Tag: mitragynine

07/16/19

Noose Tightening On Kratom

© Ilkin Quiyev | 123rf.com

The “Noose Tightens Around Kratom” as the DEA and FDA continues to underscore concerns with the herbal product. The FDA warned consumers not to use kratom, as it effects mu receptors, the same receptors as opioids, and seems to have properties “that expose users to the risks of addiction, abuse, and dependence.” The DEA listed kratom as a “drug of concern” several years ago, but it continues to be unregulated and sold as an herbal supplement after the agency backed away from Scheduling it and limiting its ability to police it. See “Kratom: Part of the Problem or a Solution?” The FDA’s ability to regulate herbal products is limited to concerns with the safety of kratom and preventing vendors from making overt, unapproved health claims.

As a dietary supplement kratom is not subject to the same safety regulations as other drugs. However, the FDA has persisted in doing what it can to monitor companies that sell this herbal product and so-called “dietary supplement.” The FDA ordered a recall of some kratom products because of Salmonella contamination in April of 2018. In May of 2018 the agency accused three sellers of kratom products of making unapproved health claims.

The FDA continues to warn consumers not to use Mitragyna speciosa, commonly known as kratom, a plant which grows naturally in Thailand, Malaysia, Indonesia and Papua New Guinea. The FDA is concerned that kratom, which affects the same opioid brain receptors as morphine, appears to have properties that expose users to the risks of addiction, abuse and dependence. There are no FDA-approved uses for kratom, and the agency has received concerning reports about the safety of kratom.The FDA is actively evaluating all available scientific information on this issue and continues to warn consumers not to use any products labeled as containing the botanical substance kratom or its psychoactive compounds, mitragynine and 7-hydroxymitragynine. The FDA encourages more research to better understand kratom’s safety profile, including the use of kratom combined with other drugs.

MedPage Today noted the FDA included kratom on “import alerts” in 2012 and 2014, which allowed it to seize kratom and kratom products worth over $5.5 million in 2014 and 2016. Several suppliers reported having tons of kratom seized during that time. There were no further seizures for a while, but they seem to be sporadically occurring again as kratom companies adjusted their marketing strategies. A Denver company, Kratom Café USA, reported recently that its order of kratom was seized by the FDA. When the FDA began tightening its restrictions, the company revised its website. Kratom Café USA now claimed it sold kratom for aromatherapy and making candles. Despite the benefits section of their website having the following disclaimer, the FDA detained 540 kilos of kratom on November 30, 2018:

We make no claims that kratom cures, prevents or treats any disease or ailment. Keep this product out of the reach of children. Kratom is not a dietary supplement, but a precise amount of an ingredient sold as a raw materials and/or bulk herbs. All information provided has not been evaluated by the FDA, and all kratom products on this site are sold for horticultural, educational and scientific use.

But what is the real story? Nicolas Moodley, the owner of Kratom Café USA, said he thought the FDA’s action was “government overreach” and a violation of his rights. Besides, he added, it was taking a toll on his business. Moodley himself became dependent on opioids as the result of chronic pain from his work as a roofer. He credited kratom with relieving his pain and helping him kick the opioid habit. Now take a look at some of the Testimonials on Kratom Café USA:

Gabe T. said: “I love to use kratom for working out and for chilling out. Your powder is off the hook! I don’t mind paying a little more to get 5 time the potency and nearly lasts twice as long.” Richard G. said: “I have been using kratom for a few years now for anxiety and mood swings. It has worked okay from some head shops I buy from. The first time I used your product I was amazed how much more effective & smooth it is. Your kratom is the best I have EVER used.” This does not sound like Moodley’s customers are using kratom bought from him for aromatherapy and candle making.

An article published in Clinical Toxicology analyzed exposures to kratom reported to poison control centers (PCCs) in the U.S. from 2011-2017. Kratom exposure increased over fifty-fold, from 13 exposures in 2011 to 682 exposures in 2017. “Almost two-thirds (65%) of these exposures occurred during 2016-2017.” Most exposures were with adults 20 years old and above (65%) and most were with males (70.8%). Exposure rates by state were highest in Idaho and Oregon and lowest in Delaware and Wisconsin. “There were seven neonatal exposures reported during the study period and five were attributed to kratom withdrawal.”

Clinical effects observed for single-substance kratom exposures among the neonates included agitation/irritability, diarrhea, and hyperventilation/tachypnea. These neonatal withdrawal cases suggest that transplacental transfer is possible and that healthcare providers should educate pregnant women on the risks of kratom use during pregnancy. Notably, although not in a neonate, one exposure was documented as having occurred through breast milk. Thus, the possibility of exposure via breast milk should also be communicated to new mothers who use kratom.

The authors said the clinical effects observed during the study highlighted the fact kratom can have serious physiologic effects. Common non-opioid effects included tachycardia (21.4%), agitation/irritability (22.9%), seizures, and hypertension. More than one-third of exposures resulted in admission to a health care facility and more than half resulted in a serious medical outcome. “These high percentages reflect the potential toxicity of the active compounds found in kratom leaves.” And they highlight the need for kratom regulation by the FDA “to ensure quality and safety.”

Despite the perception that kratom is safe because it is classified as an herbal supplement, a variety of serious medical outcomes following exposure to kratom have been documented, especially when kratom is used in combination with other substances. More research is needed to define the human response to kratom. At a minimum, kratom products should be free of potentially harmful contaminants, provide a uniform strength of active ingredients, and have appropriate labeling. Increased regulation of kratom products would help guarantee product quality and safety. Individuals who choose to use kratom should be educated about its potential risks, including the dangers of using it in combination with other substances.

While there is no federal ban yet for kratom, a number of states and some smaller jurisdictions have banned its use. Currently there are six states where kratom is a controlled substance and thus illegal to sell, possess, use and grow: Alabama, Arkansas, Indiana, Rhode Island, Vermont, and Wisconsin. Several additional states have banned kratom in certain counties or cities. Others like Illinois and New Hampshire have set a legal age limit for its use.

Then on June 25, 2019, the FDA again issued warning letters to two additional marketers and distributers of kratom products, Cali Botanical and Kratom NC for illegally selling unapproved and misbranded kratom products. The companies claimed their products could treat or cure opioid addiction, withdrawal symptoms, depression, anxiety and even cancer. The FDA has also found high levels of heavy metals in kratom products. The Acting FDA Commissioner said “Despite our warnings, companies continue to sell this dangerous product and make deceptive medical claims that are not backed by science or any reliable scientific evidence.” Some examples of the claims being made by these companies include:

Kratom is frequently used as a natural alternative to treat depression, anxiety, addiction, diabetes, chronic pain and fatigue…Kratom has been reported to have taken the place of brand name drugs like Hydrocodone or Oxycodone for individuals, all the way to weaning people off of Heroin.Some researchers have even claimed that kratom can protect you against cancer!Kratom is used for energy, to increase attention/focus, to relax, and also to treat pain and addiction. Here is just some of what our customers have used kratom to treat . . . Chronic Pain, Migraines, Opiate Addiction, ADHD/ADD, Anxiety, Depression, Arthritis, Insomnia and much more!

There is an ongoing dispute about kratom-positive overdose deaths, with kratom advocates pointing to how the herbal supplement was not the only substance found in most decedents. In the Morbidity and Mortality Weekly Report (MMWR) for April 12, 2019 the CDC analyzed data from the State Unintentional Drug Overdose Reporting System (SUDORS) for July 2016 through December 2017. SUDORS records all substances detected on postmortem toxicology testing. The CDC analyzed overdose death where kratom was detected on postmortem toxicology testing and deaths where the medical examiner or coroner determined kratom to be a cause of death.

Kratom-positive deaths occurred in only 152 of 27,338 overdose deaths (.56%) for the time period of the study. “Kratom was determined to be a cause of death (i.e., kratom-involved) by a medical examiner or coroner for 91 (59.9%) of the 152 kratom-positive decedents, including seven for whom kratom was the only substance to test positive on postmortem toxicology.” However, the presence of additional substances could not be ruled out. And here is the rub: “Postmortem toxicology testing detected multiple substances for almost all decedents.” About 80% of the decedents with a kratom-positive and kratom-involved death had a history of substance misuse.

Focusing attention on the kratom-positive decedents who only used kratom appears to be a misdirection tactic. The problem seems to be individuals with a history of substance misuse who miscalculated on the strength or influence of the kratom they used—along with the other substances they ingested—and overdosed as a result of their mistake. Remember that in the Clinical Toxicology article, Post et al. concluded: “Despite the perception that kratom is safe because it is classified as an herbal supplement, a variety of serious medical outcomes following exposure to kratom have been documented, especially when kratom is used in combination with other substances.” The noose of regulation needs to get tighter around kratom and needs to occur sooner rather than later.

09/27/16

The Secret of Kratom

36473493 - tablet with the chemical formula of kratom (mitragyna speciosa) mitragynine. drugs and narcotics
© Vitally Vodolazskyy | 123rf.com

So you’ve never heard of kratom? A CDC study of kratom exposures reported to poison centers showed a tenfold increase from 26 in 2010 to 263 in 2015. If kratom becomes more widely known and used, those figures will be increasing. The CDC published a report on kratom on June 29, 2016, citing its potential as an “emerging drug of abuse.” The cited NIDA document, “Drug Facts: Kratom,” does not refer to it as an emerging drug of abuse as claimed, but it does say, “Like other drugs with opioid-like effects, kratom might cause dependence, which means users will feel physical withdrawal symptoms when they stop taking the drug.” The CDC report itself suggested it was an emerging public health threat.

Kratom use appears to be increasing in the United States, and the reported medical outcomes and health effects suggest an emerging public health threat. Members of the public and health care providers should be aware that the use of kratom can lead to severe adverse effects, especially when consumed in combination with alcohol or other drugs.

Kratom is a tropical tree-like plant native to Thailand, Malaysia, Myanmar and other countries in Southeast Asia. It has a long history of use as a stimulant in low doses. Kratom is often brewed as a tea, but it can also be smoked or swallowed in capsules. Southeast Asian laborers and farmers chew the leaves for energy to work harder and to relieve muscle strains. It has been used as a substitute for opium when opium is not available. And it’s used to manage opioid withdrawal symptoms. Long-term kratom use has produced anorexia, weight loss, insomnia, skin darkening, dry mouth, frequent urination and constipation.

The DEA included kratom on its Drugs of Concern list and recently announced its intention classify kratom and two of its psychoactive chemicals temporarily as a Schedule I controlled substances. “The two chemicals are called mitragynine and 7-hydroxymitragynine. By banning the active chemicals, the DEA is making sure that both the plant and any synthetic versions of it are included in the new regulation.” STAT reported the DEA is authorized to temporarily place substances in Schedule I for up to two years when it believes they are a potential public health threat. If their studies demonstrate there is a threat, the ban will remain. If not, it will revert to being legal.

Like marijuana, it contains multiple alkaloids, but mitragynine and 7-hydroxymitragynine are the primary active ones in the plant. At lower doses, it produces stimulant effects. Users report increased alertness, physical energy, talkativeness and sociable behavior. At higher doses, opiate effects, including sedation and euphoria occur. “Effects occur within 5 to 10 minutes of ingestion and last 2 to 5 hours.” The DEA announcement described the following health risks from kratom in some detail.

Several deaths associated with kratom have been reported, often when it is mixed with other substances. There are also reports of drug-induced liver damage, psychosis, seizures, weight loss, insomnia, tachycardia, vomiting, poor concentration and hallucinations. Fifteen of the reported deaths occurred between 2014 and 2016. There was a cluster of nine deaths reported in Sweden from a kratom product called “krypton.” See “Krypton Can Kill You.”

The CDC kratom study said 24.5% of the reports on adverse events were for minor complications; 41.7% required some treatment and were considered to be moderate complications. There were major complications—meaning life-threatening signs or symptoms, with some residual disability—for 7.4% of the kratom exposures. The adverse effects included: tachycardia [abnormally rapid heart beat] in 25% of the reported cases, agitation or irritability in 23.8%, drowsiness in 19.4%, nausea in 14.7% and hypertension in 11.7%.

A recent article in the International Journal of Legal Medicine by Warner, Kaufman and Grundmann reported the death of a young adult who had mixed kratom with prescribed medications—Prozac and Lamictal. Another article, “A Drug Fatality Involving Kratom,” noted a 17-year-old male with a history of heroin abuse and chronic back pain who died from a “possible Kratom toxicity.” He had mixed kratom, benzodiazepines and over-the-counter cold medications (containing DXM?).

In “Pharmacology of Kratom,” Prozialeck et al. found there was an increasing level of kratom use, especially among college students. They also noted a large number of online vendors and general information websites for kratom. An Internet search they did with Google had more than 2 million hits in February of 2012. When I repeated the search in August of 2016, I had over 6.36 million hits. Prozialeck et al. said their search of websites indicated kratom was being used for pain management as well as a recreational drug.

Kratom is regulated as an herbal product in the U.S. and is currently considered a legal substance, despite the CDC concern for its abuse potential. Along with the DEA declaration that there isn’t a legitimate medical use for kratom, this meant: “it cannot legally be advertised as a remedy for any medical reason.”

Pharmacologically, the mitragynine in kratom activates the μ, δ, and κ opioid receptors. Its main activity is on the μ receptor, the one that produces the analgesic and euphoric effects with opioids; and of course results in physical dependency. Despite kratom’s reputation as a “legal opioid,” there have been few scientific studies that addressed its psychoactive properties. Most of the available information is in anecdotal reports, like those on the website, Erowid.

Erowid has a plethora of Kratom reports categorized in groups such as: First Times, Combinations, Preparation/Recipes, Difficult Experiences, Health Problems, Addiction & Habituation, Mystical Experiences and Medical Use. A nondrinking male reported it caused liver toxicity in “Killing My Liver.” A more serious reaction resulted in a hospital stay for a drug–induced hepatic injury in “”Almost Destroyed My Liver.” Then there was a disturbing report under Addiction & Habituation called “This Thing Is a Secret.”

A man with a history of drug and alcohol addiction hadn’t used any “hard stuff” like heroin, alcohol, amphetamines or cocaine in five years. He was active in Alcoholic Anonymous. Then in January of 2005, he decided to order some kratom on a whim from an online vendor. When it kicked in, it had a “Definite opiate effect.” Nine months later, when he wrote his report for Erowid, he said he was using it daily. If he forgets to place his order in time, he’ll have to go a day without it. It was just like the withdrawals from his hydrocodone/Ambien habit.

His wife doesn’t know. No one knows, except the people he orders kratom from. He said he felt guilty spending family money of the stuff, but not guilty enough to stop. “Maybe I’ll quit some time, but for now, things are maintaining. It’s better than shooting heroin or oxycontin or any stuff like that…”

 Naturally, I don’t go around blabbing to my AA associates about how I am using this plant every day. They are some of the best people I have ever met and cherish their friendship. We have a saying in AA, ‘your secrets keep you sick.’ This Kratom thing is a secret.

Prozialeck et al. reported that as kratom use has expanded to Europe and the U.S., there have been increasing reports of individuals becoming physically dependent or addicted to kratom. Most of the published studies, like this one by McWhirter and Morris were case reports. They described a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. His withdrawal symptoms were consistent with mild opioid withdrawal: anxiety, restlessness, tremors, sweating and cravings.

Evidence suggests that kratom is being used extensively for both medical and nonmedical purposes. Recent studies have shown that kratom contains a variety of active compounds that produce major pharmacologic effects at opioid and other receptors. Kratom and kratom-derived drugs may potentially be used for the management of pain, opioid withdrawal symptoms, and other clinical problems. At the same time, serious questions remain regarding the potential toxic effects and the abuse and addiction potential of kratom. This issue is further confounded by the lack of quality control and standardization in the production and sale of kratom products. The possibilities of kratom products being adulterated or interacting with other drugs are also serious concerns. Until these issues are resolved, it would not be appropriate for physicians to recommend kratom for the treatment of patients. Nevertheless, physicians need to be aware that patients may use kratom or kratom-based products on their own. Further studies to clarify the efficacy, safety, and addiction potential of kratom are needed.

Regulating kratom presents issues similar to what we are now facing with marijuana. Both plants contain dozens of compounds with some potential medical use. Both are currently not viewed by the U.S. government as having any medical use.  Where marijuana’s classification as a Scheduled I controlled substance makes scientific research into its potential medical uses difficult, the limited use and knowledge of kratom contributes to it being understudied. Each also has one or two dominant psychoactive ingredients.

There is also a lack of quality control with both. The strength of THC or CBD in marijuana and mitragynine or 7-hydroxymitragynine in kratom can vary widely. Products containing these herbal substances cannot be guaranteed to carry similar doses of the active ingredients. And they are likely to have contaminants, such as pesticides, if grown commercially. The limited, scientifically reliable knowledge of their medical usefulness, and the lack of regulation with regard to that knowledge, results in a wide variety of anecdotal claims similar to past the age of patent medicines.

What is to be done? Federal funding of research into kratom’s potential medical uses needs to occur. The two-year temporary classification as Schedule I can be extended another year if more time is needed while the studies of it medical uses are completed. A permanent classification of kratom as a Schedule I Controlled substance seems inadvisable. Remember that hasn’t worked very well with marijuana. Future classification as a controlled substance seems reasonable, given its activation of the μ, δ, and κ opioid receptors. But let’s base it upon reliable scientific information.