Alzheimer’s disease with non-transgenic rat models https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706888/
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