Kratom - NeuroSoup

Kratom
From Inti Yachay -­‐ Murple's Wiki By Murple: 18 January 2010 (2014 revision is in the works) PLEASE SEND ANY COMMENTS OR CORRECTIONS TO [email protected]
At A Glance
Kratom is a psychoactive tree indigenous to Southeast Asia. Botanical Name
Commonly written in English as kratom, the word in Thai is กระทอม
Indigenous
Range
which is pronounced [krā?tʰɔ̀ːm] (IPA transliteration). An approximate Pharmacological
equivalent in English would be "kra" Class
with a short A sound, with the second syllable having stress and sounding like the English word "tome." The Royal Active
Chemicals
Thai Institute official transliteration is krathom. Besides kratom, it also goes by the Thai names ithang, kakuam, and Dose Range
in southern regions of Thailand, thom. In Malaysia, it is called ketum or biak. Mitragyna speciosa
Southeast Asia, Indonesia, Papua New Guinea Non-­‐opioid narcotic 7-­‐Hydroxymitragynine, mitragynine, other indoles 5-­‐15 grams dried leaf (orally) Botany
Kratom refers to the plant Mitragyna speciosa Korth., a tree indigenous to Thailand, Malaysia, Indonesia and Papua New Guinea. In Thailand, kratom is mostly grown in the central and southern regions of the country, and only rarely in the north. The Mitragyna genus, part of the family Rubiaceae (coffee family), is found in tropical and sub-­‐tropical regions of Asia and Africa. Botanically and chemically, kratom is closely related to yohimbe. Other relatives include cat's claw, with which it shares several active chemicals, coffee and cinchona (the source of quinine). 1 %
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in Japan and Chulalongkorn University in Thailand began researching natural and synthetic analogues of mitragynine in search of new drugs with potential medicinal use. These studies have led to discoveries which have turned much of what was believed about kratom on its head. Results of a structure-­‐activity relationship study published in 2002 helped to clarify the essential structural moieties in the Corynanthe type indole alkaloids required for opioid agonistic activity. Two oxidative derivatives of mitragynine, mitragynine pseudoindoxyl and 7-­‐hydroxymitragynine, have been of particular interest. Mitragynine pseudoindoxyl was first created in 1974 when a team of researchers led by Zarembo used the fungus Helminthosporum sp. to biotransform mitragynine and reported it to have 10 times the anti-­‐nociceptive activity of mitragynine. A study conducted by the Japanese and Thai researchers previously mentioned has been found it to be a more potent analgesic than morphine by weight, and to act by way of mu and delta opioid receptors. Nevertheless, in a mouse tail-­‐flick test, it demonstrated only weak anti-­‐nociceptive activity compared to morphine. More important is the research on 7-­‐hydroxymitragynine (or mitragynine hydroxyindolenine), which is a naturally occurring minor alkaloid (around 2% of total alkaloids) first mentioned in a paper published in 1994. In a series of papers beginning in 2001, it has also been shown to be highly selective for mu receptors and is more potent by weight than morphine. Eventually, it occurred to the researchers that given the low potency of mitragynine, even though it is the most abundant alkaloid in the plant it can not account for the effects of kratom. Bioassays indicated that mitragynine was a much weaker anti-­‐nociceptive than kratom extracts. Starting with crude extracts of kratom and moving then to five isolated alkaloids, it was found that 7-­‐hydroxymitragynine is the most likely candidate for the chief agent of kratom's activity. It is thirty to forty-­‐six times more potent than mitragynine and seventeen times more potent than morphine by weight. Antagonism by naloxone was used to confirm opioid-­‐like activity of this alkaloid. Given that nearly all the chemical studies of kratom have been done on the assumption that mitragynine was the most important alkaloid, and that nearly all pharmacological research prior to the late 1990s was done on mitragynine or crude plant material, this discovery likely means that much of what we believe about kratom will need to be revised. Traditional Use
Traditional use in Thailand dates back far enough that its beginning can't be determined. Kratom was first mentioned to in Western literature by Low in 1836, who wrote that people in Malaysia would use it as a substitute when opium was unavailable or unaffordable. In 1895, E. M. Holmes identified kratom as Mitragyna speciosa, and again referred to its use as an opium substitute. In 1907, L. Wray described methods of use such as smoking, chewing, and tea. Hoping that 6 %
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pharmacology of kratom, it seems addiction is a strong possibility with long term use. Heavy users may chew kratom between 3 and 10 times a day. While new users may only need a few leaves to obtain the desired effects, some users find with time they need to increase doses to 10-­‐30 leaves or even more per day. In some parts of the Thailand, it was said that parents would choose to give their daughters in marriage to men who used kratom rather than men who used marijuana. The belief is that kratom users are hard working, while marijuana users are lazy. This belief is also maintained by many of the users themselves, who report beginning use because of a desire to work more efficiently, and who say using the drug gives them a strong desire to do work. Although mostly associated with Thailand (many earlier texts even indicate that kratom use is limited to that country), kratom is also used in Malaysia, where it is known as ketum. It is commonly sold at roadside booths in the form of a tea called air ketum ("kratom water") which usually sold for 1 ringgit per cup when legal and 2 ringgit since banned. A kilogram of leaf averaged 10 ringgit when legal, and has gone up to around 16 ringgit since banned. The Malay version of kratom tea is made by boiling leaves in water for two hours. This is often cooled by placing the boiling pot into a bucket of cold water, giving the drink a chill haze which is considered by some visually appealing, although it is likely that the process of chilling serves the more practical purpose of keeping the hot liquid from melting the plastic cups and bags the drink is sold in. According to Dr. Ahmad Mahmud, deputy director of enforcement at the Pharmaceuticals Services Division of Malaysia's Health Ministry, children as young as 13 have been buying air ketum from village stalls. "From what we gather from the sellers, the students are buying them before school and during their breaks," he said, adding, "Some codeine addicts are also drinking it to get high." These statements were made to a reporter from the Singaporean New Paper newspaper for an anti-­‐drug article, so that context should be considered before assuming there is an actual epidemic of childhood kratom addiction in Malaysia. The same article quotes Azwira Hassan, a kratom vendor from Kedah, as saying he boiled 20 kilograms of leaf per day and sold 250 to 300 air ketum drinks from that. Mr. Azwira also commented that some users felt thirsty after drinking it, and therefore would drink more kratom. Kratom is used in Malaysia in similar ways as in Thailand, including chewing, teas, and smoking. An article entitled "How Ketum Is Abused," which was published in a Malay newspaper in 2005, mentioned several unusual methods of use, stating, "Another not so palatable-­‐sounding process is mixing it with dried cow dung and tobacco, rolling it into a cigarette and smoking it. The leaves can also be mixed with dried coconut, ginger, onions, nutmeg and lime and rolled with daun kaduk (wild pepper leaf) and chewed like daun sirih (beetle nut leaves)." The betel-­‐like preparation is quite plausible, but whether people in Malaysia are actually smoking cow feces or this is an attempt at propaganda is an issue for the 8 reader contemplate for themselves. In addition to use as a psychoactive drug, traditional Malay healers also use the plant for de-­‐worming, to improve blood circulation, as an energizing tonic, as a cough suppressant and to treat symptoms of diabetes. A 1994 study by the Health Ministry indicated that many people had used it to get off of morphine or heroin (although continuing to use kratom). It has also been grown as an ornamental tree. While kratom grows naturally throughout Southeast Asia, there is little evidence of its use in other places where it grows. Myanmar has made it illegal, which presumably indicates at least some use there, but little is known of its role in Burmese culture. There is reportedly no tradition of kratom use in Indonesia. Its status in other countries such as Papua New Guinea, Vietnam, Laos or Cambodia is unknown. Pharmacology
While the main alkaloids in kratom are structurally related to psychedelics, their activity is radically different. The dominant effects seem to be similar to opioid drugs, and include analgesia and cough suppression. Unlike opioids, the cough suppression effect of mitragynine does not come packaged with emesis and dyspnoea (difficulty breathing). Respiratory depression is also much less than with codeine. In a 1988 paper by Jansen and Prast it was reported that mitragynine was not antagonized by nalorphine, leading to confusion as to whether kratom did or did not act in a manner similar to opioids. However, kratom suppresses opiate withdrawal and its effects are reversed by opiate antagonists such as naloxone, cyprodime, naltrindole, naloxonazine and nor-­‐binaltorphimine, showing that opioid receptor activity is clearly a major element of kratom's effects. Interestingly, while naloxone antagonizes the analgesic effects of kratom in the tail-­‐flick test, it does not reverse analgesia in the hot plate test. Kratom alkaloids are very effective pain killers, and work well when taken orally. These effects are roughly comparable in strength, but not necessarily in quality, to codeine. These opiate-­‐like effects appear to be mediated mostly by delta and mu opioid receptors, and this activity is selective for supraspinal opioid receptors (in mice, at least). According to the Micromedex Poisindex database, a 50mg of pure mitragynine produces motor excitement, giddiness, rombergism (a swaying of the body or falling when standing with the feet close together and the eyes closed; the result of loss of joint position sense), and tremors of the face, extremities and tongue. On the other hand, E. Macko noticed no evidence of toxicity such as tremors or convulsions at doses as high as 920mg/kg in dogs. In cats, Macko found that high doses had stimulating effects unlike unlike those from opiates. There was increased exploratory behavior, without the "fear and rage complex" opiates produce. 9 %
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9-­‐hydroxycorynantheidine, it appears that the C9 position is critical in determining the activity of this group of alkaloids. Mitragynine with a methoxy substituent is a full agonist, 9-­‐hydroxycorynantheidine has a hydroxy substituent and is a partial agonist, while coryntantheidine has a hydrogen atom and is an antagonist. Another alkaloid in kratom, speciociliatine, shows a 13-­‐fold decrease in opioid activity relative to mitragynine, and inhibits guinea pig ileum twitch contraction in a naloxone-­‐insensitive manner. The alkaloids speciogynine and paynantheine also inhibit twitch contraction in a naloxone-­‐insensitive manner, as well as inhibiting contraction induced by direct stimulation of muscarinic receptors on ileal smooth muscle. Kratom also contains several Uncaria alkaloids which are also found in the South American medicinal plant cat's claw. The most dominant one in kratom is mitraphylline, which has shown activity as a vasodilator and lowers blood pressure. It is also a myorelaxant (muscle relaxer). One study has shown that it increases memory retention performance in animals treated with amnesic drugs. It also acts as a diuretic. While there is some question as to whether or not it shares the ability of several other Uncaria alkaloids to enhance the activity of phagocytes, it is proven that the stereoisomer isomitraphylline, which is also present in kratom, does have this property. Isomitraphylline also has shown cytotoxic activity against some strains of cancerous cells (HL-­‐60 and U-­‐937 leukemia). Isopteropodine, an Uncaria alkaloid present in kratom, has been shown to be the most effective immunostimulant of this group of alkaloids. Rhynchophylline also lowers blood pressure by blocking the voltage-­‐dependent calcium and potassium channels, dilating peripheral blood vessels, and lowering heart rate. It also has antiarrhythmic properties, lowers cholesterol and prevents blood clots by inhibiting platelet aggregation and thrombosis. It also has anti-­‐inflammatory and anti-­‐pyretic properties. Speciophylline (also known as uncarine-­‐D) has shown cytotoxic activity against leukemic cells like isomitraphylline, slightly less effectively against HL-­‐60 and more effective against U-­‐937. Rotundifoline is another Uncaria alkaloid found in kratom, but its activities, if any, are not yet clearly understood. Corynoxine A and corynoxine B reduce locomotor activity in mice, which appears to be due to mediating activity in the dopaminergic system. Corynoxeine (not to be confused with corynoxine A and B) is an oxindole, and has verapamil-­‐like calcium channel antagonist. The alkaloid ajmalicine (also called raubasine), which is also found in Indian snakeroot (Rauvolfia serpentina) and Madagascar periwinkle (Catharanthus
roseus), has multiple pharmacological activities. It inhibits platelet aggregation by means of an inhibitory action on the release reaction of the platelets. It increases oxygen availability in the brain, which has led to its use in cognitive disorders in the elderly and in stroke ischemia, especially in a drug combination with almitrine marketed as Duxil. It has sedative and anticonvulsive properties due to agonist activity at the [3H]flunitrazepam benzodiazepine receptor. It also acts as an antiadrenergic by blocking alpha-­‐1-­‐adrenergic receptors, which makes ajmalicine lower blood pressure and act as a diuretic by relaxing smooth muscle. Another 11 indole which kratom shares with Madagascar periwinkle is tetrahydroalstonine, which has been shown to lower blood sugar levels and acts as a blocker at the alpha-­‐2-­‐adrenergic receptors. One final chemical worth mentioning is (-­‐)-­‐epicatechin. This polyphenol, the cis-isomer of catechin, is closely related to the well-­‐known EGCG. This chemical is also found in green tea, cranberry juice and dark chocolate, and has a wide array of beneficial activities. It reduces free radicals in the blood, thereby reducing cancer risks, and is a powerful antioxidant which helps prevent fat cells from oxidizing and clogging arteries. It helps treat urinary tract infections by impairing bacteria's ability to stick to the cell walls of the urinary tract. Epicatechin is used by many diabetics due to a variety of beneficial properties. It mimics insulin and protects erythrocytes in a similar manner. It also inhibits alpha-­‐amylase, preventing the digestion of starch into absorbable glucose. It also keeps blood sugar levels lower by inhibiting intestinal glucose absorption. Epicatechin also has demonstrated ability to inhibit growth of pathogenic bacteria such as E. coli and staph. It also has anti-­‐viral properties and inhibits the ability of virii to enter and infect cells. Active Chemicals in Kratom
Ajmalicine (Raubasine)
Cerebrocirculant, antiaggregant, anti-­‐adrenergic (at alpha-­‐1), sedative, anticonvulsant, smooth muscle relaxer Corynantheidine
Opioid antagonist Corynoxeine
Calcium channel blocker Corynoxine A and B
Dopamine mediating anti-­‐locomotives (-)-Epicatechin
Antioxidant, antiaggregant, antibacterial, antidiabetic, antihepatitic, anti-­‐inflammatory, anti-­‐leukemic, antimutagenic, antiperoxidant, antiviral, cancer preventative, alpha-­‐ amylase inhibitor 9-Hydroxycorynantheidine Partial opioid agonist 7-Hydroxymitragynine
Analgesic, antitussive, antidiarrheal; primary psychoactive in kratom Isomitraphylline
Immunostimulant, anti-­‐leukemic Isopteropodine
Immunostimulant Mitragynine
Analgesic, antitussive, antidiarrheal, adrenergic, antimalarial, possible psychedelic (5-­‐HT2A) antagonist Many of these secondary chemicals in kratom are present in small quantities, and their role in the overall 12 pharmacology of kratom are not yet fully understood. It seems likely that kratom is much more than a simple Mitraphylline
narcotic. Research into the pharmacology of this plant and its chemicals is still in its early stages. Paynantheine
Vasodilator, antihypertensive, muscle relaxer, diuretic, anti-­‐amnesic, possible immunostimulant Smooth muscle relaxer The pharmacology of kratom Vasodilator, and mitragynine was first antihypertensive, explored by K. S. Grewal at the calcium channel University of Cambridge in blocker, 1932. He observed that Rhynchophylline
antiaggregant, anti-­‐inflammatory, mitragynine seemed to act as a antipyretic, stimulant in both animal anti-­‐arrhythmic, tissues and a group of five antithelmintic male volunteers. Grewal noted the use of kratom by laborers Speciociliatine
Weak opioid agonist and falsely concluded that Smooth muscle mitragynine acted like cocaine. Speciogynine
relaxer This led to a mistaken notion Anti-­‐leukemic that circulated for some time Speciophylline
that kratom acted like a Hypoglycemic, mixture of opium and cocaine. Tetrahydroalstonine
anti-­‐adrenergic (at alpha-­‐2) This was also stated by Norakanphadung Prayun in the "Thai Narcotic Book" published 1966. Grewal also reported claims that addicts were thin, had distended stomachs, unhealthy complexions, dark lips and dry skin. So far, few in depth study of kratom's use and abuse have been conducted. The first and best known was the 1975 study by Dr. Sangun Suwanlert of thirty long term users in Thailand. These subjects reported that it is sedative in low doses changing over to stimulation in higher doses, this seems to be incorrect. Most other sources say that it is a stimulant in lower doses, becoming sedative in higher doses. Suwanalert's subjects reported effects come on within five to ten minutes after use, and last for several hours. The feeling was been described as happy, strong, and active, with a strong desire to do work. The mind was described as calm. Some ethnographic studies in Thailand have reported side effects from long term use include anorexia and weight loss, insomnia, and a darkening of the skin, particularly on the cheeks, giving an appearance similar to a hepatic face. Among those described as addicts, 30% report limited sexual desire and the need to use a combination of kratom and alcohol to become sexually stimulated. Suwanalert's 13 study found 5 people who had psychotic conditions which may or may not have been revealed by very heavy kratom use. A second study was conducted by the Malaysian Ministry of Health in 1994. This study surveyed 54 people who had been using kratom for 1 to 20 years. Nearly all (94.3%) had been former users of opioids or marijuana who switched to kratom. Users reported withdrawal when trying to stop kratom, but pointed out that the withdrawal was much less severe than with opioids. Medical tests showed the users to all be healthy and that biochemical tests showed no significant differences from the normal references ranges. As discussed earlier, addiction seems to be a possibility if high doses are used. Some withdrawal symptoms reported by addicts include hostility, aggression, wet nose, inability to work, flow of tears, muscle and bone aches, and jerky limb movement. The first formal report of a case of addiction was reported in 1957 by L. C. Thuan. The man had withdrawal symptoms when trying to go without kratom, but otherwise was physically and mentally "quite normal," remaining in good health, maintaining a normal weight, and never increasing his use level. A. Marcan likewise reports that kratom use in Malaysia was very common, but did not have a bad reputation and that addicts did not show any change in their character or physical health. The Swiss biologist Claude Rifat experimented with a low dose of three smoked leaves. He found the results unimpressive: "What I observed, subjectively, more or less reminds the effects of the serotonin re-­‐uptake blockers, such as zimelidine or fluvoxamine. Mitragynine, mainly, blocks motivations and induce indifference, together with a strong sense of laziness! Everything becomes boring to do." Given the usual dose ranges reported by kratom users, it seems probable that this dose was insufficient to produce anything more than placebo or threshold activity. With the increased availability of kratom outside of Asia, it has become possible to collect much new data on the effects. This is interesting because many of these new users are from Western cultures and therefore it is now possible to gather data free from traditional cultural beliefs and without going through the filter of ethnobotanical research papers. There is now a wide body of first hand reports from people who have used kratom, and it is now possible to use this data to get a clearer understanding of the effects of this plant and to resolve some of the inconsistencies and errors in earlier research conducted only in kratom's indigenous environment. For the most part, however, effects reported by non-­‐native users are in line with earlier reports. Most use is oral, in the form of teas or swallowed extracts. Doses reported depend on the quality of kratom used (which seems to have considerable variability) and tolerance of the user, but range from 5 or less grams to 20 grams. Effects reported are often compared to opioids, although there are subjective differences. Effects come on within 10 to 20 minutes and continue to build for up to an hour after consumption. The primary effects generally seem to last for 3 to 6 hours, although some users report 14 %
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While ibogaine is intended as a one time treatment to cure addiction, kratom alkaloids may be used to gradually wean the user off narcotics. Kratom or its derivatives could also perhaps be used as a maintenance drug for addicts not wishing to quit but trying to moderate an out of hand addiction. In either case, kratom serves in a manner similar to methadone or buprenorphine, as a substitute narcotic. The advantages of kratom are that it is legal in most countries and that anecdotal evidence indicates that it is both safer and easier to withdraw from. Whether or not this is actually true needs to be confirmed by controlled scientific research. In the mean time, people seeking to use kratom in a self-­‐administered treatment for narcotics addiction need to be aware that kratom is potentially addictive itself, and that if used irresponsibly, certainly will not provide a pathway to a drug-­‐free life. Kratom certainly has potential in addiction therapy as a slow detox or long term maintenance drug, but unlike ibogaine, is not seen as offering a cure. One potential advantage of kratom over currently used opioids is the array of secondary chemicals such as ajmalicine, epicatechin and the Uncaria alkaloids. These chemicals have a variety of medicinal properties, including antioxidant activity, cardiovascular benefits, and ability to fight off various viral and bacterial infections and to act as immune stimulants. This gives kratom advantages over opioid narcotics in several applications. If used as a replacement for codeine as a cough suppressant, the immune enhancing properties would offer potential benefits in helping fight off whatever infection is causing the coughs. Used as a mild pain killer in people recovering from injuries or surgeries, the immune enhancing properties could also help reduce the chance of infections in the site of the injury or operation. Used as a replacement for methadone or buprenorphine, the various health benefits of the secondary kratom chemicals could help the addict recover from the poor health that is often seen in long term drug abusers. While more research is required to find out how effective these minor drugs in kratom are, it is certain that opioid narcotics do not have these properties at all. The potential advantages certainly merit further investigation of kratom as an alternative to opioids. It would also be worthwhile to research the possibility of extracting the non-­‐narcotic chemicals from kratom and developing them into medicines. In the early 1970s, the pharmaceutical company Smith, Kline and French Laboratories researched mitragynine, including pre-­‐clinical trials in humans. In a personal letter to Karl Jansen in 1986, R. Raffauf indicated that this research was discontinued because of unacceptable acute side effects of some kind. Meeting notes from the mitragynine scheduling hearings in Australia note: "It has been speculated that a possible reason for this is the different pharmacological profiles of pure mitragynine and the unprocessed leaf, the latter containing several other alkaloids that may modify the effects of the pure drug." After being contacted by the Committee, GlaxoSmithKline (the modern incarnation of the company), said they did not object to scheduling in Australia, presumably indicating a lack of any further interest in developing medicines from kratom. 16 In 1999, Pennapa Sapcharoen, director of the National Institute of Thai Traditional Medicine in Bangkok said that kratom could be prescribed both to opiate addicts and to patients suffering from depression, but stressed that further research is needed, and that any potential use of kratom in treating addicts needs to be part of a holistic approach, saying, "We have to pay attention not only to the medicine itself but also to the application process." She said the current laws against kratom make investigation of kratom as a medicine difficult, but Viroj Sumyai, director of the Thai Food and Drug Administration's narcotics control division has denied that the law banned the use of kratom in research, adding that Chulalongkorn University chemists have isolated mitragynine which researchers can obtain for study. Material from Chulalongkorn University has been used in the extensive research based out of Chiba University in Japan. Samlee Chaidee, of Chulalongkorn University's pharmacy department, said the herb was a part of country life before the state stepped in, and that studies have shown villagers using it did not have problems with addiction. All parties have stressed the need for further research. In Malaysia in 2005, Dr. Mustafa Ali Mohd, Associate Professor at the Universiti Malaya, Pharmacology Department, announced his desire to study the effects of kratom use, pointing out that the only in depth study of kratom users has been Suwanalert's research on thirty Thai users in 1975. As of February 2006, Dr. Mohd has been conducting research at the Shimadzu-­‐Universiti Malaya Medical Centre for Xenobiotics Studies (Sucxes). Based on results found by Sucxes so far, toxicity of kratom is negligible. Mohd believes that kratom should be investigated as an alternative to methadone as it is far safer, has fewer side effects and kratom treatment programs would be around 80% cheaper than methadone programs currently cost. Unfortunately, since Malaysia made it illegal, the police have been cutting down trees. While Mohd and other scientists have been publicly upset over this campaign, Deputy Internal Security Minister Datuk Noh Omar was quoted saying that unless the scientists can find people to guard every tree to prevent youth from using the leaves to get high, the police should be allowed to chop them down. ACP Nooryah Md Anwar of the Royal Malaysian Police’s Narcotic Department at Bukit Aman has countered that planting kratom is not illegal under the Section 30 (3) of the Poisons Act, and that the police do not have the authority to cut down trees. Nooryah said, “If it is a drug, it is a drug. We would like to have it listed under the Dangerous Drugs Act as that gives us more power and governs even the planting of the tree. We have observed that the dosage and frequency of use have gone up.” Dr. Mohd believes that kratom has medicinal applications, and also should be preserved for the sake of indigenous biodiversity. Professor Datuk Ikram Said of Univeristi Kebangsaan Malaysia believes kratom alkaloids can also be turned into useful medical pain killers, anti-­‐inflammatories, cough medicines, and treatments for diarrhea. Since the plant is indigenous to Malaysia, these scientists believe development of kratom-­‐ derived drugs could save the country millions of ringgit in imported drug costs while giving a boost to the Malaysian biotechnology business. A national committee to investigate kratom has been formed in Malaysia by the Health 17 %
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by 2-­‐3 days 'lost' to relative detachment from my surroundings. Then I am welcomed back by a CRIPPLING depression." No timeline is given for how long the kratom was used, nor for how long or how many times Patient was addicted to opioids before switching to kratom. Writing under the name K-­‐ally, a user describes discovering kratom after years of occasional narcotic use culminating in a year of daily oxycodone use, writing, "back in December after getting over a three week withdrawal from heavy oxycodone (100mg to get me high) and methadone (50mg to keep me nice and level), I discovered Kratom. I learned that it was no ordinary legal high, and this stuff was actually like an opiate. I start taking it 2-­‐3 times a day and my tolerance skyrockets; at first I only required 3 grams of leaf, now I was using up to 10 grams here in March. Kratom was being used on top of occasional oxycodone, which my tolerance was quite high for, so there is without question cross-­‐ tolerance between Kratom and opioids." This person goes on to say, "I started having side effects from my use, like depression. I figured it was time to quit, for real, and I was really scared. Withdrawal has given me days of hell on earth, pure torture of the mind and soul. A week earlier I had stopped my use for almost two days, in a failed attempt to quit. The withdrawal set in in about 20 hours and was absolutely hell, so I eagerly ate more Kratom." Deciding not to continue the cycle, the user writes, "I go through the horrible process again, my final time, like I always said. This time I scattered my remaining Kratom through the garbage can. Pure anxiety hits me after a day, along with stomach problems, twitching, and horrible insomnia." On the second day of withdrawal, this person decided to take an intramuscular injection of 110mg ketamine. Interestingly, this user reported having a profound experience with the ketamine, and upon waking the next morning felt no more withdrawal symptoms. The report was written over a week after the ketamine experience, at which time the user had neither used more kratom or opioids nor experienced a return of any withdrawal symptoms. A somewhat contrasting report comes from a user named Duncan, who was not using kratom to come off opioids. He writes, "I personally used a high dose of Kratom EVERY day for about 1 1/2 years. It got to point where I began to no longer appreciate the plant and I decided to stop. There were actually NO cravings at all after that to continue using it although there were definitely withdrawal symptoms. I found it difficult to sleep at night, had bad diarrhea and was quite depressed for about 10 to 14 days. All the above symptoms gradually wore off and everything got back to normal again. I abstained for about 4 months and am now using kratom only twice a week without any negative effects." He adds, "I would say it is definitely EASY to quit but if used for a long period of time it is better to slowly stop using it over a period of time rather than suddenly thus reducing the negative symptoms." 21 Law
Kratom remains legal in most of the world. There are a few exceptions, however. Unfortunately, it is likely that more countries will eventually ban kratom or its active chemicals. The Thai government passed the Kratom Act 2486 which went into effect on August 3, 1943. This law makes planting the tree illegal and requires existing trees to be cut down. This law was not found effective, since the tree is indigenous to the country. Today, kratom is classed in the same enforcement group as cocaine and heroin by Thai law, and has the same penalties. Thailand has the death penalty for high level drug trafficking offenses, a fact which has spawned a myth in the United States that kratom possession is punishable by death. In practice, distributors are jailed for up to two years and fined up to 20,000 baht, and consumers can be jailed up to a month or fined up to 1000 baht. As with prohibition laws elsewhere in the world, this has succeeded only at increasing black market prices. In 2001, the Thai Narcotics Control Board issued a report indicating that kratom was the second most widely abused illegal drug in the country, after marijuana. 1270 kilograms were seized by Thai authorities in 2001, and it was estimated that two million Thais had used the drug. Myanmar (formerly Burma) declared Mitragyna speciosa a controlled narcotic drug under Section 30 (b) of the Narcotic Drugs and Psychotropic Substances Law in a Ministry of Health notice dated Yangon, the 6th Waxing Day Tabodwe, 1354 ME (28 January 1993). Mitragynine was made illegal in Malaysia in 2003, and kratom leaves in August 2004. In June, 2004, a four day operation by Malay authorities resulted in the arrest of 15 people and the seizure of over 800 liters of prepared tea and 245 kilograms of kratom leaves in the states of Terengganu, Pahang and Kelantan. Other operations were conducted in 2003 and 2004, and presumably are ongoing. In November 2004, Parliamentary Secretary to the Natural Resources and Environment Ministry Sazmi Miah and others spoke out against an incident where 43 policemen along with local villagers chopped down a 30 meter tall 60 year old kratom tree in Kampung Badariang (near Gerik). Home Affairs Minister Datuk Azmi Khalid said the police should have carried out a study first before cutting it, and focus instead on the more serious problem of synthetic drug abuse. Many feel that cutting down kratom trees harms the biodiversity of the region. The local deputy district police chief, Ismail Deraksa, defended the action by saying the sixty year old tree was cut down to prevent the emergence of a new addiction in the youth. Slightly more than 1000 kilograms of the leaves and under 236,000 liters of the drink have been seized since kratom was made illegal. As of April 2005, there have been 99 cases involving kratom, 29 people have been charged, but no one has been jailed. Penalties in Malaysia include fines of up to 10,000 ringgit or jail terms up to four years or both. At the start of March 2006, Deputy Internal Security Minister Datuk Mohamed Johari Baharum said that the Attorney General has been instructed to expand the Dangerous Drugs Act to make 22 consumption of kratom a criminal offense as well, since the prior law did not cover consumption. The most recent country to ban kratom was Australia. The National Drugs and Poisons Schedule Committee held several meetings between February 2003 and February 2004 to consider including mitragynine and Mitragyna speciosa into Schedule 9 of the Standard for the Uniform Scheduling of Drugs and Poisons. The NDPSC 39th Meeting in October 2003 agreed to schedule mitragynine, and 40th Meeting in February 2004 agreed to add kratom to Schedule 9 as well, pending review of public comments. Although several comments were received arguing that kratom was relatively harmless and had potential therapeutic value, the Committee pointed out the widespread sale and promotion of kratom on the internet was reason to believe it was a potential problem drug. Regarding potential medical uses, the NDPSC meeting minutes state, "A Member noted that based on the available data there was little evidence to show that M. speciosa was widely used for therapeutic purposes other than as a substitute for other addictive opiates and one other traditional use as an antidiarrhoeal. Although the pharmacology of M. speciosa suggested that analgesic effects were likely given the findings of studies quoted in several papers [e.g. Journal of Psychoactive Drugs (Vol 20[4], Oct-­‐Dec 1988], there was little data to suggest that Kratom was used traditionally as a pain reliever. On this basis, the Committee noted that despite post-­‐meeting comments about the usefulness of M. speciosa for treating migraines, there was little evidence available to support a legitimate therapeutic need for the plant and members also noted that a number of other alternatives including complementary medicines were already available. A Member observed that information on Internet websites referred mainly to the use of Kratom for producing psychoactive effects and in contrast, there was paucity of information about its therapeutic use." The NDPSC then confirmed the decision to schedule kratom, and the amended SUSDP law went into effect 1 January 2005. Furthermore, a New Zealander on the Committee suggested that Australia should officially recommend to New Zealand that it also schedule kratom. In the United States, there has been some governmental interest in kratom. In July 2005, the DEA's Microgram newsletter included a section from the NDIC's Narcotics Digest Weekly titled "Herbal Drug Update: Kratom". The article mentions that kratom is widely available on the internet and theorized that leaves may also be sold at "head shops," although no evidence for this was cited. The article has a brief one paragraph summary of kratom's effects and use, then goes on to say "NDIC has not yet received law enforcement reports regarding kratom abuse in the United States." It concludes "One potential user population for kratom is opiate addicts who may attempt to self-­‐treat if they do not have access to methadone programs or if they are reluctant to seek professional treatment. Some medical researchers have speculated that kratom may be useful as a substitute for methadone in treating opiate dependency, although more research is needed." There was no recommendation for further action, although this does show that there is some awareness of the plant in at least some parts of the US government. 23 Mellow Gold
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information available on kratom at that time, so it lingered in the back of my mind until 1999, when a very small quantity of dried leaf became available and was briefly sold by a mail-­‐order specialty botanicals supplier after an intrepid individual brought 10-­‐15 kilograms of leaf and some seeds home from Thailand. I purchased 10 grams for $25 sometime in 2000. There was no practical information available other than the catalog listing which said kratom could be used "for producing a distinctive sedation coupled with a paradoxical physical exhilaration" along with a mental state described as "putting one's pieces together" when feeling scattered or fatigued. the which suggested doses of around a gram could be chewed, smoked, or made into tea for effects that were both stimulating and relaxing. This was in line with the little information I'd run across in books, which mentioned that it was usually chewed or smoked. I tried smoking and chewing it several times, with no results. Finally when I was down to 5 grams, I decided to try tea. This finally produced results -­‐ not very strong, but certainly enjoyable. I tried to order more, but there had only been a small supply and it was already sold out. I was able to obtain a small sample of kratom from an associate a few months later, and it became possible to find real kratom commercially again beginning in 2003. Likewise, scientific information became easier to obtain, and realizing that my "Kratom: What Is It?" paper was bursting with errors, I decided to begin researching kratom for a new paper. As often happens, life and other projects delayed this project for some time, and I didn't begin seriously researching or experimenting with kratom much until the summer of 2004. For the past few months I have researched kratom in depth, and have come to have a deep appreciation for the plant. I also have found it to be a useful and enjoyable plant, and it is a valuable element of my herbal medicine cabinet. On paper, reading about the pharmacology, it can seem as if kratom is virtually interchangeable with opioids. The reality is somewhat different. Certainly there are many similarities, as would be expected of a plant with at least two opioid receptor agonist chemicals. I have had fairly extensive experience with opioids including codeine, oxycodone, buprenorphine, opium poppies and others, and I consider myself well versed in their effects and the differences between them. Kratom has a substantially different feel from opioid narcotics, both in the short and long term. Serious pharmacological research into kratom has only barely begun, and it seems likely that as more is learned about it, science will be able to quantify these differences. Perhaps 7-­‐hydroxymitragynine and mitragynine are active at more receptors than currently thought, or perhaps there are as yet undiscovered active chemicals in the plant which modify the activity of the whole. Or perhaps the properties of the kratom alkaloid molecules are such that even just binding to the opioid receptors, they produce activity which is not the same as opioids. Whatever the reason, there are notable differences. In a superficial sense, the high produced by kratom feels somewhat like that of opioids. There is a warm, 25 tingly sensation which will certainly feel familiar to people experienced with opioids. Kratom is useful as a pain killer and a cough suppressant, and I have used it for both purposes with results just as good as with opioids. While kratom is used to treat diarrhea in Thailand and Malaysia, I personally have found that it has very little constipating effect compared to opioids. Fortunately, I have not had the opportunity to try it as a diarrhea remedy, but based on the near lack of constipation I've gotten from it, I'm skeptical that it will work nearly as well as opioids. A major difference between kratom and opioids is the stimulating property of kratom. There are some opioids, mostly thebaine derivatives such as hydrocodone or oxycodone, which are stimulant in the sense that they can cause insomnia. Kratom produces more of a real stimulation, giving a focused energy which lasts for several hours and is well suited to engaging in productive and creative work, exercize, or for social situations. I am particularly fond of going on long nature hikes after a cup of kratom tea. This is in stark contrast to opioids, which tend to promote more sedentary activities (or lack thereof). While kratom is relaxing, it does not seem to act like as much of a CNS depressant as opioids do. I have never nodded off or even slid into daydreams with kratom like with opioids. The mind feels active and alert -­‐ tranquilized perhaps, but not sedated. There also is no real noticeable come down from kratom. The effects gradually and smoothly transition back to baseline consciousness, and I have never experienced a hangover or crash of any sort. In the long term, kratom does not seem to have nearly the reinforcing lure to compulsive use that opioids have. However, I'm sure that for some people, it will, and that anybody who overuses it has the potential to develop a physical and/or psychological dependence. Even with periods of frequent use, kratom does not seem to produce the effects I have experienced from opioids, such as constipation, lack of motivation, reduced sex drive, or general feelings of reduced health. In fact, when I use it, I generally feel energetic and healthy, and the pharmacology of many of its chemical components does provide evidence that occasional moderate use of kratom is not only safe but potentially beneficial. That said, kratom clearly can lead to addiction and withdrawal. Low level users generally report feeling tired for a day or two, and having a sort of warm flushed feeling that never develops into the full flu-­‐like sensations of opioid withdrawal. There may be some mild diarrhea, aches and other physical symptoms. Mentally it may be characterized mostly by feeling tired and having slightly stronger emotions than usual, and not really in comparable to opioid withdrawal in intensity. I do however suspect that somebody using kratom in high doses for many months or years may develop a much more pronounced withdrawal. Also, most of the serious withdrawal reports circulating on the internet seem to involve people who were actively addicted to opioids and trying to switch to kratom as a "cure" or intermediary to quitting, and I suspect that while kratom on its own may not lead to a full blown opioid-­‐type withdrawal, it may act similarly enough to opioids that somebody who has altered their brain chemistry through addiction to an opioid then switches to kratom may simply be maintaining the addiction and 26 will experience a delayed or combined withdrawal when they stop using kratom. While this is simply wild speculation on my part, it may be something worthy of real research, and at the very least ought to be kept in mind by anybody considering using kratom as an opioid replacement or gradual detox aid. I have mostly experimented with kratom as a tea or ground to a powder and swallowed whole with water; over time I have come to prefer swallowing the powder. With most material I have sampled, 5 grams will make a tea with noticeable effects, and 15 grams will produce the strongest effects which I still find enjoyable. With some of the more potent material I have tried, 10 grams can be rather strong, but in my experience the stronger strains which are sold as "super" or "premium" kratom are not really worth the money. While these varieties often cost four or five times more, I have found them to only be around 25-­‐50% stronger than the standard material I've used. Swallowing powdered kratom whole as opposed to making tea can nearly halve the required dose, but the trade off is having to swallow all the powder rather than drinking a tea. Some people are bothered by the texture, but for me it is barely noticeable. Similarly, some people find the taste of the tea revoltingly bitter, while others (myself included) find it in some ways good tasting in a bitter way, somewhat like yerba maté. I have found smoking kratom to be a complete waste, although an associate told me that smoking 3 grams of leaf did produce some effects. I haven't had much luck with chewing it, but I haven't really explored that route much. It works well as a tea, and since oral consumption is generally the safest way to use any drug, I probably wouldn't recommend any other methods for using it. Conclusion
In conclusion, there needs to be much more research done into this plant and its active constituents, especially in light of the recent discovery that mitragynine is not the chemical primarily responsible for kratom's activity. Although kratom has been used since time immemorial by Thai natives, Western science hasn't paid it that much attention. What research does exist contains some apparent conflicts and errors. Knowledge even of the plant's existence outside of Southeast Asia has been limited to ethnobotanists and a handful of pharmacology researchers until the last few years, and availability of live plants and dried leaves has been practically non-­‐existent until very recently. Beginning in 2004, I began seeing kratom sold in tacky, exploitive ways by people seeking to make money off it. This pattern has sadly repeated itself more times than I care to remember. An interesting drug is made available by traders and vendors with integrity and ethics, and sold discretely. Then, some greedy bastard discovers it and sets up a sleazy website and begins aggressively marketing it with no regard for the consequences. Sooner or later, people begin doing stupid things because of a lack of adequate education. The drug comes to the attention of the media or authorities, and eventually is made illegal. It saddens me greatly 27 %
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•
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