Kratom: The Dangerous “Tea” Every Parent Needs to Know About

This is a one sided fear mongering article, which is highly dismissive of the centuries old healing aspects. I'm not saying that Kratom, like any other drug cannot cause problems - what I am saying is that any drug - specifically as related to this article - those that cause 'hallucinations' should be used in a correct set and setting combined with an informed choice. Drug use does not necessarily lead to drug abuse - but it can do for many reasons. When consciousness altering drugs gain in popularity there is always someone waiting in the wings to jump on the productivity bandwagon - the natural drug is chemically manipulated and handed out like sweets - children (by which I mean immature and ignorant) people grab these sweets like kids in a candy store without thinking twice.
What is required is accurate information that explains both the risks and rewards of taking any form of 'hallucinogen' - I place that word in comma's as many people who have taken these consciousness expanding drugs will tell you that these experiences are real - the information then leads to the child becoming an adult and making a mature choice with full knowledge of all potential consequences.
From reading this article it would lead me to think that it might be beneficial if you did further research in the psychedelic arena in order to offer a more balanced perspective when discussing these drugs.

What a shameful display of ignorance by Constance Scharff. One should really educate oneself before dialing in a one-sided hysterical article like this.

Kratom has been used medicinally for thousands of years to provide physical relief in a safe and all-natural way.

As a self-proclaimed addiction expert, you may like to know that kratom has been used to treat heroin addiction and turn people's lives around successfully in many, many, may cases (Read up on a new hope for addicts on http://medicalxpress.com/news/2013-01-addicts.html).

Imagine an all-natural tea, from a plant in the coffee plant family that takes all physical addiction cravings away; that is kratom and it saves lives - every day.

As an addiction expert, you may want to stay up to date with current developments. Just because you don't know a plant does not make it new so be mindful of the ethics of your actions.

More sources:

Forbes: http://www.daviddisalvo.org/the-daily-brain/2013/4/5/results-of-my-kratom-experiment.html

Scientific American: http://www.scientificamerican.com/article.cfm?id=should-kratom-be-legal

Seriously? Articles like that make me SOOO angry. Did you ever SEE kratom? Did you ever TRY it? Do you know anyone in PERSON who ever tried it? Do you know ANYTHING about it except what you have read on government websites paid for by big pharma companies? You should be targeting things like heroin and PRESCRIPTION PAINKILLERS, because those things can actually KILL YOU, not just your pain. Kratom is just as safe as coffee and has helped THOUSANDS of people with many issues, including ADDICTION TO PAINKILLERS. So please do a little more research before posting this crap. Thanks.

Oh and PLEASE humor me and post a proof that it is "leading its way in emergency room visits". I bet you just made that up off the top of your head just to prove a (non-existent) point.

For one thing, I agree that kratom should not be sold or advertised as a legal high. Also when bought at headshops or prepackaged there is no way to know if it is actually kratom or it is mixed with other substances. Kratom should only be utilized in its pure leaf form.

The sources you quote are not thorough. In the final source you forgot to quote the follow up article by the same author David Disalvo, in which he did his own experiment on himself and came to the conclusion that Kratom was on par with Coffee
http://www.daviddisalvo.org/the-daily-brain/2013/4/5/results-of-my-kratom-experiment.html

Also, in regard to your second article there are way more emergency room visits for tylenol than Kratom. Why isn't this ever in the media to the extent that natural remedies are?

I would also like to direct you to the Scientific American journal article written late last year regarding kratom which gives credit to its therapeutic and medicinal benefits.
http://www.scientificamerican.com/article/should-kratom-be-legal/

In addition here is another article from the University of Mississippi regarding the therapeutic benefits of kratom
http://news.olemiss.edu/new-hope-for-addicts/#.UyJDhlemRFs

Furthermore if you go to the http://www.botanicallegaldefense.org/ website there are lots of research articles relating to the benefits and merits of Kratom.

I have seen alot of people regain their quality of life back from this plant, and it makes me sad to see it constantly be made the villain in the media. It should be along side herbs like Valerian root, Kava, and St John's Wort. All of which need to be taken responsibly and provide therapeutic benefit

There are people who use kratom as therapy and then there are the idiots who use kratom for recreational purposes, so to speak. The problem of addiction is a problem that exists with 100% of the legal substances and with good portion of the illegal ones. Kratom may produce dependence if used for a long period of time, but the benefits of its use are absolutely superior. It’s obvious that in case of serious chronic disease, the addiction isn’t the problem must be seen in perspective different from the consequences of the disease itself: I mean if it’s chronic disease, is also chronic the use of Kratom. It’s better to have chronic pain for a lifetime or use kratom? It’s better to commit suicide as a result of chronic DDM or use kratom? I personally absolutely don’t care addiction, if my disease is chronic. Speech is very different - as I have already said - for those idiots who use Kratom for recreational purposes. Remains intact the fact that minors should not use Kratom.

I have been using kratom responsibly for 3 years. My life had been a complete upset for 35 years. I have been on almost every antidepressant science has made. None of them worked for me, they made things worse. I am also a chronic pain patient. I will be on medication for the rest of my life. This is a false claim .."In larger doses, Kratum has a highly sedating effect and may suppress respiration to the point of death" I would love to know where you get this information????? And I would love to know the number of kratom cases you have treated. Can you give me that total??? And as far as teens knowing about this plant, that would be the media that has bought this to the attention of teens, the claims they make time after time are bound to get attention, they keep using the words drug and stimulant and opiate, heroin cocain. It is nothing at all like heroin or cocaine. I know this because as I lost all faith in big pharms and doctors I began to self medicate with pretty much every street drug there is and if I didn't find this plant I would still be struggling to find my way or worse, I may be dead. But just because I found this plant, my life has done a complete turn around over the last three years. I am no longer struggling to live under the medications that I believed was my answer. This may not be the answer for everyone but it is for me and my family. But I am only someones daughter,someones sister, someone's grandmother, someones mother seems that son't mean much to law makers and doctors that are suppose to be on my side. I wish people like yourself would do more research before you put out your thoughts on "psychology" you really have more to learn then you know. http://usnews.nbcnews.com/_news/2012/03/19/10760892-asian-leaf-kratom-making-presence-felt-in-us-emergency-rooms?lite..http://www.addictiontreatmentmagazine.com/addiction/drug-addiction/the-dangers-of-kratom-reality-or-hysteria/. these links you posted are nothing new and certainly hold no weight. You should really take more time and talk to the real people surrounding this plant. So disappointing and pretty clear as to what is surrounding this media attention...that would be "MONEY"

This article is based on fiction, nothing more. It always amazes me the way some people demonize things they don't understand. Bogus facts and straight out lies woven together as if they are truth with the sole purpose of destroying a natural substance that has been proven useful longer than the human time line would like to remember. It is ridiculous, these articles are written to distract from the real problems plaguing society, the rampant prescription abuse, and the willingness of pharmaceutical makers to make ever stronger drugs to trap people.

I reveal to you the real reason these type of articles are being written. Millions of dollars are being spent at this very moment tinkering with kratom's alkaloid structure in order to hold a patent. Kratom is a threat to the prescription painkiller black market. People are using kratom to kick opioid habits. That is the real meat and potatoes - and the real reason people are spinning together these webs of faux facts.

I'm a 54 year old male who's been using kratom for the past year for pain relief, energy, and general feeling of well being.
For me, kratom withdrawal side affects are mild.I've been
taking two 00 sized caps in the morning, the same after noon, and 2 at bed time. I'm reasonably pain free and energetic. Just got
my health exam and liver function is just fine. I buy bulk and
encapsulate at home.

Substances derived from natural products have been utilized since the beginning of time for various medical purposes including the treatment of pain. Opium, for example, has been mentioned in the earliest historical records, some 7000 years ago. In fact, research in the area of pain management and drug addiction originally focused on natural products exclusively. Prototypical examples of such natural products are the opium poppy (Papaver somniferum). Morphine, an alkaloid component of the opium poppy, is the most widely used compound among narcotic analgesics and remains the gold standard. Recently, analogs have been produced from natural substances, and completely synthetic compounds based on natural pharmacophores have been introduced to the market. However, the research and medical fields still struggle with the undesirable side-effects of these analgesic substances (McCurdy and Scully 2005).
Our research group has studied uniquely structured, nitrogen-containing compounds isolated from the traditional Thai herb Mitragyna speciosa. This herb has long been used in tropical areas for its opium- and coca-like effects (Burkill, 1935). It has been used also as a substitute for opium and to wean addicts off morphine (Grewal, 1932; Suwanlert, 1975). We have been investigating the pharmacological properties of this herb, individual components of its extracts, and structurally related compounds since the 1980s. We compared the antinociceptive effects of Mitragyna speciosa and mitragynine, the major alkaloid of this herb, in in vivo experiments, and found that the antinociceptive effect of mitragynine was less potent than that of the crude extract of Mitragyna speciosa (Watanabe et al., 1992, 1999). This finding means that one or more minor constituents of Mitragyna speciosa may have a very potent antinociceptive effect. We have investigated mitragynine-related compounds that express interesting opioid activities: an oxidative derivative of mitragynine, mitragynine pseudoindoxyl, was found to exhibit potent opioid agonistic activity in vitro and antinociceptive activity in vivo (Yamamoto et al., 1999; Takayama et al., 2002). These findings prompted us to embark on the development of novel compounds based on the mitragynine skeleton, which is quite different from the skeleton of morphine.
In the present study attempting to find a new analgesic from the Thai herbal medicine, I surveyed the opioid effects of the other constituents of Mitragyna speciosa and synthetic derivatives of
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mitragynine by the Magnus method in isolated smooth muscle preparations. Among them, I found a novel alkaloid, 7-hydroxymitragynine, a minor constituent of Mitragyna speciosa, and investigated the involvement of opioid receptor subtypes by in vitro assays. Furthermore, I investigated the antinociceptive and side effects of 7-hydroxymitragynine in vivo and compared them to the effects of morphine to evaluate the clinical utility of 7-hydroxymitragynine.
1. Historical overview of Mitragyna speciosa
Mitragyna speciosa Korth has been used for many years in Thailand, Malaysia, Borneo, the Philippines, and New Guinea; the Thai and Malay natives use it as a substitute for opium. It is called “kratom” by the natives of Thailand and “biak-biak” in Malaysia. Natives used the leaves of the plant in fresh or dried forms, and they also prepared syrup by evaporating a solution made from dried leaves. The leaves were chewed, or the syrup was drunk after dissolving it in hot water, or even smoked in a way similar to opium. Besides the use of leaves of Mitragyna speciosa as a substitute for opium, other uses are a cure for fever, treatment for diarrhea, and a cure for opioid withdrawal syndrome (Burkill, 1935). Furthermore, Suwanlert (1975) reported the use of Mitragyna speciosa as a stimulant in Thailand by market gardeners, peasants, and laborers to overcome the burden of hard work as well increasing work efficiency under a scoring sun. His study on Mitragyna speciosa users in Thailand describes the stimulant effect and strong desire to work induced by the plant as leading to its regular use, which progresses to addiction. In these addicts, symptoms such as anorexia, weight loss, stomach distention, insomnia, darkening of the skin, constipation, and withdrawal syndrome were reported (Grewal, 1932; Suwanlert, 1975).
In contrast, there are reports that Mitragyna speciosa use causes much less aggressiveness and hostility than opium smoking, that is, the absence of adverse physical conditions and character changes (Jansen and Prast, 1988). Mitragyna speciosa has a psychostimulant effect like coca and a depressive effect like opium and cannabis, which seem to be contradictory. It is also reported that it is weaker than morphine, has a milder withdrawal syndrome compared to opioids, and is less harmful
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than cocaine. Although the medical use of Mitragyna speciosa to treat opium addicts in Thailand has been documented (Jansen and Prast, 1988; Burkill and Haniff, 1930), its use has been prohibited by Thai law since 1943 because of its narcotic effects. However, this law is not effective because the tree of Mitragyna speciosa is indigenous to the country. The fact is that the herb is not under any control in many other countries and is readily available on the Internet for purchase by anyone (McCurdy and Scully 2005).
Chewing the leaves of Mitragyna speciosa
2. Pharmacology of mitragynine and its metabolite
Mitragyna speciosa (kratom) leaves
Mitragynine (Figure 1) is the major alkaloid of Mitragyna speciosa, and for this reason mitragynine was assumed to be the major chemical responsible for the effects of this herb. Hooper (1907) was the first person to isolate mitragynine, and this was repeated by Field (1921). Its structure was first fully determined by Zacharias et al. (1964). In the 1960s, the Chelsea group in the U.K. reported the isolation of several indole alkaloids from the leaves of Mitragyna speciosa from Thailand (Beckett et al., 1965, 1966a, b). Almost ten years later, Shellard et al. (1974) isolated more than twenty kinds of Corynanthe-type alkaloids, including oxindole derivatives, in their investigation of the alkaloid constituents in various samples of Mitragyna speciosa from Thailand. They pointed out that the variation in the constituents among different batches of leaves may be an indication of the presence of geographical variants of the species within Thailand (Shellard, 1974).
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The pharmacology of Mitragyna speciosa and mitragynine was first explored by K. S. Grewal at the University of Cambridge in 1932. He performed a series of experiments on animal tissues and a group of five male volunteers. He described mitragynine as having a central nervous system stimulant effect resembling that of cocaine. Macko et al. (1972) reported that mitragynine exhibited antinociceptive and antitussive actions in mice comparable those of codeine. Their findings were that, unlike opioid analgesics at equivalent doses, mitragynine did not possess the side effects common to opioids. Moreover, the absence of an antagonistic effect of nalorphine on mitragynine-induced antinociception led them postulate noninvolvement of the opioid system in the action of mitragynine.
We have studied the pharmacological effects of mitragynine on guinea-pig ileum, mouse vas deferens, radioligand binding, and the tail-flick test in mice, and found that mitragynine acts on opioid receptors and possesses antinociceptive effects (Watanabe et al., 1997; Yamamoto et al., 1999; Takayama et al., 2002). But the effect of mitragynine was less potent than that of morphine. Some pharmacological investigations of mitragynine have also revealed that it has an antinociceptive action through the supraspinal opioid receptors, and that its action is dominantly mediated by μ- and δ-opioid receptors in in vivo and in vitro studies (Matsumoto et al., 1996a, b; Tohda et al., 1997; Thongpradichote et al., 1998).
Another alkaloid of interest is mitragynine pseudoindoxyl (Figure 1), which was at first isolated as a metabolite of mitragynine by microbial biotransformation. Macko et al. (1972) reported that oral administration of mitragynine was more effective than subcutaneous administration. This finding suggested that the antinociceptive effect of mitragynine exists predominantly in its derivatives. Our previous study demonstrated a potent opioid agonistic property of compound mitragynine pseudoindoxyl in in vitro experiments (Yamamoto et al., 1999). In guinea-pig ileum, mitragynine and mitragynine pseudoindoxyl inhibit the twitch contraction through opioid receptors. The effect of mitragynine pseudoindoxyl was 20 fold more potent than that of morphine. In mouse vas deferens, the effect of mitragynine pseudoindoxyl was 35 fold more potent than that of morphine. In spite of its potent opioid effect, mitragynine pseudoindoxyl induced only a weak antinociceptive effect in the mouse tail-flick test in comparison with morphine (Takayama et al., 2002).
4
9
O
OCH3
OCH3
NNN HH
NH H H3COOC
OCH3 H3COOC OCH3 Mitragynine pseudoindoxyl
Mitragynine
Figure 1 Chemical structures of mitragynine and mitragynine pseudoindoxyl
3. Opioid receptor and analgesics
Opioid is the common name for all compounds that have the same mechanism of action as the constituents of opium. All opioids interact with the endogenous opioid receptor system, which presently includes four known receptor subtypes (Dhawan et al., 1996) that are designated μ, δ, κ, and ORL-1 (opioid receptor-like receptor 1). These receptors are widely distributed in the mammalian system and have been found in all vertebrates. Their density is relatively high in the brain and spinal cord, but they are also found in the gastrointestinal system and the cells of the immune system.
Although all three major types of opioid receptors, μ, δ, and κ-opioid receptors, are able to mediate analgesia/antinociception, their individual binding profiles and other pharmacological activities clearly distinguish one from another. Highly selective ligands that allow for receptor-type labeling have become available, and are summarized in Table 1. Of the three major classes of opioid receptors the μ-opioid receptor has proven to be the major target of opioid analgesics. Morphine is the prototypical μ-opioid analgesic that serves as the standard drug against which all analgesics are compared in determining their relative analgesic potencies. It has been recommended as the drug of choice in the management of patients with chronic cancer pain by the World Health Organization Cancer Unit in its Cancer Pain Relief Program.
However, morphine also has undesirable effects, such as tolerance, withdrawal symptoms, constipation, respiratory depression, nausea, and vomiting. The majority of clinically available opioid
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analgesics are μ-agonists derived from chemical templates that relate to the natural opium alkaloids, with progressive simplification through the morphinans to the benzomorphans and the piperidines, to the phenylpropylamines, e.g., fentanyl, pethidine, and methadone (Corbett et al., 2006).
The major goals of opioid research are to understand the underlying biology of the endogenous opioid systems, to discover new analgesic drugs devoid of the unwanted side effects associated with morphine, and to develop new therapies for the treatment of opioid addicts. To find the ideal opioid analgesic, thousands of analogues have been synthesized, but an ideal analgesic that has a powerful effect yet is free from undesirable side effects has not been found at this stage.
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Table 1 Opioid receptor and ligand relationship Currently accepted name
Currently IUPHAR name
Endogeneous ligands
μ
OP3
β-Endorphin Endomorphin-1 Endomorphin-2 DAMGO
Fentanyl Morphine
β-FNA (μ1, μ2) CTOP (μ1, μ2) Cyprodime (μ1, μ2) Naloxonazine (μ1) Naloxone Naltrexone [3H]DAMGO [3H]Naloxone
δ
OP1 Enkephalins
κ
OP2 Dynorphin
ORL1
OP4 Nociceptin/Orphanin FQ
Exogeneous agonists
DPDPE (δ1) DSLET (δ2)
U69593 (κ1) U50488 (κ1)
Nociceptin/OrphaninFQ
Selective antagonists
Naltrindole (δ1, δ2) DALCE (δ1) naltriben (δ2)
norBNI (κ1, κ2)
Non selective antagonists
Naloxone Naltrexone [3H]Naltrindole [3H]DPDPE
Naloxone Naltrexone [3H]U69593 [3H]norBNI
Radioligands of choice
[3H] Nociceptin/Orphanin FQ
Abbreviations
norBNI, nor-Binaltorphimine; CTOP, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2; DALCE, [D-Ala2,Leu5,Cys6]-Enkephalin;
DAMGO, [D-Ala2,N-Me-Phe4,Gly-ol5]-Enkephalin; DPDPE: [D-Pen2,5]-Enkephalin; DSLET, [D-Ser2,Leu5,Thr6]-Enkephalin; Endomorphin 1, Tyr-Pro-Trp-Phe-NH2; Endomorphin 2, Tyr-Pro-Phe-Phe-NH2; β-FNA, β-Funaltrexamine; U69593, (+)-(5α,7α,8β)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl)benzeneacetamide; U50488, 3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide
Part Ι. Exploration of compounds acting on opioid receptors in components of Mitragyna speciosa and its related synthetic alkaloids
1. Introduction
Mitragyna speciosa (called kratom in Thailand) has been used in Thailand for its opium- and coca-like effects. Additionally, it has been used to treat diarrhea and to wean addicts off morphine (Jansen and Prast, 1988). This medicinal herb contains many indole alkaloids (Houghton et al., 1991; Takayama et al., 1999, 2000). Mitragynine (Figure 1) is a main constituent of the leaves of Mitragyna speciosa (Takayama et al., 2000). Recently, we found that mitragynine acts on μ-opioid receptors in guinea-pig ileum (Watanabe et al., 1997; Yamamoto et al, 1999). In addition, some pharmacological studies have also revealed that mitragynine has an antinociceptive action through the supraspinal μ- and δ-opioid receptors (Matsumoto et al., 1996a, b; Tohda et al., 1997; Thongpradichote et al., 1998). The antinociceptive effect of mitragynine, however, is less potent than that of the crude extract of this plant (Watanabe et al., 1999). That is, the opium-like effect of Mitragyna speciosa cannot be fully explained by that of mitragynine. This finding suggests that minor constituents of Mitragyna speciosa have a very potent antinociceptive effect. However, this plant has not so far been investigated systematically for isolation of opioid agonistic constituents. In the present chapter, we fractionated the crude extract of Mitragyna speciosa, and explored active constituents that have opioid agonistic activities using an in vitro guinea-pig ileal contraction test. Furthermore, we surveyed the opioid agonistic activities of semi-synthetic compounds derived from mitragynine in order to elucidate specific structure necessary for its pharmacophore binding on opioid receptors.
2. Materials and methods
Animals
All experiments were performed in compliance with the “Guiding Principles for the Care and 8
Use of Laboratory Animals” approved by the Japanese Pharmacological Society. The number of animals used was kept to the minimum necessary for a meaningful interpretation of the data, and animal discomfort was kept to the minimum. Male albino guinea pigs (320–540 g, Takasugi Lab. Animals, Japan) were killed by CO2 inhalation.
Isolation of guinea-pig ileum
The guinea-pig ileum was dissected and placed in Krebs-Henseleit solution (mM): NaCl, 112.08; KCl, 5.90; CaCl2, 1.97; MgCl2, 1.18; NaH2PO4, 1.22; NaHCO3, 25.00 and glucose, 11.49. The ileum was placed under 1 g tension in a 5 ml organ bath containing the nutrient solution. The bath was maintained at 37oC and continuously bubbled with a mixture of 95% O2 and 5% CO2. Tissues were stimulated by a platinum needle-ring (the ring was placed 20 mm above the base of a needle 5 mm in length) electrode. After 60 min equilibration in Krebs-Henseleit solution, the ileum was transmurally stimulated (Cox and Weinstock, 1966) with monophasic pulses (0.2 Hz and 0.1 ms duration) by a stimulator (SEN-7203, Nihon Kohden, Tokyo, Japan). Contractions were isotonically recorded by using a displacement transducer (NEC Type 45347, San-ei Instruments Ltd., Tokyo, Japan). The effects of drug treatments on the twitch contractions evoked by transmural stimulation elicited through the ring electrodes were examined. At the start of each experiment, the maximum response to acetylcholine (3 μM) in each tissue was obtained to check its stability. The mean amplitude of the electrically-stimulated contraction was about 30% of the maximal response to acetylcholine (3 μM). The electrically-induced twitch contraction was almost abolished by tetrodotoxin (1 μM) and atropine (0.1 μM), as described previously (Watanabe et al., 1997). Thus, the electrical stimulation induced cholinergic contraction in guinea-pig ileum (Brookes et al., 1991). The height of the twitch response to transmural stimulation was measured before and after the drug challenge. Contraction (%) is expressed as a percentage of the twitch response to the transmural stimulation before the drug challenge.
Plant material
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The leaves of Mitragyna speciosa were collected on the campus of the Faculty of Pharmaceutical Sciences, Chulalongkorn University. The plant was identified by Dr. Nijsiri Ruangrungsi, Faculty of Pharmaceutical Sciences, Chulalongkorn University. A voucher sample (#1991Dec-MS) was deposited in the Herbarium of the Faculty of Pharmaceutical Sciences, Chulalongkorn University.
Extraction and isolation
Big, young leaves were powdered (165.5 g) and extracted five times with hot methanol. The solvent was concentrated under reduced pressure to give a crude extract (53.5 g), a part of which was dissolved in 10% aqueous acetic acid (AcOH). The insoluble material was removed by filtration through Celite to give the AcOH-insoluble fraction solution (AcOH-insoluble fraction, 50.3 g). The aqueous layer was basified with Na2CO3 at 0°C and extracted with chloroform (CHCl3). The organic layer was washed with water, dried over MgSO4, and then evaporated to give the crude base fraction (2.43 g). The aqueous layer was further extracted with n-Butanol (BuOH), which was concentrated under reduced pressure to yield the n-BuOH fraction (4.77 g). A part of the residual aqueous solution (10 ml) was lyophilized to give a hygroscopic solid (ca. 2 g), which was isolated with ethanol using a Soxhlet extractor in order to remove the inorganic materials. The ethanol extract was evaporated to give a residue containing the water-soluble organic materials (water-soluble fraction, 1.08 g).
The crude base fraction (2.0 g), which exhibited an opioid agonistic effect on the guinea-pig ileum, was purified by SiO2 column chromatography (6 × 17 cm) using CHCl3/ethyl acetate (AcOEt) (9:1, 370 ml; fraction A), CHCl3/AcOEt (4:1, 240 ml; fraction B), CHCl3/AcOEt (1:1, 320 ml; fraction C), AcOEt (80 ml; fraction D), MeOH/AcOEt (1:19, 120 ml; fraction E), MeOH/AcOEt (1:4, 160 ml; fraction F), MeOH/AcOEt (1:1, 80 ml; fraction G), and MeOH (150 ml; fraction H). The combined fractions C and D were further purified by SiO2 column chromatography (3 × 17 cm) using an n-hexane/AcOEt (3:2, 1:1, 1:5, 30 ml each) gradient that afforded 24 fractions. Fractions 2–8 contained mitragynine (1343 mg, 66% based on the crude base, [α]D24: –126° {c 1.2, CHCl3}) and fractions 18–22 yielded 7-hydroxymitragynine (40 mg, 2% based on the crude base, [α]D23: + 47.9° {c
10
0.55, CHCl3}). From fraction E, paynantheine (178 mg, 8.9% based on the crude base, [α]D25: + 29.4° (c 1.2, CHCl3}) was obtained. Fraction F afforded speciogynine (132 mg, 6.6% based on the crude base, [α]D24: + 26.8° (c 0.85, CHCl3}). Fraction G was subjected to MPLC (SiO2, 2.5 × 10 cm) with MeOH/CHCl3 (1:9, 3 mL/min) to provide speciociliatine (tR: 18 min, 15 mg, 0.8% based on the crude base, [α]D24: –10.5° (c 1.2, CHCl3}). The isolated compounds were identified by direct comparison with the corresponding authentic samples. The purity (> 99%) of the above compounds was checked by HPLC and 1H-NMR (500 MHz) analyses.
Chemistry
To investigate the structure-activity relationship, mitragynine was isolated from the extract of leaves of Mitragyna speciosa. Mitragynine-related indole alkaloids (Figure 2) were synthesized from mitragynine as described previously (Takayama et al., 2002, 2004). The purity (> 99%) of these compounds was checked by HPLC and 1H-NMR (500 MHz) analysis (Takayama et al., 2002).
Drugs
The drugs used in this study were acetylcholine chloride (Dai-ichi Pharmaceutical Co., Tokyo, Japan), atropine sulfate (Nacalai Tesque Inc., Tokyo, Japan), tetrodotoxin (Sankyo, Tokyo, Japan), morphine hydrochloride (Takeda Chemical Industries, Osaka, Japan), and naloxone hydrochloride (Sigma Chemical Co., St. Louis, USA). For bioassays, mitragynine-related alkaloids were first dissolved in 100% dimethylsulfoxide to yield a 10 mM solution and then subsequently diluted with distilled water. Other drugs were dissolved in distilled water.
Statistical analysis
The data are expressed as the mean ± S.E.M. Statistical analyses were performed with two-tailed t-test for comparison of two groups, and by a one-way analysis of variance, followed by a Bonferroni
11
multiple comparison test for comparison of more than two groups. A P value 99%) of these compounds was checked by HPLC and 1H-NMR (500 MHz) analysis (Takayama et al., 2002).
Mitragynine, 7-hydroxymitragynine, and 9-hydroxycorynantheidine were first dissolved in 100% dimethylsulfoxide to yield a 10 mM solution and then subsequently diluted with distilled water. β-Funaltorexamine hydrochloride were first dissolved in 100% dimethylsulfoxide to yield a 1 mM solution, and then subsequently diluted with distilled water. Other drugs were dissolved in distilled water.
Statistical analysis
The data are expressed as the mean ± S.E.M. Statistical analyses were performed with two-tailed Student’s t-test for comparison of two groups, and by a one-way analysis of variance, followed by a Bonferroni multiple comparison test for comparison of more than two groups. A P value 99%) of these compounds was checked by HPLC and 1H-NMR (500 MHz) analysis (Takayama et al., 2002).
For s.c. administration, 7-hydroxymitragynine was dissolved in phosphate-buffered saline (pH, 5.5). Mitragynine and 9-hydroxycorynantheidine were first dissolved in 100% dimethylsulfoxide and then subsequently diluted with 0.5% carboxyl methylcellulose. The final concentration of dimethylsulfoxide was 4.8%. Other drugs were dissolved in saline. For p.o. administration, 7-hydroxymitragynine was dissolved in 10 mM phosphate-buffer (pH, 5.5). Morphine was dissolved in distilled water. All the drugs were administered using a volume of 0.1 ml/10 g body weight.
The opiate antagonists, NX-M (3 mg/kg), NX (2 mg/kg) and NTI (3 mg/kg), norBNI (20 mg/kg), and NLZ (35 mg/kg) and β-FNA (40 mg/kg), were administered s.c. 15 min, 30 min, 3 h, and 24 h, respectively, before 7-hydroxymitragynine or morphine injection (s.c.).
Statistical analysis
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The data are expressed as the mean ± S.E.M. Statistical analyses were performed with two-tailed Student’s t-test for comparison of two groups, and by a one-way analysis of variance, followed by a Bonferroni multiple comparison test for comparison of more than two groups. A P value 99%) of mitragynine was checked by HPLC and 1H-NMR (500 MHz) analysis (Takayama et al., 2002). Mitragynine was first dissolved in 100% dimethylsulfoxide to yield a 1 mM solution, and then
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subsequently diluted with distilled water. Other drugs were dissolved in distilled water.
Statistical analysis
The data are expressed as the mean ± S.E.M. Statistical analyses were performed with two-tailed Student’s t-test for comparison of two groups, and by a one-way analysis of variance, followed by a Bonferroni multiple comparison test for comparison of more than two groups. A P value

From opioids to marijuana, I really cannot fathom the mindset, that brings so many people to write these fear driven peices. In general I cannot understand why so many (number seems to be growing rapidly) care sooo much about the choices others are making with their bodies. Is it jealousy?: "If I can't/wont have it, no one else should"...Is it control?: "I just don't think people should do (A,B,C)"...Or is it simply an unwillingness to even TRY to understand that different people, have different issues (issues you have never and will never experience or understand), some of which have remedies that might be alien (to you) different than what works for YOU. Mind your own business!? We see time and time again, that the most universally damaging aspect of addiction is our penal system, and that the cause of basically ALL of the questionable or undesired behaviors attributed to the use of any substance, is its regulation (noone steals, kills or lies to obtain a regularly available item). This is the glorious construct of our war on drugs, the ideologies it fosters and the profit driven design of it...its making no one safer, sober(er) or smarter; it is a primitive intolerance of anything we cannot quantify or understand. There are so many man made horrors this world now has to offer, mostly a result of governement (and its minions) intrusion ...and you (minion) chose Kratom. How about you visit a constructive idea, like why our medical system has left millions of chronic pain sufferers out to dry (simultaneously labeling them drug addicts), as a sacrifice to the aforementioned war. That practically over night, the MOST effective treatment for acute and chronic pain, is deemed unsafe and ineffective despite being one of the safest drugs we currently prescribe. For many there is no other option, and the litney of suggested excuses for alternative treatment, is broadly recognized as a cop out (because our government doesnt know how else to approach the "opioid epidemic"; many parts of which are nothing but fabrications). I think this would be a much more noble gesture, compaired to "ratting out" one of the few (lack luster) "alternatives" these pained individuals can cling to, while our government sorts out its opiophobic contradictions.

Came across this while looking for recent articles on the DEA's attempt to ban it. I'm convinced the author - working in the addiction industry - wants as many things as possible to be considered addictive, because it helps her earn her keep. So... "Illegal in many parts if Asia". No. Just one. Thailand where it is indigenous. The govt. did a study there back in 2013 and concluded the ONLY reason it was made so was it cut into opium tax revenue - NOTHING to do with public health. So..
Why foes DEA now consider it an immune t threat to public health? 660 poison control center calls. Over 5 years. Less than 8% serious. Oh my! Considering there were 127,000lbs interdicted this past year, and that was customs only. Let us assume that customs alone does as good a job as the 7 or so agencies usually involved, and they get 10%. That means about 12.7 MILLION lbs came in, or about 150,000,000 doses. With 52 "serious" call to poison control, looks like a GREAT safety record. Please tell us, what was your motivation?
Why at you not concerned about addiction to sugar and other calories that has made you look as unhealthy as you fo in your pic? Someone is making money here, and it must not be the "right" people.

here's a study that pokes holes in your erroneous opinions,Kratom also has saved my life,do some research please,folks are dying from Heroin,opiate and addicted to Suboxone type drugs and Kratom is a legitimate,non-drug alternative that works,https://www.ncbi.nlm.nih.gov/pubmed/18482427

This ridiculous article is an advertising vehicle that uses scary language to garner clicks and views. It is aimed at soccer moms—people who are educated enough to read, but who know nothing about the special subject matter being discussed. Your tactic is to play on our desire to be caring moms. "Are you a bad mom? Then protect your kids from poison!"

Shame on you for demeaning women who are caught between worlds. On the one hand, your victims are enculturated enough to be emotionally triggered by your choice of words and the desire to look good. Caring moms are fearful moms, and adding fearful words to ANY headline will get an automatic click. On the other hand, your click-bait only works on those of us who are uneducated or who have low critical intelligence.

Not all soccer moms are stupid. Shame on you for assuming that we are all uneducated and respond to your tabloid-styled pseudo-information. Your article is false, dangerous, and insulting. Being blindly anti-drug isn't sexy anymore. All foods are drugs; and most drugs are foods. This one is actually healthy, helpful, and lifesaving due to its unique chemistry. You're crusading against coffee, lady. Kratom is not merely a life-enhancer, but also a deadly addiction cure.

I think this drug is good if taken in limited amount. Everyone knows it helps for pain relief, energy and to improve mood so one can take it only that much amount which can help him to overcome the problems. But it is also true overdose can cause some serious issues.

https://kratomspot.com/

My 27 year old son began using Kratom 3 years ago and found it helpful in reducing his chronic anxiety. However, last year, he noticed the need to increase the dose. When he tried to lower the dose again, he realized he was addicted to this legal, easily obtainable substance. He detoxed at home with the help of his doctor who remained on call to us. The physical withdrawal symptoms lasted over a week and consisted of muscle jerks, crawling sensations, waves of suicidal thinking, inability to sleep among other things. It has now been two months and the cravings are still intense and he has to actively fight the urge to drive a mile or so and buy more. He questions whether he will ever get past this which has led to feelings of deep depression and helplessness.

I could find negligible info about Kratom and zero information about detoxing from it. Even his doctor had trouble finding information that was helpful. I understand that many people find relief in this substance; my son did initially. But information about its addictive qualities and possible negative side effects needs to needs to be publicized. Then, those who decide to use it will be making an informed decision and parents of teens will know that, while legal, this is not a risk free substance.

I could rant on and on about your take on Kratom, but that wouldn't be very persuasive would it...from personal experience, the one thing I could sortof agree with you is that it should not be used recreationally by children...but for adults it is an amazing alternative to pills, alcohol, IV drugs...it's almost self-regulating in that if you take too much it will make you vomit, and it's effects are fairly mild and long lasting, and it's application is nearly endless...pain, anxiety, addiction recovery...why destroy something without a thorough investigation...the bad experiences I've heard about are so rare, and it is almost universally praised by users...isn't this enough to warrant a serious study, instead of reading a few articles and then dismissing it?

Side effects of Kratom are relatively mild and are never serious. These typically include loss of appetite, upset stomach, mild headache, increased thirst, and drowsiness. Look at the amount of people taking it in high doses and the lack of serious repercussions. It having mild side affect, but any more tremendous good affect, to opiate withdrawal, diabetes cure, mood uplift, anxiety, nausea and many more. For more information: kratomcrazy

now poppy tea is something entirely different...people that abuse it ARE dying...perhaps some of your information has been convoluted with poppy tea...I'm not saying that it doesn't have legitimate uses...but people can and are ODing on it and dying...would love to have you comment on that---compare and contrast Kratom and Poppy tea...the differences are night and day

My mom has chronic pain in the wrist caused by carpal tunnel. She reports the pain from 1-10 a "9", I bought some kratom for her and send it to her, now after taking it she reports her pain a 3!

Kratom gives you a general sense of well being. It can be euphoric yes. But the fact that something out there can deter us from real bad opiate drugs is bad, is beyond me. Seems like kratom is safer competition to real hard opioids. Whoever is upset about kratom are drug pushers who hate competition. Its a shame this article is published in psychology today and shame to the person who wrote it.