Jonathan Collin, MD
What Do We Advise Patients Using Kratom?
Over the years, patients have asked me about their use of kratom. Usually it wasn’t the focus of the consultation, meaning, I didn’t really express an opinion and the topic was dropped. Those who did like its use told me that it reduced pain and made them feel better. The herb was well tolerated and easily purchased over the internet. Not knowing much, I assumed that if they kept their consumption small and watched out for mixing with alcohol and other drugs things would be okay. But there are a lot of assumptions I made in assuring the patient it was okay. The big ones were understanding how much kratom was being consumed, how often, with what other substances, and most importantly, whether alcohol and other recreational drugs were being added to the mix.
Kratom use in the US is widespread; one estimate is that 15 million Americans have used it. Like other illicit substances, kratom is mostly used by the young, 18-35, some surveys suggesting male more than female use. At low doses, as a tea drink, its effects seem to match alcohol: stimulation, talkativeness, social loosening, lower anxiety/depression, mild pain reduction, and sense of feeling better. Mind you, none of the aforementioned benefits have been well studied nor justify its use. However, given the widespread access to the herb with tons of it being imported into the US each year, kratom has found a niche among its users who generally acclaim its use.
Unfortunately, not just a few users have experienced adverse effects that were not only unpleasant but medically serious, including respiratory distress, seizure, passing out/coma, psychotic break, and, in certain circumstances, death. Dying is not rampant but occurs often enough to cause a hullaballoo with the local authorities; generally, it is thought that it is the combination of kratom with other substances, especially alcohol, that caused the fatality.
At least six states have outlawed its use because of its serious risk, and fifteen more have established regulations for its distribution and sales. As of now the FDA has specified that it has no established use for treatment of any medical condition. Although the DEA has attempted to regulate kratom like other scheduled drugs, it has remained a supplement that can be freely transported and sold. The vast majority of kratom in the US derives from farms in Indonesia. However, Indonesia passed legislation in 2021 outlawing its production effective Jan. 1, 2024; it remains to be seen where US suppliers of kratom will obtain future deliveries.
Kratom is produced from the leaf of the Southeast Asian evergreen tree, Mitragyna speciosa, indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea.1 It has been used as a traditional medicine since the 19th century and perhaps earlier. The two major constituent alkaloids, mitragynine and 7-hydroxymitragynine, are partial mu opioid agonists and delta opioid antagonists. At least 40 other biochemicals have been studied in the Mitragyna leaf, none of which have been demonstrated to have well defined drug-like activities.
Mitragynine inhibits COX-2 and interacts with brain neuroreceptors, including 5-HT, serotonin, dopamine, and adenosine receptors. It also stimulates alpha-adrenergic receptors, which inhibit norepinephrine release—possibly accounting for kratom’s capability of enhancing sedation brought on by drugs and alcohol.
From a traditional medicine point of view, the leaf itself was chewed. Chewing the leaf brought on more energy, relieved musculoskeletal pain, and stimulated sexual libido as well as appetite, similar to the use of coca. The leaf was used to provide pain relief and applied as a salve to enhance wound healing. Tinctures made from kratom were used to relieve diarrhea, nausea, and intestinal infection. For workers engaged in monotonous activity chewing on the leaf brightened the mood and relieved aches and pains.
“Recreational” use of kratom seeks to achieve some level of euphoria and well-being while reducing aching and pain. Of course, these effects were dependent on the quality and quantity of the herb that was consumed. While a dose of 1-5 mg of kratom is energizing, more than this could be sedating. Kratom supplement manufacturing is not held to high quality control standards, and many products do not carry label information that is valid or can be trusted. The possibility of the product being adulterated remains high. In 2019 a salmonella outbreak was traced back to a supplier of kratom in Idaho.
When we compare recreational use in the US with traditional use in Thailand, the American herbal concentrate is vastly higher than the traditional leaf chewing. Hence, adverse effects incurred during consumption of US products are far more frequent and devastating.
Based on what was reported to poison control centers in a 2019 report the major “signs and symptoms were agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), confusion (8.1%), seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac/respiratory arrest (0.6%).”2 Adverse effects from chronic kratom use include constipation, insomnia, weight loss, decreased appetite, tremor, hyperpigmentation, sweating, muscle and bone pain, fever, hot flushes, restlessness, diarrhea, sadness, anger, and erectile dysfunction.3
Chronic kratom use will lead to dependency, tolerance, and withdrawal symptoms. Patients attempting to withdraw from the use of other opioids by consuming kratom risk overdose and severe withdrawal. Kratom also poses a risk for development of hepatotoxicity.
Kratom use is being regulated in the US and internationally. England has banned its use. Given the lack of standardization and high-risk potential, kratom is not appropriate for the naturopathic and integrative medicine tool box. If a patient were to ask me today about using it, I would recommend against its ongoing use.
Glycans
In this issue’s featured article Peter D’Adamo, ND, tackles the subject of glycans, how they function as part of proteoglycans. A glycan is a polysaccharide, and a proteoglycan is a protein bound to a glycan. Glycans play a major role in cell physiology. We all know the cell parts: cell membranes, cytoplasm, endoplasmic reticulum, Golgi apparatus, and, of course, mitochondria and the nucleus. What makes these structures perform and perform well is accomplished entirely by the biochemistry of the glycans. Without the glycans directing the three-dimensional structuring of proteins and lipids, the cellular components would fail to be constructed satisfactorily and calcium and potassium (Ca++ and K+) could not be effectively transported across membranes.
Glycans form a critical part of the mucins that form mucus. They also are part of the membrane structure of red and white blood cells. Perhaps, most importantly, the glycans are critical for the proper functioning of the extracellular matrix. Impairment in glycan functioning has been associated with many diseases, including blood disorders, cancer, osteoarthritis, Alzheimer’s disease, and a number of genetic disorders.
For those of you who do not recognize Dr. D’Adamo, he is the same individual who wrote about and popularized the theory that the ideal diet is based on one’s blood type. He is also the author of several Townsend Letter interactive articles on bioinformatics. D’Adamo is a distinguished retired clinical medicine professor who has carried out research and educational activities at his institute at the University of Bridgeport in Connecticut. He is the developer of the acclaimed Opus23 genomic software suite and a variety of other generative apps that can be explored at www.datapunk.net. In his spare time, he brings old VW Beetles back to life in his garage. Please do take a look at his Generativity articles, such as this, published on the https://www.townsendletter.com website.
References
1. Mitragyna speciose (Kratom). Wikipedia.
2. Eggleston, William; Stoppacher, Robert; Suen, Kyle; Marraffa, Jeanna M.; Nelson, Lewis S. (2019). “Kratom Use and Toxicities in the United States”. Pharmacotherapy. 39 (7): 775–777. doi:10.1002/phar.2280. ISSN 1875-9114. PMID 31099038. S2CID 157058636.
3. Corkery JM, Streete P, Claridge H, Goodair C, Papanti D, Orsolini L, Schifano F, Sikka K, Körber S, Hendricks A (2019). “Characteristics of deaths associated with kratom use”. J. Psychopharmacol. (Oxford)(Review). 33 (9): 1102–1123. doi:10.1177/0269881119862530. hdl:2299/21622. PMID 31429622. S2CID 201095094.
Published September 23, 2023