The FDA’s proposed Kratom ban was a mistake


TonThe rust of the U.S. Food and Drug Administration (FDA) Agree with The controversial Alzheimer’s disease drug aducanumab.three Expert resigns There are allegations that the FDA has succumbed to industry pressure.Some people think its credibility Hit a new low.

These events should prompt the FDA to suspend, reflect, and work to repair its reputation. On the contrary, the agency is taking actions that may further weaken its credibility. A timely example is its location on Mitragyna speciosa, commonly called kratom, a tree related to coffee plants.

Kratom for a long time Consumption in Southeast Asia As a pain reliever and mild stimulant. Millions of Americans It is also used, claiming that it can relieve symptoms of chronic pain and addiction, which is an important impact as the number of deaths from drug overdose continues to rise.

Last year, the U.S. Centers for Disease Control and Prevention (CDC) recorded Record number Overdose deaths, two-thirds of which are caused by opioids. at the same time, limit Legal opioid prescription leave Few choices For people suffering from chronic pain. Some people turn to illegal opioids. Others turned to suicide. But many people rely on kratom, which fills an important position in the public health ecosystem.

Kratom has Dose-dependent effectAt low doses, it can act as a mild stimulant. In Southeast Asia, people chew the leaves of Mitragyna speciosa to stay focused, just like drinking a cup of coffee to stay alert. At higher doses, kratom can be used as a sedative and analgesic. Although this dose-dependent relationship is not very clear, it is well known that the active ingredient of kratom, Mitraginine and 7-Hydroxy Mitraginine, Showing affinity for the so-called mu-opioid receptor, which binds a variety of substances, including morphine and other opioids.

Through a phenomenon called biased agonism, ?-opioid receptors will produce different intracellular effects when binding different molecules, so that opioids and mitragynine have different physical effects.Specifically, opioids activate an intracellular signaling protein called ?-arrestin, and mitragynines noThis distinction is important because beta-arrestin activity is associated with the dangerous side effects of opioids, including slow, shallow breathing that cannot sustain life.

The FDA’s analysis lacks this level of detail.

For years, federal agencies have tried to ban kratom. In 2016, the U.S. Drug Enforcement Administration (DEA) Announced plan Categorize kratom as Schedule I Controlled SubstancesIt is said that compounds in this category are not currently accepted for medical use and are likely to be abused.

One year after the DEA announced its intention to ban kratom, the Federal Department of Health and Human Services (HHS) responded Letter in support of the proposed ban. These developments aroused public outcry scientists, kratom advocate, And state and federal Legislator. More than 130,000 Americans signed White House petition Against the ban, 51 members of Congress issued Letter to DEA Urge it to listen to the opinions of the public. At the same time, experts analyzed the abuse potential of kratom and concluded: Prohibition is inappropriate.

In response, HHS cancelled its scheduling recommendations. However, the FDA did not follow suit and change the kratom policy, but redoubled its efforts.Since it failed to ban kratom domestically, the agency may soon Recommend to the World Health Organization Make it banned internationally.

If the FDA obtains a global ban on kratom, countless people may die of suicide and unintentional overdose. Many Americans say that kratom suppresses cravings for opioids, which are often obtained on the illicit market and often contain synthetic opioids such as fentanyl. According to the CDC, Synthetic opioids It is the “main driving factor of drug overdose deaths”, leading to nearly three-quarters of opioid-related overdose. The ban will make people who use kratom commit crimes, eliminate the legal source of the plant, and cause many users to resort to using more harmful substances.

The ban would also prevent researchers from studying the effects of kratom, which would be a costly mistake, reminiscent of what happened when psychedelic research was banned in the 1970s and 1980s.When psychedelics become Schedule I Controlled Substances, It became illegal for scientists to produce and study them, and promising research on their therapeutic potential ceased.Now, decades later, there is a The revival of psychedelic research.

The results of Phase 1 and Phase 2 clinical trials reflect The promise of hallucinogens To treat mental illness. But their Schedule 1 status continues to hinder research: DEA approval is required but not always approved, the agency imposes annual restrictions on production, and it is almost impossible to obtain federal funding for psychedelic research. When the rate of suicide and drug overdose is rising, and innovative therapies for mental illness are scarce and far apart, the harm caused by the ban on psychedelics is immeasurable.

The FDA is prepared to make the same mistake on kratom.

A careful examination of the FDA’s arguments against kratom reveals many weaknesses. The agency relied on calling the poison control center as evidence of kratom’s risk. However, people say that there are many reasons for poison control, and not all of the reasons are serious. Compared with the voice of ordinary household products, the voice of kratom is pale and weak.

According to the CDC, there are 1,807 calls about kratom From the beginning of 2011 to the end of 2017, there were an average of 258 calls per year. In contrast, during the same period, the disposable laundry generated 12,157 calls per year.use annual report Based on data from the American Association of Poison Control Centers, I calculated that antihistamines cause 94,977 calls each year, and painkillers cause 294,812 calls each year.

When kratom was in their system, some people had already died. However, the causal relationship between kratom and death has not yet been determined. In 2019, CDC analysis 27,338 overdose deaths Occurs within 18 months. Of these deaths, Kratom was detected in 152 (less than 1%), but in most cases, tests also showed the presence of drugs known to cause overdose. Only seven people tested positive for kratom, and the researchers concluded that “the presence of other substances cannot be ruled out.”

Most kratom-related deaths Attributable to other substances, including opioids and alcohol, these two substances cause nearly 100,000 deaths each year. However, the FDA acted as if people who died of kratom in their system were only injured by kratom. The data does not support this conclusion. The FDA should not ban kratom, but should encourage manufacturers to label contraindications on it, such as the use of active opioids or alcohol.

A sort of 2011 report It describes nine people being injured by a kratom product mixed with a drug called O-desmethyltramadol.Others may be harmed by pollutants, such as Heavy metalFDA has determined this in certain kratom products.But these problems are all related to kratom Production, Not the plant itself. Consumers are often forced to buy from overseas suppliers who may not follow good manufacturing practices.

The FDA did not use this information to adapt its narrative about the harmful effects of kratom, but rather Kratom should be regulated To ensure its safe production. The American Kratom Association has developed good practices for kratom production, labeling and safety verification.Although some states have Banned kratom, It is still legal in most states, and four states even passed Kratom Consumer Protection Act Regulate its domestic production and sales. Others are considering similar legislation.

In order to further condemn the use of the plant, the FDA used the so-called public health assessment by the structure assessment (PHASE) method, which is a kind of Experimental computer model, Predict the effects of kratom and conclude that it contains harmful opioids. Experts think the FDA is wrong Rely on this too simple model. PHASE ignores the absorption rate of substances in the gastrointestinal tract, how easily they cross the blood-brain barrier, and what happens inside the cell after the drug binds to its surface receptor. This system cannot explain the biased agonistic effect of mu-opioid receptors and the lack of mitragynines to activate ?-arrestin. These factors will affect the physical effects of kratom, but the PHASE model does not consider these factors, and the FDA ignores its limitations.

When so many stakeholders found flaws in their arguments, why did the FDA denigrate kratom? Could it be that pharmaceutical companies are commercializing a synthetic version of kratom and banning the plant would protect their interests?Companies that have a financial interest in Schedule I substances have Benefit from their banWhen drugmakers obtain DEA and FDA permits to commercialize illegal drugs, the ban protects them from potential competition. It strengthens the government-granted monopoly provided by patents and marketing franchise.

In July, the FDA solicit opinions Regarding the proposed global kratom ban, there are only two weeks left for people to respond.The American Kratom Association sued the agency and HHS in federal court, and the deadline has been extended Until August 24, 2021I urge the FDA to listen to the opinions of scientists and advocates who explain that kratom’s effects are different from opioids. The ban will only encourage people to consume more harmful illegal substances, such as heroin or fentanyl, and many people will die by suicide or accidentally overdose. Regulation of kratom is preferable to prohibition because it creates a safer supply and does not hinder research.

Kratom may not be the safest substance. But it may not be more dangerous than many household products or over-the-counter drugs, and there is no data to support a complete ban. Banning the use of substances without sufficient evidence may be as harmful as approving them without sufficient evidence.

This article was originally published In STAT August 23, 2021.



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