The Definitive Guide to Kratom Potentiators
What is Kratom?
For those that don’t know, kratom is powdered leaf from the Mitragyna speciosa tree which grows wild in Indonesia. The leaves are dried, ground and imported into the USA to be resold.
The naturally-occurring alkaloids in the kratom leaf partially bind to our opioid receptors. This offers both both pain relief and mental stimulation when consumed.
Blate Papes pouches with kratom from Your Leaf Your Life
What is a Potentiator?
To potentiate something means to increase the potency of that thing, especially when referring to medicine.
Today the term “kratom potentiator” has become a blanket statement which means any substance that can be taken to increase the effect kratom has on an individual.
But technically this isn’t correct, and not knowing the difference can affect your desired outcome! That’s why we’ve divided it into the following subcategories:
1. Kratom Potentiators – Substances that increase the available strength of the kratom itself.
2. Kratom Bioavailability Enhancers – Substances that increase the percentage amount your body absorbs from the kratom. These increase the effect kratom has by increasing the percentage of alkaloids your body absorbs from the amount you already take.
3. Kratom Tolerance Reducers – Substances that reduce a user’s tolerance to kratom’s effects. These can indirectly increase the effect of kratom you feel by reducing your accumulated tolerance to it.
Depending on which subcategory the substance falls under, you would likely want to take it at different times and frequencies. Typically, (1) potentiators are taken with kratom, (2) bioavailability enhancers are taken before you take kratom, and (3) tolerance reducers are taken at other times or on days when you don’t consume kratom.
However, because many of the substances commonly called “potentiators” don’t fall into any of these 3 categories, we’ve defined a fourth type just for them:
4. Kratom Synergizers – Substances that have their own effect on the mind and/or body, and that are believed to increase the desirable effects of kratom through synergy alone. Any substance under this type does not directly increase the strength of kratom. Instead, its own effects are thought to go well when combined with the effects of kratom.
Since the effects of synergizers are to be felt at the same time as the effects of kratom, they’re usually taken together with kratom (unless there is a delay between the consumption of the substance and the time it takes for its effects to “kick in”).
Why Would Someone Want to Potentiate their Kratom Dosage?
Some reasons to increase your kratom’s strength are:
1. To get more out of less
Using less kratom to get a larger effect means that you will waste less, thus saving money.
Consider this hypothetical situation: You take kratom daily for pain relief. This morning you go to take your kratom but realize you are very low on powder. Instead of running out to buy more locally from a place you don’t know or trust, you could try potentiating with lower amounts. This could allow you enough time to wait for your next purchase to arrive if you buy online.
2. To Reduce tolerance
Users who take kratom regularly may want to lower their tolerance, thereby decreasing the overall amount they must take to achieve the same effect.
3. To feel a stronger effect
Users may not be satisfied with the strength of the kratom that they take, and thus potentiating their dosage could bring the effect up to satisfactory levels.
4. To increase the duration of effect
Instead of redosing, users may be able to use a substance that slows the removal of kratom alkaloids from the body, thereby increasing the time before it wears off.
5. To Swallow less Powder at one time
Using regular kratom powder requires you to consume from 1 to 5 grams at a time. But kratom tastes like dirt and tree leaves. That’s why kratom users look for better ways to consume it.
Combining potentiation methods with edible gel films like Blate Papes make taking kratom quick, easy, and effective.
Is it Safe to Potentiate Kratom?
Although a small number of cases have been reported involving deaths with combined drug intake and kratom use, not one cause of death has ever been linked to kratom alone, or kratom combined with any of the substances listed here.
That said, we’re not doctors, and none of this is medical advice… nor should it be considered as such. We simply want to provide you with a full wealth of information, unlike most sources about how to potentiate kratom powder.
It’s our personal opinion that our bodies work the way they do for a reason. So long as we are healthy individuals with healthy habits who eat healthy foods and take healthy supplements… nature and our bodies should do the rest. But that’s not to say we can’t improve how our bodies absorb nutrients naturally.
However, we also believe that taking unnatural chemicals/drugs for the sole purpose of stimulating a stronger effect from a natural product (like kratom) seems counterproductive. But since the internet is full of recommendations like this, we will include every one we've found and discuss it with research and user reports.
What are the Best Kratom Potentiators Out there?
With a quick Google search, you can find all sorts of advice for potentiating your kratom doses. But this stuff isn’t some sort of voodoo magic… it should be based on the most current scientific research.
Unfortunately, much of the available data has no evidence to support it and is oftentimes just plain wrong.
For example, some sources recommend taking anti-acids before ingesting kratom.
This may seem like a good idea because science suggests putting your body into a more alkaline state helps absorption. However, although antacids produce an alkaline environment in the stomach, they ironically contribute to metabolic acidosis.
Meanwhile, consuming citrus and other acids actually put us in a more alkaline state, and thus may do better to increase the bioavailability of kratom.
There being so much conflicting data on the internet can be confusing. And considering the placebo cure rate in medical trials ranges from 15% to 79%, many of the suggestions out there could be due to the placebo effect alone!
This is one of the many reasons why we can’t be 100% sure that any kratom potentiators actually work. All we can do is present the current data available and let you decide for yourself what may or may not be useful.
List of Kratom Potentiators
The following is an alphabetical list we compiled of all the “kratom potentiators” that can be found across the internet. Because of this, we can’t speak to the safety or efficacy of any of them.
We will list the substance, the suggested reasoning for why it works, any evidence or user experience available, and a special “crapometer” rating from 1 to 5, with 1 being “may actually work” and 5 being “pure crap.”
Acetaminophen (Tylenol)
Type: Synergizer
Suggested reasoning: Tylenol will provide increased pain relief and hence an increased anxiolytic (anxiety-reducing) effect.
Evidence or experience:
Crapometer: 3 - Meh
Justification: Depending on what the goal is of the person taking the kratom, it may or not help. If someone is looking for increased pain relief, then it may actually be of benefit to them. This can be seen by the fact that many prescription pain relievers currently come bundled in a pill with acetaminophen included. But if the goal is to increase any of the other effects, there is no evidence that says taking Tylenol does anything but make your liver work harder.
Agmatine
Type: Tolerance reducer & Potentiator
Suggested reasoning:
Tolerance reducer: Agmatine acts as an NMDA antagonist. NMDA antagonists are believed to help with tolerance build up.
Potentiator: Agmatine modulates alpha(2-) adrenergic receptors and has been studied to increase the pain-relieving effect of morphine, while simultaneously lowering the development of dependence and withdrawal symptoms.
Evidence or experience:
Crapometer: 2 - Maybe
Justification: Agmatine has been studied to both increase the analgesic effect of morphine while simultaneously lowering dependence and withdrawal symptoms after use. For the nerds out there, the mechanism by which this happens is thought to have to do with modulation of the alpha-2 adrenoreceptors and potentially cAMP (cyclic adenosine monophosphate), which is a secondary messenger inside our cells that signals a wide variety of hormones and neurotransmitters.
Study (2) done with rats and morphine determined that “cotreatment of agmatine with morphine produces antinociceptive (increased blocking of pain from sensory neurons) enhancement via an alpha(2-)adrenergic receptor-mediated mechanism and agmatine-morphine combination may be an effective therapeutic strategy for medical treatment of pain.”
Study (1) concluded by stating that “the most fascinating aspect of agmatine, an endogenous molecule, is its ability to potentiate the analgesic effect of morphine and at the same time to reduce the morphine dependence and withdrawal.”
Although the user reports we did find seem to contradict each other, the evidence from studies done with morphine look promising. Kratom is not an opioid, but it’s alkaloids show significant binding affinities at alpha-2A, 2B, and 2C adrenergic receptors, and thus may also share the benefit of both tolerance reduction and analgesic potentiation such as is seen with agmatine and morphine.
But we should also consider that analgesic (pain-releiving) potentiation does not necessarily mean increased euphoria, with some users even reporting the opposite effect. At any rate, more studies and feedback would be of great benefit here.
*Personal Experience*
We’ve actually taken about 0.5g-1g of agmatine sulfate 3-5 days a week for many years. That wasn’t for potentiating kratom, but rather as part of our do-it-yourself pre-workout mix. That’s because agmatine is a very popular nitric oxide booster, which is said to help blood flow and pumps for more effective workouts. As many of you know, we originally created Blate Papes gel films to make taking pure, unflavored powdered supplements easier and more pleasant, and agmatine falls into that category as a single-ingredient powder.
Unfortunately, I can’t speak to how it reduces tolerance to kratom because I haven’t specifically used it for this purpose. With the pre workout mix we make, I also take magnesium, pink salt, creatine, citrulline, beta alanine, betaine and taurine. While it’s true that a rising tolerance has never been an issue for me, I can’t say definitively what that relates to. I also take other supplements such as black seed oil, mushroom powders, moringa, acerola cherry, etc..
Agmatine definitely works great for increasing pumps during your workouts though!
Akuamma Seed
Type: Potentiator & Tolerance Reducer
Suggested reasoning:
Potentiator: Akuamma tree (Picralima nitida) seeds contain alkaloids that have mild opioid receptor binding affinity. Therefore, combining the two is supposed to help prolong the effects of kratom.
Tolerance Reducer: Because of its mild opioid receptor binding affinity, some people suggest taking this on breaks from kratom usage to combat feelings of discomfort.
Evidence or experience: Users describe mild effects similar to those of kratom, with nausea, vomiting, and unpleasant taste being frequently reported.
Journal Article: Pharmacologic Treatment of Opioid Use Disorder
Journal Article: Opioid activity of alkaloids extracted from Picralima nitida
Crapometer: 4 – Probably crap (potentiator), 2 – Maybe (tolerance reducer)
Justification: There are a couple things here that don’t sit right. First, what is the benefit of adding a mild-opioid receptor binder to your dose of a moderate opioid receptor binder? It seems like this would be a waste of time and money.
However, akuamma’s strongest alklaloid (akuammine) binds to and is an agonist at the kappa-opioid receptor… but it’s an antagonist at the mu-opioid receptor, which is what kratom agonizes! So taking it alongside kratom seems very counter-productive, as mu-opioid sites are where the analgesia, euphoria and sedation all come from.
But if your goal is to reduce your tolerance, perhaps taking it during breaks from kratom could be useful.
Apple Cider Vinegar (ACV)
Type: Potentiator & Bioavailability Enhancer
Suggested reasoning:
Potentiator: like citrus and other acids, ACV is said to help break down the plant cell walls and release more kratom alkaloids.
Bioavailability enhancer: consuming ACV puts the body in a more alkaline state, which is said to aid in the body’s absorption of kratom.
Evidence or experience:
Crapometer: 3 - Meh
Justification: Many people say that acidic juices like lemon juice, ACV, etc. potentiate their kratom powder when either ingested around the same time or mixed and soaked together for a while before ingesting. But there needs to be a comparison where one takes an amount of powder and drinks something acidic, and then another where someone soaks that same amount of powder in the acidic liquid for a period of time before swallowing it.
Soaking powder is annoying, time-consuming, and pretty gross to ingest. So is it enough to justify the amount of time and effort it takes to prepare each single dose of kratom in advance and then force-swallow it?
*My Personal Experience* I feel it my duty to explain that ACV is best left alone. After taking 3 liters over the course of a few months, I noticed when I would sweat at the gym, I would smell like ACV… and ACV smells horrible. There are far better acidic choices and general health supplements that can do a better job than ACV without that side effect.
Ashwagandha
Type: Potentiator
Suggested reasoning: Websites say that ashwagandha potentiates other anxiolytics… therefore the belief is that it can do the same for kratom.
Evidence or experience:
Crapometer: 5 - Crap
Justification: There’s no scientific evidence or reasoning supporting the use of ashwagandha for kratom potentiation and user reports go both ways. However, you can find plenty of websites that sell ashwagandha alongside kratom and say it will potentiate it! Classic.
Black pepper
Type: Bioavailability Enhancer
Suggested Reasoning: The alkaloid piperine within black pepper is known to enhance the absorption of other substances. Therefore it may help the absorption of kratom. It's also included in some supplements such as turmeric.
Evidence or experience:
Crapometer: 2 – Maybe
Justification: The research on this subject definitely proves interesting. On this alone, it seems like there could be reason to try it. However, there has been no study relating to it helping kratom and its alkaloids specifically. For that reason, we really need more users to try it and write about how the effects are different when taken together.
Black seed oil
Type: Potentiator
Suggested reasoning: May mildy act on the opioid receptor/may block drug pathways to increase effects
Evidence or experience:
Crapometer: 2 – Maybe
Justification: Because we’re not exactly sure how black seed’s mu-opioid receptor activity affects kratom, we’ve based this entirely on all the user reports we could find being much more positive than negative.
Interesting side note: Black seed (Nigella sativa) was found in the Egyptian tomb of King Tut and the muslim prophet is believed to have said it can cure any disease other than death. It’s also a very popular health supplement that we take on a daily basis for its thymoquinone content.
BLue Lotus Flower
Type: Synergizer
Suggested reasoning: Blue lotus flower has two psychoactive alkaloids, apomorphine and nuciferine, which contribute to its use as a sleep aid and anxiety reliever, and it’s also been described as a mild stimulant. For these reasons, blue lotus flower is believed to synergize with the relaxation and euphoria effects of kratom.
Evidence or experience:
Crapometer: 3 – Meh
Justification: Apomorphine is a nonselective dopamine receptor agonist and activates serotonin receptors and α-adrenergic receptors. It’s been used as a sedative-hypnotic since the late 1800s to treat insomnia, depression, or schizophrenia. It’s also been used in the treatment of erectile dysfunction, Parkinson’s disease, and alcohol and morphine addiction.
Nuciferine also has agonist and antagonist effects at some serotonin and dopamine receptors. Behavioral effects in rats reported included morphine analgesia and anticonvulsant action.
As for whether or not it’s worth using alongside kratom, user reports vary very widely. Some people say it synergizes and they enjoy it, while others say they don’t notice it.
Although it’s true these alkaloids don’t directly potentiate kratom, that’s not to say there isn’t a synergy that can be felt. And blue lotus flower on its own seems like it could be an interesting herb to try if you have the opportunity.
Our friends over at Herba Rosa Kratom recently showed how to make a “love potion” of blue lotus extract. They reported feeling an “enriched sense of well-being and mindfulness, enhanced senses, increased libido/bloodflow, and improved focus on the task at hand” after 30 minutes of ingestion.
Caffeine/Coffee
Type: Synergizer
Suggested reasoning: Caffeine inhibits adenosine, delaying fatigue and sleepiness. So consuming caffeine simultaneously may provide synergistic effects.
Evidence or experience:
Crapometer: 3 – Meh.
Justification: Being that caffeine is only a kratom synergizer, it doesn’t make kratom stronger.
Mixing the two would be a highly subjective experience, as some people enjoy and drink caffeine regularly, while others do not. Also, the first study linked above actually suggests caffeine may be a “buzzkill” for opiate-receptor binders; i.e., kratom!
Cat’s Claw
Type: Tolerance Reducer
Suggested Reasoning: As an NMDA antagonist, people claim it may lower tolerance.
Evidence or Experience:
Crapometer: 3 – Meh
Justification: No scientific proof and user evidence isn’t very extensive.
Cayenne Pepper/Capsaicin
Type: Potentiator & Bioavailability Enhancer
Suggested reasoning:
Potentiator - Consuming chili prior your dose or whenever enhances the blood flow in the intestinal barrier. This leads to better absorption of alkaloids and strengthens effects.
Bioavailability Enhancer - It may be a CYP3A4 inducer which is the main channel of kratom alkaloids that converts mitragynine into the more potent mu-opioid receptor agonist, 7-hydroxymitragynine.
Evidence or experience:
Double-M post: Taking capsaicin to induce cyp3a4 as a kratom potentiator
Reddit post: Capsaicin but not black pepper potentiates kratom?
Crapometer: 2 – Maybe (as a potentiator), 3 - Meh (as a bioavailability enhancer)
Justification: It’s interesting to say the least and seems like it could be legitimate. But since we don’t know for sure whether it’s better to induce or inhibit the CYP3A4 metabolic pathway… we can’t be sure about its efficacy as a bioavailability enhancer.
Chamomile
Type: Synergizer
Suggested reasoning: Helps with nausea and increases relaxation.
Evidence or experience:
Crapometer: 3 – Meh
Justification: Chamomile doesn’t potentiate kratom in any way, it’s only listed here as a possible synergizer. But unless your goal from taking kratom is sedation, it seems the beneficial effect chamomile can have is to help you sleep. This could be useful during tolerance breaks, but we haven’t seen any reason to add it to your regimen.
Cimetidine (Tagamet)
Type: Potentiator
Suggested reasoning: Inhibits the CYP3A4 metabolic pathway which restricts opioids from being metabolized out of the body.
Evidence or experience:
Crapometer: 3 – Meh
Justification: People think this is the holy grail of kratom potentiators. And rightly so because it may help keep mitragynine from metabolizing quickly…. but it’s also blocking it from metabolizing into the stronger mu-opioid receptor agonist, 7-hydroxymitragynine. Yes, Tagamet is known to potentiate some opioids by blocking their inactivation.
But mitragynine is not an opioid and the CYP3A4 pathway is necessary to convert mitryaginine into 7-hydroxymitragynine. So, this could be actually inhibiting the effects!
Oh, and Tagamet can cause gynoclamastea… otherwise known as MAN BOOBS!
However, many people still claim it makes their kratom stronger. Perhaps mitragynine has a different feel to it than 7-hydroxymitragynine?
Honestly though, the thought of man boobs should have been the first and last thing you needed to see here before moving on… unless you’re female of course. Then, pardon the booby-talk.
Cinnamon
Type: Potentiator
Suggested reasoning: It increases absorption.
Evidence or experience: None.
Crapometer: 3 - Meh
Justification: There’s very little information about this combination available. Additionally, there are two types: Ceylon Cinnamon and Cassia. Apparently, most of the cinnamon available is cassia, which has side effects and little health benefit. Ceylon cinnamon has a high ORAC score (antioxidant rating) and it may help absorption by making the body more alkaline. However, there is no evidence to prove this fact, and thus, we can’t be sure.
Citrus Juices:
Type: Potentiator & Bioavailability Enhancer
Suggested reasoning:
Potentiator – Soaking kratom with acidic liquid like citrus will break down the cell walls, preparing the alkaloids to be more readily absorbed.
Bioavailability Enhancer – Consuming citrus juice puts your body into a more alkaline state and this allows the body to absorb more alkaloids from the kratom.
Evidence or experience:
Crapometer: 2 – Maybe
Justification: Almost unanimously across all the kratom potentiation information, it’s agreed that citrus will potentiate kratom by breaking down the cell walls. And while this is true, more needs to be explained. While researching this, some sources say that if kratom is soaked with a lot of citrus for too long, after breaking down the cell walls, the acid may nullify the base alkaloids as well. If that’s true, then taking them at the same time may be better than soaking them altogether.
Additionally, the body absorbs alkaloids much better in an alkaline state. Although citrus is acidic, oddly enough, it puts the body in a more basic state (alkaline). This is because it’s not the acidity of food that affects our blood pH levels, but rather the acidity of the acid waste that’s produced when that food is digested! And so because being more alkaline has a positive effect on the amount of nutrients we absorb from our food, consuming citrus juice an hour or two before taking kratom may be a better use of the citrus than soaking or mixing it with kratom. We actually just posted a TikTok discussing a famed herbalist and how specific foods affect our alkalinity.
At any rate, more scientific research is needed into this with mitragynine as the primary topic of study.
Damiana
Type: Synergizer
Suggested reasoning: Damiana is a relaxing, euphoric stimulant that provides some anxiolytic and aphrodisiac properties
Evidence or experience:
Crapometer: 3 – Meh
Justification: Damiana is an herb with its own relaxing and euphoric effects. We’ve seen it added to many supplements such as pre workout powders and fat burners. So although people have reported the combination gave them positive effects, it’s not any of the three types of substances we’re discussing in this article.
Dark chocolate / Cacao
Type: Synergizer
Suggested reasoning: These contain theobromine. Like caffeine theobromine acts as an antagonist of adenosine receptors. Used with kratom, some believe it can increase the mood-boosting effects and euphoria.
Evidence or experience:
Crapometer: 4 – Probably crap
Justification: Although people may like to combine this with the kratom dosage, it is not a potentiator, enhancer or tolerance reducer. I’ve also seen some accounts of people saying it lowers the euphoric feeling of kratom.
However, if you want to feel a little better during kratom withdrawal, some people believe cacao can help.
Diphenhydramine (Benadryl)
Type: Potentiator
Suggested reasoning: It’s a CYP2D6 inhibitor like kratom. Therefore, it is thought that it will keep more kratom from being metabolized, keeping more of it in your system for a longer period of time.
Evidence or experience:
Journal Article: Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers
Journal Article: Mitragynine 'Kratom' related fatality: a case report with postmortem concentrations
Crapometer: 3 - Meh
Justification: Antihistamines historically have been used to combat morphine histamine reactions. There are cases of deaths reported of people with diphenhydramine and kratom in their systems, but in nearly every case they also have morphine in their system. And if they don’t have morphine, they have other chemicals including benzodiazepines, other opioids, etc.
The science does seem to support that it may inhibit some of the kratom alkaloids from being metabolized as quickly.
However, diphenhydramine makes you tired and can affect you in other ways. If you want to feel more effect, it’s hard to justify taking a synthesized medication that both has side effects and can interact with drug metabolism rather than just taking more of the kratom itself.
Dextromethorphan (DXM)
Type: Tolerance Reducer
Suggested reasoning: DXM is an NMDA antagonist. NMDA antagonists are said to lower tolerance to kratom and opioids.
Evidence or experience:
Crapometer: 2 – Maybe
Justification: There is scientific research that support NMDA antagonists lowering tolerance. However, some users say that DXM and other NMDA antagonists lower the feeling of euphoria from taking kratom. Some therefore suggest only taking low doses of DXM and other NMDA antagonists during breaks from kratom use, when you wish to reset your tolerance levels as quickly as possible.
Freezing Kratom
Type: Bioavailability Enhancer
Suggested Reasoning: Mixing kratom in citric juice and freezing it is believed to help break down the cell walls, thus releasing more of the alkaloids for absorption. This is called the “red bubble tea” method.
Evidence or experience:
Crapometer: 2 - Maybe
Justification: In general, freezing herbs in liquid does cause cell lysis (the breakdown of cell walls). However, kratom is ground to a powder to break down the cell walls and make it easier to digest in the first place. Some people swear by this red bubble freezing technique, and some say it doesn’t make their kratom dose any stronger. Additionally, the red bubble tea method is a very tedious process that involves boiling, mixing, freezing and filtering, and takes about 12-24 hours to complete. Unless you’re trying to filter out all the powder without losing most of the alkaloids, this process seems like quite a lot of work.
If just taking kratom normally, your stomach acid and normal digestive process soak and break down cell walls naturally. So although it may be good for those who want to filter the powder out of their dosages, it doesn’t seem like a sustainable way to take kratom over the long-term unless you’ve got a ton of time on your hands to waste every week.
Ginger
Type: Potentiator & Tolerance Reducer
Suggested reasoning: It reduces stomach disturbances, increases absorption, and inhibits the development of opiate tolerance.
Evidence or experience:
Crapometer: 2 – Maybe
Justification: Although kratom is not morphine, the studies done with ginger, morphine and rats are very, very interesting to say the least. There are also many use accounts of increased analgesic effect of taking ginger alongside kratom. Ginger is also known to ease an upset stomach, so it’s been commonly used to help those that suffer from kratom-related stomach issues.
This definitely warrants more research, but it’s probably one of our personal favorite options in terms of potential benefits! Ginger is all-natural and full of other health benefits… if you know what we stand for, you best believe that we’re interested!
Grapefruit Juice
Type: Potentiator & Tolerance Reducer
Suggested reasoning: Grapefruit juice is one of the original main recommended potentiators for kratom use for the same reasons as citrus juice, but also because it inhibits the metabolic pathway CYP3A4 which is responsible for metabolizing mitragynine. For this reason, people believe slowing this pathway’s metabolism will decrease the clearance rate of mitragynine from the body, resulting in a higher peak and longer duration of effect.
Evidence or experience:
Crapometer: 3 - Meh
Justification: The big question here is whether inhibiting CYP3A4 is a good thing or a bad thing. While it is true that mitragynine is primarily metabolized by CYP3A4, this pathway is also responsible for converting mitragynine into the stronger mu-opioid receptor agonist 7-hydroxymitragynine (about 10 times stronger). A more recent study (linked above) even suggests that 7-hydroxymitragynine is most responsible for the analgesic effects of kratom, and that normal mitragynine has very little affinity to the mu-opioid receptors. If that were true, then the real goal would be to induce CYP3A4 to metabolize mitragynine into 7-hydroxymitragynine more.
So what does this mean? It means that no one really knows what the hell is going on.
There are plenty of reports all of the internet of people claiming CYP3A4 inhibitors made the effect of their kratom stronger. There are also many that say the exact opposite. So we can be either dealing with a working potentiator or a placebo effect. So contrary to popular opinion, it’s probably best to avoid inhibiting or inducing any metabolic pathways until more is known about the pharmacological mechanisms of kratom’s alkaloids.
Kanna
Type: Synergizer
Suggested reasoning: The main effects of kanna are considered to be euphoric, sedating and anxiolytic (anxiety-reducing). Since these are similar to kratom, some think they should synergize well together.
Evidence or experience:
Crapometer: 4 - Probably crap
Justification: This is not a potentiator, and we haven’t found a definitive answer on whether it synergizes well with kratom. It would also likely be very subjective. It’s also a natural selective serotonin reuptake inhibitor (SSRI), which is what most anti-depressants are. But in our experience, SSRIs and are not something to play around with mixing.
Kratom: Stem & Vein
Type: Tolerance Reducer
Suggested reasoning: During the production of Kratom, the stems and veins are removed. Some vendors sell them as separate product. Some claim that the stem and vein have more of the kratom alkaloids that aren’t the common ones in the leaves. Therefore, some users mix this with their kratom dose, while lowering the amount of normal kratom leaf powder they take. This is supposed to help reduce kratom tolerance.
Evidence or experience:
Crapometer: 4 - Crap (but it DOES technically reduce your tolerance)
Justification: I understand the attraction of this idea. But I can almost guarantee that the only reason that stem and vein kratom “works” for reducing tolerance, is that it’s a much lower dose of kratom than the person is used to taking. That’s it. Think about it, the stem and veins also have the same alkaloids the leaves have, right? But the leaves have the most. So when a person takes stem and vein, or mixes in stem and vein with their kratom dose, they are effectively just lowering their dose for a bit. Of course it’s going to decrease your tolerance. And taking a lesser amount of kratom (or any opioid for that matter) does make you feel better than you did without it! So you’ll of course feel “better.”
But there isn’t some special alkaloid that’s doing this. It’s the same ones that’re in the leaves. It’s all a trick of the mind. You want to see the same amount of powder you take daily, and this way you can. But do I think it’s worth buying stem and vein kratom, just to take less? Well, that depends on what you believe is happening. For someone that finds it too difficult to take a break, it could help trick them into lowering their dose. And for the vendors that sell it.. hey, if your customers want to buy it, you might as well offer it.
L-Tyrosine
Type: Potentiator
Suggested reasoning: When consumed, L-tyrosine is the precursor to L-DOPA, which is then converted into dopamine. Dopamine then turns into norepinephrine and epinephrine, which means L-tyrosine increases the levels of dopamine, norepinephrine and epinephrine in the brain, causing euphoric and mood-boosting effects. The suggested reasoning is that combining this with a dose of kratom will have synergistic effects, both boosting and replenishing these neurotransmitters.
Evidence or experience:
Crapometer: 2 - Maybe
Justification: If we’re talking about potentiation of the euphoric effects of kratom, this could have merit. There is scientific evidence that shows kratom has a binding affinity to dopamine receptors. However, one study in rats that monitored dopamine release after treatment with mitragynine concluded that it did not increase dopamine release after a single exposure (one dose of mitragynine). However, on day 4, after repeated exposures to mitragynine, dopamine began being significantly released with dosing.
This seems to show that once the brain learned to associate the pleasurable effects of mitragynine with dosing, it began to support consumption by releasing dopamine. However, because we really don’t know too much about how neurotransmitters work together, we can’t be sure that taking dopamine/norepinephrine/epinepherine precursors is actually helping this reaction to produce more euphoric effects.
*My own personal experience* Although I don’t usually discuss my own experiences, I have and currently do take L-tyrosine on an as-needed basis. From my past experience, when particularly depleted, I’ve noticed L-tyrosine 500mg-2g does have a leveling-out like effect. But when combined with stimulants, it has only ever increased my anxiety and precipitated psychosis. So in my personal opinion, (and I am not a doctor at all) the brain seems to know the right level of balance. It doesn’t need us throwing more neurotransmitters into the mix while it's in the middle of a release. But when it comes to replenishment, I see no problem with taking L-tyrosine as it is a naturally occurring ingredient that has a very safe history of use profile.
It's my opinion that when used to replenish these neurotransmitters, it could possibly potentiate by ensuring there will be adequate neurotransmitters available for the subsequent release following kratom dosing.
Lavender
Type: Tolerance Reducer & Synergizer
Suggested reasoning: Lavender oil is known widely as a natural sleep-aid and anti-anxiety essential oil, as it is said to provide a calming effect by just scent alone. But it is studied to have anxiolytic and antidepressant-like effects due to antagonism on the NMDA-receptor and inhibition of the serotonin reuptake transporter. As we discussed about NMDA antagonists earlier, this may be reason to believe it can help with tolerance, as well as add well to the relaxing effect kratom has.
Evidence or experience:
Crapometer: 3 - Meh
Justification: Given its NMDA action and known anti-depressant capabilities, it stands to reason that it may have a positive effect when taken alongside kratom. However, as discussed with NMDA antagonists earlier in this article, it may be a better idea to take lavender during a break or withdrawal period from kratom, depending on your goal. It’s definitely possible that there’s a synergistic effect of combining the two at one time, but whether that is significant enough to be noticeable, or even if the NMDA activity won’t hinder the acute euphoria is a whole other story.
We linked to a reddit post in which someone claimed lavender oil greatly reduced their kratom withdrawals and even strongly potentiated their low dose. Either way, being that lavender has been safely used for generations, it couldn’t hurt to give it a try.
Magnesium
Type: Tolerance Reducer
Suggested reasoning: Magnesium is a potent NMDA receptor antagonist, and so just like we discussed with DXM, it should help with reducing kratom tolerance. However, some people have said NMDA antagonists reduce euphoria when taken together.
Evidence or experience:
Journal Article: Zinc, magnesium and NMDA receptor alterations in the hippocampus of suicide victims
Crapometer: 2 - Maybe
Justification: Given the NMDA activity, it would seem the best thing would be to take magnesium toward the end of your dose, or even a few hours before bed, so that it will help guard against tolerance building. Additionally, magnesium sulfate (pure epsom salt) is a saline laxative and thus may help combat kratom-induced constipation problems.
*Personal Experience* I personally took epsom salt over many years for these effects. Although I took it side by side kratom for a long time, I couldn’t say whether or not it hindered or helped the euphoria. Regardless, not long ago I began taking it later in the day instead of the morning or before dosing. I found that taking it just before bed made my throat very dry, and I had to get up to urinate multiple times during the night. But taken a few hours before bed instead seemed to do the trick.
Magnesium is also a very good supplement for those who take stimulants, as stimulants cause the body to rapidly deplete magnesium. Magnesium protects against a whole host of common side effects for this reason alone. However, Epsom salt (magnesium sulfate) isn’t the most optimal form for consumption, albeit very cheap. Magnesium glycinate seems to be more popular for this purpose.
Moringa Oleifera
Type: Potentiator
Suggested reasoning: Some sources say it inhibits the cytochrome enzymes responsible for mitryginine metabolism, leading to increased levels in the blood.
Evidence or experience:
Crapometer: 5 - Crap
Justification: The only study about moringa (linked above) inhibiting cytochrome pathways also compares 8 other herbs, and moringa only shows very weak inhibition of CYP1A2. Considering also that kratom is predominately metabolized by the CYP3A4 pathway, the idea that this will potentiate a kratom dose is unlikely. Moringa is a superfood though, and as such, it definitely wouldn’t hurt to try adding it to your current health regimen.
Mulungu
Type: Synergizer
Suggested reasoning: It’s suggested that because mulungu is a strong anxiolytic, they will go well together for those that like the anti-anxiety effects of kratom.
Evidence or experience:
Crapometer: 5 - Crap
Justification: Not only is this not a potentiator of any kind, it’s not even synergistic with kratom as it’s mostly used as a sleep aid rather than anti-anxiety. Studies suggest the pharmacological action of mulungu is via the inhibition of neuronal nicotinic receptors (what nicotine works on). This has no known benefit to kratom or the effects of kratom.
N-Acetyl Cysteine (NAC)
Type: Potentiator
Suggested reasoning: Could not find any real reasoning… but people seem to think it’s a potentiator and that it helps with withdrawals.
Evidence or experience:
Crapometer: 5 - Crap
Justification: We couldn’t find any real reasoning for why NAC would potentiate kratom or help with withdrawal. But there are reports of NAC dulling the euphoric effects of kratom. This is basically a contradiction saying it attenuates the effects of kratom and doesn’t potentiate it.
So what’s going on here? We can’t be sure, however, we do know that NAC is a very strong antioxidant and a good stand alone supplement.
Nicotine
Type: Synergistic
Suggested reasoning: The stimulant effect of nicotine is said to enhance the euphoric effects of kratom.
Evidence or experience:
Web Article: What’s The Deal With Combining Kratom and Nicotine?
Reddit user report saying nicotine dulls the effects of kratom
Reddit user report saying kratom may help them to quit smoking
Crapometer: 5 - Crap
Justification: It’s crap because it’s not a potentiator, but many people claim smoking or vaping synergizes well with the effects of kratom. Pharmacologically, nicotine has no mechanism that definitively potentiates kratom. But many people claim there’s a synergistic euphoria from the combining the two. Then again, some others claim the opposite.
*My personal experience* About 10 years ago when I was in my early twenties, I combined the two many times. Although I was not a habitual smoker, the only time I smoked or vaped was when I had kratom in my system. I honestly did not (and do not) like cigarettes or vaping while clean and sober. My main concern was always that smoking made me a little nauseous and that I would have to poop, but when I took kratom, I could smoke without having to.
Did it feel better? I wish I could say. I’m not sure that it felt better as much as it felt “different.” And being that I was always looking for a new high when I was in my younger years, this was just another way for me to exert control over my mental condition. If I had to say definitively whether it synergizes with it, I would say it depends on the person and whether they already use nicotine or not. If they do, then it will probably synergize (from their perspective).
Noopept (Omberacetam)
Type: Potentiator
Suggested reasoning: Noopept is a popular nootropic (smart drugs). It’s said to have great cognitive-enhancing capabilities by increasing brain-derived neurotrophic factor (BDNF), working on AMPA glutamate receptors and increasing the availability of acetylcholine in the brain. How this relates to kratom potentiation… who knows?
Evidence or experience:
Web Article: Noopept: Everything You Need to Know About This Nootropic
Reddit user report on combining noopept and alpha GPC with kratom
Crapometer: 4 - Leaning towards crap
Justification: The truth is that we just don’t know what the heck it does or exactly how it works, so we can’t be sure it has any potentiating effects on kratom. However, there are ample user reports of noopept and other racetams increasing the euphoria of common stimulants. But kratom isn’t a classic stimulant, although people report it having stimulant-like effects. The real problem here is we have no proof and little evidence of its effectiveness in potentiating kratom.
Phenibut
Type: Synergizer
Suggesed reasoning: Phenibut has a very similar chemical structure to GABA, which reduces the excitability of neurons. When consumed, it reduces anxiety and promotes feelings of well-being, relaxation and sedation. It’s for this reason that some think phenibut compliments the effects of kratom.
Evidence or experience:
Journal Article: Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug
Reddit user report on taking kratom and phenibut for over a year
Crapometer: 3 - Meh
Justification: Originally, phenibut was going to be excluded from this list for harm reduction and because it’s not a potentiator pharmacologically. But we decided it’s better to explain this thoroughly rather than to ignore it. With that said, phenibut has a very high potential for addiction and abuse. That’s because it’s similar to benzodiazepines; if taken continuously for a long period of time, your body becomes dependent on it. When you don’t have it, the withdrawals are proclaimed to be horrific.
With that said, some think that taking it at most twice per week in moderation and alongside doses of kratom, it synergizes the effects. While this may be true, it’s almost certainly dose and person-dependent. The general consensus, from what we’ve gathered, is that if the user has any type of addiction potential, it would do more harm than good to use this as well.
*Personal Experience* As some of you may or may not know from reading our story, I was an addict for much of my twenties. I bought and used phenibut multiple times during that period. I don’t remember combining it with kratom specifically on any occasion, but I do remember that phenibut is a very strong chemical with a very long half-life. It takes about 2 hours to feel any effects, which is a very long time. Additionally, if you take too much, it is very over-powering and can make you feel dizzy, nauseous and out of it for up to 2 days. My main reasoning for using it was to negate the strong anxiety from my stimulant abuse during that time period. (NOTE: This was addictive behavior and I do NOT condone this).
My personal opinion is that it’s much better left alone.
THC/CBD
Type: Synergizer
Suggested reasoning: Some people claim they go well together because they both relax you.
Evidence or experience:
Crapometer: 4 – Probably crap
Justification: We’re claiming this is crap mostly because THC and CBD don’t directly potentiate kratom by pharmacological actions. And while it is true that there are many user accounts of both marijauana and CBD synergizing with kratom, there are just as many accounts of marijuana overpowering it or making them too paranoid… and others saying CBD has no effect.
Additionally, a lot of the argument being made toward CBD potentiating or synergizing with kratom is made by companies that sell them both. For this reason, and because results are highly subjective, we recommend being wary of any such advice.
Turmeric (Curcumin) with Black Pepper (Piperine)
Type: Potentiator
Suggested reasoning: Curcumin, the main alkaloid of value in turmeric, slows the absorption of substances by inhibiting the CYP3A4 metabolic pathway. For this reason, it’s believed that curcumin can increase kratom’s duration in the body and extend its effects. Turmeric should always be taken together with piperine (the alkaloid of value in black pepper) as it greatly increases the bioavailability and absorption of curcumin.
Evidence or experience:
Crapometer: 3 - Meh
Justification: Being that curcumin is a CYP3A4 inhibitor and that we really don’t know for sure whether inhibiting CYP3A4 is a good or a bad thing (see grapefruit juice), we can’t say whether this is a valid potentiator. Generally the mixture of turmeric and black pepper is very common and has numerous studied benefits. But whether the combination is effective when paired with kratom, that’s impossible to say with the current science. Black pepper alone with kratom may be the more promising option due to piperine’s known ability to increase bioavailability
*Personal Experience*
Being that I first began consuming kratom on and off in 2010, I did a lot of research and testing with these combinations. From my experiences, I never really felt that the combination of turmeric and black pepper made much of a difference to the effect of my kratom dosages. I felt the same way about star fruit and grapefruit juice.
Valerian
Type: Synergizer
Suggested reasoning: Valerian provides anxiotlytic and sedating effects, therefore it may synergize with kratom based on individual’s goals.
Evidence or experience:
Crapometer: 4 - Crap
Justificaton: The two studies linked above contradict each other, one stating that valerian inhibits CYP3A4 while the other says it induces it. Not that we know which is better anyway, but most user reports either say it’s worthless with kratom or that valerian just helps them sleep at night. Side note: the smell of valerian is alarming… but luckily, you wouldn’t taste that or kratom when using blate pouches.
Watercress
Type: Potentiator
Suggested reasoning: The only reasoning found anywhere was on the kratom “psychonaut wiki” in which they say, “Ingesting watercress approximately 45 minutes before kratom is said to potentiate its effects. This works because watercress functions as a cytochrome P450 CYP2E1 enzyme inhibitor which results in altered drug metabolism.”
Evidence or experience:
Crapometer: 5 - Crap
Justification: Other than the kratom “Psychonaut Wiki” that lists watercress as a potentiator, there is no evidence that it offers any sort of ability to potentiate kratom. And the justification they list for watercress potentiating refers to cytochrome CYP2E1 which has absolutely nothing to do with kratom metabolism! The cytochrome pathways responsible for kratom alkaloid metabolism are CYP3A4 with minor contributions by CYP2D6 and CYP2C9
The other websites saying it’s a potentiator either give no reasoning, or they say something ridiculous like it’s “packed with nutrients that could help ease digestion.”
It seems like what happened here is one website wrote a sentence about it, and 50 others copy-and-pasted it without doing any research whatsoever. Another perfect example of what’s wrong with most things you read on the internet. Unsurprisingly, many of those same websites will happily sell it to you alongside your kratom powder.
Kratom Potentiators from Best to Worst
Rating: 1 - It Works
None - Why didn’t we give any 1’s? Because we just can’t be sure any of them really work… and kratom isn’t expensive enough to justify going to such lengths to increase its potency. Instead, just buy it in bulk.
Rating: 2 - maybe it works
Agmatine - Tolerance reducer & Potentiator
Akuamma Seed - Tolerance Reducer
Black pepper - Bioavailability Enhancer
Black Seed Oil - Potentiator
Cayenne Pepper/Capsaicin - Potentiator
Citrus Juices - Potentiator & Bioavailability Enhancer
DXM - Tolerance Reducer
Freezing Kratom - Bioavailability Enhancer
Ginger - Potentiator & Tolerance Reducer
L-Tyrosine - Potentiator
Magnesium - Tolerance Reducer
Rating: 3 - Can’t Tell Either Way
Acetaminophen (Tylenol) - Synergizer
Apple Cider Vinegar (ACV) - Potentiator & Bioavailability Enhancer
Blue Lotus Flower - Synergizer
Caffeine/Coffee - Synergizer
Cayenne Pepper/Capsaicin - Bioavailability Enhancer
Cat’s Claw - Tolerance Reducer
Chamomile - Synergizer
Cimetidine (Tagamet) - Potentiator
Cinnamon - Potentiator
Damiana - Synergizer
Diphenhydramine (Benadryl) - Potentiator
Grapefruit juice - Potentiator & Tolerance Reducer
Lavender - Tolerance Reducer & Synergizer
Phenibut - Synergizer
Turmeric (Curcumin) with Black Pepper (Piperine) - Potentiator
Rating: 4 - Probably Doesn’t Work
Akuamma Seed - Potentiator
Dark chocolate / Cacao - Synergizer
Kanna - Synergizer
Kratom: Stem & Vein - Tolerance Reducer** (It’s crap… but it does technically reduce your tolerance)
Noopept (Omberacetam) - Potentiator
THC/CBD - Synergizer
Valerian - Synergizer
Rating: 5 - Doesn’t Work
Ashwagandha - Potentiator
Moringa Oleifera - Potentiator
Mulungu - Synergizer
N-Acetyl Cysteine (NAC) - Potentiator
Nicotine - Synergistic
Watercress - Potentiator
We tried to include every suggested potentiator we could find, but if you know of anything we’ve missed, please comment below to help others learn as well! And as more research develops, we will continue to update this list! But your comments could be more useful than any of the information we’ve assembled above, so feel free to include data, links, your experiences, etc! Thanks so much, we appreciate you!
