Kratom is NOT an Opiate plant! Some information to better understanding Kratom.

[CLICKHEREx]

This thread is to address the misconceptions that float around the Kratom forum and with general users who do not fully understand the plant in its contents and nature.

Mitragyna speciosa (Kratom) contains many alkaloids including mitragynine, mitraphylline, and 7-Hydroxymitragynine. There are also many other alkaloids that give it stimulant, appetite suppressant, and other effects, but we will stick with the ones that show the nature of kratom and how it interacts with the body to become an analgesic.

Mitragynine, mitraphylline, and 7-Hydroxymitragynine are all indole alkaloids of various sorts:

 

• Mitagynine: indole
  
• Mitraphylline: oxyindole
  
• 7-Hydroxymitragynine: a terpenoid indole
  

 

None of these are opiate alkaloids, which makes it structurally a different thing all together. Poppy plants contain your known principal sources of opiate alkaloids such as: morphine, thebaine, codeine and oripavine. None of these types of materials are contained in the Mitragyna speciosa plant as a matter of fact. So it is, in that sense, opiate-free with the idea that it contains no structure that is opiate-like.

However, the indole alkaloids contained in this plant does have opioid agonistic activity, which leaves you thinking it has the same effects overall. This is what makes it so confusing. It is not an opiate, but the organic chemical compound has an affinity for those receptors. The effects are primarily based on the 7-Hydroxymitragynine indole alkaloid, which has been shown in the paper "Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands" to actually be an an active μ-opioid agonist for certain. The antagonism of naloxone (an inverse agonist) on concentration-response curves confirms its opioid effect. This in fact makes it an opioid instead of an opiate.

So it is an indole-containing plant; this hopefully dispels those that will call it an "opiate-like," but instead define it as an opioid. This also dispels any belief or confusion of it failing a drug test. It cannot simply do that being as the chemical metabolites created would not be confirmed on the GC/MS test as it would be a different NMR pattern. Of course, this can change as drugs become public and more known, but at this time, Kratom is virtually unknown in the testing community.

I hope this helps the people in this forum better understand this plant. Some drugs simply have different functioning structures with the same receptor effects, which makes it an opioid pharmacologically.

Here is the paper's abstract if you all are interested. It is rather cool to read the abstract actually, so I recommend taking a gander:

Quote: Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal herb, Mitragyna speciosa, and has been proven to exhibit analgesic activity mediated by opioid receptors. By utilizing this natural product as a lead compound, synthesis of some derivatives, evaluations of the structure−activity relationship, and surveys of the intrinsic activities and potencies on opioid receptors were performed with guinea pig ileum. The affinities of some compounds for μ-, δ-, and κ-receptors were determined in a receptor binding assay. The essential structural moieties in the Corynanthe type indole alkaloids for inducing the opioid agonistic activity were also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice.

A nice fact to know:

"The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice."

With this being said, it has been found to have a higher potency than that of morphine in its compound form alone. Now there's some news you can use when debating the strength of Kratom. It is just the contents of the plant you buy, the extract levels, or "how much you are getting" that makes it strong or weak. Yet in just the chemical sense, it can actually be a very potent little plant. I wish I had access to the full paper, but it costs money to receive. If anyone finds it, we need to upload this. It has valuable member information to dispel this belief of kratom being an "opiate" as some may think of it as.

Reference:

Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids:  Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands

Hiromitsu Takayama,*,†, Hayato Ishikawa,†, Mika Kurihara,†, Mariko Kitajima,†, Norio Aimi,†, Dhavadee Ponglux,‡, Fumi Koyama,§, Kenjiro Matsumoto,§, Tomoyuki Moriyama,§, Leonard T. Yamamoto,§, Kazuo Watanabe,§, Toshihiko Murayama,§ and, and Syunji Horie*,§

Journal of Medicinal Chemistry 2002 45 (9), 1949-1956

Read more: http://www.drugs-forum.com/forum/showthread.php?t=203727#ixzz2HuzXDKbF

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There are several responses in that thread at drugs-forum.

[Roopey]

I was always under the assumption that it was opioid and didn't actually have the same compounds that poppy does, but if it is acting on your opiate receptors then really what's the difference other than we found poppy first and one might be stronger than the other?

If they found another plant that acted on your cannabinoid receptors, which they have found a few, they would not necessarily have THC or CBD, but they are still giving you what you were looking for, aren't they?

[endorfinder]

Some kratom alkaloids are opioids, acting on the ope receptors, but none are structurally related to opium alkaloids - opiates. This is really splitting hairs.

The important point is that other alkaloids are present with other mechanisms of action and effects.

[Sonny Jim]

"Mitragynine, mitraphylline, and 7-Hydroxymitragynine are all indole alkaloids of various sorts:"

the fact that they are indoleamines found to be present in kratom catches my eye and does IMO make this article more than just splitting hairs.

it's interresting to me because indolemaines are often found to be active in serotonergic pathways. edit : indole alkaloid's/indoleamine's such as serotonin, melatonin, DMT, psilocybin, LSD etc etc

"The essential structural moieties in the Corynanthe type indole alkaloids for inducing the opioid agonistic activity were also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice."

ths is kind of the most interesting part of the article for me because they are saying this indole alkaloid (indoleamine) has been found to activate opiate pathways, which is/was not a particularly well known property of indoleamine type molecules. Not to my knowledge.

Edited January 29, 2013 by Sonny Jim

[endorfinder]

Don't get caught up on the whole "indoleamine" thing. Indole groups are found widely of substances in nature, mitragynine and others have them yes but they're a tiny portion of its structure. Compare the receptor binding insanity of the complex "indole" ibogaine with simple tryptamines.

By the same logic cocaine is an atropine-related compound. You can argue it based on the structure but... When it comes to the crunch.

[Sonny Jim]

Well I kinda hear you about not getting tooooooo caught up in the whole indoleamine thing but

indoleamines are well worth getting caught up in IMHO

"Indole groups are found widely of substances in nature, mitragynine and others have them yes but they're a tiny portion of its structure."

yes they are widely found in all life forms due to them being derived from the amino acid tryptophan but this makes them all the more worth getting caught up in.

also mitragynine is actually mostly indolamine not just a tiny part indoleamine but that's not necessarilyn an important concern when it comes to speculating on the properties of a given indoleamine.

I and many others are fascinated by indoleamines in general because we know that they tend to be amazingly important factor of biochem that's been a tad neglected by entheogentic forums...to my knowledge.

for example did you know that it seems all simple indolemaines are antioxidant and some are rediculaously powerful antioxidants. melatonin for example is suggested to be a very important antioxidant in the human. Just think, every time you catch eight hours sleep in the dark your functioning (hopefully functioning because, lots of adults succumb to calcification of the pineal gland and probably) pineal gland spews out heaps of indolemaines like melatonin which bath your brain in a powerful antioxidants, which probably also makes you dream like a champion at the same time.

Got to sleep in the dark!

So i am looking at papers that are giving me the impression that all indolemaine are potentially antioxidant… am guessing it’s the amines in the structure but i will have to check that.

Anyway, I got to go but i will post some supporting articles when i get back or do some indolemaine/pineal/antioxidant googling if you can’t wait.

Edited January 30, 2013 by Sonny Jim

[Sonny Jim]

"By the same logic cocaine is an atropine-related compound. You can argue it based on the structure but... When it comes to the crunch."

if your trying to say that there aren't important structural themes common to neurotransmission and that they aren't worth being interested in then I probably would disagree with that because structure and reactivity are pretty fundamental to all medicinal chemistry and looking for themes in nature is useful to understand any part of biochemistry. The indoleamines are a case in point, now we can learn about this aspect of their function in the animal that's all to do with keeping it alive and well. Very intersting to see this side to the biochemistry of indoleamines because it makes me feel good about tripping naturally on indoleamines. edit: and it's good thing there will be more to learn about indoleamines like how they regulate other hormones in the body like i am reading about thier role in puberty. easy find with google but i will try and the specific article i read a few weeks back if i can find it.

edit:sorry crazy typos everywhere

Edited January 30, 2013 by Sonny Jim

[Sonny Jim]

sorry for all the posts but that part about the "The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice."

that's pretty nice to know as the author states.

[endorfinder]

I think you would enjoy doing some org chem and pharmacology study part time or externally... are you close to a university?

[Sonny Jim]

did i do something wrong?

[Sonny Jim]

anyway i read back through the thread and I wonder if I have inadvertantly made my first post sound like I was disagreeing or something like that with you in my first post when I said I don't think it is actually splitting hairs. Of course your response to the thread title was valid because the thread title kinda made it seem like the OP was trying to say Kratom is not an opiate...of course it is not an opiate but they are opioud type of compound in the sense that they reckon it works like one and does effect the right opiate receptors

I should have written something to concur with the first two post before I got carred away talking about indoleamines.

and it's OK I have already studied a lot of pharmacology and organic chemistry at uni, I don't like to be specific about my background because I don't want to identify my self but I am currently working through my second degree (just over half way finished) which happens to be in medicinal chemistry and my first degree was in the medical sciences so I am OK with a lot of the current theory if that's why you asked about uni. But I will also say that I don't think the usual pharmacology and chemistry units people have to do to get science degreess are necessary to put one's self through to be able to understand the current theory on what ever related subject, it just helps but it is also a lot of over kill and in the case of chem I know they put a lot of stuff into the work load of students that make it more about weeding people out and ranking students rather than making a semester that's all about building a genuine appreciation for chem. I have done chem subjects in both my degree which were at separate uni's and i have always been disappointed by the way organic chem in-particular is taught and the things they emphasize in exams. Org-chem and biochem for that matter were presented as exercises in wrote learning, not so much in the lectures and the pracs are usually grate. I have actually learnt more useful org chem in the year after i did the actual units, so much of org chems really is a waste of time to memorise and it takes ages to memorise, lie I could have spent every waking moment studying org-chem and nothing else (pretty much did) and ALL of it had been forgotten a couple of week after the exam.

Sorry for rambling on a bit I just wanted to say all that about uni study.

edits: for clarity

Edited February 1, 2013 by Sonny Jim

[endorfinder]

There are a finite number of useful functional groups in chemistry, and I finite number of orientations of those. Of course the number of permutations is huge, but the point is that a lot of active substances in humans will contain indole/indoleamine groups regardless of their functionality... there is no intrinsic tie to psychs like tryptamines/lsd/etc.

If you want to look at LSD selectively it can be seen as a phenethylamine, an indole, and contains enough other substructures that you can go wild. Of course the same also applies to ergotamine, which is of interest only as a vasodilator and perhaps as a precursor.

[Anodyne]

With this being said, it has been found to have a higher potency than that of morphine in its compound form alone. Now there's some news you can use when debating the strength of Kratom. It is just the contents of the plant you buy, the extract levels, or "how much you are getting" that makes it strong or weak. Yet in just the chemical sense, it can actually be a very potent little plant. I wish I had access to the full paper, but it costs money to receive. If anyone finds it, we need to upload this. It has valuable member information to dispel this belief of kratom being an "opiate" as some may think of it as.

Thanks for the abstract. Someone has attached the full pdf to the drugs-forum thread (link in 1st post) if anyone is interested.

While that post has some interesting info, it doesn't actually seem to achieve its stated purpose "to address the misconceptions that float around the Kratom forum and with general users who do not fully understand the plant in its contents and nature". I'm with the Ewok here, it really does seem to be splitting semantic hairs, and I've watched this particular debate play out too many times already. Usually by people who are trying to convince themselves that kratom isn't addictive like "real" opiates. I'm pretty sure that not many folks around here actually believe that mitragynine comes from opium poppies, so when they use the term "opiate", they're probably talking about its pharmacology, not its lineage.

The important points are:

*kratom contains compounds with mu-opioid agonist activity.

*kratom is an S9 scheduled substance, so research into its fascinating pharmacology is totally off-limits to Australian researchers.

*TGA are corrupt fuckwads.

Kratom pharmacology is quite complex. I lost my collection of kratom pdfs years ago (if anyone has access, could they please upload or send them to me?), but from memory there was even something which had partial-[mu?]-opioid-agonist activity, and therefore potential to be used as a lower-addiction-risk painkiller or detox drug, in the same way that buprenorphine is. Ah nup, it's no good. I'm getting angry at the TGA again, have to come back later when I've calmed down.

[Bigred]

whoops wrong thread

Edited February 8, 2013 by bigred82

[endorfinder]

In regards to the original topic "Kratom is NOT an Opiate plant", I think it actually brings up an interesting question.

The definition of opiate as opposed to opioid is sometimes "substance extracted from opium", "semi-synthetic opium derivative", or "opioid of plant origin". In which case Kratom would technically fall into the last, most inclusive category.