Several weeks ago, I was approached by local commentator Benita Zahn of Channel 13, to interview as part of an exposé on kratom, a popular over-the-counter natural remedy that has been used for centuries as a mild stimulant and analgesic. Mitragyna speciose known as kratom is an evergreen plant similar is some ways to the coffee plant family which grows naturally in Indonesia, Malaysia, Papua New Guinea, and Thailand.
I must say, the attention this got upon release of the initial trailer early on February 2nd was surprising, but the sequalae to follow the full story was astonishing. I received several welcomed phone calls, e-mails, and social media posts from patients and kratom support groups nationwide. While I certainly understand their concerns about loosing a natural drug that has helped them, many of them ignored the potential pitfalls or harm that were reported. Like any drug, kratom has benefits and risks.
As a follow-up to all the hoopla, I decided to post this blog in order to clarify the pharmacology of kratom, outline the benefits, and risks, and publicly answer some of the questions posed to me. But before diving in, I will say this…
KUDOS TO THE KRATOM COMMUNITY AND ADVOCATES FOR LOOKING OUT FOR EACH OTHER AND PROMPTING THIS BLOG!
Here are some of the questions and comments and my responses:
Kratom is a natural product, so how can it be harmful.
Lots of natural plant products are beneficial in low doses and harmful at a miniscule amount more, and other drugs obviously require much higher doses than their recommended amount to cause harm. Three examples of natural products that have a very narrow therapeutic and toxic index (small differences above therapeutic dose can cause harm or death) include: 1) vincristine and vinblastine from the periwinkle plant, popular to treat various cancers; 2) digitalis from foxglove used to treat supraventricular heart arrhythmias or to strengthen heart rhythm ; and 3) various atropine alkaloids from belladonna (also known as deadly nightshade), the ingredient from berries used by Romeo and Juliet to cause death.
Show me one article that proves kratom can be harmful.
See below, 1-7.
Dr. Fudin implies kratom is an opioid. It’s not. You can simply Google it, and then look up the definition of opioid.
The original definition of an “opiate” is a drug derived from the poppy plant, or opium, that combines with one or more opiate receptors in the body. Opium is a concentrated form of morphine. Kratom is the only naturally occurring non-poppy derived opiate-type drug, but not an opiate by the strictest definition. It combines with more than one opiate receptor including the mu receptors as a partial agonist. Most often, the receptors we refer to are those found in the central nervous system such as mu-type receptors responsible for typical outcomes such as analgesia, euphoria, sedation, respiratory depression, constipation, etc. Semi-synthetic opiates have been renamed collectively as opioids. The semi-synthetics share a chemical nucleus with opium. Some of these include heroin (2-molecules of morphine connected by a 2-carbon chain), oxycodone, hydrocodone, and several others. Kratom does in fact have opioid activity at higher doses because it does in fact combine with mu and other opiate receptors. More specifically, certain kratom alkaloids are partial agonists at the mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors.
If kratom is an opiate, why doesn’t it cause a positive urine screen for opiates?
This is one of my favorite questions! It has to do with the chemistry. Typically, when a urine screen is performed in a doctor’s office, it is of the immunoassay (IA) variety, a less sophisticated test compared to chromatography. This test is specific for morphine, not all opioids. Drugs that will always test positive for morphine include codeine (which is metabolized to morphine), morphine, opium (concentrated morphine), and heroin (diacetyl-morphine). The semi-synthetics which share the morphine nucleus will only test positive at higher doses. Certain opioids will never test positive for an opiate screen because the chemistry is completely different than morphine. Some examples include fentanyl and derivatives, meperidine (Demerol), methadone, and tramadol. Kratom has a different chemical structure than all of these, and also will not test positive on an IA urine screen for opiates. Just like fentanyl and derivatives, meperidine (Demerol), methadone, and tramadol, kratom require a specific urine tests by chromatography to be identified. To see a picture of what I’m describing, see Chemical Classes of Opioids.
Dr. Fudin incorrectly stated that kratom can interact with other drugs and cause agitation, heart attack and stroke.
In order to understand why these are very real possibilities, one must understand the pharmacology of kratom. Kratom’s effects are clearly dependent on dose escalation. At lower doses it is a CNS stimulant (working similarly to antidepressants and low dose cocaine) and at higher doses it may do the opposite because the opiate activity becomes more prevalent. At low doses it is an alpha-2-adrenergic agonist with sympathomimetic activity – this is the very same thing that cocaine does, although these activities of cocaine happen at lower relative doses. More specifically, kratom combines with serotonin (5-HT2A), and dopamine type 1 and 2 receptors, and is also a dopamine type 2 receptor antagonist. All of these activities have common pharmacology with various prescription antidepressants alone or combined, including but not limited to specific serotonin reuptake inhibitor (SSRIs) like fluoxetine (Prozac), paroxetine (Paxil), and serotonin norepinephrine reuptake inhibitors like venlafaxine (Effexor), duloxetine (Cymbalta), and atypicals like bupropion (Wellbutrin), mirtazapine (Remeron), and tricyclic antidepressants such as amitriptyline and others. Of important note also is that all of these drugs in their own right have significant drug interactions with various foods and drugs because they reduce or enhance liver enzymes that may increase or decrease blood levels of other drugs that rely on those liver enzymes to be metabolized to more active or less active forms of the parent drug that is taken by a patient. But irrespective of these liver enzyme interactions, combining any or all of these drugs together and/or with kratom could end in agitation, heart attack or stroke simply by layering them on top of each other due to overlapping similar pharmacology. And there are many other drugs used for multiple disease states that are not antidepressants which can also be problematic in terms of drug interactions and toxicity when combined with kratom. One such drug is tramadol with enhances norepinephrine and serotonin, but also has weak opiate activity. Interestingly, one commercial product called Krypton combines kratom with tramadol. Since tramadol has complex metabolism that depends in part on your genetic make-up, it could cause harm or death as seen in Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. Some drug interactions with kratom and various “designer drugs” are outlined in Practical Pain Management’s Interactions Between Pain Medications And Illicit Street Drugs.
Dr. Fudin either made this up off the top of his head, or someone told him this.
Not true – see above.
There is no use for using naloxone on a kratom overdose. If you “overdose” you get sick and puke.
If someone takes high doses of kratom, we are dealing with two emergencies; 1) noradrenergic overstimulation which can be treated with combined benzodiazepine (alprazolam, diazepam, etc.) to reduce agitation plus beta blockers (propranolol and others) to slow the heart rate and reduce blood pressure; and 2) opioid overdose which can be treated with naloxone to block the opioid receptors.
Dr. Fudin, what are your thoughts on keeping kratom and marijuana legal?
This is probably my second favorite question. There’s a part of me that believes all drugs should be declassified and legalized in order to eliminate a black market and reduce crime. If people want advice or direction, they can seek professional advice from their doctor or pharmacist. If they want to abuse drugs, they can do that too, because they’re doing it anyway. But as you can see from the outrage among innocent kratom users, many don’t have all the facts in order to make an informed, educated choice simply by searching Google.
Another part of me believes that the government should put controls in place to protect the public, however this is not the case with tobacco or alcohol because they are heavily taxed and a tremendous revenue source for the government. Notwithstanding, this past November, FDA Commissioner Dr. Scott Gottlieb, M.D. issued an FDA advisory about “deadly risks associated with kratom”. That may be viewed HERE.
I do believe that kratom has incredible potential to be used therapeutically in the right patients as long as they are carefully monitored for medical conditions and drug-drug or drug-food interactions. This is the case with most prescription medications. I have seen much harm and death over more than 3-decades from innocent persons that went to multiple doctors and pharmacies where drug interactions were overlooked just because of poor communication. I have seen similar outcomes in people who purchased bath salts, spice, or other products from head shops or gas stations. I have seen people purchase more common drugs like cough and cold products from a grocery store or gas station that ended in death because of drug interactions that the pharmacist never had an opportunity to evaluate. Perhaps one way to avoid such risks is to have a class of drugs, such as kratom, that are available through a pharmacy and require evaluation and counseling by a prescribing community pharmacist.
The true is, I don’t have an answer to the problems associated with kratom but I do acknowledge there could be benefits in a controlled environment where every purchase assured consistency with all the labeled alkaloids and milligram strengths – this is something that is currently missing and adds to the dangers.
And finally, “Dr. Fudin is not a patient advocate and doesn’t have his facts straight” at least in my opinion couldn’t be further than the truth. It is because I care that I have taken the time to write this blog post.
So, after reading this blog, you decide.
Should anyone have access to kratom (save ‘em)?
Are you being lured by political and advocacy rhetoric without having all the facts (bait ‘em)?
Will you end up a statistic because a drug interaction was missed (crate ‘em)?
As always, comments are encouraged and welcome!
References per request:
- Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following Kratom (Mitragyninaspeciosa Korth) exposure. Journal of medical toxicology. 2010 Dec 1;6(4):424-6.
- Neerman MF, Frost RE, Deking J. A drug fatality involving Kratom. Journal of forensic sciences.2013 Jan 1;58(s1).
- Trakulsrichai S, Tongpo A, Sriapha C, Wongvisawakorn S, Rittilert P, Kaojarern S, Wananukul W.Kratom abuse in Ramathibodi Poison Center, Thailand: a five-year experience. Journal ofpsychoactive drugs. 2013 Nov 1;45(5):404-8.
- Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum andKratom. Clinical Toxicology. 2008 Jan 1;46(2):146-52.
- Warner ML, Kaufman NC, Grundmann O. The pharmacology and toxicology of kratom: fromtraditional herb to drug of abuse. International journal of legal medicine. 2016 Jan 1;130(1):127-38.
- Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M. Intrahepaticcholestasis following abuse of powdered kratom (Mitragyna speciosa). Journal of MedicalToxicology. 2011 Sep 1;7(3):227-31.
- Galbis-Reig D. A case report of kratom addiction and withdrawal. WMJ. 2016 Feb;115(1):49-52.