Hello friends,Thanks for checking out the blog! I'm going a little deeper in this post, and there's a little more science than usual. I hope you find it interesting - and please let me know if you have any comments or suggestions.Just like so many herbs, supplements and foods, your body will develop a tolerance to kratom if you make it a daily habit. The body is always seeking balance -- homeostasis -- and will naturally adjust your biochemistry to be less noticeably affected by things you use regularly. This is something we encounter with so many things in our life, and it's an important capability that keeps us healthy and adaptable in a huge range of situations.Kratom biochemistry is still relatively unstudied, and the large number of alkaloids in the plant definitely complicate any simple understandings about the way it interacts with the body. We know that some of the compounds in kratom are µ-opiate receptor agonists (the little squiggly u is the Greek letter "mu"), and the plant also appears to affect the serotonin and catecholamine (dopamine, epinephrine and norepinephrine) systems.If the body is exposed things that activate these various receptors, often it's response is tothe expression of the receptors (make less of them), which makes whatever you are ingesting less active, this is a main factor in the development of tolerance.Many people at some point in their journey with kratom notice tolerance developing and wonder if there is anything you can do to prevent or lessen tolerance from forming. Others may simply wish to enhance the effects of kratom. Enter potentiators.There are a number of things that can act as potentiators, and there are different reasons why they work. Most of the things I am going to mention are things that are related to the µ-opioid receptor, so in theory these things could have an effect on things other than kratom. Bear in mind, no medical claims or suggestions are being made - just passing on information. Please use caution.So - there are a number of different points we can approach the subject of potentiation. One is the liver, specifically an enzyme system called cytochrome P450 . This liver enzyme system is responsible for metabolizing a large number of substances from the body, including herbs and pharmaceutical drugs. By inhibiting this enzyme system - basically slowing down the process of clearing the body of these compounds, the various substances last longer in the system and may have a stronger effect. The most well known of the P450 inhibitors is probablyBear in mind that this can be quite dangerous in the case of certain pharmaceutical drugs, and it's important to limit your consumption of grapefruit juice if you take certain pharmaceutical drugs. Kratom appears to be metabolized by the P450 system, and anecdotal reports do suggest that GF juice can be an effective potentiator. However, many feel that the body quickly adjusts by raising your tolerance.The next group to go over isNMDA antagonists are known to not only act as potentiators, but also to actuallytolerance (to µ-OR agonists). There are some NMDA antagonists that also happen to be powerful dissociative drugs (ketamine, MXE, PCP, DXM, and related compounds are NMDA antagonists). Probably not most peoples idea of a helpful step to reducing tolerance (although to each their own, I suppose). The good news is that there are a few natural, non-psychoactive substances that also act as NMDA antagonists. An excellent option is. Magnesium is an NMDA antagonist as well as being. This makes it double duty, it acts as a natural muscle relaxant as well as a mild, non-habit forming laxative. I should add that most forms of magnesium are not absorbed well in the body (magnesium oxide is especially poorly absorbed), so I recommend using eitheror an(pronounced key-late). Another interesting and useful natural NMDA antagonist is found in the herbaka). The compound in question is called, and is present in several species of cat's claw. I've heard that the asian form of cat's claw () is higher in this compound, but my experience has been that the south American species is at least equal in subjective effect. Interestingly, kratom contains rhynchophylline too, although it isn't clear how much. It may actually play a role in the effects of kratom., commonly known as blackseed or black cumin seed is a powerful medicinal herb. Used in middle eastern cooking and medicine for millenia, it has also been found to be helpful in treating opioid withdrawal. It is likely that multiple mechanisms are at work, but one of the things happening is that blackseed compounds act as calcium ion channel blockers (like magnesium). µ-Opioids also have this effect - blocking calcium ions. Calcium ions are normally used in the body to signal muscle contractions, so by blocking excess calcium ions, you can relax the muscles and prevent spasms. As I mentioned before, magnesium is also a calcium ion channel blocker, so magnesium is double duty as a potentiator in that sense. Anecdotally, blackseed seems to potentiate kratom as well as other µ-opiate receptor agonists - sometimes powerfully.is a naturally occurring derivative of the amino acid arginine. While agmatine is sometimes used by body builders to increase muscle "pump" (due to it's activity on nitric oxide), it has also been studied for it's interesting relationship to opiate tolerance and withdrawal. Not only does agmatine seem to somewhat prevent tolerance from forming, it also seems to mitigate withdrawal symptoms. A list of relevant articles can be found here. is a form of the amino acid phenylalanine, and some studies suggest that DPA helps to prevent the breakdown of enkephalins - which are a type of endorphin. Endorphins are the bodies own opiate, and DPA may be able to help keep them circulating in your system a little longer. DPA is available as a supplement, as is DLPA, which is a combination of both forms of the amino acid.is another important factor - the artful combining of herbs or supplements. Certain herbs might enhance the effects of kratom by virtue of their own effects, not by directly interacting with kratom metabolism. The herbis an excellent herb in it's own right. It is considered an adaptogenic herb, and has been shown to be an anti-depressant as well. I know many find that rhodiola has a synergy with kratom, and I find it to complement nicely. Herbs and supplements likealerianKava, and GABA also have some excellent synergy with kratom worth exploring.One of the great things about Mu Synergetics is that they tend to stay pretty close the science and have basically come to the same conclusions I have about potentiators. You can get pretty much everything I mention here on their site.