Preemptive Steps Taken by FDA Seen As Disrupting Kratom Supplies and Forcing Reliance on “Substandard” Product; Salmonella Issue Shows Need for Properly Regulated Marketplace, Not DEA Scheduling that Would Ban Product; No Persuasive Case on Addiction or Death Made on Scientific Grounds Against Herb.
WASHINGTON, D.C. — April 25, 2018 — The U.S. Food and Drug Administration (FDA) may have inadvertently contributed to the current small number of kratom-associated salmonella cases (fewer than 150 out of 1 million from all sources annually) when it preemptively imposed import restrictions on the herb and also focused on banning kratom rather than regulating its manufacture consistent with good manufacturing practices used with other supplements, according to statements made today during a news conference of leading kratom scientists.
By imposing an effective ban on importing kratom (including seizures at ports), the FDA forced manufacturers to shift from high-quality sources of the herb to lesser suppliers, thus increasing the potential for issues such as salmonella, which had never previously been an issue with kratom in the U.S. Further, the risk of adulteration and other issues increased when the FDA opted to push for a ban of kratom, rather than enforcing the mandatory 2007 current good manufacturing practice (CGMP) rule for dietary supplements, which also would have reduced salmonella risks.
Cautioning against the demonization of kratom, the scientists underscored the fact that the history of use by three million or more Americans and recent published scientific surveys indicate the herb is not a significant public health problem (including death and addiction) and is consumed in much the same way as many other botanical dietary supplements widely and legally available across the United States. Further, in some cases kratom is a lifeline away from often deadly opioids.
The statements of the experts below:
Paula N. Brown, Ph.D., director of applied research, BC Institute of Technology, Canada Research chair, Phytoanalytics and adjunct professor of biology, University of British Columbia.
“The salmonella outbreak is not a reflection on kratom per se and underscores the need for FDA enforcement, not scheduling. The FDA’s designation of kratom alkaloids as opioids is consequential for both regulation and quality of marketed products. While traditional use is not a standard of evidence recognized in the US, where market access is based on presence prior to 1994, ultimately the focus needs to be ensuring the public has access to products that are safe and of high quality. The FDA issued import alert that permits automatic detention of kratom materials without physical examination, has resulted in several kratom product being seized at ports and has forced many existing consumers to obtain products through internet distributors and dubious sources. The recent salmonella contamination of kratom products highlights the inconsistent enforcement of the mandatory 2007 current good manufacturing practice (CGMP) rule for dietary supplements by the FDA. The import alert and failure to enforce CGMP regulations has forced kratom products into an illicit market where adulterated and substandard products may flourish while driving legitimate products out of the marketplace.”
Michael McGuffin — leading expert on dietary supplement regulations and executive director, American Herbal Products Association.
“Trade associations serve a unique role in the interface between regulatory agencies and the relevant regulated trade, both by providing guidance and encouraging best practices for industry and by communicating with regulators on behalf of the trade. When it comes to the particular case of kratom, AHPA views this as just one of the many herbs or other botanicals that are allowed under U.S. law to be marketed as a dietary supplement. But AHPA also notes that the Food and Drug Administration has identified kratom as a ‘new dietary ingredient’ (or NDI) and so AHPA has recommended that companies that want to market kratom comply with FDA’s new dietary ingredient requirements by submitting an NDI notification in conformity with FDA’s rules. At the same time, we encourage FDA to treat any such kratom NDI notification exactly as it would a notification for any other new herb. AHPA has also circulated suggestions that kratom marketers understand and meet all of the other regulations required for any herbal product sold as a dietary supplement, such as registering as a food facility, meeting the extensive good manufacturing practice rules, refraining from making any drug claims, and submitting to FDA all serious adverse event reports received in association with their kratom products.”
Oliver Grundmann, Ph.D., clinical associate professor, College of Pharmacy, University of Florida.
“The science doesn’t support kratom nor its alkaloids as being labelled a dangerous opioid. Instead, further research is necessary to support its unique pharmacology which may lead to safer drugs for the treatment of pain. Surveys and observational studies indicate the majority of kratom use is for alleviation of mild to moderate acute or chronic pain, to reduce anxiety or elevate mood. A smaller number of users indicate they consume kratom as a substitute for using opioids or to mitigate withdrawal symptoms from illicit or prescription drug dependence. Kratom use in the US is on the rise, independent of its intended use and it is in the best interest of public health if consumers have access to products that adhere to established FDA CGMP rather than driving this market into the grey area of internet sales or unregulated international distributors.”
Jack Henningfield, Ph.D. vice president of research, Health Policy and Abuse Liability, at PinneyAssociates, and adjunct professor of Behavioral Biology, Johns Hopkins University School of Medicine.
“With the opioid crisis claiming the lives of more than 100 people daily it is clear much more needs to be done to expand access to existing opioid use disorder treatment and research into new approaches for prevention and treatment. While the White House Opioid Report did not explicitly discuss complementary and alternative therapies, kratom, which is marketed as a dietary supplement in the US, has been used for nearly a century for anxiety, improving mood, minor pain and treating opioid addictions in South East Asia (SEA) and at least two decades in the US. This is supported by thousands of comments to FDA dockets, four Internet surveys and is consistent with the neuropharmacology of the main kratom alkaloid, mitragynine. The results of the surveys and recent research suggests kratom and its alkaloids may be among the promising next generation of safer treatments for pain and addiction, but also anxiety and minor depression. Unfortunately, research and the use of kratom by many people to sustain abstinence from opioids is threatened by FDA’s recommendation to the Drug Enforcement Administration (DEA) to ban lawful sales and possession of kratom by placing it in the Controlled Substances Act as a Schedule I drug. Recent statements and actions by FDA actually make the case for responsible regulation/marketing — not a ban. The importance of access to product for millions of American consumers cannot be understated nor can the dangers of an illicit market.”
For the full text of the statements, please click here: Brown; McGuffin; Grundmann; and Henningfield.
MEDIA CONTACT: Patrick Mitchell, (703) 276-3266 or pmitchell@hastingsgroup.com.
EDITOR’S NOTE: A streaming audio recording of the news event will be available online at www.bitly.com/kratomscience as of 4 p.m. ET/1 p.m. PT on April 25, 2018. None of the speakers has accepted compensation for participating in this news event. Dr. Brown provides scientific research guidance on dietary supplement manufacture and regulatory compliance to companies, associations and government. Dr. Henningfield provides scientific research guidance to the American Kratom Association, which is not affiliated in any way with today’s news event. Limited and unrestricted support for this news event is being provided by the nonprofit People Plants Health.
Listen to streaming audio of news event here.
FOUR LEADING KRATOM RESEARCHERS URGE FDA TO FOCUS ON SCIENCE RATHER THAN RHETORIC
Top Experts Reject FDA Statements that Compounds in Natural Botanical Are Dangerously Addictive, Similar to “Narcotics Like Opioids” or Pose Claimed Death Risks.
WASHINGTON, D.C. — March 7, 2018 — Four of the world’s leading kratom researchers today called on the U.S. Food and Drug Administration (FDA) to cease the agency’s scientifically unsupported attacks on the coffee-like herb kratom. The scientists strongly believe that the current body of credible research on the actual effects of kratom demonstrates that it is not dangerously addictive, nor is it similar to “narcotics like opioids” with respect to “addiction” and “death” as stated by the FDA in its public advisories and subsequent warnings. It is the scientists’ position that a ban on kratom could result in a “serious public health threat” as consumers are pushed to dangerous alternatives in the black market, while at the same time halting much needed scientific research on the risks and benefits of kratom and its alkaloids.
The four kratom experts organized today’s news conference and were not paid to participate in it. The scientists are: Marc T. Swogger, Ph.D., associate professor of psychiatry, University of Rochester Medical Center; Oliver Grundmann, Ph.D., clinical associate professor, College of Pharmacy, University of Florida; Paula N. Brown, Ph.D., director of applied research, BC Institute of Technology, Canada Research chair, Phytoanalytics and adjunct professor of biology, University of British Columbia; and Dr. Jack Henningfield, vice president of research, Health Policy and Abuse Liability, at PinneyAssociates, and adjunct professor of Behavioral Biology, Johns Hopkins University School of Medicine.
Instead of a de facto ban on kratom, the scientists urged the promotion of good manufacturing practices (GMP) complying to FDA standards, as is the case with other widely available supplements in the United States.
The following are the statements of the four experts:
Science suggests removing kratom from market would be a risk, not benefit, to public health — Marc T. Swogger, Ph.D., associate professor of psychiatry, University of Rochester Medical Center
– Risks associated with scheduling and loss of access
– Contrary to the President’s Commission on Combating Drug Addiction and the Opioid Crisis
“We have science-based objections to the scheduling of kratom under the Controlled Substances Act. The existing science indicates that many of the millions of people in the U.S. who use kratom rely on it as a lifeline away from potentially deadly opioids. People use kratom to ease opioid withdrawal and to manage acute and chronic pain. Scheduling kratom would remove a valuable pain treatment option for millions, leading to greater opioid use with the likely consequences of increasing dangerous opioid dependence and overdose deaths.”
“Our objection to the scheduling of kratom is supported by data from four national scientific surveys conducted in the past two years, as well as decades of information from Southeast Asia, where this plant has been widely used as a safer alternative to opioids for more than a century. We cannot say that kratom is harmless for everyone, nor can we say that we know everything there is to know about the plant; rigorous, well-controlled studies are necessary. At this juncture, however, there is no high-quality evidence to indicate that kratom is a serious public health threat, and much evidence to suggest that banning it would be.”
“If the government fails to seriously consider the unintended consequences of banning kratom, they will be abdicating their duty to protect the safety of consumers — the expressed purpose of the enactment of the CSA by the U.S. Congress. Neglecting the available science and scheduling kratom are exactly what one would do if their aim was to worsen the opioid crisis.”
The FDA has pointed to 44 deaths over the last decade in the U.S. as their basis for concern, while the actual role of kratom in these deaths is speculative — Oliver Grundmann, Ph.D., clinical associate professor, College of Pharmacy, University of Florida
– Speculative; lack of causality for deaths involving kratom
– Differentiation of mode of action for kratom alkaloids from opioids; do not cause respiratory depression upon binding the same opioid receptors
“It is our strongly held belief that the claims that kratom has caused the deaths of all or even most of the 44 individuals cited by the FDA cannot be supported by any reasonable scientific or medical standard. Unlike overdose deaths that are rightly attributed to classical opioids, which reliably cause respiratory depression and death at high doses, the fatalities that the FDA lists as having been associated with kratom include deaths with a wide variety of apparent causes in people suffering from various diseases and/or taking other substances, thus allowing for no conclusive determination of the causative agent(s) responsible for deaths.”
“The FDA used a computer simulation, the PHASE model, to justify classifying Kratom and its major alkaloids, mitragynine and 7-OH mitragynine as opioids. Using a computational model alone is not sound science and fails to consider the additional scientific literature that has reported a distinct difference in how the alkaloids in kratom interact with the same opioid receptors in the brain. In isolated receptors and animals alike, the alkaloids presented with different effects from that of classical opioids like morphine or heroin, primarily not presenting with potentially fatal respiratory depression at higher doses.”
Publicly available research documents illustrate kratom has a long history of acceptably safe consumer use — Paula N. Brown, Ph.D., director of applied research, BC Institute of Technology, Canada Research chair, Phytoanalytics and adjunct professor of biology, University of British Columbia
– Import advisory of February 2014 by FDA identifies kratom as dietary ingredient
– History of safety for traditional use and modern use for pain relief
– Regulation as a dietary ingredient means compliance with Good Manufacturing Practices
“The FDA issued an import alert in February 2016 that stated, ‘Kratom is a botanical that qualifies as a dietary ingredient under section 201(ff)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 321(ff)(1)].’ When marketed as a dietary ingredient, FDA also considers kratom to be a new dietary ingredient under section 413(d) of the Act [21 U.S.C. 350b(d)] because, to the best of the agency’s knowledge, there is no information demonstrating that this substance was marketed as a dietary ingredient in the United States before October 15, 1994.”
“So while we can argue whether FDA’s consideration of kratom as a New Dietary Ingredient is substantiated or not, the focus should be on compliance with Good Manufacturing Practices (GMP) to ensure the public has access to products that are not adulterated with opioids (e.g., fentanyl, carfentanil, and other morphine-derived products), spiked with concentrated amounts of mitragynine and 7-OH mitragynine that are not consistent with levels in historical products and are tested for microbials to meet purity specifications. We agree that these concerns should be eliminated with a single kratom-based product regulatory standard that would protect both kratom manufacturers and consumers.”
“Documented literature demonstrates widespread use of kratom leaves for centuries; traditionally used as an energizer, relaxant, and to relieve stress and/or minor aches and pain (Suwanlert 1975; Watanebe et al., 1997; Vicknasingam et al., 2010, Adkins, 2011; Stolt et al., 2014; Brown et al. 2017). Kratom has also been increasingly used as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain, as shown in the recent four published surveys. The current scientific research suggests that kratom provides some pain relief without the dangerous and potentially deadly respiratory suppression induced by classical opioid medications. Risk assessments must rely on laboratory, clinical, and epidemiological evidence including the four national surveys of kratom use and other federal survey data and not the non-validated computer model referenced by the FDA in its February 6th Advisory.”
“Rather than foster an illicit and dangerous kratom market, the FDA could protect the American public by appropriate regulation of kratom, as the FDA’s Office of Dietary Supplements has been working toward. This could provide consumers and health professionals with the information to help guide safe use, and ensure that lawfully marketed products meet the same standards as other natural and dietary products relied upon by American consumers.”
The federal government should be encouraging additional research into the potential therapeutic benefits of kratom, while ensuring that the products available are not adulterated — Dr.Jack Henningfield, vice president of research, Health Policy and Abuse Liability, at PinneyAssociates, and adjunct professor of Behavioral Biology, Johns Hopkins University School of Medicine
– Scheduling would stymie research
– Possibility of breakthrough in pain and addiction treatment
– Need alternate regulatory pathways — drug model too costly for non-patentable plant
“In the report issued on November 1, 2017 by the President’s Commission on Combating Drug Addiction and the Opioid Crisis, where the Commission strongly supported research and development of alternatives to opioids for pain management, the powerful conclusion offered was that ‘[F]irst, individuals with acute or chronic pain must have access to non-opioid pain management options.’ The available science is clear that kratom, although having effects on opioid receptors in the brain, is distinct from classical opioids (e.g. morphine, heroin, oxycodone, etc.) in its chemistry, biological effects, and origin (kratom is a tree in the coffee family, not the opium poppy family).”
“The possibility that extracts of kratom and/or new medicines that are similar to kratom’s active ingredients might serve as breakthroughs in pain relieving medicines that are so desperately needed, should not be ignored. However, this latter path will not be a rapid one, since the average time and cost of new drug development is more than 10 years and 2.5 billion dollars. Placing kratom into Schedule I of the CSA will also have a profound and pervasive chilling effect on this needed additional research.”
“The assertion that scheduling recommendations can be based on claims of deaths ‘associated with kratom’ rather than deaths ‘caused by Kratom’ is not, in our judgement, either scientifically valid nor the standard that was contemplated by the U.S. Congress for scheduling of any substances, and would appear to be a significant overreach of the regulatory powers of the FDA and DEA beyond the currently established, rigorous, and clearly limited eight factors set forth by CSA for scheduling a substance.”
“We encourage you to support efforts to ensure continued lawful access to kratom, guide balanced regulation by the FDA, and facilitate research, thereby protecting and not harming public health.”
MEDIA CONTACT: Max Karlin, (703) 276-3255 or mkarlin@hastingsgroup.com.
EDITOR’S NOTE: Limited and unrestricted support for this news event is being provided by the nonprofit People Plants Health.
