With Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP
Earlier this week, FDA issued an advisory regarding the unapproved and harmful use of kratom leaves, which naturally grow in several parts of Asia and have entered the United States market as an herbal supplement that promises to treat chronic pain symptoms and other conditions.¹⁻² FDA Commissioner Scott Gotlieb, MD, stated that there is a public perception kratom may be a safe alternative to prescription opioids, or used to treat opioid addiction and withdrawal.¹
As hype over this product grows, Practical Pain Management decided to ask Editorial Board Member Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP, about the significance behind this warning and its potential impact on pain management from the healthcare provider’s perspective.
In the current state of the industry, where opioid addiction has been declared a national public health emergency, are patients and providers alike more actively seeking out opioid alternatives such as kratom?
Dr. Fudin: Patients and providers alike are seeking alternative analgesics, for different and overlapping reasons. Providers are being frightened away from opioids due to all the press, various restrictions by states, third-party payors, chain pharmacies, and others. There is also a reasonable fear of State Narcotic Bureaus, some of which have taken a hardline approach to morphine daily equivalent doses. So, providers clearly are looking for opioid alternatives in addition to the usual other analgesic options, such as NSAIDs, SNRIs , and anticonvulsants to name a few. Patients often suffer from the backlash of all this due to opioid withdrawal, pain, or both when taken off their opioids abruptly and even over time. Unlike the prescribers, many patients are left in a panic without many options, often scrambling to find a new medical provider that may prescribe opioids. This cycle may lead to patients seeking out street drugs such as heroin or alternative products like kratom.
Are products like kratom being sought out for the wrong reasons given its potentially detrimental effects?
Dr. Fudin: Absolutely! Persons seeking to use kratom to treat withdrawal or pain may not realize the complex pharmacology of the agent. At lower doses, it acts like a combination of antidepressants by blocking reuptake of norepinephrine, serotonin, and dopamine. These activities are the same as the very first antidepressants used in the pain care industry as monoamine oxidase inhibitors. Combined, these activities may cause agitation, raise blood pressure to dangerous levels (especially if there is already elevation from opioid withdrawal), and increase nervousness.
Kratom also serves as a centrally acting alpha agonist, which might blunt some of these symptoms. The central alpha activity should presumably help to prevent opioid withdrawal in the same way as prescribers may recommend clonidine. However, as the dose increases, opioid agonist activity begins to occur at the mu and kappa receptors. Similar to antidepressants, the use of kratom may therefore also increase the risk of suicidality in an already vulnerable population. Overall, I consider it to be a dangerous drug if used haphazardly, and even more so in the face of several medical problems.
Evidence shows that kratom may produce similar effects to those of opioids and carries similar risks of abuse, addiction and, in some cases, death, according to the FDA statement.1 In your opinion, should kratom be banned from use until it can be further studied or formulated into a safe and effective drug? In other words, what would you propose as the next step for this alleged herbal painkiller?
Dr. Fudin: In my mind, kratom is a sloppier form of tramadol, the latter of which is already a nightmare in terms of side effects, tolerability, and pharmacokinetics for many patients with chronic pain. However, I do I believe there are some attributes of kratom that could be uniquely used to benefit patients if chemically manipulated to isolate those potential benefits and eliminate or minimize the pitfalls. It may even be useful in its natural state at various fixed doses in a controlled environment when prescribed with consideration to patient individuality, concomitant medications, and comorbid disease states.
However, the way it has been distributed—with a lack of controls—is quite dangerous. I’m not sure banning the product is the right thing to do, but it should somehow be restricted and the FDA needs to oversee its purity and milligram availability. This, of course, is not feasible unless a pharmaceutical company wishes to bring it to market by conducting clinical trials with subsequent application to the FDA.
What would you recommend pain care and primary healthcare providers do in the interim if patients ask about kratom?
Dr. Fudin: I’ve had this question posed to me many times. I tell my patients that it is a very dangerous drug with some very serious drug interactions. As stated by FDA, there have been several reports of death related to kratom, and in most, if not all cases, these deaths involved combining kratom with other opioids, alcohol, and/or benzodiazepines. Its use is extremely risky in a hypertensive patient and in a patient without underlying hypertension that may also have an elevated heart rate and blood pressure due to opioid withdrawal. The risks include electroconductive abnormalities to the heart, stroke, and death.
Of note, providers may wish to review a previously published article in Practical Pain Management on the Interactions Between Pain Medications And Illicit Street Drugs, which clearly outlines kratom risks associated with various drug combinations.
What more should pain practitioners know about this evolving conversation?
Dr. Fudin: If you suspect a patient may be using potentially dangerous natural food products or illicit drugs, such as kratom, cathinones, or synthetic cannabinoids known as “Spice,” it is prudent to order specific tests for these compounds in addition to typical urine monitoring. For example, If I witness odd symptoms consistent with any of these drugs in my patients, I request add-ons for one or more of these drugs, as they are not picked up in general immunoassays or even comprehensive chromatography panels.
If the third-party payer refuses to cover these additional tests, I would carefully note the history and current unexplainable behavior or symptomology in the patient, and remind whomever denied the request that in case of harm or death, the denial will be noted in the medical record.
-Q&A by Angie Drakulich
