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Isoliquiritigenin | The Mood Boosting Power Of Licorice

Take a journey with our product specialist, Emiel to uncover the secrets of licorice root and Isoliquiritigenin and how its responsible for some amazing mood boosting properties.

Licorice's Mood Boosting Power

Throughout the years at Nootropics Depot, we have combed through enormous amounts of data on Traditional Chinese herbs and formulations. One botanical that routinely pops up in Traditional Chinese formulations intended for cognitive function and mood, is licorice. However, we could never quite get licorice right. It either wasn’t mood boosting enough, or it contained compounds such as glycyrrhizic acid which could have negative effects on overall health. Thus, over the years, licorice was one of those challenging botanicals we didn’t quite know how to approach. However, one day we have a eureka moment when reading through a pile of licorice studies. It finally occurred to us that one of the primary mood boosters in licorice root was likely an interesting chalcone called isoliquiritigenin. In the research studies we started to dig through, isoliquiritigenin was found to act as a positive allosteric modulator of GABA-A receptors, but more interestingly, it was also found to act as a GABA-B agonist! GABA-B is always an interesting receptor to target, but there are very few natural GABA-B agonists. Thus, when we discovered that isoliquiritigenin is a GABA-B agonist, we started to get very excited! This excitement was further compounded by the fact that isoliquiritigenin is also acting as a monoamine oxidase A & B inhibitor, in addition to acting directly on dopamine receptors. Overall, a very complex effects profile, which should lead to a unique relaxing, yet slightly stimulating effect. On paper, it sounded like isoliquiritigenin was the missing link we had been looking for, but there was only one way to find out if this was actually the case.

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!

Licorice's Mood Boosting Power

Throughout the years at Nootropics Depot, we have combed through enormous amounts of data on Traditional Chinese herbs and formulations. One botanical that routinely pops up in Traditional Chinese formulations intended for cognitive function and mood, is licorice. However, we could never quite get licorice right. It either wasn’t mood boosting enough, or it contained compounds such as glycyrrhizic acid which could have negative effects on overall health. Thus, over the years, licorice was one of those challenging botanicals we didn’t quite know how to approach. However, one day we have a eureka moment when reading through a pile of licorice studies. It finally occurred to us that one of the primary mood boosters in licorice root was likely an interesting chalcone called isoliquiritigenin.

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. Licorice root and a selection of candies made from the root

Sourcing some high purity isoliquiritigenin to bioassay! After the first dose of isoliquiritigenin, we immediately knew that we were onto something. The initial tingles started to set in at around the 30 minute mark. A unique and ultra-smooth stimulating sensation is what first started to present itself. It felt a little bit reminiscent of the classic caffeine + L-theanine stack, but much smoother. At around the 60 minute mark, we started to feel our muscles relax a little bit, and the relaxing effects started to really kick in at this point.

While the relaxing effects were ramping up, the stimulation also started to increase, but it was nicely balanced against the GABAergic effects of isoliquiritigenin. At this point, there was also some slight sensory enhancement, and a significant lift in mood. Needless to say, we were deeply impressed and immediately knew that this is what we had been looking for in licorice!

Figure 2. Isoliquiritigenin has a very complex pharmacodynamic profile, however, all of the different components are perfectly balanced. This leads to a unique calming yet uplifting effects profile.

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!

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.

Why Isoliquiritigenin Over Licorice Root?

I (Emiel, product specialist and author of this blog) have a lot of experience with licorice in all sorts of forms. This is due to the fact that I’m from the Netherlands and we have a lot of candies and teas here which contain licorice root. In fact, as a child, I would sometimes just chew on dried licorice roots. These roots, interestingly enough, are bright yellow on the inside which just so happens to be the same color as isoliquiritigenin! They also have a pleasant sweet flavor and upon revisiting dried licorice root recently, a pronounced mood boosting effect was also clearly present. However, it is also common knowledge in the Netherlands that licorice can have a negative effect on blood pressure, and thus the warning of not eating too much licorice is often circulated around. Some bags of licorice candy even carry a warning that excessive consumption of licorice could have detrimental effects on blood pressure. The bulk of these negative effects can be traced back to two compounds found in licorice. One of which is glycyrrhizic acid, which also gives licorice its unique sweet flavor, and the other is enoxolone.

The problem with glycyrrhizic acid and enoxolone, is that they interact with mineralocorticoid hormone biosynthesis. Both glycyrrhizic acid and enoxolone can inhibit the 11-β-hydroxysteroid dehydrogenase enzyme, which can alter cortisol biosynthesis.  By modulating cortisol levels, glycyrrhizic acid and enoxolone can elevate sodium levels while lowering potassium levels throughout the body. The changes in these minerals can cause undesirable cardiovascular effects and thus limiting their consumption is always a good idea.

Figure 3. By optimizing our extraction of licorice, we were eventually able to isolate 98% pure isoliquiritigenin. This then bypasses the issues with glycyrrhizic acid and enoxolone, while dialing in the mood boosting effects of isoliquiritigenin.

While glycyrrhizic acid and enoxolone are not ideal compounds to be consuming in high amounts, they do also have some beneficial effects such as enhancing gastric function and balancing inflammation. Thus, lower potency licorice extracts can still have a highly beneficial effect, however, to really boost the mood elevating effects, we would definitely run into issues with consuming too much glycyrrhizic acid and enoxolone in traditional licorice extracts.

With this in mind, I was especially excited about isoliquiritigenin because it captured the unique comforting mood boosting effect of licorice, dialed it up to 11, while also removing the glycyrrhizic acid and enoxolone. In our opinion, this gives isolated isoliquiritigenin a clear edge over traditional licorice extracts when the main focus is on mood boosting effects. That being said, isoliquiritigenin is also very versatile and has some unique benefits other than its mood boosting effects!

A Highly Versatile Compound

When we first started to explore isoliquiritigenin, we were highly fixated on its mood boosting effects. These mood boosting effects were so compelling that we immediately knew that we wanted to start carrying it. However, after reading through every paper on its neurological effects, we started to dig into some of the other interesting effects it has. We quickly realized that isoliquiritigenin was more than just a mood booster. For example, isoliquiritigenin also produces significant gastroprotective, inflammation balancing, and metabolic function promoting effects. This makes isoliquiritigenin a particularly versatile supplement, one that could even be taken completely as a standalone while ticking lots of different boxes!

Figure 4. Isoliquiritigenin is highly versatile in its mechanism of action, thus allowing it to be used in lots of different scenarios.

In terms of mood, isoliquiritigenin hits a very unique range of targets. As we mentioned earlier, the bulk of its effects are coming from the GABAergic system. Isoliquiritigenin acts as a positive allosteric modulator of GABA-A receptors, which means that the GABA-A receptors are becoming more sensitive to the effects of endogenous GABA and other GABAergics. This mechanism of action usually produces a very relaxed mood.

The second effect isoliquiritigenin has, is that it activates another GABA receptor, the GABA-B receptor. GABA-B receptor activation usually leads to muscle relaxation in addition to a somewhat uplifted, yet relaxed mood state. Combining a GABA-A positive allosteric modulator with a GABA-B agonist, results in a very unique and pleasant relaxation effect. In isolation, this effects profile likely would cause some degree of lethargy for many people. However, isoliquiritigenin has some other tricks up its sleeve which prevents this from happening!

In addition to modulating the GABAergic system, isoliquiritigenin also modulates the monoamine system. It does this by inhibiting both of the monoamine oxidase enzymes, MAO-A and MAO-B. These enzymes normally degrade monoamine neurotransmitters such as dopamine, norepinephrine and serotonin. Thus, by inhibiting MAO-A and MAO-B, isoliquiritigenin can slow down the degradation of monoamine neurotransmitters, thereby producing elevated levels of dopamine, norepinephrine and serotonin. This produces a crisp stimulating effect which contrasts very nicely with the GABAergic effects of isoliquiritigenin. Due to this, isoliquiritigenin can be very calming and mood boosting, while also not producing much if any lethargy. This makes isoliquiritigenin an excellent choice for taking the edge off during the day! The mix of GABAergic and monoaminergic effects reminds us a lot of the classic caffeine + L-theanine stack, which also contrasts a calming effect with a stimulating effect. However, in the case of isoliquiritigenin we find the effects to be even smoother and much more mood boosting!

Isoliquiritigenin also has some very unique direct effects on the dopaminergic system. It acts as an agonist at dopamine D3, while acting as an antagonist at dopamine D1. The dopamine D3 receptor has a major effect on mood, and dopamine D3 agonists have been shown to be potent mood enhancers. While it is not entirely clear what kind of effect dopamine D1 antagonism would have in the context of the effects profile of isoliquiritigenin, research on dopamine D1 antagonists seems to indicate that they may have a calming effect, while also smoothing locomotor function. Additionally, isoliquiritigenin also appears to be an agonist of the Vasopressin receptor 1A. This is a very unique target, and may have beneficial effects on socializing! Overall, when combining all of the unique neurological targets of isoliquiritigenin, it is likely easy to see why it has such a unique mood boosting effect!

Isoliquiritigenin also has a unique pain management effect. This is partially coming from the muscle relaxation effects that are being mediated by GABA-B agonism, but this is further getting ramped up by isoliquiritigenin’s prominent inflammation balancing effects. Pair this with the sodium channel inhibitor effects of isoliquiritigenin, and you end up with a very comprehensive pain modulating effect.

Moving down into the gut, isoliquiritigenin also exerts some highly beneficial effects. First and foremost, it produces a robust gastroprotective effect. This effect is likely  being mediated by isoliquiritigenin’s ability to support COX-2 levels in the stomach. Furthermore, isoliquiritigenin also has a positive effect on our gut microflora. It enhances the growth and diversity of gut bacteria, likely by acting as a prebiotic.

As if the list of benefits couldn’t get any longer, isoliquiritigenin also appears to have beneficial effects on both cardiovascular and metabolic health.  The bulk of the metabolic effects are likely being mediated by isoliquiritigenin’s AMPA activation effects and mTORC1 inhibition. The majority of the cardiovascular benefits seem to be mediated via isoliquiritigenin’s oxidation balancing effect and its platelet activity modulating effect. The oxidation modulating effects are mainly mediated through Nrf2 and HO-1 activation.

"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."

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.

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

Figure 1. Licorice root and a selection of candies made from the root.

In the research studies we started to dig through, isoliquiritigenin was found to act as a positive allosteric modulator of GABA-A receptors, but more interestingly, it was also found to act as a GABA-B agonist! GABA-B is always an interesting receptor to target, but there are very few natural GABA-B agonists. Thus, when we discovered that isoliquiritigenin is a GABA-B agonist, we started to get very excited! This excitement was further compounded by the fact that isoliquiritigenin is also acting as a monoamine oxidase A & B inhibitor, in addition to acting directly on dopamine receptors. Overall, a very complex effects profile, which should lead to a unique relaxing, yet slightly stimulating effect. On paper, it sounded like isoliquiritigenin was the missing link we had been looking for, but there was only one way to find out if this was actually the case. Sourcing some high purity isoliquiritigenin to bioassay!

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

Figure 2. Isoliquiritigenin has a very complex pharmacodynamic profile, however, all of the different components are perfectly balanced. This leads to a unique calming yet uplifting effects profile.

After the first dose of isoliquiritigenin, we immediately knew that we were onto something. The initial tingles started to set in at around the 30 minute mark. A unique and ultra-smooth stimulating sensation is what first started to present itself. It felt a little bit reminiscent of the classic caffeine + L-theanine stack, but much smoother. At around the 60 minute mark, we started to feel our muscles relax a little bit, and the relaxing effects started to really kick in at this point. While the relaxing effects were ramping up, the stimulation also started to increase, but it was nicely balanced against the GABAergic effects of isoliquiritigenin. At this point, there was also some slight sensory enhancement, and a significant lift in mood. Needless to say, we were deeply impressed and immediately knew that this is what we had been looking for in licorice!

Why Isoliquiritigenin Over Licorice Root?

I (Emiel, product specialist and author of this blog) have a lot of experience with licorice in all sorts of forms. This is due to the fact that I’m from the Netherlands and we have a lot of candies and teas here which contain licorice root. In fact, as a child, I would sometimes just chew on dried licorice roots. These roots, interestingly enough, are bright yellow on the inside which just so happens to be the same color as isoliquiritigenin! They also have a pleasant sweet flavor and upon revisiting dried licorice root recently, a pronounced mood boosting effect was also clearly present. However, it is also common knowledge in the Netherlands that licorice can have a negative effect on blood pressure, and thus the warning of not eating too much licorice is often circulated around. Some bags of licorice candy even carry a warning that excessive consumption of licorice could have detrimental effects on blood pressure. The bulk of these negative effects can be traced back to two compounds found in licorice. One of which is glycyrrhizic acid, which also gives licorice its unique sweet flavor, and the other is enoxolone.

The problem with glycyrrhizic acid and enoxolone, is that they interact with mineralocorticoid hormone biosynthesis. Both glycyrrhizic acid and enoxolone can inhibit the 11-β-hydroxysteroid dehydrogenase enzyme, which can alter cortisol biosynthesis.  By modulating cortisol levels, glycyrrhizic acid and enoxolone can elevate sodium levels while lowering potassium levels throughout the body. The changes in these minerals can cause undesirable cardiovascular effects and thus limiting their consumption is always a good idea.

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

Figure 3. By optimizing our extraction of licorice, we were eventually able to isolate 98% pure isoliquiritigenin. This then bypasses the issues with glycyrrhizic acid and enoxolone, while dialing in the mood boosting effects of isoliquiritigenin.

While glycyrrhizic acid and enoxolone are not ideal compounds to be consuming in high amounts, they do also have some beneficial effects such as enhancing gastric function and balancing inflammation. Thus, lower potency licorice extracts can still have a highly beneficial effect, however, to really boost the mood elevating effects, we would definitely run into issues with consuming too much glycyrrhizic acid and enoxolone in traditional licorice extracts. With this in mind, I was especially excited about isoliquiritigenin because it captured the unique comforting mood boosting effect of licorice, dialed it up to 11, while also removing the glycyrrhizic acid and enoxolone. In our opinion, this gives isolated isoliquiritigenin a clear edge over traditional licorice extracts when the main focus is on mood boosting effects. That being said, isoliquiritigenin is also very versatile and has some unique benefits other than its mood boosting effects!

A Highly Versatile Compound

When we first started to explore isoliquiritigenin, we were highly fixated on its mood boosting effects. These mood boosting effects were so compelling that we immediately knew that we wanted to start carrying it. However, after reading through every paper on its neurological effects, we started to dig into some of the other interesting effects it has. We quickly realized that isoliquiritigenin was more than just a mood booster. For example, isoliquiritigenin also produces significant gastroprotective, inflammation balancing, and metabolic function promoting effects. This makes isoliquiritigenin a particularly versatile supplement, one that could even be taken completely as a standalone while ticking lots of different boxes!

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

Figure 4. Isoliquiritigenin is highly versatile in its mechanism of action, thus allowing it to be used in lots of different scenarios.

In terms of mood, isoliquiritigenin hits a very unique range of targets. As we mentioned earlier, the bulk of its effects are coming from the GABAergic system. Isoliquiritigenin acts as a positive allosteric modulator of GABA-A receptors, which means that the GABA-A receptors are becoming more sensitive to the effects of endogenous GABA and other GABAergics. This mechanism of action usually produces a very relaxed mood. The second effect isoliquiritigenin has, is that it activates another GABA receptor, the GABA-B receptor. GABA-B receptor activation usually leads to muscle relaxation in addition to a somewhat uplifted, yet relaxed mood state. Combining a GABA-A positive allosteric modulator with a GABA-B agonist, results in a very unique and pleasant relaxation effect. In isolation, this effects profile likely would cause some degree of lethargy for many people. However, isoliquiritigenin has some other tricks up its sleeve which prevents this from happening!

In addition to modulating the GABAergic system, isoliquiritigenin also modulates the monoamine system. It does this by inhibiting both of the monoamine oxidase enzymes, MAO-A and MAO-B. These enzymes normally degrade monoamine neurotransmitters such as dopamine, norepinephrine and serotonin. Thus, by inhibiting MAO-A and MAO-B, isoliquiritigenin can slow down the degradation of monoamine neurotransmitters, thereby producing elevated levels of dopamine, norepinephrine and serotonin. This produces a crisp stimulating effect which contrasts very nicely with the GABAergic effects of isoliquiritigenin. Due to this, isoliquiritigenin can be very calming and mood boosting, while also not producing much if any lethargy. This makes isoliquiritigenin an excellent choice for taking the edge off during the day! The mix of GABAergic and monoaminergic effects reminds us a lot of the classic caffeine + L-theanine stack, which also contrasts a calming effect with a stimulating effect. However, in the case of isoliquiritigenin we find the effects to be even smoother and much more mood boosting!

Isoliquiritigenin also has some very unique direct effects on the dopaminergic system. It acts as an agonist at dopamine D3, while acting as an antagonist at dopamine D1. The dopamine D3 receptor has a major effect on mood, and dopamine D3 agonists have been shown to be potent mood enhancers. While it is not entirely clear what kind of effect dopamine D1 antagonism would have in the context of the effects profile of isoliquiritigenin, research on dopamine D1 antagonists seems to indicate that they may have a calming effect, while also smoothing locomotor function. Additionally, isoliquiritigenin also appears to be an agonist of the Vasopressin receptor 1A. This is a very unique target, and may have beneficial effects on socializing! Overall, when combining all of the unique neurological targets of isoliquiritigenin, it is likely easy to see why it has such a unique mood boosting effect!

Isoliquiritigenin also has a unique pain management effect. This is partially coming from the muscle relaxation effects that are being mediated by GABA-B agonism, but this is further getting ramped up by isoliquiritigenin’s prominent inflammation balancing effects. Pair this with the sodium channel inhibitor effects of isoliquiritigenin, and you end up with a very comprehensive pain modulating effect.

Moving down into the gut, isoliquiritigenin also exerts some highly beneficial effects. First and foremost, it produces a robust gastroprotective effect. This effect is likely  being mediated by isoliquiritigenin’s ability to support COX-2 levels in the stomach. Furthermore, isoliquiritigenin also has a positive effect on our gut microflora. It enhances the growth and diversity of gut bacteria, likely by acting as a prebiotic.

As if the list of benefits couldn’t get any longer, isoliquiritigenin also appears to have beneficial effects on both cardiovascular and metabolic health.  The bulk of the metabolic effects are likely being mediated by isoliquiritigenin’s AMPA activation effects and mTORC1 inhibition. The majority of the cardiovascular benefits seem to be mediated via isoliquiritigenin’s oxidation balancing effect and its platelet activity modulating effect. The oxidation modulating effects are mainly mediated through Nrf2 and HO-1 activation.

"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."

When To Take Isoliquiritigenin

Figure 5. Due to the unique effects profile of isoliquiritigenin, special attention must be paid to timing your doses. Taken too late in the evening for example, it may negatively impact sleep.

Due to the GABAergic effects, many people have assumed that perhaps isoliquiritigenin would be ideal to take close to bed or at night for its relaxing properties. However, in our experience, isoliquiritigenin can be stimulating enough where it keeps lots of people up at night. With this in mind, we would not recommend taking it close to bed, as it is likely to negatively impact your sleep quality.

Instead, we would recommend taking isoliquiritigenin either in the morning as a relaxing pick-me-up or in the afternoon to overcome that mid-day slump! If you are a regular caffeine user, be forewarned however, because your morning or mid afternoon coffee could feel much stronger if you have taken isoliquiritigenin due to the MAO-A & B inhibitor effects. This brings us to stacking with isoliquiritigenin, and this is where things start to get a little bit tricky!

Isoliquiritigenin is also a good example of a supplement that works exceptionally well on an “as needed” basis. Lots of supplements require at least a few days of supplementation to really get the most out of it, but the effects of isoliquiritigenin on mood kick in very quickly. This makes it an ideal supplement to reach for on a particularly stressful day where you want to take the edge off yet remain cognitively dialed in. Isoliquiritigenin is also great as a fun relaxing supplement every once in a while if you just want to kick back and relax, or if you want to go on an adventure in nature!

When To Take Isoliquiritigenin

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

Figure 5. Due to the unique effects profile of isoliquiritigenin, special attention must be paid to timing your doses. Taken too late in the evening for example, it may negatively impact sleep.

Due to the GABAergic effects, many people have assumed that perhaps isoliquiritigenin would be ideal to take close to bed or at night for its relaxing properties. However, in our experience, isoliquiritigenin can be stimulating enough where it keeps lots of people up at night. With this in mind, we would not recommend taking it close to bed, as it is likely to negatively impact your sleep quality. Instead, we would recommend taking isoliquiritigenin either in the morning as a relaxing pick-me-up or in the afternoon to overcome that mid-day slump! If you are a regular caffeine user, be forewarned however, because your morning or mid afternoon coffee could feel much stronger if you have taken isoliquiritigenin due to the MAO-A & B inhibitor effects. This brings us to stacking with isoliquiritigenin, and this is where things start to get a little bit tricky!

Isoliquiritigenin is also a good example of a supplement that works exceptionally well on an “as needed” basis. Lots of supplements require at least a few days of supplementation to really get the most out of it, but the effects of isoliquiritigenin on mood kick in very quickly. This makes it an ideal supplement to reach for on a particularly stressful day where you want to take the edge off yet remain cognitively dialed in. Isoliquiritigenin is also great as a fun relaxing supplement every once in a while if you just want to kick back and relax, or if you want to go on an adventure in nature!

Stacking With Isoliquiritigenin

Due to the highly complex effects profile of isoliquiritigenin, it can be a little bit tricky to stack with it. This is due to the fact that it produces quite a pronounced effect, with that effect producing an almost perfect mix of stimulation and relaxation. This means that if you stack isoliquiritigenin with other stimulants, the mix could become too stimulating and similarly, if you stack isoliquiritigenin with other calming supplements, the mix could become too relaxing. As a quick example, caffeine is potentiated quite a bit by isoliquiritigenin due to its MAO A & B inhibitor effects. Thus, if you take isoliquiritigenin with your morning cup of coffee hoping that it will smooth out the effects of caffeine, you may be in for quite a surprise when that morning cup of coffee feels significantly stronger, albeit it smoother. With this in mind, we have to be very calculated in our approach to stacking with isoliquiritigenin, because it’s a little bit more volatile within stacks than many other ingredients.

Figure 6. Because isoliquiritigenin has an almost perfectly balanced effects profile, stacking with it can sometimes be a difficult balancing act!

Figure 6. Because isoliquiritigenin has an almost perfectly balanced effects profile, stacking with it can sometimes be a difficult balancing act!

Due to isoliquiritigenin being so perfectly balanced between relaxation and stimulation, with the correct approach, it is also possible to take advantage of this phenomenon. For example, if you are looking at creating a smooth yet stimulating stack, isoliquiritigenin could be the glue that holds it all together.

Alternatively, if you are looking at creating an intensely relaxing stack, but just want to shave a bit of the lethargy off, then isoliquiritigenin is once again the glue that can hold it all together. With this in mind, we created three stacks. One which exploits the stimulating side of isoliquiritigenin, one that exploits the calming effects and one which takes a balanced approach to dialing in mood.

Basic Stimulating Isoliquiritigenin Stack*

Isoliquiritigenin + Polygala tenuifolia

In order to bring out the stimulation of isoliquiritigenin a touch while keeping the overall stack balanced, we decided to stack isoliquiritigenin with Polygala tenuifolia. This gently enhances the stimulating effects, while also rounding out the mood boosting properties of isoliquiritigenin.

Advanced Stimulating Isoliquiritigenin Stack*

Isoliquiritigenin + NALT + Sabroxy + Fenugreek

For our advanced stimulating isoliquiritigenin stack, we take a couple of different approaches. The base of the stack starts with NALT, a dopamine precursor that we find to have a rounded and “warm” effect which perfectly complements the effects of isoliquiritigenin. Next, we dial up the stimulation significantly by adding in Sabroxy, which functions as a dopamine reuptake inhibitor. To round out the stack, we add in fenugreek to take advantage of its ability to help release dopamine via the trigonelline content. The overall effects profile results in punchy, yet smooth and warm stimulation!

Basic Calming Isoliquiritigenin Stack*

Isoliquiritigenin + Lemon Balm

In order to make the calming effects of isoliquiritigenin more robust, we decided to stack it with one of our favorite GABAergics, lemon balm. Lemon balm inhibits GABA transaminase, an enzyme that normally break down GABA. This results in higher GABA levels in the brain which synergizes nicely with the GABA-A positive allosteric modulator effects of isoliquiritigenin!

Advanced Calming Isoliquiritigenin Stack*

Isoliquiritigenin + Supercritical Coriander + Ultra Potent Reishi + Tetrahydromagnolol

In order to make the calming effects of isoliquiritigenin more robust, we decided to stack it with one of our favorite GABAergics, lemon balm. Lemon balm inhibits GABA transaminase, an enzyme that normally break down GABA. This results in higher GABA levels in the brain which synergizes nicely with the GABA-A positive allosteric modulator effects of isoliquiritigenin!

Basic Balanced Mood Isoliquiritigenin Stack*

Isoliquiritigenin + 7,8-DHF

The main goal of this stack is to lift up the mood boosting effects of isoliquiritigenin a bit more, while not changing its stimulating or calming properties too much. To pull this off, we decided to stack isoliquiritigenin with 7,8-DHF.

Advanced Balanced Mood Isoliquiritigenin Stack*

Isoliquiritigenin + Saffron + Cognance + Magtein

Designing the advanced balanced mood stack was a lot trickier, because with more ingredients comes the possibility of shifting the effects too much towards the calming or stimulating side. After some testing though, we found a very nice balance when combining isoliquiritigenin with saffron, cognance and magtein. The mood elevating effects become enhanced, as do the sensory enhancement effects. Overall, this is a very comprehensive and smooth mood boosting stack!

Stacking With Isoliquiritigenin

Due to the highly complex effects profile of isoliquiritigenin, it can be a little bit tricky to stack with it. This is due to the fact that it produces quite a pronounced effect, with that effect producing an almost perfect mix of stimulation and relaxation. This means that if you stack isoliquiritigenin with other stimulants, the mix could become too stimulating and similarly, if you stack isoliquiritigenin with other calming supplements, the mix could become too relaxing. As a quick example, caffeine is potentiated quite a bit by isoliquiritigenin due to its MAO A & B inhibitor effects. Thus, if you take isoliquiritigenin with your morning cup of coffee hoping that it will smooth out the effects of caffeine, you may be in for quite a surprise when that morning cup of coffee feels significantly stronger, albeit it smoother. With this in mind, we have to be very calculated in our approach to stacking with isoliquiritigenin, because it’s a little bit more volatile within stacks than many other ingredients.

Figure 6. Because isoliquiritigenin has an almost perfectly balanced effects profile, stacking with it can sometimes be a difficult balancing act!

Figure 6. Because isoliquiritigenin has an almost perfectly balanced effects profile, stacking with it can sometimes be a difficult balancing act!

Due to isoliquiritigenin being so perfectly balanced between relaxation and stimulation, with the correct approach, it is also possible to take advantage of this phenomenon. For example, if you are looking at creating a smooth yet stimulating stack, isoliquiritigenin could be the glue that holds it all together. Alternatively, if you are looking at creating an intensely relaxing stack, but just want to shave a bit of the lethargy off, then isoliquiritigenin is once again the glue that can hold it all together. With this in mind, we created three stacks.

One which exploits the stimulating side of isoliquiritigenin, one that exploits the calming effects and one which takes a balanced approach to dialing in mood.

Basic Stimulating Isoliquiritigenin Stack*

Isoliquiritigenin + Polygala tenuifolia

In order to bring out the stimulation of isoliquiritigenin a touch while keeping the overall stack balanced, we decided to stack isoliquiritigenin with Polygala tenuifolia. This gently enhances the stimulating effects, while also rounding out the mood boosting properties of isoliquiritigenin.

Advanced Stimulating Isoliquiritigenin Stack*

Isoliquiritigenin + NALT + Sabroxy + Fenugreek

For our advanced stimulating isoliquiritigenin stack, we take a couple of different approaches. The base of the stack starts with NALT, a dopamine precursor that we find to have a rounded and “warm” effect which perfectly complements the effects of isoliquiritigenin. Next, we dial up the stimulation significantly by adding in Sabroxy, which functions as a dopamine reuptake inhibitor. To round out the stack, we add in fenugreek to take advantage of its ability to help release dopamine via the trigonelline content. The overall effects profile results in punchy, yet smooth and warm stimulation!

Basic Calming Isoliquiritigenin Stack*

Isoliquiritigenin + Lemon Balm

In order to make the calming effects of isoliquiritigenin more robust, we decided to stack it with one of our favorite GABAergics, lemon balm. Lemon balm inhibits GABA transaminase, an enzyme that normally break down GABA. This results in higher GABA levels in the brain which synergizes nicely with the GABA-A positive allosteric modulator effects of isoliquiritigenin!

Advanced Calming Isoliquiritigenin Stack*

Isoliquiritigenin + Supercritical Coriander + Ultra Potent Reishi + Tetrahydromagnolol

In order to make the calming effects of isoliquiritigenin more robust, we decided to stack it with one of our favorite GABAergics, lemon balm. Lemon balm inhibits GABA transaminase, an enzyme that normally break down GABA. This results in higher GABA levels in the brain which synergizes nicely with the GABA-A positive allosteric modulator effects of isoliquiritigenin!

Basic Balanced Mood Isoliquiritigenin Stack*

Isoliquiritigenin + 7,8-DHF

The main goal of this stack is to lift up the mood boosting effects of isoliquiritigenin a bit more, while not changing its stimulating or calming properties too much. To pull this off, we decided to stack isoliquiritigenin with 7,8-DHF.

Advanced Balanced Mood Isoliquiritigenin Stack*

Isoliquiritigenin + Saffron + Cognance + Magtein

Designing the advanced balanced mood stack was a lot trickier, because with more ingredients comes the possibility of shifting the effects too much towards the calming or stimulating side. After some testing though, we found a very nice balance when combining isoliquiritigenin with saffron, cognance and magtein. The mood elevating effects become enhanced, as do the sensory enhancement effects. Overall, this is a very comprehensive and smooth mood boosting stack!

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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