Research on Kratom

Here you can share your experiences with substances that are ingested, inhaled, or otherwise consumed for the purpose of relieving RLS/WED, other than prescription medications. For example, herbal remedies, nutritional supplements, diet, kratom, and marijuana (for now) should be discussed here. Tell others of successes, failures, side effects, and any known research on these substances. [Posts on these subjects created prior to 2009 are in the Physical Treatments forum.]

Important: Posts and information in this section are based on personal experiences and recommendations; they should not be considered a substitute for the advice of a healthcare provider.
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Research on Kratom

Postby jul2873 » Sun Jan 11, 2015 9:56 pm

I've just read a book titled Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source, ed. by Robert B. Raffa. In the preface, Professor Raffa explains the book evolved from an elective course taught at Temple University School of Pharmacy, and is a collection of essays by experts in various fields (chemistry, biology, pharmaceutics, forensic toxicology, etc.)

I don't have the background to understand all of the book. I found myself looking up terms every couple of minutes while reading. Also, many of the essays are descriptions of the chemical and biological elements of kratom, and I pretty much skipped these, as they were very dense reading, and I was more concerned with the way kratom functioned as a drug. I've summarized below the parts of the book I did read, and--since it's very expensive--I am offering to loan it to anyone with a scientific background who is interested in the more technical chapters.

Short Review:

Kratom has enough opioid properties that it should be classified as an opioid, albeit a new one. Kratom has significant pain-relieving properties. It also seems to suppress coughs, has some anti-depressive properties, and can produce euphoria at high doses. It does suppress breathing but less so than classic opioids. It also causes much less constipation. It seems to be less toxic than classic opioids, as there are no verified reports of it acting alone to cause deaths. There is much concern in the scientific community about its potential for addiction. Most of the chapters call for more research to be done.

Below are my notes from the chapters I read:

Chap 2

Makes the case that kratom can be classified as an opioid. Has two alkaloids—mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG)—that show binding affinity for opioid receptors. Also shows pain relief, miosis (constriction of pupils), constipation, respiratory depression, and tolerance. Also, when an alkaloid is injected into mice, and then an opioid antagonist (blocks opioid action) is also injected, the mice show signs of opioid withdrawal.

A non-opioid property is that very high doses injected into rodents did not seem to poison them. No evidence of toxicity was found. In addition, the compounds in kratom “appear to produce less emesis (vomiting) and respiratory depression than does codeine, although much more detailed investigation is needed.”

The chapter concludes by asserting that “these alkaloids are a novel (or at least distinct) class of opioids. It appears that biodiversity has provided an alternative natural source of opioid compounds.”

Chapter 13

Points out that the pain-relieving effects of kratom cannot be explained by just the MG alkaloid, which is less potent than morphine. The 7-OH-MG alkaloid (small amount present in kratom) produces the strongest pain-relieving effect, maybe ten times stronger than morphine. The chapter urges more research into all of the alkaloids in kratom, concluding that “unknown ancient treasures are still hidden in the Thai traditional medicine M. speciosa, and we should hunt for them.”

Chapter 14

Compares the non-pain relieving aspects of kratom and other opioids

Both inhibit coughs. They were “equipotent.”

Both produce respiratory depression, but kratom’s effect is milder.

Euphoria: the authors note that kratom users report that a high dose of kratom is needed to produce euphoria and they speculate there is some compound in kratom that blocks euphoria at low doses.

Animals didn’t show as marked a preference for places where they received kratom, as they did for places where they got other opioids. Authors concluded the kratom extract used either did not have a sufficiently high concentration of active compounds, or that it contained some compound that blocked its effects.

They found some antidepressant activity in kratom.

Chapter 15

There is a discussion on opioid-induced constipation here. They found that morphine and the 7-OH-MG alkaloid in kratom slowed the travel of food through the large intestine to the same degree. However, since 7-OH-MG is ten times more potent than morphine for pain relief, you would need ten times less 7-OH-MG and therefore constipation would not be such a problem. When the MG alkaloid is compared to morphine and codeine as far as causing constipation, it was found that MG didn’t slow the food down nearly as much as morphine and codeine. So both of the pain-reducing elements in kratom cause less constipation than traditional opioids. The authors present this as a “possible clinical benefit, as opioids are commonly associated with constipation.”

Chapter 16

The authors quote fragments from postings by kratom users to a site called Erowid. Most of the quotes are from people trying to use kratom to detox from harsher opioids, or to feel euphoria, or to manage chronic pain. There was also some discussion of withdrawal symptoms. The authors also publish what they say is a “small number” of people who feel they may have caused themselves temporary liver or gall-bladder problems by using kratom.

Chapter 18

This is a long chapter detailing “adverse effects and toxicity” of opioids from the opium plant—not kratom.

Chapter 19

This is on the “Toxicology of Mitragynine and Analogs,” i.e. on how toxic kratom is.

The chapter begins by pointing out that “To date, there have been no reports of fatal overdose of kratom per se. If there are such occurrences, they are probably the result of kratom products contaminated with synthetic adulterants.”

Most of the studies are with animals. One interesting thing found was that the Mitragynine content in the kratom extracts vary significantly by geographic origin. So the kratom in Thailand reported a higher mitragynine content than an extract from Malaysia.

The researchers tested the safety of MG by giving higher and higher doses to the rats. They concluded that it was only at the highest doses that any liver or kidney damage was found, and even then, “there were no significant effects of other biochemical parameters, such as cholesterol, triglycerides, total protein, creatinine, albumin, alkaline phosphates, or glucose levels.”

There don’t seem to have been any studies on humans but “despite informal and unsupervised widespread use of kratom, there are no reports of mortalities after ingestion of kratom alone, even after chronic and high-dosage consumption, but serious adverse reactions have been reported in several cases.” The cases referred to involve people who took adulterated kratom products, or mixed kratom with other substances. The chapter concludes by calling for more studies, so the “risk-benefit” equation for kratom can be more fully known.

One interesting point that came up in this chapter is that MG is a “poorly water-soluble drug . . . and has an acid-degradable nature.” That must be why it seems to dissolve in orange juice but not in water.

Chapter 20

This chapter is really looking ahead, to talk about what kinds of studies should be done. It recommends animal studies to see the abuse potential of the alkaloids in kratom. This chapter was very difficult to read, but I think it essentially said that pain-relieving properties have been established so now studies should focus on the dangers of the drug. It concludes that “many strides . . .have been made . . . regarding its potential therapeutic uses as an analgesic, anti-inflammatory agent, and muscle relaxant.” It calls now for studies of kratom's "relative liability for abuse and dependence." It also concludes that kratom can produce tolerance and physical dependence. It asks for studies “to assess the positive reinforcing and drug-seeking effects of mitragynine and drug discrimination assays to assess mechanistic similarities between mitragynine and prototypic drugs of abuse.”

Chapter 21

The author of this chapter, Professor Aziz Zoriah from the University of Malaya in Malayasia, gives the background of kratom. It was exclusive to Southeast Asia until around 1990, when the Internet made it easy to order it. In Southeast Asia it is widely used, mostly as a stimulant to increase work production and treatment for opioid withdrawal symptoms. He cites a Malaysian study and a Thai study that both show a large percentage of the users reported they had trouble stopping. Professor Zoriah thinks this is because kratom is so easily available there, and so cheap, that users regularly take large doses. Along with all of the other researchers, he calls for more substantive research to be done on this drug.

My own takeaway from this research: I am much less worried now about potential toxic effects of kratom, and now I know why I never get a stomach upset when I let it dissolve into orange juice rather than taking it in a capsule; the acid in the orange juice helps break down the kratom. The chief worry of the researchers seems to be about kratom's potential for addiction, but I'm guessing it operates like other opioids, i.e. when you take a small amount for a medical reason you are unlikely to become addicted.

It's too bad no researcher seems to be interested in studying this as a potential WED drug.

Polar Bear
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Re: Research on Kratom

Postby Polar Bear » Sun Jan 11, 2015 11:36 pm

Thank you for this and for putting such effort into providing a 'layman' post on Kratom.
Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation

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Re: Research on Kratom

Postby ViewsAskew » Mon Jan 12, 2015 8:06 am

Wow, thanks for the detailed info. Very much appreciated.
Ann - Take what you need, leave the rest

Managing Your RLS

Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation, and are not medical advice.

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Re: Research on Kratom

Postby badnights » Sun Jan 18, 2015 7:33 pm

Thanks for making the effort to make that available to all of us. It's a very informative summary.
Beth - Wishing you a restful sleep tonight
I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.

crazy joe
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Re: Research on Kratom

Postby crazy joe » Fri Sep 25, 2015 5:29 pm

Great research... I just got the book yesterday... Will read up on it...I guess since there has been little research on kratom my question would be what is cosider low or high dosage..Anyway I am getting orange juice and will take 1 teaspoon tomorrow night to see if it helps. Im still on 1 mg of requipp however if kratom helps then ill get off the requipp. Jules do you have any mood swings during the day with kratom? Again thank you for the research done for all of us....

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Re: Research on Kratom

Postby jul2873 » Sat Sep 26, 2015 2:18 am

When I first started taking it, I would get a bit of a mellow feeling, but that disappeared quickly. From what I understand, you develop tolerance very quickly to the euphoric qualities of kratom while, luckily, you don't develop such a quick tolerance to its pain-relieving qualities. Other than that, taking it only affects my mood in that I'm so relieved to be free of the squirmy feeling in my legs. But I take small doses--usually just 1/2 tsp. Over the course of 24 hours I'll probably take 6-7 doses. When I fly, I double that amount and then do feel a little mellow. Good luck. Hope it works for you.

I also posted my review of that book on reddit, and got many, many comments, some from very knowledgable people. Here is the main thread, and then, if you search, other research on reddit, there are other comments on that book, as well as more research. ... on_kratom/?

crazy joe
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Re: Research on Kratom

Postby crazy joe » Sun Sep 27, 2015 1:19 pm

for me it is pain that i hope it releives... my legs have been kicking pretty bad..i have a moderate to severe case but dont want to go on anything strong like methadone. early in the evening and around 4:30 in the morning is when i get sxs.... I did get 5 1/2 hrs in a row last night however with cbd capsules but got up abruptly with leg kicks... tried another 25mg of cbd at that time and it did nothing. will try kratom tonight....

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Re: Research on Kratom

Postby jul2873 » Mon Sep 28, 2015 12:49 am

Oh I hope it works ...

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