Is Kratom Right for You?

By Forest Tennant, PNN Columnist

The answer to the headline on this column depends upon whether you can get enough prescription opioids to control Intractable Pain Syndrome (IPS).

In many locales in the country, doctors — for multiple reasons — will not prescribe enough opioids to control IPS and its cardiovascular, endocrine and autoimmune manifestations. If you can’t get enough prescription opioids to keep your pain under control, you should give kratom a try.

What Is Kratom?  

Kratom is a compound found in the tree leaves of the mitragyna speciosa plant that grows in southeast Asia.

It is an herb and not an opioid, but it produces pain relief like an opioid. Biologically, it attaches to the opioid receptors (pain relief sites) in the brain and spinal cord, and relieves pain just like an opioid. 

Kratom is legal in most of the United States and is widely advertised and promoted on the Internet. It is available as a pill, capsule or powdered extract.

It can be used by itself for pain relief or taken simultaneously with a prescription opioid. Most persons with IPS who report kratom use take it between opioid dosages or use it just for flares.

How Do I Know How Much to Take? 

There are several formulations and many brands of kratom. In fact, we have received so many different reports that we can’t really say that one form, color or source is better than another. Our recommendation is that you acquaint yourself with someone who already takes kratom for pain relief. This person is in the best position to “show you the ropes” relative to dosage, types and sources. 

As with any new drug, start at a low dose and work up over time to maximize its effectiveness and prevent any severe side effects. Kratom is available without a prescription, but check with your state laws first. It is currently illegal in a few states and some communities.

Do not let today’s opioid restrictions ruin your health and life by leaving you in severe pain. Kratom may be just right for you. 

Forest Tennant is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.    

Researchers Warn of Deadly New Illicit Opioid

By Pat Anson, PNN Editor

A new illicit opioid that is 20 times more potent than fentanyl has been linked to at least eight fatal overdoses in the U.S. in the last month, according to a public safety alert released by a Pennsylvania research laboratory.

The Center for Forensic Science Research & Education (CFSRE) said its scientists detected N-pyrrolidino etonitazene -- also known as etonitazepyne -- in eight blood samples taken during recent death investigations in West Virginia, Pennsylvania, New York, Florida and Colorado.  Four of the deaths occurred in West Virginia.

“The toxicity of N-pyrrolidino etonitazene has not been examined or reported but recent association with death among people who use drugs leads professionals to believe this synthetic opioid retains the potential to cause widespread harm and is of public health concern. Identifications of N-pyrrolidino etonitazene have also been reported recently from agencies in Europe,” the safety alert said.

Etonitazepyne is a synthetic opioid that is chemically similar to etonitazene, another powerful narcotic that started appearing in illicit drug markets and counterfeit pills in the U.S. and Canada last year.  While etonitazene is classified as an illegal Schedule I controlled substance by the DEA, etonitazepyne has not specifically been scheduled. Several websites even list it for sale for “chemical research.”

"The current drug landscape in the United States is unstable and unpredictable – especially the opioid market – which can ultimately lead to deadly outcomes," said Dr. Alex Krotulski, an associate director at CFSRE. "The purpose of this public alert is to raise awareness about a new and already deadly synthetic opioid so that way people who use drugs are able to modify use patterns and so that laboratories know to test for this new drug in their states or jurisdictions.”

Etonitazepyne may be new to law enforcement, coroners and public health officials, but illicit drug users have been warning each other about the drug for several months in online message boards.

“I got a report about an overdose with only 1 MG of Etonitazepyne (snorted) that caused a pretty high tolerance user to become unconscious and stopped breathing, and he had to be rescued from paramedics,” a poster said on Reddit.

“Everyone needs to be careful with this one. It's not for anyone who has no tolerance to opioids, and can still be dangerous for those who do,” another poster wrote.

Are Cannabis Dispensaries Really Associated with Fewer Opioid Overdoses?

By Roger Chriss, PNN Columnist

A new study published in The BMJ claims that U.S. counties with medical and recreational cannabis dispensaries have fewer opioid-related deaths.

Researchers at Yale and University of California at Davis found that an increase of just one or two storefront dispensaries in a county was associated with a 17% reduction in all-opioid mortality rates. Deaths involving illicit fentanyl and other synthetic opioids fell by 21 percent.

Although the researchers cautioned that “the associations documented cannot be assumed to be causal,” cannabis supporters were quick to praise the findings.

“The data to date is consistent and persuasive: For many pain patients, cannabis offers a viable alternative to opioids, potentially improving their quality of life while possessing a superior safety profile,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group.

While the study findings are interesting, they highlight the importance of considering the complex supply side of legal and illegal drug markets, and how it shapes opioid use and misuse. The study looked at data from over 800 counties with legal dispensaries, and compared them to counts of fatal overdoses between 2015 and 2018.

It turns out many of these counties were on the West Coast, where illicit fentanyl had yet to became as pervasive on the black market as it had in other parts of the country. Since 2018, deaths involving fentanyl have soared on the West Coast. 

“If you were to do the same study with current data, you’d find something different because of the way both opioid deaths and cannabis dispensaries have shifted since then,” Chelsea Shover, PhD, an assistant professor at UCLA School of Medicine told Healthline. 

In general, the opioid overdose crisis has gotten worse in the past couple of years. The CDC recently reported that in the 12 months ending in May 2020, ten western states reported a nearly 100 percent increase in deaths involving illicit fentanyl and other synthetic opioids. The increase was particularly sharp in states that legalized recreational cannabis.  

This is the problem with ecological data and associational findings. If you pick the right time or place, you can get an appealing result. And you may ignore other important issues.  

States that legalized cannabis tend to have better public health and more addiction treatment services. They generally have adopted the Affordable Care Act and Medicaid expansion, and have stronger social safety nets. All of these factors are believed to contribute to rates of substance use disorders and overdose risk.

Ecological data alone never proves anything. It merely suggests associations. If the association holds up over time, then researchers can look into a possible causal relation. If however, the association does not hold up, then claims about causality are pointless.

At this point cannabis does not seem to reliably reduce opioid overdose deaths. Further research will be needed to tease out the effects of cannabis legalization amid all the other factors involved in the overdose crisis.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

Growing Concerns About Opioid Tapering

By Roger Chriss, PNN Columnist

A common belief about the opioid crisis assumes that patients develop a substance use disorder from taking opioid medication, and that many derive no long-term benefit from opioids and need to be tapered.

There is some truth to this, but reality is much more complicated.

First, not all patients who take opioids become addicted. The National Institute on Drug Abuse reports between 8 and 12 percent of patients prescribed opioids for chronic pain develop an opioid use disorder (OUD). Even that estimate may be too high, because the diagnosis of OUD is sometimes mistaken.  

In a recent study of 90 patients diagnosed with OUD at three Veterans Health Administration medical centers, physician Ben Howell and colleagues found that nearly a third of the diagnoses were probably wrong.

“Our study identified significant levels of likely inaccurate OUD diagnoses among veterans with incident OUD diagnoses. The majority of these cases reflected readily addressable systems errors,” researchers concluded. “If these inaccuracies are prevalent throughout the VHA, they could complicate health services research and health systems responses.”

Second, not all people who are tapered off prescription opioids improve. A new study in the Journal of Pain Research looked at 40 chronic pain patients who were tapered from an average daily dose of 80 MME (morphine milligram equivalent) down to 19 MME. The results were disappointing. There was only minor improvement in the patients’ cognitive function and no improvement in their quality of life, depression and anxiety.

There is at present no well-established approach to opioid tapering and little effort made to study patient outcomes.  In a recent paper, lead author Stefan Kertesz, MD, and colleagues say there is a “pill dynamic” approach to tapering that focuses on dose reduction alone.

"When a multi-faceted, complex health issue becomes a public health crisis, the desire to ‘solve’ or ‘mitigate’ takes hold with a momentum of its own. A crisis deserves no less. However, nationally adopted quality metrics have convinced some patients with pain that their survival and functioning are no longer concerns for the systems in which they receive care. This outcome is unacceptable," they concluded.

Patient Suffering and Suicides

The risks of forced opioid tapering are so urgent that nearly 100 physicians, academics and patient advocates recently published an open letter in the journal Pain Medicine warning of “an alarming increase in reports of patient suffering and suicides” caused by aggressive tapering:

“We therefore call for an urgent review of mandated opioid tapering policies for outpatients at every level of health care — including prescribing, pharmacy, and insurance policies — and across borders, to minimize the iatrogenic harm that ensues from aggressive opioid tapering policies and practices.

We call for the development and implementation of policies that are humane, compassionate, patient-centered, and evidence-based in order to minimize iatrogenic harms and protect patients taking long-term prescription opioids.”

The public health issue of opioid overdoses is complex, urgent and largely driven by street drugs, not pain medication. Opioid prescriptions are at 20-year lows, and the American Medical Association recently said it was “alarmed by an increasing number of reports of opioid-related overdoses, particularly from illicit fentanyl.”

And as National Institute of Drug Abuse director Nora Volkow, MD, stated in a recent blog post:

“Although deaths from opioids continue to command the public’s attention, an alarming increase in deaths involving the stimulant drugs methamphetamine and cocaine are a stark illustration that we no longer face just an opioid crisis. We face a complex and ever-evolving addiction and overdose crisis characterized by shifting use and availability of different substances and use of multiple drugs (and drug classes) together.”

Opioid tapering is no more a universal good than opioid prescribing was a universal evil. And opioid tapering will no more solve the overdose crisis than opioid prescribing alone caused it. Instead, opioid tapering may harm the very people it is intended to help, and it may not help the crisis that it is motivated by. Better public health policy and clinical practice are urgently needed.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

Can Cannabis Be Used to Treat Opioid Addiction?

By Pat Anson, PNN Editor

Canadian researchers – with funding from U.S. taxpayers – are proposing a novel treatment for opioid use disorder: Cannabis.

In a paper published in the journal Drug and Alcohol Dependence, researchers from the University of British Columbia (UBC) and the BC Centre on Substance Use (BCCSU) say cannabis could help people being treated for opioid addiction by reducing their risk of exposure to illicit fentanyl and other street drugs.

The finding is based on urine drug tests of 819 people being treated for opioid addiction in Vancouver, BC, the first major city in North America to experience an outbreak of fentanyl-related overdoses. Addiction treatment usually involves taking opioid agonist drugs (OATs) such as buprenorphine or methadone.

The researchers found that over half the participants (53%) tested positive for fentanyl, suggesting they were still using street drugs. Those who tested positive for THC -- the psychoactive compound in cannabis -- were about 10 percent less likely to have fentanyl in their urine.

"These new findings suggest that cannabis could have a stabilizing impact for many patients on treatment, while also reducing the risk of overdose," said lead author Eugenia Socías, MD, a clinician scientist at BCCSU. "With overdoses continuing to rise across the country, these findings highlight the urgent need for clinical research to evaluate the therapeutic potential of cannabinoids as adjunctive treatment to OAT to address the escalating opioid overdose epidemic."

Socias and her colleagues say cannabis may play an important role in keeping people in addiction treatment programs. Previous research at BCCSU found that drug users initiating OAT who used cannabis daily were about 21 percent more likely to be retained in treatment after six months than non-cannabis users. People who stay in treatment face much lower risks of dying from an overdose, acquiring HIV or suffering other harms of drug use.

‘Gateway Drug’

The research at UBC and BCCSU was funded, in part, by grants from the U.S. National Institute on Drug Abuse, which is part of the National Institutes of Health (NIH).

The NIH has taken a dim view of cannabis in the past, calling marijuana a “gateway drug” for some users, particularly adolescents. A 2015 study funded by NIH found that nearly a third of those who use marijuana develop some degree of marijuana use disorder.

“Whether smoking or otherwise consuming marijuana has therapeutic benefits that outweigh its health risks is still an open question that science has not resolved,” said Nora Volkow, MD, Director of the National Institute on Drug Abuse.

Public health officials in British Columbia have proposed some controversial solutions to the opioid crisis, including decriminalization of all illicit drugs. A treatment center in Vancouver currently provides diacetylmorphine -- prescription heroin – to drug users to keep them from using street heroin that is often laced with fentanyl, a synthethic opioid that is 50 to 100 times more potent than morphine.

The Canadian Institutes of Health Research recently approved funding for a pilot study in Vancouver to evaluate cannabis as an adjunct therapy to OAT.

"Scientists are only just beginning to understand the role cannabis might play in supporting people's well-being, particularly those who use other substances," said co-author M-J Milloy, PhD, the Canopy Growth professor of cannabis science at UBC. "This study will help us understand if and how cannabis might have a role in addressing the overdose crisis."

A Little Shop of Horrors: VA Opioid Guideline for Veterans

By Richard Lawhern, PNN Contributor

As a volunteer patient advocate and healthcare writer, I read a very large volume of scientific and policy literature. And as a 21-year military veteran myself, I am particularly interested in Veterans Administration policies for treatment of chronic pain. Thus I reviewed with interest the VA’s 2017 Clinical Practice Guideline for Opioid Therapy for Chronic Pain.  

I also checked with a medical professional who practices in the VA hospital system to verify that the “guidance” of this document is still in force. It is. 

In my view, the VA opioid guidance is a “little shop of horrors” guaranteed to drive patients into medical collapse, and in some cases suicide. These direct quotes from the VA guideline should illustrate my concerns:

• “Since [2010], there has been growing recognition of an epidemic of opioid misuse and opioid use disorder (OUD) in America, including among America’s Veterans…. At the same time, there is a mounting body of research detailing the lack of benefit and severe harms of [long-term opioid therapy].”

• “We recommend against initiation of long-term opioid therapy for chronic pain.”

• “We recommend alternatives to opioid therapy such as self-management strategies and other non-pharmacological treatments.”

• “If prescribing opioid therapy for patients with chronic pain, we recommend a short duration… Consideration of opioid therapy beyond 90 days requires re-evaluation and discussion with patient of risks and benefits.”

• “We recommend against long-term opioid therapy for pain in patients with untreated substance use disorder.”

• “If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits…. There is no absolutely safe dose of opioids.”   

• “As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose… Risks for opioid use disorder start at any dose and increase in a dose dependent manner. Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose.” 

My VA colleague, who asked not to be identified, offers the following observations concerning VA policies in treating pain. This is paraphrased to protect the physician from retaliation:   

“The VA simply does not allow me the flexibility I need to manage my patients’ pain. All that is said about honoring our veterans and all the expressions of pride in the level of care the VA provides veterans thus ring hollow. The VA exhibits far greater pride in the percent reduction in opioid prescriptions it has been able to achieve, even giving out awards to physicians who make particularly large contributions to this effort.”

Let’s also compare these highly restrictive policies with a June 2020 letter from the American Medical Association to the CDC’s Chief Medical Officer on the pending revision of the 2016 CDC guideline:

• “We can no longer afford to view increasing drug-related mortality through a prescription opioid-myopic lens.”

• “Some patients with acute or chronic pain can benefit from taking prescription opioid analgesics at doses that may be greater than guidelines or thresholds put forward by federal agencies.”

• “A CDC Guideline only focused on ‘opioid prescribing’ will perpetuate the fallacy that by restricting access to opioid analgesics, the nation’s overdose and death epidemic will end.”

• “The CDC Guideline has been misapplied as a hard policy threshold by states, health plans, pharmacy chains, and PBMs.”

• “It is clear that the CDC Guideline has harmed many patients — so much so that in 2019, the CDC authors and HHS issued long-overdue … clarifications that states should not use the CDC Guideline to implement an arbitrary threshold.”  

The AMA recommended that the CDC should advocate explicitly for the repeal of all federal and state legislation that places hard limits on opioid prescribing.  Another recommendation is that physicians should treat both chronic pain and opioid addiction among the few patients who deal with both issues.  Discharging these patients or forcibly tapering them should no longer be automatic.

AMA is also on public record with the position that so-called “high prescriber” letters issued by prosecutors and state Prescription Drug Monitoring Programs (PDMPs) constitute a witch hunt against physicians and their sickest patients, and is a violation of legal due process.  

Not addressed by either the AMA or the VA is the reality that there are presently no field-tested tools that reliably evaluate quantitative risk of opioid tolerance, dependence or addiction in individual patients. 

As Nora Volkow, MD, and Thomas McMillan, PhD, of the National Institutes of Health wrote in The New England Journal of Medicine:  

“Unlike tolerance and physical dependence, addiction is not a predictable result of opioid prescribing. Addiction occurs in only a small percentage of persons who are exposed to opioids — even among those with pre-existing vulnerabilities... Older medical texts and several versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) either overemphasized the role of tolerance and physical dependence in the definition of addiction or equated these processes (DSM-III and DSM-IV).

However, more recent studies have shown that the molecular mechanisms underlying addiction are distinct from those responsible for tolerance and physical dependence, in that they evolve much more slowly, last much longer, and disrupt multiple brain processes.”  

A further complicating factor for the VA is that we now know beyond any reasonable contradiction that their attempt to restrict opioid prescribing is unsupported by science. 

There is no relationship between rates of opioid prescribing versus rates of overdose-related mortality. The demographics simply don’t work:  Although they have the highest rate of opioid prescribing for pain, seniors over age 62 have the lowest rates of overdose-related mortality.  Youths under age 19 receive the fewest number of opioid prescriptions, but have three to six times higher overdose mortality relative to seniors.

It is arguable that the VA guideline is just as fatally flawed as the CDC guideline, and is responsible for significant numbers of patient medical collapses and suicides among veterans.  Both documents fail conclusively on grounds of both medical science and medical ethics and both should be withdrawn immediately.

Richard “Red” Lawhern, PhD, has for over 20 years volunteered as a patient advocate in online pain communities and a subject matter expert on public policy for medical opioids.  Red is co-founder of The Alliance for the Treatment of Intractable Pain.

AMA ‘Greatly Concerned’ By Rising Number of Opioid Overdoses

By Pat Anson, PNN Editor

The American Medical Association is once again urging states, regulators and policymakers to waive limits and restrictions on prescriptions for opioid medication and other controlled substances during the COVID-19 pandemic.

In a briefing paper released this week, the AMA said it was alarmed by an increasing number of reports of opioid-related overdoses, particularly from illicit fentanyl. The AMA cited recent reports from the Pacific Northwest that thousands of people were unexpectedly dying from causes other than COVID-19, such as fentanyl-laced counterfeit pills and medical conditions aggravated by delays in getting routine healthcare.    

“The AMA is greatly concerned by an increasing number of reports from national, state and local media suggesting increases in opioid-and other drug-related mortality—particularly from illicitly manufactured fentanyl and fentanyl analogs,” the AMA said. “More than 40 states have reported increases in opioid-related mortality as well as ongoing concerns for those with a mental illness or substance use disorder.”

The AMA urged states to adopt new DEA guidance giving more flexibility to physicians treating patients with opioid use disorder (OUD). The DEA has already waived federal requirements for in-person visits before prescribing addiction treatment drugs such as buprenorphine (Suboxone), methadone and naltrexone.

For patients in pain, the AMA recommended that states take a number of steps to make it easier to obtain pain medication during the pandemic:

• Authorize physicians to prescribe opioid medication to existing patients without an in-person visit

• Waive limits on prescriptions for opioids and other controlled substances, including limits on dose, quantity and refills

• Waive requirements on electronic prescribing; authorize prescriptions to be sent to pharmacies via telephone

• Waive drug testing and in-person counseling requirements for opioid refills; allow for telephone counseling

• Enhance home-delivery medication options for patients with chronic pain

The AMA urged many of these same measures be adopted in the early stages of the pandemic.

In a recent letter to the DEA, the AMA strongly recommended that the agency keep its relaxed prescribing guidelines in place indefinitely.

“There is an urgent need to ensure that patients with pain and patients with OUD receive evidence-based care, and this need will not cease with the end of the COVID-19 pandemic,” wrote James Madara, MD, Executive Vice President and CEO of the AMA..

“The AMA strongly recommends, therefore, that all of the flexibilities that have been put in place by DEA during the COVID-19 PHE (public health emergency) be kept in place at a minimum until both the COVID-19 and the opioid public health emergencies come to an end.”

What If the Opioid Crisis Is Worse Than We Think?

By Roger Chriss, PNN Columnist

A recent study in the journal Addiction reports that the opioid crisis in the U.S. may be worse than we’ve been led to believe. The number of overdose deaths linked to legal and illicit opioids over the past two decades could be about 28 percent higher than reported.

Economists Andrew Boslett, Alina Denham and Elaine Hill looked at drug overdose deaths between 1999 and 2016 in the National Center for Health Statistics. Of 632,331 deaths, over one in five had no information on the drugs involved. The researchers estimated that as many as 72% percent of those deaths likely involved opioids. This yields an additional 99,160 deaths involving prescription opioids, heroin, fentanyl and other street drugs that were not counted.

This estimate may or may not be right, but it is definitely not new. Claims like this have been around for years.

In 2017, Business Insider reported on an investigation by CDC field officer Dr. Victoria Hall, who looked at the Minnesota Department of Health's Unexplained Death (UNEX) system. She found that 1,676 deaths in the state had “some complications due to opioid use,” but were not reported as opioid-related deaths.

A 2018 study at the University of Pittsburgh found that as many as 70,000 overdose deaths were missed because of incomplete reporting.

‘Cooking the Data’

It has long been suspected that the CDC’s opioid overdose death toll is faulty – either too high or too low, depending on your point of view. Public health data in the U.S. is shoddy, the result of a fractured and fragmented system that has little central guidance or administrative oversight. The overdose numbers aren’t as reliable as they should be, which raises suspicion they are being manipulated.

The Atlantic makes a similar point about the coronavirus outbreak.

"Everyone is cooking the data, one way or another. And yet, even though these inconsistencies are public and plain, people continue to rely on charts showing different numbers, with no indication that they are not all produced with the same rigor or vigor," wrote Alexis Madrigal. “This is bad. It encourages dangerous behavior such as cutting back testing to bring a country’s numbers down or slow-walking testing to keep a country’s numbers low.”

The implications of under-counting deaths in the overdose crisis require careful consideration. Political campaigns, public policy, state laws and regulations, and clinical practice are built on these numbers. For instance, the Trump administration was recently touting a 4% decline in overdose deaths, but that reduction may not exist.

Similarly, cannabis advocacy groups argue that state legalization has reduced overdose deaths. But again, that reduction may evaporate with better data. State laws and regulations are built on the assumption that trend lines were going in a particular direction. But maybe they aren’t.

Most important, policy groups have argued strenuously that reducing prescription opioid utilization would alleviate the overdose crisis. But if there are vastly more deaths than recognized, where does that leave these groups?

Of course, determining cause of death is a process fraught with difficulties. The New York Times reports that morgues are overburdened and understaffed, many suspected overdose deaths are not fully evaluated, and reporting on the cause of death is not standardized.

Making a probabilistic assessment is even more fraught. For instance, a recent attempt to use stool samples to measure how many rodents, birds and other wildlife are eaten by domestic cats was undone by the discovery that cat food manufacturers regularly change their ingredients.

In other words, there are many known problems and occasional surprises in public health data, so any estimate has to be treated with caution. But if opioid overdoses are vastly undercounted, then we should reassess the policies and politics of the crisis.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

Is Ketamine an Opioid?

By Pat Anson, PNN Editor

A drug used to treat depression and pain is being touted as possible solution to the opioid crisis.

This week a South Carolina drug maker said it would partner with a medical device company to sell ketamine in take home medication bags that can be administered by an ambulatory pain pump. The idea is to give patients recovering from surgery a safer alternative to opioids.

“We are proud to partner with InfuTronix Solutions to deliver opioid-free pain medication to patients across the country,” Nephron Pharmaceuticals CEO Lou Kennedy said in a statement. “The overuse of opioids is a crisis in America. Non-narcotic pain management is a cost-saving way that companies like ours can help save lives.”

Non-narcotic? Opioid-free?

That’s not what a team of researchers at Stanford University concluded last year after studying how ketamine works in the brain. In a small clinical study, they gave a dozen patients diagnosed with depression a combination of ketamine and naltrexone – an opioid-receptor blocker. To their surprise, naltrexone stopped ketamine from working as an antidepressant.

In effect, the researchers discovered that ketamine works just like oxycodone, hydrocodone and other painkillers – by activating opioid receptors in the brain. 

“Everything that I was taught, and everything that I’ve always taught my students — all of the evidence supports the fact that ketamine is not an opioid,” said lead author Boris Heifets, MD, a clinical assistant professor of anesthesiology, perioperative and pain medicine. “I was really surprised at the results.”

“And the results were so clear that we ended the study early to avoid exposing additional patients to the ineffective combination treatment,” said co-lead author Nolan Williams, MD, a clinical assistant professor of psychiatry and behavioral science.

The Stanford research, published in The American Journal of Psychiatry, caught psychiatrists and pain management experts by surprise. Some urged caution about the long-term use of ketamine until more can be learned about potential side effects such as addiction. Some depressed patients taken off ketamine have shown signs of withdrawal and became suicidal.

“Given the rapid relapse and potential suicide risk, it is hard to know what to recommend to clinicians. Should they really continue to use the agent beyond an acute course? For how long? In whom?” Alan Schatzberg, MD, a Stanford professor of psychiatry and behavioral sciences, warned in a commentary. “The drug’s opioid properties need to be considered when considering how best to use it.”

‘A Black Eye to Ketamine’

Talk like that has given ketamine a bad rap, according to experts at Johns Hopkins University School of Medicine. They’ve published a commentary of their own, defending the use of ketamine as a necessary treatment for depression that doesn’t respond to typical antidepressants.

“A (Stanford) study done late last year delivered a black eye to ketamine, and as a result of the coverage, there was a wholesale acceptance by both potential patients and physicians that ketamine is an opioid,” says Adam Kaplin, MD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins.

“This is most worrisome if people continue to think this way, particularly in the wake of the opioid epidemic; clinicians won’t refer patients for a treatment, despite that it has been shown to be incredibly effective for many patients with treatment-resistant depression.”

Kaplin says there is ample evidence that ketamine sticks to NMDA receptors in the brain that are involved in learning and memory. Because these NMDA receptors are found together with opioid receptors, Kaplin says it’s no surprise that the can meddle with one another, like interference picked up on a phone call or static on the radio.

“This interference and cross-talk does not mean that ketamine is an opioid, and to wrongly label it as such could eventually keep patients from essential antidepressant medications that could make a huge difference in their quality of life,” said Kaplin, who plans on opening a ketamine clinic.

The debate over whether ketamine is an opioid comes at a time when its use is expanding.  Ketamine was approved by the FDA in 1970 solely as a surgical anesthetic to be taken intravenously or by injection. But a growing number of clinics now offer off-label infusions of ketamine to treat depression, post-traumatic stress disorder and difficult chronic pain conditions such as Complex Regional Pain Syndrome (CRPS).

Demand has grown so much there are reports of ketamine shortages. Although ketamine itself is inexpensive, the infusions can cost several hundred dollars and are not covered by insurance.

Ketamine Nasal Spray

Not until this year did the Food and Drug Administration approve the use of ketamine to treat depression, when it okayed a nasal spray (Spravato) made by Janssen Pharmaceuticals that contains a ketamine compound.

The FDA approved Spravato even though 2 out of 3 short term trials failed to prove its effectiveness. The spray was effective in a longer trial, but only when taken with a conventional antidepressant.

Because of the risk of abuse and side effects, Spravato can only be administered in a doctor’s office, where patients can be observed for two hours after taking a dose. A single dose will cost about $900.

The FDA has called the herbal supplement kratom an opioid because it acts on opioid receptors, but the agency has not taken that step with ketamine. Given current attitudes about opioids, it’s fair to say the FDA would have never approved Spravato if it was considered an opiate.

In addition to its medical uses, ketamine is used as a recreational party drug – known as “Special K” -- because it can cause hallucinations and intense dream-like states.

Whether taken to get high or to treat pain and depression, it’s clear that ketamine is a potent drug that has both harms and benefits. And experts say it needs to be viewed with caution until we know with more certainty how it works.

“Unfortunately, when one approaches ketamine as another antidepressant rather than a drug of abuse, this type of trap is easy to fall into, and in the end, such mistakes can be catastrophic,” Schatzberg said in his commentary. “We have witnessed four decades of supposedly new and safer opioids that have turned out often to be, if anything, even more abusable and lethal."

Guideline Paranoia

By Carol Levy, PNN Columnist

I recently posted an article to an online chronic pain support group about the CDC’s opioid prescribing guideline.

“For treating acute pain, the guideline recommends a quantity no greater than what is needed for the expected duration of pain severe enough to require opioids, specifying that three days or less will often be sufficient and more than seven days will rarely be needed,” the guideline states.

It makes sense to me. And I assumed that would be the response my post would get. The recommendation is only for treating acute pain and acute pain shouldn’t need chronic, long term opioid treatment.

Instead, the replies were quick, angry and knee jerk:

“How dare they decide what and how many we need? This will hurt chronic pain patients.”

“They always come after us. These may be for acute pain patients, but you just know more draconian guidelines are just around the corner for chronic pain patients.”

The CDC guideline does not say, “And no one, even if their acute pain continues longer than 3 or 7 days, will be able to get the pain meds they need.” But that was how it was interpreted.

And then the people replying went one step further: “Soon they will be writing guidelines that even those in chronic pain can only have opioids for a specified period of time and a specific dosage, and not one grain more or one day longer.”

I see this common response and reaction as a major issue. When any new guideline is proposed (and people forget these are guidelines, not absolutes), it is a major catastrophe: “They are coming after us.”

Too often we act in a way that appears akin to addictive behavior. We have to have our opioid medications. And any restriction, even when it is not related to chronic pain, is one restriction too many: “They are going to take away my drugs. Then what will I do?”

We seem to have lost the concept of consideration. No time is taken to think through the new suggestions. Instead it is an immediate jump to: “This will hurt me. I won't be able to get the meds I need.”

For many of us, opioid medication is all that is left or the only option. The idea that someone, especially the government, may rip them from us is truly terrifying.

But I wonder. Maybe if we did not take any and all new guidelines as a frontal attack on us, maybe we would not be seen and referenced so often as a major component and cause of the “opioid epidemic.”

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

How Common Is Opioid Addiction?

By Roger Chriss, PNN Columnist

As the opioid crisis continues to worsen, there is increased scrutiny of both prescribing levels and fatal overdose rates. The goal of reducing opioid prescriptions is to decrease the exposure to opioids, on the theory that medical use of opioid analgesics is closely linked with addiction and overdose risk.

But how valid is that theory? A key issue in the crisis is opioid addiction rates, which can be divided into medical and non-medical addiction.

Medical Opioid Addiction Rates

The National Institute on Drug Abuse (NIDA) reports that 8 to 12% of patients on long-term opioid therapy develop an opioid use disorder.

“The best and most recent estimate of the percentage of patients who will develop an addiction after being prescribed an opioid analgesic for long-term management of their chronic pain stands at around 8 percent,” NIDA Director Nora Volkow, MD, told Opioid Watch.

The NIDA estimate is well-researched and widely accepted. But there are other estimates, each with important qualifications.

Cochrane found in a major review of studies of long term opioid therapy for non-cancer pain that only 0.27% of participants were at risk of opioid addiction, abuse or other serious side effects.

In another large study, The BMJ reported that only about 3% of previously opioid naïve patients (new to opioids) continued to use them more than 90 days after major elective surgery.

Other addiction rates include numbers as low as 1% and as high as 40%. But details matter. Much of the difference in addiction rates stems from three factors:

1. How well screened the patient population is

2. How carefully monitored the patients are during opioid therapy

3. How the criteria for opioid use disorder are applied

In other words, a well-screened and closely monitored population of adults with no risk factors may well have an addiction rate of 1%. The recent SPACE study by Erin Krebs, MD, in which over 100 people with knee osteoarthritis and low back pain were put on opioid therapy for a year, saw no signs of misuse, abuse or addiction. There were also no overdoses.

Non-Medical Opioid Addiction Rates

It’s also important to look at the percentage of people who become addicted to opioids without ever having an opioid prescription. Here the addiction rates are much higher.

A 2009 study in the American Journal of Psychiatry found that among treatment-seeking individuals who used OxyContin, 78% had not been prescribed the drug for any medical reason. The OxyContin was “most frequently obtained from nonmedical sources as part of a broader and longer-term pattern of multiple substance abuse.”  

The 2014 National Survey on Drug Use also found that about 75% of all opioid misuse starts outside medical care, with over half of opioid abusers reporting that the drugs were obtained “from a friend or relative for free.”

Heroin is considered highly addictive, with nearly one in four heroin users becoming dependent. Importantly, most people who try heroin already have extensive experience with other substances, including opioid medication, and many have serious mental illness. There is no research on the addictive potential of heroin in drug-naive people.

Relatively little is known about the complex and concealed world of nonmedical opioid use. Researchers like UCSF’s Daniel Cicerone are working to fill this gap by collecting information on overdoses to get a more accurate picture on the type of opioids being used.  

Risk Management

Opioids remain an essential part of modern medicine, from trauma and battlefield medicine to surgery, end-of-life care and long-term management of chronic, progressive degenerative conditions. This makes risk management vital.

Current tools to screen patients include the long-standing COMM tool and the new NIDA TAPS tool. Novel approaches using genetic testing for opioid risk may eventually help clinicians better assess risk, too. And improved data analytics may also help reduce addiction.

"Understanding the pooled effect of risk factors can help physicians develop effective and individualized pain management strategies with a lower risk of prolonged opioid use," says Ara Nazarian, PhD, a researcher at Beth Israel Deaconess Medical Center.

The Krebs SPACE study achieved an admirable level of safety by carefully screening and monitoring patients during opioid therapy. A similar patient-focused approach that acknowledges the low rate of medical opioid addiction and works to minimize it further is likely to bring benefits to both individuals and society at large.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Mayo Clinic: Opioid Prescribing Has Not Changed

By Pat Anson, Editor

Numerous studies have shown that opioid prescriptions are falling. The trend started in 2011 and appears to have accelerated since the release of the CDC’s 2016 opioid prescribing guidelines.

The volume of opioid medication filled last year fell by 12 percent, the largest decline in 25 years, according to the IQVIA Institute.  Prescriptions for hydrocodone – once the most widely prescribed drug in the country – have fallen by a third since their peak. Even the CDC has reported that opioid prescriptions have dropped by about 5% each year between 2012 and 2016.

Anecdotally, many patients tell us opioids are harder, if not impossible, to obtain. Nearly half of the 3,100 patients PNN surveyed last year said they were getting a lower dose. And one in four said they were no longer prescribed opioids.

But according to Mayo Clinic researchers, opioid prescribing hasn't changed that much and remains at high levels. In a study published in the British Medical Journal (BMJ), they report that opioid prescriptions for Medicare and privately insured patients have remained relatively stable over the past few years. And the average daily dose of opioids is well above what it was 10 years ago.

“If you’re hearing the message that prescription opioid use is starting to decline, I think we need to counter that message and say in most populations it really isn’t moving very much.” says lead author Molly Jeffery, PhD, scientific director of the Mayo Clinic Division of Emergency Medicine Research. “Our data suggest not much has changed in prescription opioid use since about five years ago.”

Why the discrepancy? Jeffrey says most of the previous studies only looked at market-level data – the amount of opioids that drug makers reported producing and selling. She and her colleagues dug a little deeper, looking at insurance claims for 48 million U.S. patients between 2007 and 2016.  

Over that 10-year period, the rate of opioid use by privately insured patients remained relatively flat at 6 to 7 percent. The average daily dose for that group, about two pills of 5-milligram oxycodone, remained the same.

The rate of opioid use by Medicare patients 65 and older peaked at 15% in 2010 and decreased slightly to 14% by 2016. Their average daily dose, three 5 mg pills of oxycodone, also remained relatively unchanged.

Rates of opioid use by disabled Medicare patients also haven't changed much, peaking at 41% in 2013 and falling to 39% in 2016. Their average daily dose remains relatively high, about eight 5 mg oxycodone pills. 

“Our research of patient-level data doesn’t show the decline that was found in previous research,” says Jeffery. “We wanted to know how the declines were experienced by individual people. Did fewer people have opioid prescriptions? Did people taking opioids take less over time? When we looked at it that way, we found a different picture.”

The Mayo study includes an interesting disclaimer. While the researchers looked at data from patient insurance claims, they never surveyed or spoke to any patients about their opioid use. The researchers said they would “engage” with patients in future blog posts and press releases.

You can share your views with Molly Jeffery by email at jeffery.molly@mayo.edu or @mollyjeffery on Twitter.

I Have to Drive 6 Hours for Pain Care

By Bailey Parker, Guest Columnist

I feel so alone and isolated. There have been times I wanted to die, but my 5-year old son keeps me going. I get up every day for him.

About two years after he was born, I had a car wreck. I hit a coyote at 60 mph and ripped the radiator off my car. The doctors told me I had the spine of an 80-year old and needed a double level fusion in my neck.

I was 34 then and in tremendous amounts of pain. But after reading online stories in spine health forums, I was skeptical about the surgery. Everything told me to wait. So I did, for a year. I saw three surgeons and a neurologist. They all told me to have the surgery.

I live in a small city in southwest Colorado. When it comes to opioid pain medication, all the doctors here seem to have taken the stance, “We just don’t do that here.” The nearest city is Albuquerque, New Mexico, which means a 4-hour drive for me across state lines, or a 6-hour drive to Denver over mountain passes.

Before my surgery, one of the doctors of orthopedic medicine prescribed my pain medication. For two months, I was able to work again and was beginning to get back on my feet. I remember thinking at the time that I didn’t want to take medication for the rest of my life, but the fusion sounded worse.

The third month in I called for a refill of my medication. They told me no, but wouldn’t say why or give me a follow up exam with the doctor. He was too busy and couldn’t see me for a month. I waited one excruciating month and went to see him, asking what happened.

BAILEY PARKER

He had looked at my prescription records and saw a prescription for narcotics from another doctor for when I had cystic fibroids on my ovaries. It was not the same pain medication as what he prescribed me, and I didn’t even know they were the same type of medicine.  

Even though I had a broken neck, he did not feel comfortable prescribing to me anymore. His office then took 6 months to get my medical records sent to my primary care doctor. I had to physically go in and yell at them that I was about to have major surgery. This was the first time I felt treated like an addict, but not the last.

I went to my primary care physician and explained what happened with this other doctor. We have a very good relationship. She knows all of my medical history. She handled my pain medication before my surgery but was very clear that she would not do it for an extended period.

I never take more medication than prescribed. I am not an addict. I do everything they tell me. I was walking and doing yoga every day, just as the doctors recommended. I took my vitamins and a fruit shake every day.

After the fusion surgery, things just didn’t feel right. I was in tremendous pain again and this time there was more of it in different places. I told the physician’s assistant at my surgeon’s office and he told me to just get off all the drugs. He said it would help. He told me I would be fine. I wasn’t.

I struggled for another month before I demanded to see the surgeon. He told me I would benefit from OxyContin and gave me a week’s supply. For the first time since my accident, I was able to work and properly care for my son. My depression lifted. But when I called to tell them that I was doing good on the medication, they said it was time to go back to my primary care doctor and any further medication would have to be prescribed by her.

I went to see her, but she still did not feel comfortable handling my care and referred me to a pain clinic 6 hours away. I was in despair, thinking that I had crippled myself for life and would lose my job, my son and my husband. All of these relationships were strained at this point.

The pain clinic helped me get my life back. They are compassionate and good to the people that come through their doors. It’s a common misconception that pain patients want to take medication. We don’t. We just want some of our lives back and pain medication helps us have that.

A year after my fusion, the surgeon met me again. The fusion had failed, and he wanted to do a revision that would be more painful than the first. He also told me he thought my pain might be caused by fibromyalgia. I’ve never been so angry. I have pain because of my broken neck. Pompous arrogant doctor with no aftercare.

Here is my dilemma, I’ve gotten better care in a big city, where they do not treat me like an addict. I’ve gotten my life back. At first, I was able to go there every three months to get my medication, but with the laws changing, they now say I have to go every month. Driving 6 hours both ways with a 5-year-old and a broken neck is hard. But quality of life and pain are great motivators.

My experience has left me with so much anger towards doctors in my area. It seems their Hippocratic oath has been trumped by the opioid crisis and fear of administrative action. I do not tell people about the medication that helps my quality of life for fear of judgement and stigma. Unless they have been through chronic pain, they simply don’t understand.

I wouldn’t wish this on my worst enemy.

Bailey Parker lives in Colorado.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

DEA Adopts Rule to Further Limit Opioid Production

Pat Anson, Editor

The U.S. Justice Department has finalized a new rule that will allow the Drug Enforcement Administration to reduce the amount of opioid pain medication a drug maker can produce if it finds the opioid is being diverted or misused.

The controversial change in the opioid production quota system was adopted despite warnings from patients, doctors and drug makers that it targets the wrong the problem and could worsen shortages of some pain medications.

The DEA maintains the rule change will “encourage vigilance” on the part of opioid manufacturers to prevent their drugs from being abused.

“These common-sense actions directly respond to the national opioid epidemic by allowing DEA to use drug diversion as a basis to evaluate whether a drug’s production should be reduced,” said DEA Acting Administrator Uttam Dhillon in a statement. “This also opens the door for increased communication and better information sharing between DEA and individual states, as we work together to address the opioid problem plaguing our country.”

The final rule greatly enhances the roles played by states and other federal agencies in setting opioid production quotas. It requires DEA to share proposed quotas with state attorneys general, who could object to a quota and demand a hearing.

The rule also allows DEA to consider “relevant information” from all 50 states, the Department of Health and Human Services, Food and Drug Administration, the Centers for Disease Control, and the Centers for Medicare and Medicaid Services, before setting a quota.

"DEA must make sure that we prevent diversion and abuse of prescription opioids. Today's new rule, by taking diversion of these opioids into account, will allow the DEA to be more responsive to the facts on the ground. More importantly, it will help us stop and even prevent diversion from taking place,” said Attorney General Jeff Sessions.

Sessions announced the proposed rule changes in April, and DEA received over 1,500 public comments during an unusually short comment period. A clear majority opposed the new rule.

“This does nothing to stop addiction or overdose deaths. Addicts will find a high anywhere and where they find it now is street drugs! Illicit drugs are what’s killing, not doctor prescribed opioids filled at a pharmacy. The reporting you all are using is inaccurate and false,” wrote Amy Vallejo.

“By creating quotas, and thereby shortages, you are committing torture,” said Kimberley Comfort, who lives with arachnoiditis, a chronic spinal disease. “There is no reason why people having surgeries, people who suffer from incurable diseases, should be left to suffer when we are a nation that has the ability to take care of its citizens. The DEA does not have a clear understanding of the so-called opioid crisis and therefore needs to cease and desist making opiates harder to get.”

“Again, we have the DEA making laws and quotas on something they should not be. Let them worry about the drugs coming in from China, Mexico etc. which are illegal,” said Sarah Yerxa. “By cutting the quotas all they are doing is sending needy pain patients to the streets, which will just raise the addiction... and overdose problem.”

Opioid Shortages

The DEA has already made substantial cuts in opioid production quotas, reducing them by 25 percent in 2017, followed by another 20 percent cut in 2018. This year’s cuts were ordered despite warnings from drug makers that reduced supplies of opioids “were insufficient to provide for the estimated medical, scientific, research and industrial needs of the United States.”

Many hospitals and hospices now face a chronic shortage of intravenous and injectable opioids, which are used to treat patients recovering from surgery or trauma. The shortage has been primarily blamed on manufacturing problems, although some critics say it has been worsened by the DEA production cuts.

“I believe Attorney General Jeff Sessions needs to sit down and talk to some of these physicians who are pain specialists and understand that what he’s doing is going to put the chronic pain patient, the post-operative patient, and the patient that comes to the emergency room in serious jeopardy,” Tony Mack, CEO and chairman of Virpax Pharmaceuticals, told PNN in an earlier interview.

“I think that Jeff Sessions is not educated well. I think he is picking on something that sounds good politically but doesn’t make sense socially. It’s socially irresponsible.”

In a public notice announcing the rule change, the DEA said it was not responsible for “perceived shortages” of injectable drugs and blamed the “manufacturer induced shortages” on “internal business decisions.”

The agency also deflected criticism that it was targeting the wrong problem. Recent studies indicate that overdoses involving illicit fentanyl, heroin and other street drugs now outnumber deaths linked to prescription opioids.   

“The DEA acknowledges that prescriptions for opioid drug products have decreased over the last several years due to the stepped up civil, criminal, and regulatory enforcement efforts of the agency. However, while there is a downward trend in prescribing, these Schedule II prescription opiates continue to have a high potential for abuse and dependence and require the annual assessment of quotas,” the DEA said.

The agency also claimed prescription opioids were “inextricably linked” to overdoses from heroin and illicit fentanyl, because many addicts start by taking pain medication from family medicine cabinets and then move on to street drugs.

The DEA statement defies some of its own analysis. Less than one percent of legally prescribed opioids are diverted, according to a 2017 DEA report, which also found that admissions for painkiller abuse to publicly funded addiction treatment facilities have declined significantly since 2011, the same year that opioid prescriptions began dropping.

FDA Ends Probe into Kratom Salmonella Link

By Pat Anson, Editor

The Food and Drug Administration has ended its investigation of a small salmonella outbreak linked to kratom – but not without taking some parting shots at the herbal supplement used by millions of Americans to treat chronic pain, addiction, depression and other conditions.

“It appears the salmonella problem with kratom uncovered earlier this year has probably been occurring for some time and is ongoing. We have closed our outbreak investigation, concluding that anyone consuming kratom may be placing themselves at a significant risk of being exposed to salmonella,” said FDA commissioner Scott Gottlieb, MD, and Stephen Ostroff, MD, FDA Deputy Commissioner for Foods and Veterinary Medicine, in a lengthy joint statement.

The FDA ended its investigation five weeks after the Centers for Disease Control and Prevention wrapped up its own probe of the salmonella outbreak that sickened 199 people in 41 states. The CDC investigation began in February of this year, but salmonella illnesses linked to kratom were traced back as far as January 2017.

No single source of the outbreak was ever identified, but kratom was considered the “likely source.” A little over half of the 81 kratom samples that were analyzed tested positive for strains of salmonella bacteria.

“This means that users of these products had essentially a one in two chance of being exposed to this pathogen,” Gottlieb and Ostroff said. “The more than 50 percent contamination rate is stunningly high. It represents a level rarely seen in outbreak investigations of this nature. It shows that a high proportion of kratom being shipped into the United States may be contaminated with salmonella.”

Kratom comes from the leaves of a tree that grows in southeast Asia, where it has been used for centuries as a natural pain reliever and stimulant, particularly in rural areas of Indonesia and Thailand.  

“In these locations, the plant is being grown, harvested and processed in problematic conditions that readily create the circumstance for widespread contamination with foodborne pathogens. Although some of the kratom is further processed once in the United States into capsules, powders or herbal remedies, based on our findings, these procedures do not appear to be eliminating microbial contamination,” wrote Gottlieb and Ostroff.

In recent years, millions of Americans have discovered kratom and started buying it online or in convenience stores and “head shops.” But not until this year did federal health officials show any concern that kratom products were contaminated with salmonella bacteria. Their primary focus was that kratom was being marketed as an unapproved medical treatment, particularly for pain and addiction.

The FDA has even started calling kratom an addictive “opioid,” when in reality its active ingredients are mitragynine and 7-hydroxymitragynine, two alkaloids that are believed to act on opioid receptors in the brain. Earlier this year, the FDA released a computer analysis that found kratom contains over two dozen opioid-like substances – a report that critics say was biased and amounted to “junk science.”

Over a dozen kratom products were recalled during the FDA and CDC salmonella investigations. Salmonella is a bacterial infection usually spread through contaminated food or water. Most people who become infected develop diarrhea, fever and stomach cramps. Severe cases can result in death.

There have been several other salmonella outbreaks this year, including infections linked to melons, raw sprouts, dried and shredded coconut, live poultry, chicken salad, pet guinea pigs, and Kellogg’s Honey Smacks cereal.