India: FDA Intensifies Its Warning Against Kratom, Classifying It As An ‘Opioid' Underscoring Potential For Abuse

On February 06, 2018, the United States Food and Drug Administration (US-FDA) intensified its warnings about Kratom, stating that new research provides strong evidence that the unregulated botanical substance has 'opioid properties'43.

A new analysis by scientists at the US -FDA shows that compounds in Kratom act like prescription-strength opioids. The agency also said that Kratom has now been linked to 44 deaths. The agency said that over the past several months, many questions have been raised about the botanical substance known as Kratom. FDA has taken some significant steps to advance the scientific understanding of this product and how it works in the body. The agency provided 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.

The agency 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. The agency also learnt more about deaths that involved Kratom use and have identified additional adverse events related to this product. This new data adds to the substantial scientific evidence supporting agency's concern about the safety and abuse potential of Kratom.

The agency has been especially concerned about its use 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 also exist. The agency further said that it recognizes the need and desire for alternative treatments for both the treatment of opioid addiction, as well as the treatment of chronic pain, and stands ready to evaluate evidence that could demonstrate a medicinal purpose for Kratom. However, to date, the agency has not received any such submissions and is not aware of any evidence that would meet the agency's standards for approval.

About Kratom

Mitragyna speciosa (commonly known as Kratom also ketum) is a tropical evergreen tree in the coffee family (Rubiaceae) native to Southeast Asia in the Indochina and Malaysia phytochoria (botanical regions). M. speciosa is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea44.

The FDA's PHASE model used to assess Kratom

The FDA developed the Public Health Assessment via Structural Evaluation (PHASE) methodology – a tool to help 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.

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 compounds share the most structural similarities with controlled opioid analgesics, such as morphine derivatives. Next, the 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, the agency generated to look at, not just where these compounds bind, but how strongly they bind to their biological targets. The agency found out that Kratom has a strong bind to mu-opioid receptors, comparable to scheduled opioid drugs.

Learnings from reports of death associated with Kratom

US-FDA has 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. The agency has also conducted several product seizures. These actions were based, in part, on a body of academic research, as well as reports the agency has received, suggesting harm associated with its use. Numerous countries, states and cities have banned Kratom from entering their jurisdictions.

The agency also shared more information about the tragic reports it has received of additional deaths involving the use of Kratom. Looking at the information the agency has received from sources like academic research, poison control data, medical examiner reports, social science research and adverse event reports – it is reported that 44 deaths are associated with the use of Kratom.

The agency also released the reports of the 36 deaths it had referenced to in November last year. 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. The FDA is continuing to investigate this report, but the information it has received so far reinforces its 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 the agency now has 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. The FDA also recently took steps to help reduce abuse of loperamide by requesting packaging restrictions for these products sold "over-the-counter45."

Overall, the scientific evidence of the agency provides a clear picture of the biological 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. The agency further said that claiming that Kratom is benign because its "just a plant" is shortsighted and dangerous. After all, even heroin, which is derived from the seed pod of various opium poppy plants, is an illegal, dangerous, and highlyaddictive substance containing the opioid morphine. Further, as the scientific data and adverse event reports have clearly revealed, compounds in Kratom make it, even though a plant, an opioid. And this opioid is associated with novel risks because of the variability in how it is 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.

USFDA added that individuals seeking treatment for opioid addiction, who are being advised that Kratom can be an effective treatment, should 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. Also, there are safer, non-opioid options to treat pain.

FDA to oversee destruction and recall of Kratom products

Further, the agency on February 21, 2018, announced the voluntary destruction and recall of a large volume of Kratom-containing dietary supplements manufactured and distributed nationwide under various brand names. The FDA said all companies currently involved in the sale of products containing Kratom intended for human consumption should take similar steps to take their products off the market and submit any necessary evidence, as appropriate, to the FDA to evaluate them based on the applicable regulatory pathway. Additionally, the FDA and the U.S. Centers for Disease Control and Prevention were also monitoring an active nationwide outbreak across 20 states of a rare type of salmonella associated with Kratom products46. This outbreak associated with Kratom-containing capsules, teas and powders, underscores the risk that harmful bacteria may contaminate these products when not subjected to manufacturing controls to eliminate that risk, in addition to the overall safety concerns regarding Kratom itself.

Conclusion:

The U.S. Food and Drug Administration is warning consumers not to use Mitragyna speciosa, commonly known as Kratom. 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 dependency. Further, the agency has reiterated that currently there are no FDA-approved uses for Kratom.

Footnotes

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

44. https://en.wikipedia.org/wiki/Mitragyna_speciosa

45. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594443.htm

46. https://www.fda.gov/Food/RecallsOutbreaksEmergencies/Outbreaks/ucm597265.htm

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Authors
 
In association with
Related Topics
 
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
Mondaq on Twitter
 
Mondaq Sign Up
Gain free access to lawyers expertise from more than 250 countries.
 
Email Address
Company Name
Password
Confirm Password
Position
Industry
Mondaq Newsalert
Select Topics
Select Regions
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.

Disclaimer

The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.

General

Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions