Scott Gottlieb, former head of the Food and Drug Administration (FDA), says he is "convinced" that kratom, a pain-relieving leaf from Southeast Asia, is "fueling the opioid addiction crisis." To the contrary, kratom enthusiasts argue, the plant is "the cure for the opioid epidemic."
There is not much evidence to support either position. But as a recent Twitter tiff between Gottlieb and former Assistant Secretary for Health Brett Giroir shows, the argument about whether the federal government should ban kratom hinges on the question of where the burden of proof belongs.
Gottlieb seems to think any potentially dangerous psychoactive substance should be banned unless it meets the FDA's strict criteria for approval as a medicine. If a drug is not explicitly permitted, in other words, it should be prohibited by default. Giroir, by contrast, thinks the federal government has an obligation to present compelling evidence that kratom poses an intolerable threat to public health and safety.
Kratom—which acts as a stimulant or a sedative, depending on the dose—has been used for centuries in countries such as Thailand, Malaysia, and Indonesia to ease pain, boost work performance, and wean people from opiate addiction. In recent years, kratom has gained a following in the United States, sold by online merchants and head shops as an herbal medicine, a dietary supplement, or a legal high.
In August 2016, the Drug Enforcement Administration (DEA), invoking its emergency powers under the Controlled Substances Act, announced that it planned to put kratom's active ingredients in Schedule I. That category supposedly is reserved for drugs with "a high potential for abuse," "no currently accepted medical use," and "a lack of accepted safety" even under medical supervision. The fact that Schedule I drugs still include marijuana, which is legal for medical or recreational use in 36 states, suggests how loosely and arbitrarily those criteria are applied.
The DEA's announcement, which claimed kratom posed "an imminent hazard to public safety," provoked an uproar among consumers, businesses, and members of Congress, prompting the agency to backtrack two months later. Instead of imposing an emergency ban on kratom, the DEA said, it would seek advice from the Department of Health and Human Services (HHS), which includes the FDA, about how to proceed.
Gottlieb thought the answer was obvious. In October 2017, HHS recommended that kratom join marijuana in Schedule I. But Giroir rescinded that recommendation in August 2018, saying there was not enough evidence to justify it.
"We were prevented by HHS from moving forward with the scheduling of Kratom," Gottlieb complained on Twitter last Friday, "and I'm convinced it's fueling the opioid addiction crisis." He urged the Biden administration to proceed with a kratom ban.
"FDA's recommendation was rejected [because] of embarrassingly poor evidence & data, and a failure to consider overall public health," Giroir replied. "If #Kratom is fueling opioid addiction, prove it; and then [HHS] should reconsider."
Giroir's strong language is fully justified in light of Gottlieb's weak case for banning kratom, which leaned heavily on unverified anecdotes. The FDA claimed kratom, which according to federal survey data is consumed by about 2 million Americans every year, had been implicated in 44 deaths worldwide over nine years. But those cases typically involved multiple drugs and/or underlying medical conditions.
In a 2018 paper commissioned by the American Kratom Association, Jane Babin, an attorney and molecular biologist, noted that "the FDA did not independently verify or perform any due diligence on the death reports" and that the "FDA's own documents indicate that every reported case involved other factors." This example, which Kayla Stetzel described in a 2018 Reason piece, gives you a sense of how rigorous the FDA's approach was:
A 22-year-old man consumed a kratom mixture he ordered online along with an "unknown tablet." This consumption "was followed by an incident, during which the patient fell from a window of the first floor before going to bed" without receiving medical treatment. He was found dead the next morning, and the medical examiner determined that he choked on his vomit while he slept. The man had a history of mental illness, and a prescription drug history that included pipamperone (an antipsychotic used for treating schizophrenia), fluoxetine (an SSRI used to treat anxiety, OCD and depression), queiapine (another antipsychotic), olanzapine (another antipsychotic), etizolam (a benzodiazepine analog), pregabalin (a nerve pain medication often used to treat seizures), lorazepam (a benzodiazepine) and triazolam (a benzodiazepine used to treat severe insomnia that can also cause psychotic episodes). Oh, and he also used kratom. The FDA report does not discuss the extent to which these drugs may have contributed to the man's mental state, instead summarizing his demise with this line: "The patient was found dead in his bed on the morning following the consumption of an herbal mixture."
Babin concluded that "the FDA has relied on a strategy of manipulating, obscuring, and ignoring science in its inexplicable zeal to impede public access to the natural botanical kratom." While you might dismiss that gloss as self-interested pleading by the kratom industry, it is consistent with earlier research on kratom's hazards.
"Kratom is considered minimally toxic," noted a 2015 literature review in the International Journal of Legal Medicine. "Although death has been attributed to kratom use, there is no solid evidence that kratom was the sole contributor to an individual's death." As Giroir noted in 2018, the FDA never performed "a scientifically valid assessment of causality in the current few deaths in which kratom was co-utilized with known lethal drugs such as fentanyl."
Even if the FDA's tally of deaths is accepted at face value, it suggests that kratom is far less hazardous than many commonly used intoxicants and medications. The FDA cited an average of fewer than five possibly kratom-related fatalities per year worldwide.
According to the Centers for Disease Control and Prevention (CDC), alcohol causes about 88,000 deaths a year in the United States alone. The CDC counted nearly 50,000 opioid-related deaths (primarily involving fentanyl and heroin) in 2019, and it expects the 2020 total will be substantially higher. Commonly prescribed benzodiazepines such as Xanax, Valium, and Ativan were involved in nearly 10,000 drug-related deaths in 2019. Even FDA-approved, over-the-counter analgesics such as aspirin, ibuprofen, and acetaminophen are implicated in thousands of deaths a year.
Kratom looks pretty benign by comparison. Perhaps recognizing that fact, Gottlieb is now emphasizing an alleged link between kratom use and opioid addiction. But as Giroir pointed out in 2018, the FDA never made "a scientific determination based on data" of whether kratom "actually serves as a gateway drug that promotes further use of more dangerous opioids." It had not even done "a scientific assessment of the actual scale of dependence and/or addiction" to kratom itself.
Giroir cited an animal study that found mitragynine, kratom's main psychoactive ingredient, "does not have abuse potential and actually reduced morphine intake," which is consistent with the notion that kratom is a harm-reducing alternative to more dangerous drugs. He suggested such findings, if confirmed, indicate that kratom does not meet the "high potential for abuse" criterion for inclusion in Schedule I.
Giroir warned that banning kratom could cause "adverse consequences" such as "intractable pain, psychological distress, [and] risk of suicide"; "transition to proven deadly opioids"; or "transition to other potent or harmful drugs." That is what he means when he refers to the FDA's "failure to consider overall public health." Giroir also worried that placing kratom in Schedule I could stifle "critical research" on kratom's "complex and potentially useful chemistry."
Gottlieb's position, by contrast, is that kratom should be banned until someone invests millions of dollars and years of research to persuade the FDA that it is safe and effective as a treatment for a specified condition. "It's very troubling to the FDA that patients believe they can use kratom to treat opioid withdrawal symptoms," he said in 2017. "I understand that there's a lot of interest in the possibility for kratom to be used as a potential therapy for a range of disorders. But the FDA has a science-based obligation that supersedes popular trends and relies on evidence. The FDA has a well-developed process for evaluating botanical drug products where parties seek to make therapeutic claims and is committed to facilitating development of botanical products than can help improve people's health. We have issued guidance on the proper development of botanical drug products. The agency also has a team of medical reviewers in the FDA's Center for Drug Evaluation and Research that's dedicated to the proper development of drug applications for botanicals. To date, no marketer has sought to properly develop a drug that includes kratom."
In the meantime, even if kratom remains unscheduled, the FDA will continue to treat dietary supplements that contain it as "adulterated." The Twitter spat between Gottlieb and Giroir was prompted by the FDA's announcement that it had seized "207,000 units of dietary supplements and bulk dietary ingredients that are or contain kratom, including over 34,000 kilograms of bulk kratom." Citing "substantial concern regarding the safety of kratom, the risk it may pose to public health and its potential for abuse," Judy McMeekin, the FDA's associate commissioner for regulatory affairs, promised that the agency "will continue to exercise our full authority under the law to take action against these adulterated dietary supplements." She noted that "there are currently no FDA-approved uses for kratom."
The FDA cannot abide the idea that Americans might use psychoactive substances, regardless of how dangerous they actually are, that have been neither approved as medicines nor, like alcohol and tobacco, explicitly exempted from scheduling. But that is exactly the opposite of the presumption that should prevail in a free society.