Kratom contains more than 40 alkaloids, although most of their pharmacological properties are related to two active compounds: mitragynine and its metabolite 7-hydroxymitragynine. Kratom is reported to have both opioid and non-opioid effects. In traditional settings in Malaysia and Thailand, rural communities have traditionally used kratom as a medicine to treat common health ailments, and the practice/tradition of kratom consumption does not cause significant health problems.
The results of several anonymous online surveys have shown that the use of kratom products may be useful for the self-medication of acute and chronic pain, and in fact, their use has only been self-reported to be associated with some adverse effects. Findings from a recent clinical trial confirmed the analgesic properties of kratom in healthy volunteers lasting for about 2 hours with a mean blood concentration of mitragynine at 2,000 ng/mL. These results indicate that kratom has the potential to be used as a centrally acting herbal analgesic.
Although kratom is reported to be used as a safe substitute for opioids in the management of pain, dependence, and withdrawal, it is not free from side effects and risks. Kratom dependence has been reported when the product is used in larger amounts over a long period of time, and negative effects such as sleep problems, depressed mood, diarrhea, and flu-like symptoms including muscle and joint pain can develop with sudden withdrawal. Deaths involving kratom are rare and, autopsy findings suggest that in those cases kratom was used concurrently with a banned substance or anti-depressant, and not kratom per se, or the user had an underlying health condition. So far, there have been no specific reports of incidents of fatal kratom overdose.
There is growing evidence, however, that kratom is safer when used as a pure kratom product or herbal decoction that is brewed in small doses and for a limited period of time. Should be avoided consumption in large quantities (more than 15 grams per dose) and high frequency (more than 3 times / day for a long period of time) because of the risk of developing dependence. Several cases have been reported in the West, including cases of neonatal abstinence syndrome, and Eastern countries, where those who used kratom for a long time experienced both physical (eg, constipation) and psychological (eg, anxiety) withdrawal symptoms. Recently an article was published by Muller et al in which individuals prescribing kratom for the treatment of pain reported increasing the dose required and eventually developing dependence.
Considering the conflicting evidence and the lack of randomized control studies, the balance between the benefits and risks of kratom is unclear, but some data suggest that kratom may cause fewer problems than opioids and retrospective data suggest that kratom reduces the prevalence of opioid side effects. in users (24) and among users of illicit opioids.
*Case Persentation
The subject of this report is a 29 year old male, US citizen. His medical history was unremarkable, except for the fact that at the age of 16 he was diagnosed with ulcerative colitis and primary sclerosing cholangitis. Since then, he has been successfully treated with mesalamine (1.2 g, 2 times per day), azathioprine (50 mg, 3 times per day), and ursidiol (300 mg, 2 times per day). Subjects have been able to lead an active lifestyle and participate in various sports including running, weightlifting, basketball, and baseball. Subject denied any history of smoking or use of alcohol, opioids, or illegal drugs.
On April 22, 2020, the subject’s father, who lives with the subject, and works for a large shipping company, was diagnosed with COVID-19. This is about 2 months after the first case of COVID was confirmed in his state of residence, which was one of the early active zones of COVID-19 transmission in the US.
On April 25, the patient began to experience general malaise and fatigue. Over the next 24 hours, symptoms worsen including severe fatigue and weakness, loss of appetite, fatigue, mild dry cough, body aches, muscle aches, loss of taste and smell, sore throat and fever. The patient was then examined by a general practitioner.
Vital signs at the time of examination were BP 110/72, pulse 97 BPM, respiration 14 times per minute, oxygen saturation 98%, and body temperature 101.7°F. The patient was given a nasopharyngeal swab, real-time RT-PCR test [SARS-COV-@ COBAS(R) test, Labcorp Laboratories, South Bend, IN] which confirmed the diagnosis of COVID-19. In accordance with standard medical practice standards, the patient was instructed to self-isolate and start azithromycin for 5 days (250 mg, daily), and also take 1 g of paracetamol (acetaminophen) every 6 hours for the treatment of pain and fever. Despite good adherence to the recommended medication, symptoms other than fever, did not improve, and she also began to feel depressed, lost motivation, and spent long periods of time in bed.
During this period, the patient experienced generalized myalgia and persistent musculoskeletal pain. He described the pain as persistent and relatively severe (rated a 7 on a scale of 1-10). Due to this discomfort, after 4 days the patient decided to take kratom to relieve his symptoms. According to the patient, he had first used kratom 14 months earlier before becoming infected with COVID-19. She uses kratom sporadically (no more than 4-5 times in total) as a cognitive enhancer and not to treat pain on her own.
*Treatment
The patient decided to take 2.5 gms (or grams) of green kratom (as ground leaf powder suspended in water). The product was purchased at a local shop in April 2020 sold under the name “Green Bali.” After 30 min, he noticed a significant improvement in the intensity of the physical symptoms (mainly pain and fatigue), and within 60 min he felt a sensation of mild euphoria and well-being that lasted for about 5 h. After 6 h following consumption the effects of kratom wore off, and the patient administered another dose. He used kratom three times a day continuously for 3 days (for a total of 9 doses of 2.75 g each) with significant benefit.
*Outcome
When asked to rate from 0 to 100%, the improvements that kratom had on COVID-19 symptoms: fatigue and weakness (80% improvement), fatigue (70% improvement), body aches (80% improvement), muscle aches (90% improvement) %)., “much better than paracetamol/acetaminophen”). Kratom does not appear to have any effect on: fever, cough, or sore throat. The patient also stated: “I don’t have any anxiety or psychological symptoms. For me, kratom mainly provides an increase in physical reactions.” “It also improves my mood and makes me feel less miserable, to the point where I can get out of bed, shower, view work email without feeling completely tired and drained”; “Kratom helps me more than antibiotics”; “I slept better, I basically fell asleep right away. Without kratom, sleep is not good, with kratom not waking up, about 6 hours.” Over the next 2 weeks, the patient’s symptoms gradually subsided and on May 13 he had a television check-up with his doctor and a follow-up swab test which was negative for COVID-19.
Subjects can end quarantine and return to work in early June. In a follow-up interview with us, the patient reported that he experienced no side effects from using kratom, except for a very bad taste when ingesting it. Patients can also stop using kratom immediately without evidence of physical or psychological withdrawal symptoms. The patient also informed us that he still had some of the kratom product he took and he agreed to provide us with samples for chemical analysis.
*Discussion
To our knowledge, this is the first case report that aims to highlight the use of kratom in reducing symptoms and pain associated with COVID-19 infection. Our findings suggest that short-term use of kratom has the potential to reduce symptoms of COVID-19 infection, particularly pain, and does not appear to cause physical and psychological withdrawal symptoms when kratom is discontinued after short-term use.
The antinociceptive effects of mitragynine have been studied in animal models, and human data, mainly from surveys or retrospective studies on users, clearly indicate that kratom is used for pain relief and mood enhancement. The exact dose-response relationship is still unknown, but a median daily consumption of 76.3-114.8 mg of mitragynine (equivalent to 3.5 cups of tea/kratom juice) appears to be well tolerated among users in traditional settings.
COVID-19 is a global emergency, and most clinical trials and research are dedicated to finding effective treatments against the virus and the consequences of infection. However, like many other viral and bacterial infections, COVID-19 infection is also associated with aches, pains and malaise and usually has a negative impact on patients’ quality of life. Current treatment for this symptom is based primarily on paracetamol and/or NSAIDs. These compounds, however, are not always effective or should sometimes be avoided. Therefore, it is necessary to consider alternative and more effective treatments that can provide an immediate suspension of COVID-19 infection.
Side effects are rarely observed with consumption of pure kratom products or herbal decoctions brewed in different doses and frequencies among users in traditional settings. Although findings from various studies continue to support the therapeutic potential of kratom especially for pain relief, at this time, there is no solid scientific evidence to prove its usefulness. More controlled clinical studies are needed to identify the pharmacological properties, safety of kratom dosage, and its efficacy with current standard treatments for pain relief.
*Author’s Note
We (the authors of the journal) confirm that this work is original and has not been published elsewhere, or is being considered for publication elsewhere. It is the result of a collaborative effort between the School of Life and Medical Sciences—University of Hertfordshire (United Kingdom), NHS—Camden and Islington Trust (United Kingdom), Sapienza University of Rome (Italy), Center for Drug Research—Universiti Sains Malaysia ( Malaysia), Department of Medicinal Chemistry, College of Pharmacy—University of Florida (United States), Department of Pharmacology, Midwestern University (United States), and Department of Pharmaceutical Sciences—Midwestern University (United States).
This publication emerged from collaborative activities and staff exchanges among collaborating institutions.
The authors state that the study was conducted without any commercial or financial relationship that could be construed as a potential conflict of interest.
Disclaimer: this article as a whole is the result of research that we quoted from the following figures 10.3389/fpsyt.2020.594816 while the research was written by several people, namely; Antonio Metastasio, Elisabeth Prevete, Darshan Singh, Oliver Grundmann, Walter C. Prozialeck, Charles Veltri, Giuseppe Bersani, and Ornella Corazza.
