In a statement released yesterday, Gottlieb voiced his grave concerns about the use of the botanical. In the agency’s view, the botanical has no reliable safety data on file, and most of the assertions of safe use from proponents such as the American Kratom Association are based on anecdotal reports.
Lack of safety data
“Proponents argue that it’s a safe substance largely because it’s a plant-based product,” Gottlieb said. “Evidence shows that kratom has similar effects to narcotics like opioids, and carries similar risks of abuse, addiction and in some cases, death.”
Among the safety issues associated with the botanical, Gottlieb cited a rising tide of reports to poison control centers connected with the botanical. “Calls to US poison control centers regarding kratom have increased 10-fold from 2010 to 2015, with hundreds of calls made each year. The FDA is aware of reports of 36 deaths associated with the use of kratom-containing products. There have been reports of kratom being laced with other opioids like hydrocodone. The use of kratom is also associated with serious side effects like seizures, liver damage and withdrawal symptoms,” Gottlieb said.
At the recent annual meeting of the Council for Responsible Nutrition in Tucson, AZ, Rick Kingston, PharmD, of the consulting firm SafetyCall International, said that poison center control data has to be taken with a grain of salt. The data is collected in the raw, so to speak, and does not have the kind of integrity and statistical power that data collected in a clinical study might have. And each adverse event, including those associated with fatalities, can have confounding factors that militate against coming to the quick conclusion that x caused y. Nevertheless, if Gottlieb’s statistics are accurate, it could form the kind of safety signal that Kingston, who is also a pharmacy professor at the University of Minnesota, has said warrants more investigation and/or quick action.
Ramped up inspections
Gottlieb said FDA will work with the Drug Enforcement Administration to determine the proper regulatory categorization for the drug. Last year DEA attempted to use an emergency listing authority put kratom on the Schedule 1 list of controlled substances. DEA backed off on that attempt after pushback from stakeholders who said the move would set a bad precedent. That feedback included a report submitted by AKA written by addiction expert Jack Henningfield, PhD that downplayed the botanical’s addiction potential.
That setback notwithstanding, Gottlieb’s statement yesterday is another brick in the wall that FDA has been building around the botanical. FDA issued its first import alert in 2012 on kratom, identifying it at that time as an unapproved drug. It renewed that in 2014 with an alert on kratom-containing dietary supplements and bulk kratom ingredients. Since 2014, the agency has also seized $6 million or more worth of kratom raw material and finished products from marketers in California and Illinois.
Gottlieb said in addition to those seizures, FDA personnel have detained “hundreds of shipments of kratom at the international mail facilities.” Gottlieb linked kratom to the general opiod crisis and the flood of illegal narcotics imports. He said the agency has beefed up enforcement, by almost tripling the number of personnel in the IMF inspection effort and planning to double the number of port of entry special agents from six to 12.
Drug indications
Gottlieb said that as it works with DEA to determine the proper scheduling for the botanical, the agency is looking to industry to provide safety data that could inform that effort. To some extent, kratom proponents may have shot themselves in the foot in their enthusiasm for the botanical and all they claim it can do. Treating pain, ameliorating depression, helping to wean addicts off of more potent opiods—these are all viewed as drug indications by FDA. Gottlieb’s statement yesterday seemed to close the door once and for all for kratom as a dietary ingredient. He called for proponents of the botanical to step up to prove its benefits and categorize its risks via the drug approval process.
“The FDA knows people are using kratom to treat conditions like pain, anxiety and depression, which are serious medical conditions that require proper diagnosis and oversight from a licensed health care provider,” Gottlieb said. “There is no reliable evidence to support the use of kratom as a treatment for opioid use disorder.”
“We believe using the FDA’s proven drug review process would provide for a much-needed discussion among all stakeholders. Until then, I want to be clear on one fact: there are currently no FDA-approved therapeutic uses of kratom. Moreover, the FDA has evidence to show that there are significant safety issues associated with its use. Before it can be legally marketed for therapeutic uses in the US, kratom’s risks and benefits must be evaluated as part of the regulatory process for drugs,” he said.