At least once a month I get this question and its not an easy one. In most cases the causes for the inactive kratom are easy to discover and to solve.
But what if you tried all and still no luck ?
The you might need to read a bit more, since there is a little chance that you are one of the few that simply cannot get any good results, due to the enzymes in your body that metabolize the kratom powder. But before jumping to this sad conclusion do check the following first.
a. Did you buy the right powder? Although there are many online vendors claiming that they sell the best powder, quality differs a lot. Independent tests have shown that at least 10% of a random sample from online kratom sellers was far below quality and some even did not include real kratom. (1) Always test your powder together with another kratomite to ensure your powder is fine.
b. Are you taking the normal dosage? Sellers often do not include dosage information on their websites, mostly for legal reasons, and although there is a lot of information online regarding amounts of kratom used, some simply do not take enough. 1-2 grams of Kratom normally does not work well, 3-4 grams of good kratom can have good effects for some, but certainly not for all people. A first try of the powder in the range of 5-7 grams is pretty safe. 5 if you are skinny and 7 gram if you consider yourself a bit bigger then average. If you have to take way over 10 grams to notice only little effects, then there is reason to check the other points.
c. Are you dealing with some cross tolerance? When taking other opiates or certain prescription drugs you might be dealing with an unexpected tolerance for kratom, eventhough you never touched the leaves before. Heroine, amphetamines and certain pain relievers are reported to create cross tolerance. If possible try tapering your usage of the first and see if the kratom effects increase. (2)
d. Did you just eat before trying kratom? Its a bit of a no-brainer, but since kratom is taken orally it does not work very well on a full stomach. Certain food and drinks might even lessen the effect because due to the inducing effect on the enzymes that break down kratom or for other reason. Some have reported that fish oil and milk products have a bad effect on their kratom experience.
e. Are you feeling ok? Kratom effects can be subtle, being really sick, having lack of sleep or a high temperature can certainly lessen the effects. Kratom simply works best if your body is fit to respond to the alkaloids. So once slept well, eaten well and exercised a bit, the effects are in general better.
f. Do you take alcohol with your kratom? Although a bit of alcohol might enhance the effects a little, a few glasses extra can simply kill the kratom experience.
If you more or less observed all possible options and kratom is still not working for you then it might be useful to look into the following.
Poor Metabolizers and enzymes CYP2D6 and CYP3A4.
One of the important enzymes responsible for the metabolism of kratom in our body is the cytochrome P450 2D6 (CYP2D6), which is involved in the oxidase system an other enzyme, another, the CYP3A4 plays a role in “cleaning up” the active substances of your kratom. A good function of the first in combination with a low function of the second will give the best results. The way these enzymes work is partly determined by genes and partly influenced by your diet, simply said. All people have a different level of CYP2D6 functioning (which activates the kratom) but those with no or little metabolizing function of the CYP2D6 will have less effect of kratom then others, or only at very high dosage. 6% to 10% of the Caucasian population are thought to have little or no metabolizing function of the CYP2D6! (3) and will therefor experience less from the kratom then others.
The other enzyme, the CYP3A4, plays a role in “cleaning up” the kratom and its metabolites, an active function of this enzyme will therefor result in shorter and less profound kratom effects. The good news however is that the function of this enzyme can be inhibited (4). Various spices herbs and supplements can play a role in slowing down the function, so CYP3A4 inhibitors can help to enhance the overal kratom experience. We will soon make a complete list of this on kratomsources.com. There are also a number of known CYP3A4 inducers, including some medicine like; anticonvulsants (phenytoin), mood stabilizers, phenobarbital,efavirenz, nevirapine, modafinil (stimulant), hyperforin (constituent of St Johns Wort), cyproterone (antiandrogen, progestin) (6), these are likely to speed up the cleaning process and will therefor reduce the kratom experience.
You are unlucky, if your CYP2D6 function is low, as a result kratom will have considerably less effect. The CYP2D6 enzyme itself also plays a primary role in the metabolism of various beta blockers, antidepressant and psychotics like Tagament, Prozac, Hydrocone and many others. (5) If you have had past experience with adverse/low reactions of any of these, then this can be an indication that you will be less sensitive to kratom as well. There are some inducers known, that can speed up the enzymes’ function, but before going into that direction, one should realize that these are mostly prescription drugs that can cause serious side effects.
The chance of a low CYP2D6 functioning is not high, but it is a real option. So, if all of the above is checked and kratom is still not working in a satisfying way, than it might just not be the right herb for you. If that is the case, try looking for other natural alternatives that work better for you.
1. In a study done by Takayama et all in 2009, some 13 samples were bought from known online sellers and tested, 2 of them were not even kratom and only half of them had acceptable levels of Mitragynine and 7-hydroxymitragynine. If the test would be repeated today similar results would be found. Go for specialized sellers and check objective forums like kratomconnoisseurs.com for feedback on sellers before you buy. Source for the report mentioned is table 3 from Kikura-Hanajiri R, Kawamura M, Maruyama T, Kitajima M, Takayama H, Good Y. Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and Other alkaloids into the psycho tropic flat “kratom” (Mitragyna speciosa) by LC-ESI -MS. Forensic Toxicol. 2009; 27:67-74.
2. Drug-forum is a good source for reports on issues of tolerance for the various drugs and medicine in combination with kratom. Check http://www.google.com/#hl=en&q=+site:drugs-forum.com+kratom+cross+tolerance for more information.
3. This is a rough estimate from a medical handbook, some sources estimate it 7-14% . See for more info http://www.healthanddna.com/healthcare-professional/p450-2d6-genotyping.html
4. The “cleaning” role of the CYP3A4 for kratom is very clear. Experiments with various CYP3A4 inhibitors like Turmeric, psoralen, quinine etc have resulted in enhanced kratom effects for various users.
5. See for a big list here http://medicine.iupui.edu/clinpharm/ddis/table.asp
6. see for a list of the inducers http://en.wikipedia.org/wiki/CYP3A4