Kratom, a plant native to Southeast Asia, has gained significant attention due to its therapeutic potential for pain management, opioid withdrawal, and mood enhancement.1 Kratom is an atypical opioid with a structure distinct from typical ones like morphine.2 Preliminary research suggests that Kratom is not only an effective and less-addictive alternative to prescription opioids for pain relief, but it also reduces withdrawal symptoms in opioid-dependent individuals. However, among all of the interest in kratom for pain management, it is also important to be aware of its dangers and risks.
Garcia-Romeu et al.’s study found that American kratom users typically fall into the following demographic groups – white, middle aged, middle income, college educated and female. Kratom was used to self-medicate pain symptoms and opioid withdrawal, along with anxiety and depression. This study also noted that patients with a medical diagnosis of back pain had the highest incidence of kratom use (72.5%). Some believe that kratom has serious potential to act as a pain reliever and opioid substitute, while others argue that current research is not sufficient to discredit the serious concerns about the dangers of kratom, namely its addiction and overdose potential, toxicity, and poor regulation. There is a need for more controlled human studies examining kratom uses and effects.1,2
Kratom can be addictive, particularly when used in high doses or over extended periods, and there have been reports of overdose when kratom was taken with other substances. Studying the dangers of kratom use in American society is a challenge because it is emerging onto a landscape where misuse of pain medication, especially opioids, is already a large problem. Eastlack et al. delves into this significant nuance by explaining that most users who become dependent on kratom were already dependent on opiates and were in search for a superior replacement; thus, assigning addiction to kratom itself is heavily compromised. Since the US Drug Enforcement Administration (DEA) does not currently recognize kratom as a controlled substance, it remains readily accessible.
Preclinical studies looking at the effects of kratom alkaloids has confirmed its addiction potential and its effect of cognitive impairment. Addiction and toxicity are dependent on 7-OH-mitragynine, one of the 40 identified psychoactive alkaloids found in the plant. Mitragynine has a minor contribution to addiction but makes up the majority of the alkaloid content (66%) while 7-OH-mitragynine is present in far lower quantities, typically under 0.02%. Speciogynine, speciociliatine, and paynantheine are the other dominant alkaloids in kratom whose pharmacology is not fully understood. The diversity of alkaloids in the kratom plant poses a challenge to understanding the physiological effects it causes, what dangers it presents, and its mechanism of pain control, as each alkaloid has its own unique pharmacodynamic properties.3
Both mitragynine and 7-OH-mitragynine can bind the human μ-opioid receptor (hMOR). They are also G protein-based agonists of the mu-opioid receptor (MOR). These additively create a complex physiological response in users – stimulant-like at low quantities and opioid-like at higher doses. 3 Research in mice showed that mitragynine is in the brain at very high concentrations compared to the opioid receptor binding affinity. This demonstrated that kratom alkaloids do not directly activate opioid receptors. This partial affinity explains why kratom’s addictive and toxicity potential is lower than typical opioids.
References
1. Prozialeck WC, Avery BA, Boyer EW, Grundmann O, Henningfield JE, Kruegel AC, McMahon LR, McCurdy CR, Swogger MT, Veltri CA, Singh D. Kratom policy: The challenge of balancing therapeutic potential with public safety. Int J Drug Policy. 2019 Aug;70:70-77. doi: 10.1016/j.drugpo.2019.05.003. Epub 2019 May 16. PMID: 31103778; PMCID: PMC7881941.
2. Garcia-Romeu A, Cox DJ, Smith KE, Dunn KE, Griffiths RR. Kratom (Mitragyna speciosa): User demographics, use patterns, and implications for the opioid epidemic. Drug Alcohol Depend. 2020 Mar 1;208:107849. doi: 10.1016/j.drugalcdep.2020.107849. Epub 2020 Feb 3. PMID: 32029298; PMCID: PMC7423016.
3. Eastlack SC, Cornett EM, Kaye AD. Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review. Pain Ther. 2020 Jun;9(1):55-69. doi: 10.1007/s40122-020-00151-x. Epub 2020 Jan 28. PMID: 31994019; PMCID: PMC7203303.
4. Kruegel AC, Uprety R, Grinnell SG, Langreck C, Pekarskaya EA, Le Rouzic V, Ansonoff M, Gassaway MM, Pintar JE, Pasternak GW, Javitch JA, Majumdar S, Sames D. 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Cent Sci. 2019 Jun 26;5(6):992-1001. doi: 10.1021/acscentsci.9b00141. Epub 2019 May 29. PMID: 31263758; PMCID: PMC6598159.