The Original Nootropic
The concept of nootropics is quite new, dating back to the 1970’s when Corneliu E. Giurgea, a Romanian chemist and psychologist, coined the term. According to Giurgea, for a compound to be considered a nootropic, it had to adhere to a few criteria, such as:
● Enhancing learning and memory abilities
● Elevating acquired behaviors despite disruptive conditions
● Provides a neuroprotective effect
● Generally very safe
If you read through this list of criteria, you will quickly realize that lots of plants that have been used in ayurvedic and traditional Chinese practices for centuries already, also very closely adhere to this set of criteria. Some of these plants are particularly famous for their cognition enhancing properties, with a particular standout being Bacopa monnieri. In ayurvedic practices, it is referred to as a medhya-rasayana. Medha refers to intellect, and rasayana refers to rejuvenation. The concept of medhya-rasayana sounds very similar to the concept of nootropics, and unsurprisingly modern studies on medhya-rasayana herbs, are referring to these herbs as ‘nootropic herbs’ now! This means that while the formalized concept of nootropics is quite new, humans have already been using nootropic herbs for centuries!
While there are quite a few medhya-rasayan herbs, such as Centella asiatica and Celastrus paniculatus, Bacopa monnieri particularly stands out due to the sheer amount of modern day research on it. This is mostly due to one particular standardized Bacopa monnieri extract called CDRI-08.
In the 1970’s, which interestingly is around the same time Corneliu E. Giurgea coined the term ‘nootropic’, researchers at India’s Central Drug Research Institute (CDRI) realized that in order to properly study Bacopa monnieri, they needed a consistent research material. In order to achieve this, they dove into the science behind this fascinating plant, determining what compounds it contained and how to standardize them. During this research, they made lots of interesting discoveries, which eventually materialized as perhaps the world’s first standardized Bacopa monnieri extract. They named it CDRI-08.
Figure 2. Fresh Bacopa monnieiri, one of the most studied natural nootropics!
CDRI-08 completely changed the game for Bacopa monnieri research, allowing for the first time ever for organized human clinical trials to take place. Due to this, there is an enormous wealth of human research on Bacopa monnieri. At this point you may be thinking, I wish I could get my hands on CDRI-08! That’s actually surprisingly easy. Eventually CDRI-08 was commercially licensed, and it made its way onto the supplement market. In North America, CDRI-08 is currently known as Synapsa, which we have carried for many years! Synapsa is a unique extract, because according to many anecdotal reports it is one of the least lethargy inducing Bacopa monnieri extracts.
We were never totally sure why this was the case, but when we started to dive into our own Bacopa monnieri research project, we picked up on a few hints. For example, various research studies state that CDRI-08 is unique because it focuses not only on the bacosides, but also their metabolites: the bacogenins. To understand why this is important, we first have to dive into a bit of chemistry and pharmacokinetics!
A Scientific Adventure
Many years ago, before modern analytical chemistry became more accessible, it was oftentimes extremely difficult to pinpoint what exactly in a plant was producing benefits. This was certainly the case for Bacopa monnieri. However, eventually compounds from this plant were isolated and named. One of the first compounds that was isolated from Bacopa monnieri was called bacoside A. At the time, it was thought that bacoside A was a single compound. However, many years later we discovered that it is actually a mixture of bacoside A3, bacopasaponin C, bacopaside II and bacopaside X.
The reason why it was initially thought that bacoside A was a single compound is because the compounds which make up bacoside A are all saponins. This means that they have soap-like qualities, and like to stick together. This makes it very hard to separate these compounds from each other in an HPLC column, and in the early days of Bacopa monnieri research it was showing up as a single compound. As the analytical chemistry improved, another phenomenon started to emerge during sample preparation. It was found that some of these bacosides were hydrolysing and turning into different compounds, such as jujubogenin, pseudojujubogenin and the bacogenins.
All of the compounds that are collectively known as bacoside A are glycoside compounds. This means that they have a similar core structure, which then has various sugar groups attached to it in different locations. These sugar groups readily fall off during human metabolism, yielding their aglycone (no sugar groups) counterparts. The two main aglycones that are formed are jujubogenin and pseudojujubogenin. Due to their physically smaller size (the sugar groups make the molecules very big!) they have a much easier time absorbing. However, jujubogenin and pseudojujubogenin can be reduced in size even further via acid hydrlosis which occurs in the stomach, which yields a class of compounds known as the bacogenins. The bacogenins are even more bioavailable and produce drastically different effects. We go into this process in much more detail in our cognance blog if you are curious about learning more!
The Central Drug Research Institute (CDRI) was clearly aware of the metabolic fate of the bacosides and while it is unclear how they implemented this, studies do seem to hint at the fact that CDRI-08 was developed with controlled levels of these bacogenins present. Circling back to what we mentioned earlier in the blog, this could explain why synapsa is less lethargy inducing when compared to other Bacopa monnieri extracts.
When we were developing cognance, we wanted to closely mimic the metabolic processes in our body which turn the bacosides into their more active counterparts. We developed two different extracts during this research.
One extract performed mostly the first hydrolysis step, turning the bacosides into jujubogenin and pseudojujubogenin. When we beta-tested this novel extract, we all felt a strong calming GABAergic effect. This is not surprising when you consider that a very famous sleep promoting herb from traditional Chinese practices, Ziziphus jujuba, contains a compound called jujuboside A which during hydrolysis also turns into jujubogenin! Jujubogenin and pseudojujubogenin then turn into the bacogenins after further acid hydrolysis and we could not find any data suggesting that the bacogenins had strong GABAergic effects. Thus, we developed a second extract, which fully acid hydrolyzed jujubogenin and pseudojujubogenin into their bacogenin counterparts. When we beta-tested this extract, we noticed a distinct lack of lethargy inducing effects and a significant uptick in nootropic effects! This second fully acid hydrolyzed Bacopa monnieri extract was subsequently patented by us, and is now available as cognance, which in our opinion is one of the most unique Bacopa extracts on the market!
If the CDRI performed similar research in the 1970’s, then they must have discovered similar effects too and via tweaking off their extraction methods, they may have also found a way to convert some, but not all of the bacosides to the bacogenins. With this in mind, it makes sense why anecdotally, many individuals report less lethargy with synapsa, and stronger nootropic effects. However, it is important to note that many people still report lethargy with synapsa. To understand why this happens better, and in order to accurately compare all of our Bacopa monnieri extracts, we now have to jump into the pharmacology of Bacopa!
A Fascinating & Highly Modifiable Effects Profile
Bacopa monnieri exhibits a very unique pharmacological profile, interacting with lots of different neurotransmitter systems. The two main neurotransmitter systems Bacopa monnieri interacts with are the GABAergic and serotonergic systems. Within the GABA system, Bacopa monnieri appears to gradually upregulate GABA receptor density, which is a very unique mechanism!
Most GABAergic supplements simply make the GABA receptors more sensitive through positive allosteric modulation, or they directly activate GABA receptors. Rarely do we see significant upregulation of GABAergic receptors occurring, which make Bacopa very unique. However, this unique effect may also be responsible for the gradual increase in lethargy many people can experience from Bacopa monnieri. Usually, the first few days of Bacopa monnieri supplementation does not present itself with much lethargy, yet after a week, a gradually increasing intensity of lethargy is not uncommon.
Since GABAergic tone is important for relaxation, and also sleep, it means that increasing the density of GABA receptors with Bacopa monnieri can eventually lead to very prominent relaxation effects, which for some can result in pronounced lethargy. That being said, for individuals who struggle to unwind and relax throughout the day, Bacopa monnieri makes for a fantastic supplement. For example, I (Emiel, product specialist and author of this blog), benefit a lot from increased GABAergic activity.
Due to this, GABAergic supplements are usually my favorites, and recently our Bacopa monnieri 24% bacosides extract has become one of my go-to GABAergics. From the first dose, the effects were very pleasant and overtime the calming effects have become more pronounced yet remain balanced, leaving me with a great mood.
The majority of the GABAergic effects appear to be coming from jujubogenin which is formed from the bacosides during metabolism. Jujubogenin also appears to be able to directly activate GABAA receptors, which explains why Bacopa monnieri has acute GABAergic effects too. Keeping in mind that Bacopa monnieri as a whole can also increase GABA receptor density, the direct GABAA agonist effect of jujubogenin will also be getting stronger overtime. We believe that this combined GABAergic mechanism likely is too much for some people, which results in lethargy. However, since GABAergic tone is also very important for sleep, Bacopa monnieri actually makes for a fantastic sleep promoting supplement. Due to this, we often recommend that individuals who experience lethargy during the day with Bacopa monnieri take their Bacopa before bedtime. In fact, in our own internal beta-testing, this strategy proved so effective, that we even ended up including Bacopa monnieri in our sleep support formulation! One of the reasons you can take Bacopa monnieri at night if it makes you feel lethargic, while still reaping the memory enhancing benefits, is because the memory enhancing effects of Bacopa monnieri takes a few weeks to kick in. This means that the time at which Bacopa is dosed, is actually not very critical for the bulk of its nootropic effects, which results in a high degree of dosing flexibility!
The long term memory enhancing effects are likely being produced by some of the complex interactions Bacopa monnieri has with the serotonergic and cholinergic systems. Bacopa monnieri has been shown to speed up the activity of an enzyme called tryptophan hydroxylase. This enzyme hydroxylates the dietary amino acid L-tryptophan, which forms 5-HTP. 5-HTP is subsequently converted to the neurotransmitter serotonin. The tryptophan hydroxylase enzyme can only convert a certain amount of L-tryptophan to 5-HTP, and due to this it is considered to be the rate limiting step in serotonin synthesis
Thus, by boosting tryptophan hydroxylase activity with Bacopa monnieri, we can overcome this rate limiting step, thereby enhancing serotonin levels! What’s fascinating about Bacopa monnieri, is that it also increases the expression of the serotonin transporter (SERT). Normally, the common strategy for increasing serotonin levels is by inhibiting SERT. However, this can actually cause some cognition, and even mood issues for some people. With this in mind, the fact that Bacopa monnieri can increase serotonin synthesis, while also enhancing its uptake and distribution via upregulating SERT, results in a fascinating serotonergic effects profile. Furthermore, Bacopa monnieri also appears to upregulate the density of serotonin 5-HT3A receptors, while normalizing the density of serotonin 5-HT2C receptors. This collective serotonergic effect leads to marked neuroplasticity, and this is likely where the bulk of the long term memory enhancing effects are coming from.
Bacopa monnieri gets even more fascinating when we start looking at the metabolic fate of the bacosides. As we just discussed, the first conversion of bacosides to jujubogenin and pseudojujubogenin leads to pronounced GABAergic effects. However, if jujubogenin and pseudojujubogenin undergo further acid hydrolysis, they yield the bacogenins which no longer seem to possess pronounced GABAergic effects. It is somewhat unclear what many of the bacogenins do, but we do know quite well what one of the bacogenins is doing, which is ebelin lactone. This bacogenin has a fascinating mechanism of action, by acting as a positive allosteric modulator of serotonin 5-HT2A receptors and muscarinic acetylcholine M1 receptors. If you’ve ever looked into microdosing, the serotonin 5-HT2A receptor is likely quite familiar to you. It’s a unique serotonin receptor which plays a major role in sensory processing, but also in cognition and memory. The muscarinic acetylcholine M1 receptor is also a major nootropic target, and plays a very important role in memory and learning. Since ebelin lactone is formed after oral ingestion of Bacopa monnieri extracts, it is likely that gradual accumulation of this compound in the body is responsible for many of the nootropic effects of Bacopa. When we discovered this, we immediately wanted to bring out a standardized ebelin lactone extract, and this is eventually what cognance became. Since we removed the jujubogenin and pseudojujubogenin content for the most part, and instead converted them into 10% ebelin lactone, cognance lack the pronounced GABAergic effects, while retaining and improving upon the unique serotonergic and cholinergic nootropic effects.
Choosing The Best Bacopa Monnieri Extract
Now that you have a solid understanding of the phytochemistry, pharmacokinetics and pharmacology of Bacopa monnieri, we have arrived at the most important part of the blog, choosing the best extract! Finding the best extract is going to be a highly personal endeavor, and this is why we carry a wide range of Bacopa monnieri extracts. Below follows a convenient overview of all of the different extracts we carry:
You can’t go wrong with any of these Bacopa monnieri extracts, but you can definitely pick one that is most tailored towards your goals. If you want to go with a traditional Bacopa monnieri extract, but are unsure of which one to pick, then our advice would be to go for the Bacopa monnieri 24% bacosides extract. This is the least “specialized” extract, and delivers incredible value for money. It doesn’t focus strongly on any particular aspect of Bacopa monnieri, meaning that it is often the most agreeable Bacopa monnieri extract. The Bacopa monnieri 24% bacosides is my personal favorite amongst the traditional Bacopa monnieri extracts and I’m a huge fan of its calming, mood boosting, adaptogenic and nootropic effects.
If you instead want to focus more on the mood boosting properties of a traditional Bacopa monnieri extract, then bacognize would be the ideal extract for you. It often produces the most pronounced mood boosting and calming effects, but is also most likely to produce lethargy in those that do not require much help with relaxation. If you are most interested in the nootropic effects of traditional Bacopa monnieri extracts, then synapsa is going to be a perfect choice. This is especially the case if you love reading research, because chances are, most of the research you have been reading on Bacopa monnieri uses CDRI-08/Synapsa as their Bacopa monnieri extract!
If you already have experience with traditional Bacopa monnieri extracts, and you want to experience the next generation of cutting edge Bacopa monnieri extracts, then certainly take a look at cognance! Cognance feels nothing like traditional Bacopa monnieri extracts, and produces a very unique effects profile that is unlike anything we have ever tried. The effects can be subtle for the uninitiated, but if you’re very familiar with nootropics already, then you’ll quickly pick up on the unique nootropic effects it offers. However, if you are completely new to Bacopa monnieri, it may be better to start off with an extract like Bacopa monnieri 24% bacosides, because cognance is not a good representation of the effects profile of traditional Bacopa monnieri. Cognance will not produce the pleasant relaxing effects that traditional Bacopa monnieri extracts can, and instead can even be slightly energizing for some. Thus, if you are after some calming adaptogenic effects, then stick with a traditional Bacopa monnieri extract. That being said, if you quickly become lethargic from other calming supplements, then certainly skip right ahead to cognance, as it will provide you with all of the nootropic benefits sans the lethargy!
For the most advanced nootropic enthusiasts, we actually would recommend combining cognance with one of our traditional Bacopa monnieri extracts. While cognance is fantastic for its nootropic effects, it’s clearly also missing some aspects of Bacopa monnieri that can be really beneficial for some. For example, I took cognance for 6 months and was entirely enamored with its unique nootropic benefits. However, after switching back to Bacopa monnieri 24% bacosides recently in order to compare the two again, I realized just how unique and pleasant the calming, mood boosting and adaptogenic effects of traditional Bacopa monnieri can be. That being said though, I do miss the very unique acute nootropic effects of cognance now. This means that for me, the ultimate Bacopa monnieri extract, would actually be a combination of Bacopa monnieri 24% bacosides and cognance!
Stacking With Bacopa Monnieri
When it comes to stacking with Bacopa monnieri, selecting the right extract becomes quite critical. In fact, stacking with traditional Bacopa monnieri extracts can actually be fairly tricky. Since traditional Bacopa extracts can enhance GABA receptor density, it can greatly potentiate the effects of other GABAergics in your stack. For example, I was taking Bacopa monnieri 24% bacosides together with shoden ashwagandha because I had been doing this previously with cognance. The first week was great, but on the second week, the lethargy started to kick in. I dropped the shoden, and almost immediately the lethargy went away. This was likely due to the fact that shoden activates GABA receptors, and thus this effect was significantly enhanced by the Bacopa monnieri 24% bacosides extract. On the flipside, Bacopa monnieri 24% bacosides is perfect for taking the edge off the more stimulating components of my stack, such as C3G and Rhodiola rosea 3% salidroside. In general though, traditional Bacopa monnieri extracts definitely attract a lot of attention to themselves, and due to this, it takes a bit more effort and skill to seamlessly integrate them into stacks.
This brings us to the stacking king, cognance! If you are an advanced nootropic user, and like to put together highly specialized and large stacks, then cognance is oftentimes the better option to go for. In my experience, it stacks well with pretty much anything, and can enhance the effects of lots of different plants and compounds. For example, I really like our saffron extract as a standalone, but when I combine it with cognance the effects go to the next level. With this in mind, it can be a lot of fun to try out lots of different stacking options with cognance, especially because it is very forgiving since it doesn’t attract a whole lot of attention to itself, but adds a unique nootropic layer onto basically anything you stack it with.
Due to the fact that stacking with Bacopa monnieri can be a tricky endeavor, we have provided some stacking examples with all of our Bacopa monnieri extracts. We have put together two stacks for every Bacopa monnieri extract, one of which is a simple stack consisting of Bacopa monnieri and one other component, whereas the other stack consists of Bacopa monnieri and three other synergistic components.