On the surface, kratom leaves are green, glossy, and unassuming. But within each leaf lies over forty alkaloids (Ellis et al., 2020), a class of naturally-occurring organic compounds. Two of these alkaloids, mitragynine and 7-hydroxymitragynine (7-HMG), are primarily responsible for the plant’s psychoactive properties (Cinosi et al., 2015).
The main difference between mitragynine and 7-hydroxymitragynine is potency. Research indicates that the pain-relieving potency of 7-HMG is 46 times higher than mitragynine and 13 times higher than morphine (Cinosi et al., 2015).
7-HMG is also the most controversial kratom alkaloid. In particular, the alkaloid’s high potency and potential for addiction have raised concerns among scientists and legislators. Nevertheless, this powerful alkaloid also appears to play a fundamental role in kratom’s effects — and without it, it’s likely that kratom wouldn’t function the same way.
If 7-HMG is an Alkaloid, What’s an Alkaloid?
Alkaloids are nitrogen-containing compounds that are present in 20,000 different molecules across 20% of all known vascular plants. They’re considered to be the primary source of kratom’s psychoactive effects (Matsuura et al., 2017).
Scientists believe that plants developed alkaloids to ward off predators (Matsuura et al., 2017). When herbivores eat plants that contain certain alkaloids, they can become sick. As a result, an herbivore might think twice before eating that particular plant in the future.
Don’t worry, though: while some alkaloids are toxic, alkaloids like mitragynine and 7-HMG aren’t inherently toxic to humans. In fact, while the term alkaloid might sound unfamiliar, you’ve probably consumed alkaloids before. Caffeine is a popular alkaloid present in tea and coffee, and nicotine is the primary alkaloid found in cigarettes. Both alkaloids are readily consumed and accepted in modern society (Matsuura et al., 2017).
What Does 7-HMG Do?
7-HMG is largely believed to be “a major contributory factor” for kratom’s pain-relieving properties (Cinosi et al., 2015). And yet, despite its potency, 7-HMG concentrations in natural kratom leaves are quite limited.
While the alkaloid content of kratom can vary, mitragynine is far more prevalent in natural kratom in comparison to 7-HMG. Scientists analyzing an alkaloid extract from Thailand kratom leaves found that mitragynine made up 66% of the total alkaloids while 7-HMG accounted for only 2%. However, the 7-HMG alkaloid content was believed to be much more potent, even in such a lower concentration (Hassan et al., 2013).
If 7-HMG is So Potent, is it Safe?
Although kratom has a well-established history in Southeast Asia as an effective means to enhance work productivity and relieve pain (Cinosi et al., 2015), the safety of 7-hydroxymitragynine is still being studied.
However, 7-HMG’s inconclusive scientific status hasn’t stopped some kratom vendors from fortifying their kratom powders and products with additional 7-HMG. And although stronger kratom products might seem like a win for consumers, scientists and regulators are more skeptical.
In one study, researchers tested several kratom products and found that some of them contained twice to four times as much 7-HMG as natural kratom leaves (Lydecker et al., 2016). They also noted that artificially increased 7-HMG levels could make kratom products more addicting.
After researching the addictive potential of mitragynine and 7-HMG, a different team of scientists concluded that 7-HMG had a “high abuse potential,” especially in isolated forms or high concentrations (Hemby et al., 2018).
In response, organizations like the American Kratom Association have lobbied for US states to restrict the amount of 7-HMG in kratom products to no more than 2% — the level present in natural kratom leaves.
Is 7-HMG an Opioid/Opiate?
Much like mitragynine, 7-HMG has opioid-like properties. However, scientists have asserted that it behaves differently from opioids and opiates.
Like opioids, 7-HMG binds to and activates μ-opioid receptors in the brain (Matsumoto et al., 2006). However, it only seems to act as a partial agonist, meaning that it doesn’t activate the receptor to the same extent as opioids or opiates (Kruegel et al., 2016).
Due to their similarities, many people use kratom to relieve opioid withdrawal symptoms. At present, no large-scale trials have investigated kratom’s effectiveness as an opioid alternative (Hassan et al., 2013). Still, a substantial portion of kratom users use it for this purpose (Garcia-Romeu et al., 2020), sometimes successfully (Boyer et al., 2008).
In small, natural quantities found in kratom leaves, 7-HMG appears to be a safe and effective mediator of kratom’s effects. Without it, kratom might not work as well or work the same way. However, consumption of 7-HMG in larger, unnatural quantities might carry an elevated risk of addiction and abuse. If you do decide to try kratom products that contain adulterated levels of 7-HMG, exercise caution by starting with small, controlled doses.
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Matsumoto, K., Hatori, Y., Murayama, T., Tashima, K., Wongseripipatana, S., Misawa, K., Kitajima, M., Takayama, H., & Horie, S. (2006). Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa. European Journal of Pharmacology, 549(1–3), 63–70. https://doi.org/10.1016/j.ejphar.2006.08.013
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Lydecker, A. G., Sharma, A., McCurdy, C. R., Avery, B. A., Babu, K. M., & Boyer, E. W. (2016). Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine. Journal of Medical Toxicology, 12(4), 341–349. https://doi.org/10.1007/s13181-016-0588-yDownload
Hassan, Z., Muzaimi, M., Navaratnam, V., Mohammad Yusoff, N., Suhaimi, F., Vadivelu, R., Vicknasingam, B., Amato, D., von Hörsten, S., Ismail, N. I. W., Jayabalan, N., Hazim, A., Mansor, S., & Müller, C. (2013). From Kratom to mitragynine and its derivatives: Physiological and behavioural effects related to use, abuse, and addiction. Neuroscience & Biobehavioral Reviews, 37, 138–151. https://doi.org/10.1016/j.neubiorev.2012.11.012Download
Ellis, C. R., Racz, R., Kruhlak, N. L., Kim, M. T., Zakharov, A. V., Southall, N., Hawkins, E. G., Burkhart, K., Strauss, D. G., & Stavitskaya, L. (2020). Evaluating kratom alkaloids using PHASE. PLOS ONE, 15(3), e0229646. https://doi.org/10.1371/journal.pone.0229646Download
Garcia-Romeu, A., Cox, D. J., Smith, K. E., Dunn, K. E., & Griffiths, R. R. (2020). Kratom (Mitragyna speciosa): User demographics, use patterns, and implications for the opioid epidemic. Drug and Alcohol Dependence, 208, 107849. https://doi.org/10.1016/j.drugalcdep.2020.107849
Cinosi, E., Martinotti, G., Simonato, P., Singh, D., Demetrovics, Z., Roman-Urrestarazu, A., Bersani, F. S., Vicknasingam, B., Piazzon, G., Li, J.-H., Yu, W.-J., Kapitány-Fövény, M., Farkas, J., Di Giannantonio, M., & Corazza, O. (2015). Following “the Roots” of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries [Research Article]. BioMed Research International. https://doi.org/https://doi.org/10.1155/2015/968786 Download
Matsuura, H., & Fett-Neto, A. (2017). Plant Alkaloids: Main Features, Toxicity, and Mechanisms of Action (pp. 243–261). https://doi.org/10.1007/978-94-007-6464-4_2