Unapproved kratom products: FDA issuing new warning letters

September 11, 2018

Statement from FDA Commissioner Scott Gottlieb, M.D., on new warning letters FDA is issuing to companies marketing kratom with unproven medical claims; and the agency’s ongoing concerns about kratom

Epidemics don’t occur overnight. As we deal with the devastating crisis of opioid abuse and overdose plaguing our nation, the U.S. Food and Drug Administration must remain vigilant and aggressive against trends that threaten to reverse our progress, or substances that have the potential to cause new epidemics of abuse.

Mitragyna speciosa, known more commonly as kratom, is a plant native to Thailand, Malaysia, Indonesia and Papua New Guinea. While it is important to generate more evidence, there is evidence that certain substances found in kratom are opioids and data suggest that one or more may have a potential for abuse. And its use has been on the rise and is of concern to the FDA. We’re not alone in our concern about the opioids found in kratom – it’s already illegal or controlled in several other countries including Australia, Denmark, Germany, Malaysia and Thailand. The substance is also banned in a number of states and municipalities in the U.S.

Science and evidence matter in demonstrating medical benefit, especially when a product is being marketed to treat serious diseases like opioid use disorder (OUD). However, to date, there have been no adequate and well-controlled scientific studies involving the use of kratom as a treatment for opioid use withdrawal or other diseases in humans. Nor have there been studies on how kratom, when combined with other substances, may impact the body, its dangers, potential side effects, or interactions with other drugs. Today’s action is based on these concerns. The FDA issued warning letters to two more unscrupulous vendors, Chillin Mix Kratom and Mitra Distributing, for marketing kratom products with scientifically unsubstantiated claims including to “relieve opium withdrawals” and to “treat a myriad of ailments including but not limited to: diarrhea, depression, diabetes, obesity, high blood pressure, stomach parasites, diverticulitis, anxiety, alcoholism, and opiate withdrawal.” Simply, selling these unapproved kratom products with claims that they can treat opioid withdrawal and addiction and other serious medical conditions is a violation of federal law.

Yet despite our warnings and previous regulatory and enforcement actions, we continue to find marketers actively selling kratom with unsubstantiated claims.

Fraudulent health claims can pose serious health risks. They may keep some patients from seeking appropriate, FDA-approved therapies. Reliance on products with unsubstantiated claims may delay those who suffer from OUD from entering recovery and may put them at greater risk of overdose and death. We know that patients receiving FDA-approved medication-assisted treatment (MAT) cut their risk of death in half, according to the Substance Abuse and Mental Health Services Administration.

As U.S. Department of Health and Human Services and the others in the federal government work to reduce the number of Americans who are addicted to opioids ad other substances, the FDA will continue to promote innovation and more widespread access to FDA-approved treatments for OUD. While HHS is taking new steps to make safe and effective MAT available to those who suffer from OUD, we must also work to reduce the stigma that is sometimes associated with use of these therapies. In parallel, we cannot allow kratom products with unsubstantiated claims to prevent those with OUD from seeking treatments that have been demonstrated to be safe and effective.

At HHS and within the FDA, we have great concern for the many Americans who misuse any drugs, especially opioids. In support of the public health, we continue to urge consumers not to consume kratom and to seek appropriate medical care from their health care provider. We will also continue to take action against those who put the safety of Americans at risk and who violate federal law by making unsubstantiated health claims about products that they seek to sell.

The Food and Drug Administration, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA keeps warning about the controversial supplement kratom, but companies keep deceptively selling it  
Published: Sept 11, 2018 12:42 p.m. ET
“Simply, selling these unapproved kratom products with claims that they can treat opioid withdrawal and addiction and other serious medical conditions is a violation of federal law,” the FDA said in a Tuesday statement. “Yet despite our warnings and previous regulatory and enforcement actions, we continue to find marketers actively selling kratom with unsubstantiated claims.”

The two companies in question, Chillin Mix Kratom and Mitra Distributing, also claimed that their kratom products could treat conditions like obesity, depression, alcoholism and high blood pressure, according to the FDA. Continue reading: https://www.marketwatch.com/story/fda-keeps-warning-about-the-controversial-supplement-kratom-but-companies-keep-deceptively-selling-it-2018-09-11

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Poisonings from kratom, sold as an herbal supplement, are rising. But no one knows how much 

Mari A. Schaefer Tuesday, August 21, 2018 

Kratom is an unregulated herbal product that has been linked to at least four deaths in the Philadelphia region. 

PHILADELPHIA — An unregulated herbal product that advocates say can relieve pain and help with opioid withdrawal has been linked to at least four deaths in the Philadelphia region, but with many authorities failing to track kratom poisonings, there’s no way to know if there are more deaths related to the substance.

Kratom, derived from the leaves of a Southeast Asian tree that is part of the coffee family, has gained popularity in recent years. It is sold online, in gas stations and in smoke shops, and is typically brewed as a tea, chewed, smoked or ingested in capsules.

An estimated 3 million to 5 million people use kratom, according to the American Kratom Association, a Colorado-based nonprofit founded in 2014 to promote the herbal product. It has become a billion-dollar business, according to the Botanical Education Alliance, another kratom advocacy group.

Read more: Boston Herald 

FDA warns companies selling illegal, unapproved kratom products marketed for opioid cessation, pain treatment and other medical uses

FDA Press Release

The U.S. Food and Drug Administration has issued warning letters to three marketers and distributors of kratom products – Front Range Kratom of Aurora, Colorado; Kratom Spot of Irvine, California and Revibe, Inc., of Kansas City, Missouri – for illegally selling unapproved kratom-containing drug products with unproven claims about their ability to help in the treatment of opioid addiction and withdrawal. The companies also make claims about treating pain, as well as other medical conditions like lowering blood pressure, treating cancer and reducing neuron damage caused by strokes.

“Despite our warnings that no kratom product is safe, we continue to find companies selling kratom and doing so with deceptive medical claims for which there’s no reliable scientific proof to support their use,” said FDA Commissioner Scott Gottlieb, M.D. “As we work to combat the opioid epidemic, we cannot allow unscrupulous vendors to take advantage of consumers by selling products with unsubstantiated claims that they can treat opioid addiction. Far from treating addiction, we’ve determined that kratom is an opioid analogue that may actually contribute to the opioid epidemic and puts patients at risk of serious side effects. If people believe that the active ingredients in kratom have drug-like effects that can treat pain or addiction, then the FDA is open to reviewing that data under our new drug approval process. In the meantime, I promised earlier this year that the FDA would step up our actions against unapproved and unsafe products that are being deceptively marketed for the treatment of opioid addiction and withdrawal symptoms. At the same time, we also promised to make the approval process more efficient for novel, safe and effective medical treatments aimed at the treatment of addiction; and to help more people suffering from addiction get access to approved therapies. In fulfilling these commitments, we’ll continue to take enforcement actions against unscrupulous products to protect the public health.”

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.

The companies receiving warning letters use websites where they take orders for kratom products or they use social media to make unproven claims about the ability of their kratom drug products to cure, treat, or prevent a disease, which is against the law. Examples of claims being made by these companies include:

• “Along with helping drug addiction, the health benefits of kratom leaves include their ability to lower blood pressure, relieve pain, boost metabolism, increase sexual energy, improve the immune system, prevent diabetes, ease anxiety, eliminate stress, and induce healthy sleep.”
• “The mood elevation qualities of kratom reduces opiate withdrawal effects.”
• “Kratom, like any other pain killer, relieves temporary or even chronic pain.”
• “This plant can relieve headaches, vascular pain, arthritic pain, muscle pain among others.”
• “Kratom can be used as a remedy for stroke-related ailments and condition as it is a powerful antioxidant that works to reduce neuron damage.”
• “It can . . . help in lowering blood pressure.”
• “Kratom is also said to have elements that control blood sugar level in the body for diabetic patients.”
• “It is said, that kratom is very effective against cancer.”

Health fraud scams like these can pose serious health risks. These products have not been demonstrated to be safe or effective and may keep some patients from seeking appropriate, FDA-approved therapies. Selling these unapproved products with claims that they can treat opioid addiction and withdrawal and treat other serious medical conditions is a violation of the Federal Food, Drug, and Cosmetic Act.

Reducing the number of Americans who are addicted to opioids and cutting the rate of new addiction is one of the FDA’s highest priorities. This work includes promoting more widespread innovation and access to opioid addiction treatments for the more than 2 million of Americans with an opioid use disorder. The FDA is taking new steps to make safe and effective medication assisted treatments (MAT) available to those who suffer from opioid use disorder and to reduce the stigma that is sometimes associated with use of these therapies. Using products with unsubstantiated claims may prevent those addicted to opioids from seeking treatments that have been demonstrated to be safe and effective. Reliance on products with unsubstantiated claims may delay their path to recovery and put them at greater risk of addiction, overdose and death. In fact, patients receiving FDA-approved medication-assisted treatment cut their risk of death in half, according to the Substance Abuse and Mental Health Services Administration.

The warning letters included more than 65 kratom products. Some of these products include:

Front Range Kratom:

• “Maeng Da Red Vein Powder”
• “Maeng Da White Vein Capsules”
• “Liquid Kratom Red Maeng Da Enhanced Pain Formulation”
• “Bali White Vein Kratom Powder”
• “Bali Green Vein Powder”
• “Maeng Da White Energizing Formula”

Kratom Spot:

• “Red Thai Kratom Powder”
• “Indo White Vein Kratom Powder”
• “Borneo White Vein Kratom Powder”
• “Green Malay Kratom Powder”
• “Super Green Indo Kratom Capsules”
• “Ultra Enhanced Malay Kratom Powder”
• “Kratom Extract 8x Kratom Powder”

Revibe:

• “50x Black Diamond Extract”
• “Green Horn Kratom”
• “Green Indo”
• “Green Sumatra,” “Lucky 7”
• “Red Borneo”
• “Super Elephant”
• “White Sumatra”
• “Yellow Vietnam Kratom”

The FDA requested responses from each of the companies within 15 working days. The companies are directed to inform the agency of the specific actions taken to address each of the agency’s concerns. The warning letters also state that failure to correct violations may result in law enforcement action such as seizure or injunction.

Previous FDA testing also confirmed salmonella contamination in kratom products distributed by Revibe. On March 26, 2018, the FDA contacted Revibe regarding a recall of all Revibe kratom containing products that may be contaminated with salmonella. On April 3, 2018, the agency oversaw the destruction of products at Revibe’s facility, but, as of April 19, 2018, the company has not provided the FDA information to confirm that they have recalled the products it distributed. The FDA reminds consumers of the risks and urges them not to use these or any other kratom products.

Health care professionals and consumers are encouraged to report any adverse events related to these products to the FDA’s MedWatch Adverse Event Reporting program. To file a report, use the MedWatch Online Voluntary Reporting Form. The completed form can be submitted online or via fax to 800-FDA-0178.

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm608447.htm

FDA Statement - Kratom potential for abuse, addiction, and linked to 44 deaths

FDA Statement

Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom, underscoring its potential for abuse

Additional adverse events associated with kratom use identified.

Over the past several months, there have been many questions raised about the botanical substance known as kratom. Our concerns related to this product, and the actions we’ve taken, are rooted in sound science and are in the interest of protecting public health. However, we recognize that there is still much that is unknown about kratom, which is why we’ve taken some significant steps to advance the scientific understanding of this product and how it works in the body. Today, we’re providing details of some of the important scientific tools, data and research that have contributed to the FDA’s concerns about kratom’s potential for abuse, addiction, and serious health consequences; including death.

Notably, we recently conducted a novel scientific analysis using a computational model developed by agency scientists, which provided even stronger evidence of kratom compounds’ opioid properties. These kinds of models have become an advanced, common and reliable tool for understanding the behavior of drugs in the body. We also have learned more about deaths that involved kratom use, and have identified additional adverse events related to this product. This new data adds to our body of substantial scientific evidence supporting our concerns about the safety and abuse potential of kratom.

We have been especially concerned about the use of kratom to treat opioid withdrawal symptoms, as there is no reliable evidence to support the use of kratom as a treatment for opioid use disorder and significant safety issues exist. We recognize the need and desire for alternative treatments for both the treatment of opioid addiction, as well as the treatment of chronic pain. The FDA stands ready to evaluate evidence that could demonstrate a medicinal purpose for kratom. However, to date, we have received no such submissions and are not aware of any evidence that would meet the agency’s standard for approval.

The FDA’s PHASE model used to assess kratom

Federal agencies need to act quickly to evaluate the abuse potential of newly identified designer street drugs for which limited or no pharmacological data are yet available. This is why the FDA developed the Public Health Assessment via Structural Evaluation (PHASE) methodology – a tool to help us simulate, using 3-D computer technology, how the chemical constituents of a substance (such as the compounds/alkaloids found in kratom) are structured at a molecular level, how they may behave inside the body, and how they can potentially affect the brain. In effect, PHASE uses the molecular structure of a substance to predict its biological function in the body. For example, the modelling platform can simulate how a substance will affect various receptors in the brain based on a product’s chemical structure and its similarity to controlled substances for which data are already available.

Using this computational model, scientists at the FDA first analyzed the chemical structures of the 25 most prevalent compounds in kratom. From this analysis, the agency concluded that all of the compounds share the most structural similarities with controlled opioid analgesics, such as morphine derivatives.

Next, our scientists analyzed the chemical structure of these kratom compounds against the software to determine its likely biologic targets. The model predicted that 22 (including mitragynine) of the 25 compounds in kratom bind to mu-opioid receptors. This model, together with previously available experimental data, confirmed that two of the top five most prevalent compounds (including mitragynine) are known to activate opioid receptors (“opioid agonists”).

The new data provides even stronger evidence of kratom compounds’ opioid properties.

The computational model also predicted that some of the kratom compounds may bind to the receptors in the brain that may contribute to stress responses that impact neurologic and cardiovascular function. The agency has previously warned of the serious side effects associated with kratom including seizures and respiratory depression.

The third aspect of the model is the 3-D image we generate to look at not just where these compounds bind, but how strongly they bind to their biological targets. We found that kratom has a strong bind to mu-opioid receptors, comparable to scheduled opioid drugs.

So what does this body of scientific evidence mean? The FDA relies on this kind of sophisticated model and simulation to supplement its data on how patients react to drugs; often as a way to fully elucidate the biological activity of a new substance. The data from the PHASE model shows us that kratom compounds are predicted to affect the body just like opioids. Based on the scientific information in the literature and further supported by our computational modeling and the reports of its adverse effects in humans, we feel confident in calling compounds found in kratom, opioids.

Furthermore, this highlights the power of our computational model-based approach to rapidly assess any newly identified natural or synthetic opioids to respond to a public health emergency.

Learnings from reports of death associated with kratom

We’ve been carefully monitoring the use of kratom for several years, and have placed kratom products on import alert to prevent them from entering the country illegally. We have also conducted several product seizures. These actions were based, in part, on a body of academic research, as well as reports we have received, suggesting harm associated with its use. And we are not alone in our evaluation and our public health concerns. Numerous countries, states and cities have banned kratom from entering their jurisdictions. We described some of this information in a public health advisory in November 2017, in which we urged consumers not to use kratom or any compounds found in the plant.

Now, I’d like to share more information about the tragic reports we have received of additional deaths involving the use of kratom. Looking at the information we have received – including academic research, poison control data, medical examiner reports, social science research and adverse event reports – we now have 44 reported deaths associated with the use of kratom. This is an increase since our November advisory, which noted 36 deaths associated with these products. We’re continuing to review the newly received reports and will release those soon. But it’s important to note that these new reports include information consistent with the previous reports.

Today, we’re releasing the reports of the 36 deaths we referenced in November. These reports underscore the serious and sometimes deadly risks of using kratom and the potential interactions associated with this drug. Overall, many of the cases received could not be fully assessed because of limited information provided; however, one new report of death was of particular concern. This individual had no known historical or toxicologic evidence of opioid use, except for kratom. We’re continuing to investigate this report, but the information we have so far reinforces our concerns about the use of kratom. In addition, a few assessable cases with fatal outcomes raise concern that kratom is being used in combination with other drugs that affect the brain, including illicit drugs, prescription opioids, benzodiazepines and over-the-counter medications, like the anti-diarrheal medicine, loperamide. Cases of mixing kratom, other opioids, and other types of medication is extremely troubling because the activity of kratom at opioid receptors indicates there may be similar risks of combining kratom with certain drugs, just as there are with FDA-approved opioids.

However, unlike kratom, FDA-approved drugs have undergone extensive review for safety and efficacy, and the agency continuously tracks safety data for emerging safety risks that were previously unknown. So we have better information about the risks associated with these products; and can better inform the public of new safety concerns. For example, in August 2016, the FDA required a class-wide change to drug labeling to help inform health care providers and patients of the serious risks (including respiratory depression, coma and death) associated with the combined use of certain opioid medications and benzodiazepines. In June 2016, the agency also issued a warning that taking significantly high doses of loperamide, including through abuse or misuse of the product to achieve euphoria or self-treat opioid withdrawal, can cause serious heart problems that can lead to death. We also recently took steps to help reduce abuse of loperamide by requesting packaging restrictions for these products sold “over-the-counter.”

Taken in total, the scientific evidence we’ve evaluated about kratom provides a clear picture of the biologic effect of this substance. Kratom should not be used to treat medical conditions, nor should it be used as an alternative to prescription opioids. There is no evidence to indicate that kratom is safe or effective for any medical use. And claiming that kratom is benign because it’s “just a plant” is shortsighted and dangerous. After all, heroin is an illegal, dangerous, and highly-addictive substance containing the opioid morphine, derived from the seed pod of the various opium poppy plants.

Further, as the scientific data and adverse event reports have clearly revealed, compounds in kratom make it so it isn’t just a plant – it’s an opioid. And it’s an opioid that’s associated with novel risks because of the variability in how it’s being formulated, sold and used recreationally and by those who are seeking to self-medicate for pain or who use kratom to treat opioid withdrawal symptoms. We recognize that many people have unmet needs when it comes to treating pain or addiction disorders. For individuals seeking treatment for opioid addiction who are being told that kratom can be an effective treatment, I urge you to seek help from a health care provider. There are safe and effective, FDA-approved medical therapies available for the treatment of opioid addiction. Combined with psychosocial support, these treatments are effective. Importantly, there are three drugs (buprenorphine, methadone, and naltrexone) approved by the FDA for the treatment of opioid addiction, and the agency is committed to promoting more widespread innovation and access to these treatments to help those suffering from an opioid use disorder transition to lives of sobriety. There are also safer, non-opioid options to treat pain. We recognize that some patients have tried available therapies, and still have unmet medical needs. We’re deeply committed to these patients, and to advancing new, safe and effective options for those suffering from these conditions.

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm595622.htm