Bacopa Monnieri | An Amazing Ayurvedic Adaptogen | Cognance vs Bacognize vs Synapsa vs 24%

Dive into the world of Bacopa monnieri and learn everything you need to knaow about the differences between Cognance, Bacognize, Synapsa, and our 24% Bacopa monnieri.

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!

A Rare Newcomer In The Functional Mushroom Space

Lignosus rhinocerus, also known as tiger milk mushroom, is one of the most exciting newcomers to the functional mushroom space. This mushroom has historically been incredibly rare, with wild tiger milk mushroom being almost impossible to come by in meaningful quantities. This is largely due to the fact that tiger milk mushrooms do not grow close to each other. Instead, single mushrooms are separated by vast distances in wild jungles. This is also partially where Lignosus rhinocerus gets its ‘tiger milk mushroom’ nickname from. In folklore, it is thought that the mushroom grows on spots where drops of milk from a lactating tiger have fallen. Of course, tigers are rare and travel incredible distances everyday, so within folklore this seems like a perfectly reasonable explanation why the mushrooms grow so far apart from each other! However, this is more of an old wives tale. Tiger milk mushroom does not need to grow on the spots where a mother tiger's milk fell. Even so, the name stuck, and now everyone refers to it as tiger milk mushroom. This is very similar to how Hericium erinaceus is called lion's mane mushroom, despite not being related to lions at all. Even with tiger milk mushroom's rarity, there is a very long history of human use associated with it. Tiger milk mushroom is primarily gathered in the wild, and consumed by indigenous Malaysian people who hunt for this mushroom in the jungle. This amazing fungi is prized by many for its numerous beneficial effects!

The Original Nootropic

● Enhancing learning and memory abilities
● Elevating acquired behaviors despite disruptive conditions
● Provides a neuroprotective effect
● Generally very safe

What is Ashwagandha?

Ashwagandha is a herb that belongs to the night shade family of plants. The nightshade family of plants is a very interesting one and includes a lot of vegetables that make up large parts of many diets. Notable nightshade members are potatoes, tomatoes, chili peppers, goji berries and even tobacco! Another name for the nightshade family is Solanaceae. This is where Ashwagandha gets its Latin name from; Withania somnifera. Ashwagandha is a short perennial shrub, with a large root system that develops small deep orange fruits. The fruits resemble a small cherry and the leaves look frosty due to the many tiny hairs that are on them. This one of the reasons why Ashwagandha is also referred to as ‘winter cherry’. Traditionally, the Ashwagandha root is used, however new research has found high concentrations of key components in the leaves too. Various manufacturers have taken notice of this. One of the most notable being Natreon who produce a specialized extract of Ashwagandha called Sensoril. Sensoril is made from the leaves of Ashwagandha, giving it a unique chemical composition, which produces noticeable calming effects.

Throughout history, tiger milk mushroom has piqued the interest of many individuals. Most notably, the first Western reference to this mushroom was made all the way back in 1664 in the diary of English writer, John Evelyn. In a section of his diary, he describes a collection of rarities from Asia, with one of these rarities being tiger milk mushroom.

At the time, tiger milk mushroom was referred to as ‘Lac Tigridis’, which is Latin for ‘tiger milk’:

Figure 1. Tiger’s roam great distances throughout the jungle everyday, and thus a lactating tiger would leave behind drops of milk every few kilometers. This is likely where the folklore story that inspired the “tiger milk mushroom” nickname comes from, because tiger milk mushrooms grow in the same habitat Malaysian tigers reside in, and single mushrooms are usually separated by several kilometers in the wild!

Figure 1. Nootropics are a class of compounds and plants which have an ability to promote cognitive function.

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!

Figure 2. A portrait of the English writer John Evelyn. Reportedly painted in 1689 which is 25 years after he wrote about tiger milk mushroom in his diary.

This diary entry reveals two very interesting pieces of information. First of all, the name ‘tiger milk’ has been around for at least 358 years, which means that the folklore story about how tiger milk mushrooms grow has been around for a very long time! Secondly, based on the fact that tiger milk mushroom was included in a list of spectacular rarities from Asia, it is clear that it was held in very high regard, even in 1664!

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.

Figure 3. The Central Drug Research Institute (CDRI) in Lucknow, India. This is where the first standardized Bacopa monnieri extract (CDRI-08/Synapsa) was developed!

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!

Figure 3. A picture of Henry Nicholas Ridley, who is often referred to as the father of the Malaysia rubber trade, and potentially made one of the first documented attempts at cultivating tiger milk mushroom

He noted that the tiger milk mushroom was very important to the health of indigenous communities in Malaysia, and with this in mind, he hoped to cultivate tiger milk mushroom. However, he was not successful, and this is because tiger milk mushrooms are incredibly hard to cultivate! In fact, it is so tricky to cultivate that it was only successfully cultivated more than 100 years after Henry Nicholas Ridley’s initial attempt.

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.

Figure 4. An HPLC instrument in the lab of Nootropics Depot

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.

Figure 5. The molecular structure of bacoside A3. Notice how large this compound is? This physical size gets in the way of bioavailability, but luckily the compound is reduced drastically in size when the sugar groups are ripped off during metabolism!

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.

Figure 6. Bacopa monnieri can produce a deeply relaxing effect, which for most is very pleasant, but for those who do not need the extra relaxation, this can lead to lethargy.

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 GABA_A 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 GABA_A 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

Figure 7. The memory enhancing effects of Bacopa monnieri can take quite a while to fully kick in. It is commonly accepted that the memory enhancing effects take about 2-4 weeks of regular Bacopa monnieri dosing before they become noticeable.

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-HT3_Areceptors, while normalizing the density of serotonin 5-HT2_C 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-HT2_A receptors and muscarinic acetylcholine M1 receptors. If you’ve ever looked into microdosing, the serotonin 5-HT2_A 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.

"Research has shown that magnesium levels are decreasing in most foods... With the magnesium content decreasing in crops and the increase in the consumption of processed foods, magnesium deficiencies in the population are becoming more prevalent."

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 1. Nootropics are a class of compounds and plants which have an ability to promote cognitive function.

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 which they named CDRI-08.

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

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, and 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!