Everything You Ever Wanted to Know About Kratom

Kratom is becoming increasingly popular across the United States. You can often find it alongside CBD products sold in gas stations and smoke shops. Since it is becoming more and more popular, we decided to pull together a comprehensive overview about kratom.

Kratom comes from the plant Mitragyna speciosa, and it goes by a variety of names including mitragynine, ketum, or biak. This plant is native to the Southeast Asian region, including the Philippines, Thailand, and Northern Malaya.¹ It is part of the coffee family and has been used for centuries as an herbal medicine. It can be used to treat a variety of things from anxiety and depression to pain and discomfort, and some have even found use for it to help with opioid withdrawal.² In fact, in Southeast Asia, kratom has been used as a pain mitigator, cough suppressant, an antidiabetic, and even a deworming agent.¹ Kratom contains many different alkaloids, but the two that are most important are mitragynine and its metabolite 7-hydroxymitragynine. The structures for these two analytes can be seen in Figure 1 and Figure 2 below. When it is consumed, typically as a tea, capsule, or in its raw leaf form, in low doses, Kratom can give a stimulant like effect, and an opioid-like effect when ingested in high quantities.³ Doses of kratom range from less than 1 gram and up to 8 grams. When it is consumed in reasonable doses, kratom can be effective for treating many different ailments; however, when it is not used properly, there are many side effects to using the plant including vomiting, dizziness, low blood pressure, and gastrointestinal issues¹.

Figure 1: Mitragynine	Figure 2: 7-Hydroxymitragynine

 

Kratom first appeared on the DEA’s radar in 2012, and it was placed in the list of scheduled drugs as a Schedule I substance in 2016.⁴ However, after much backlash, debates, and even public petitions, it was removed from the list of scheduled drugs completely.⁴ The DEA still has kratom listed as a “drug and chemical of concern,” and the FDA has not approved any medical use for the drug.⁵ However, while it may not be scheduled federally, some states may have their own rules regarding the possession and use of kratom. For example, currently in Pennsylvania there are no laws regulating the sale or possession of kratom (these could change with pending legislation), but it is banned completely in Alabama, Arkansas, Indiana, Vermont, and Wisconsin.⁴ It gets even trickier in states like Florida, where it is currently legal in all counties for those above the age of 21, with the exception of Sarasota County (as of December 2023).

While there is no medically approved use for kratom, this herbal substance is commonly used both for medicinal and recreational purposes. Mitragynine is frequently used alongside other opioids and has been found in drug related death cases. In most death cases involving mitragynine, there were other opioids present.⁶ There have also been death cases where an “herbal blend” was ingested, which involved adulterated kratom and other drugs.⁶ When performing clinical or toxicological testing, labs that are looking for use of this drug usually look for both mitragynine and its metabolite 7-hydroxymitragynine. The presence of both compounds is important for analysis and determination of usage. Below you will find a chromatogram for mitragynine and 7-hydroxymitragynine using a Raptor Biphenyl 100 x 2.1 mm, 2.7 µm column (Cat. #9309A52).

Figure 3. Method Parameters and Chromatogram for 7-Hydroxymitragynine and Mitragynine by LC-MS/MS.

Mobile Phase A:	0.1% Formic Acid in Water
Mobile Phase B:	0.1% Formic Acid in Methanol
Flow:	0.7 mL/min
Gradient:	Time (min)	%B
	0.00	20
	1.00	90
	2.00	100
	2.1	20
	3.00	STOP
Column Temp:	40°C
Injection Volume:	5 µL

 

If you are interested in adding these compounds to your testing menu, but are unsure how to do that, be sure to check out Restek’s Pro EZLC Chromatogram Modeler (https://ez.restek.com/proezlc). This useful tool allows you to select your analytes of interest as well as method conditions and will generate a chromatogram. This tool is extremely useful when testing out the addition of analytes to an existing method. Mitragynine is already in the extensive Pro EZLC library, with 7-hydroxymitragynine to be added in 2024.

Pro EZLC Chromatogram Modeler

Without federal regulation, Kratom products arriving on the market will not be tested for quality and safety measures to keep consumers safe. This is a problem because kratom is a natural product and there is risk of it being contaminated in several ways. Comprehensive testing is important because it analyzes the product for heavy metals, Salmonella, Listeria, mold, E. coli, and several other contaminants. All of these can cause illness to the consumer if the kratom they are ingesting is tainted. In a study (https://www.fda.gov/news-events/public-health-focus/laboratory-analysis-kratom-products-heavy-metals) done by the FDA, multiple sources of kratom products were tested for heavy metals. In most of the sources, significant levels of lead and nickel were found, most being at concentrations that exceeded the safe exposure level for daily users. A long-term user of kratom could be at risk of heavy metal poisoning with symptoms including kidney damage, anemia, or even an increased risk of certain cancers.

Along with contaminant testing, it is also important to perform potency testing, or mitragynine concentration testing, on kratom. Again, kratom is a natural product, meaning that different varieties can have higher concentrations of the active substances than others. While all kratom is harvested from the same plant, the concentration and effects can change based on different factors such as where the plant is grown and when it is harvested.⁷ Kratom is broken down into different varieties and different veins. The most popular types of kratom are red vein, white vein, and green vein, with red being the most popular for its calming effects.⁷ The different varieties of kratom include Malay, Sumatra, and Maeng Da.⁷ The variety name typically comes from the region that it was originally grown. The kratom plant is affected by heat and humidity so different climates will affect the potency of the plant.⁷ Like THC in cannabis, potency testing is often done with the use of an LC-UV instrument because these instruments tend to be cheaper and more robust compared to LC-MS. Below you will find an example method for analysis of kratom using LC-UV.  This chromatogram was generated using a Raptor C18 50 x 2.1 mm, 2.7 µm column (Cat. #9304A52).

Figure 4. Method Parameters and Chromatogram for 7-Hydroxymitragynine and Mitragynine by LC-UV

Mobile Phase A:	0.1% Formic Acid in Water
Mobile Phase B:	0.1% Formic Acid in Methanol
Flow:	0.5 mL/min
Gradient:	Time (min)	%B
	0.00	10
	2.00	90
	4.00	10
	6.00	STOP
Column Temp:	40°C
Injection Volume:	5 µL

 

In conclusion, the herbal substance kratom is becoming increasingly popular on the market. Whether you are a toxicology lab or a quality control lab, it is likely you will be seeing more and more of kratom in the future. Simple methods like the ones shown above can be beneficial in the testing for these compounds.

References and Further Reading

1. Singh, Darshan, et al. Traditional and Non-Traditional Uses of Mitragynine (Kratom): A Survey of the Literature. Brain Research Bulletin. 2016, 126, 41-46.
2. Coe, Marion A, et al. Kratom as a Substitute for Opioids: Results from an Online Survey. Drug and Alcohol Dependence. 2019, 202, 24-32.
3. Swogger, Marc T, and Walsh, Zach. Kratom Use and Mental Health: A Systematic Review. Drug and Alcohol Dependence. 2018, 183, 134-140.
4. Prozialeck, Walter c. et. al. Kratom Policy: The Challenge of Balancing Therapeutic Potential with Public Safety. International Journal of Drug Policy. 2019, 70, 70-77.
5. Hassan, Zurina, et. al. From Kratom to Mitragynine and Its Derivatives: Physiological and Behavioral Effects Related to Use, Abuse and Addiction. Neuroscience and Biobehavioral Reviews. 2013, 37 (2), 138-151.
6. Brown, Paula, N, Lund, Jenna, and Murch, Susan. A botanical, phytochemical and ethnomedicinal review of the genus Mitragyna korth: Implications for products sold as kratom. Journal of Ethnopharmacology. 2017, 202 (18), 302-325.
7. https://katsbotanicals.com/the-different-strains-of-kratom/