Naturopathic Perspective

Saul Marcus, ND

Mitragyna speciosa (common name, kratom) is an herb from Southeast Asia. Traditionally, it has been used by workers to help them have more stamina during long workdays. A tea would be brewed from leaves, and consumed throughout the day. In this form, Mitragyna has been used safely for hundreds of years.

Over the past 20 years it has made its way into the Western market. Anecdotally, Mitragyna is able to do 2 things very well. It is a strong analgesic, thus used for chronic pain. It also helps people get off opioids. Kratom has thousands of advocates, and there are many testimonials from people who believe it has changed their lives for the better.

Kratom is also a controversial herb. The US Food and Drug Administration (FDA) claims it is associated with deaths, and has even attempted to ban it as a Schedule I drug. Any quick internet search will find many articles claiming that kratom is a dangerous natural opioid. This is partly due to its history. It was not sold as an herbal medicine in health food stores or by practitioners; rather, it was discovered by the smoke and head shop industry.

Just being sold in this market may have contributed to a perception that it is a dangerous herb, used simply to get high. What is worse is a history of low quality and adulterated products. For example, in 2009, 9 deaths in Sweden were reported from people using a kratom product sold as “Krypton.” This was not pure kratom. It was intentionally adulterated with an opioid analgesic, O-desmethyltramadol.¹ 

On the other side of the controversy are thousands of kratom consumer advocates who want kratom available as a life-saving herbal medicine. Both sides have flooded the internet with information supporting their perspectives, which creates a confusing situation for those simply looking for reliable information.

This controversy came to a head on August 31, 2016, when the Drug Enforcement Administration (DEA) published a Notice of Intent to place 2 alkaloids in kratom – mitragynine (MG) and 7-hydroxymitragynine (7-MG) – on the list of banned, Schedule I substances.² They cited 33 deaths associated with kratom use as the reason for doing this. The scheduling notice included reference to the 9 deaths in Sweden without ever mentioning that the product responsible for those deaths was adulterated.²

A large grassroots effort to fight the ban followed this proposal. On October 14, 2016, the DEA withdrew the scheduling notice.³ It asked the FDA to create, by December 1, 2016, an “expedited 8-factor analysis (8-FA)” to justify scheduling of kratom. The FDA failed to do this. However, in response, the American Kratom Association (AKA) did. For an extremely detailed review of the history and safety of kratom, this 126-page document is available on their website.⁴

Facts Taken Out of Context

There are some common arguments made by people who believe kratom is dangerous and should be banned. These are that it is an opioid, it is deadly, and it is addictive. In the following, I will review these points.

Mitragyna contains over 25 different alkaloids, which give it its medicinal properties. MG and 7-MG are the 2 most well known of these alkaloids. MG makes up about 60% of total alkaloids, and 7-MG about 2%. Much less is known about the other alkaloids. Since kratom is typically not standardized to either of these alkaloids, the actual percentages can vary from product to product.

Our bodies contain 4 different types of opioid receptors, including delta, kappa, mu, and nor. Both MG and 7-MG are mu-opioid receptor agonists. However, this does not make kratom an opioid. As defined by the Controlled Substances Act, opioids are substances having “an addiction-forming or addiction-sustaining liability similar to morphine or [being] capable of conversion into a drug [with such liability].”⁵

Black cohosh is a mu-opioid receptor agonist. Yet no one is claiming it is dangerous, addictive, potentially fatal, and should be banned.⁶

Interestingly, in a study conducted on the effect of these alkaloids in rats, it was found that, “MG [the main kratom alkaloid] does not have abuse potential and reduces morphine intake, desired characteristics of candidate pharmacotherapies for opiate addiction and withdrawal.”⁷ So, the research seems to confirm what is known from anecdotal use: kratom is not addictive.

To be fair, that same rat study found that isolated 7-MG does have high abuse potential in rats. Keep in mind that 7-MG makes up only 2% of aklaloid total.⁷ Nature somehow decided to give us kratom with about 30 times more MG than 7-MG.

Pharmacological research is often quoted out of context. It is easy to find statements that kratom’s alkaloids are 5 or 13 times more potent than opioid drugs. These numbers are repeated by different articles and websites that reference each other. Articles are written to give the reader the impression that using kratom as a whole herb is multiple times stronger and more dangerous than actual opioid drugs.

Getting back to the original research, this perspective is based on studies in which isolated alkaloids are injected into rodents. Twitch response and reaction to pain stimuli are then measured.⁸ Rodent research does indicate an addictive and opioid-like effect from the 7-MG alkaloid. So how much kratom would a person have to consume in order to get this effect?

Isolated alkaloids from Mitragyna are not readily available. Research labs may have the equipment and expertise to extract the alkaloids, but it is not realistic for a typical consumer to do this. Unlike substances typically used to get high, kratom is not injected or smoked. In the United States it is most often sold as bulk powdered leaves or capsules. Occasionally, it is sold as a tincture.

Since the oral route is the only one available to consumers, huge quantities of kratom would need to be consumed in order to match the effect in animals that are injected with isolated alkaloids.

The AKA 8-FA cites research that demonstrates how much kratom a person would need to consume to get a morphine-type reinforcing dose of the alkaloid MG.⁹ The result came to 200 grams for MG, which makes up 60% of kratom’s alkaloids. There is about 30-times less 7-MG in kratom. Someone would need to consume literally thousands of grams of kratom in order to get a reinforcing dose of 7-MG. It is beyond the scope of this article to go through the math in detail; however, the AKA 8-FA is freely available online for anyone who wishes to look over it.⁹

Taking a few too many grams can cause symptoms such as nausea or upset stomach. The oral dose of kratom required to potentially mimic the effect observed in animals injected with isolated alkaloids is impossible to achieve.¹⁰

Regardless, websites still warn the public that “7-hydroxymitragynine is 13 times more potent than morphine milligram for milligram,”¹¹ and without any comment on how unrealistic it is to get the same milligram dose of isolated 7-MG.

Misleading Press Releases

An understanding of MG and 7-MG may also be important in understanding laws surrounding kratom.

An Arizona bill regulating kratom, which passed in 2019, limits the amount of 7-MG in kratom products to 2%. The bill also forbids sales of kratom to minors and establishes that the percentages of MG and 7-MG must clearly be labeled on kratom products.¹²  

The FDA has cited numerous deaths associated with kratom. In actuality, these deaths have occurred in people with underlying medical conditions and/or who were engaged in polydrug use with medications such as opioids. This is why you will always read “associated with kratom.” Association does not prove causality.

I found the following report a good example of the types of deaths which have been associated with kratom. A 2018 case study is headlined “Fatal mitragynine-associated toxicity in Canada.”¹³ The article describes a 56-year-old woman who died after using a kratom product. She also had a history of COPD, developed bronchopneumonia, and was prescribed acetaminophen with oxycodone. Investigation showed that she has used many more pills than directed in the prescription. The toxicology report found blood levels of oxycodone at 0.19 mg/L (lethal reference value: >0.21 mg/L). Other substances found in her system were lorazepam and significant amount of mitragynine. The investigators concluded that it was “a case of accidental death secondary to multidrug toxicity whereby mitragynine toxicity is primarily implicated.”¹³

We do not know if mitragynine had a synergistic effect with the illnesses and other substances this woman was using. It is all speculation. What we do know is that a woman with COPD and bronchopneumonia took what would have been, by itself, a near-fatal dose of acetaminophen/oxycodone and died. Yet the article headline primarily implicates kratom.

Mitragyna does not recruit beta-arrestin to opioid receptors. This is the mechanism by which opioid drugs purportedly cause respiratory depression.¹⁴

A well-publicized case from 2014 is that of Ian Mautner – a young man with a history of emotional issues and drug abuse. At 19 years of age he jumped to his death in Florida. The media sensationalized the story, claiming that it was kratom addiction that led to his suicide. His mother, Linda Mautner, had since been advocating against kratom.¹⁵

This case was covered in the documentary film about kratom, Leaf of Faith. What is not made clear is why, with everything going on in this young’s man life, kratom has been singled out as the cause of his suicide?¹⁶  

Data from the National Survey on Drug Use and Health (NSDUH) is used to monitor substance-use trends and to estimate the need for treatment and inform public health policy. In 2018, the NSDUH reported opioid misuse among 10.3 million people aged 12 or older within the past year.¹⁷ There was no mention of kratom anywhere in the report.

How is it that kratom is both a dangerous, addictive opioid substance – which should perhaps be banned as a Schedule I substance – and at the same time is used by millions of people but goes unnoticed by a government system designed to track trends in drug addiction?

From 2011 to 2017, there were 1807 cases of calls to poison control centers about kratom. However, for the whole category of herbs and dietary supplements, there were 275 000 such calls about dietary supplements from 2000 to 2012.^18,19

The Importance of Education

Reporting calls to poison control centers about kratom as cause for alarm, without reference to the whole dietary and supplement industry, is taking the facts out of context. As naturopathic doctors, we should be aware that herbs are not always safe. Even generally safe herbs can have adverse effects when used improperly or by the wrong person.

People who use herbal medicine can experience adverse effects. Much of the solution to this is proper education and guidance on how to properly use herbs. This is currently significantly lacking when it comes to kratom, which although widely used, is not well known among natural healthcare practitioners.

One of the interesting observations in the AKA 8-FA is that kratom is traditionally used to enhance occupational demands and social functioning. It does not inhibit people’s ability to work, as taking actual opioid drugs do. If someone is looking for a drug to help them escape from life, kratom is a very bad choice. Other drugs, such as alcohol, cannabis, or opioids, will suit that purpose much better.

The 8-FA likens kratom to coffee and tea – a stimulating herb that helps people get through the day. Like coffee, it is also possible to develop a dependency on it. Practitioners should be aware of this, and it may be best to caution individuals regarding the amount of kratom they use, so as to avoid the development of a dependency. A dependency like that with coffee implies symptoms of tolerance and withdrawal. Addictive substances are also associated with behavioral changes. An addiction causes irrational behavior when addicts no longer have the drug in their system. We do not see kratom cause changes in personality.

One of the frustrating things about researching kratom is that it is not part of the traditional herbal library with which we are most familiar. It was never used in Europe, nor do we have descriptions from Ayurveda or TCM that go back hundreds of years.

Therefore, I do think some caution is warranted with kratom. If someone comes in with low energy during the work day, I’m not going to recommend kratom over other herbs such as ashwagandha or rhodiola, which we know so much more about.

However, if someone is using this herb and feels benefits from it, they should not be given wrong information about its supposed dangers.

The potential dangers of kratom must be balanced with its benefits. Opioid addiction and chronic pain are serious issues. Naturopathic doctors should be aware of kratom and that it has anecdotally helped thousands of people who otherwise do not have easy solutions for these problems.²⁰ For many people, this is a life-saving herb.

A confusing aspect of kratom is the variety of strains it comes in. Some online retailers carry dozens of different strains, each with supposedly different qualities. Dosing recommendations can also vary widely.

In a 40-minute discussion I had with the head of kratom wholesaler, I was told the following: There are really just 4 different types of kratom. The white and green strains are similar, and are the best strains for boosting energy and enhancing mood. These strains have higher amounts of MG and 7-MG alkaloids. Red kratom is higher in other alkaloids and is the best for pain. Yellow kratom, which is fermented and dried longer, is in between these other strains in terms of effects. Dosing should be individualized. He recommended that people take the minimum amount that works for their symptoms. Once the right dose is found, taking more will not produce better results.

Due to problems with quality and adulterated products, the AKA has recently started a GMP standards program.²¹ Getting products through companies that are approved by this program is one way to insure a high-quality product.

Closing Comments

In summary, Mitragyna speciosa has been an unfairly maligned herb. It is time for kratom to leave the smoke shops and be treated just like any other herbal medicine. Thousands of people claim that this herb has changed their lives for the better. People will be coming into your office either asking about it or already using it. Naturopathic doctors need to be familiar with kratom.

References:

1. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol. 2011;35(4):242-247.
2. Federal Register. Schedules of Controlled Substances: Temporary Placement of Mitragynine and 7-Hydroxymitragynine Into Schedule I. August 31, 2016. Agency/Docket No. DEA-442. Document Number: 2016-20803. Available at: https://www.federalregister.gov/documents/2016/08/31/2016-20803/schedules-of-controlled-substances-temporary-placement-of-mitragynine-and-7-hydroxymitragynine-into. Accessed December 5, 2019.
3. U.S. Department of Justice. Diversion Control Division. Rules — 2016. Withdrawal of Notice of Intent to Temporarily Place Mitragynine and 7-Hydroxymitragynine Into Schedule I. October 13, 2016. Available at: https://www.deadiversion.usdoj.gov/fed_regs/rules/2016/fr1013.htm. Accessed December 5, 2019.
4. American Kratom Association. Kratom Eight Factor Analysis [document link]. 2019. Available at: https://www.americankratom.org/science.html. Accessed December 5, 2019.
5. U.S. Department of Justice. Diversion Control Division. Title 21 United States Code (USC) Controlled Substances Act. Subchapter I — Control and Enforcement. Available at: https://www.deadiversion.usdoj.gov/21cfr/21usc/802.htm. Accessed December 5, 2019.
6. Reame NE, Lukacs JL, Padmanabhan V, et al. Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause. 2008;15(5):832-840.
7. Hemby SE, McIntosh S, Leon F, et al. Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine. Addict Biol. 2010;24(5):875-885.
8. Matsumoto K, Hatori Y, Murayama T, et al. Involvement of μ-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragn speciosa. Eur J Pharmacol. 2006;549(1-3):63-70.
9. Pinney Associates. Assessment of Kratom under the CSA Eight Factors and Scheduling Recommendation. November 28, 2016. Available at: https://d3n8a8pro7vhmx.cloudfront.net/americankratomassociation/pages/21/attachments/original/1485630505/Henningfield_Eight_Factor_Analysis.pdf?1485630505. Accessed December 6, 2019.
10. Henningfield JE, Fant RV, Wang DW. The abuse potential of kratom according to the 8 factors of the Controlled Substances Act: implications for regulation and research. Psychopharmacology (Berl). 2018;235(2):573-589.
11. White CM. The Dangers and Potential of ‘Natural’ Opioid Kratom. November 29, 2017. UConn Today Web site: https://today.uconn.edu/2017/11/dangers-potential-natural-opioid-kratom-2/#. Accessed December 5, 2019.
12. Bossman. What You Need to Know About Arizona’s Kratom Consumer Protection Act.  August 1, 2019. Available at: https://kratomspot.com/what-you-need-to-know-about-arizonas-kratom-consumer-protection-act/. Accessed December 6, 2019.
13. Wang C, Walker AE. Fatal Mitragynine-Associated Toxicity in Canada: A Case Report and Review of the Literature. Acad Forensic Pathol. 2018;8(2):340-346.
14. Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology. 2018;134(Pt A):108-120.
15. Kemp P. Did Kratom Kill Ian Mautner? 2014. Speciosa.org Web site. https://speciosa.org/did-kratom-kill-ian-mautner/. Accessed December 6, 2019.
16. Kratom.com. News n Views. Official Trailer for the documentary “A Leaf of Faith.” January 13, 2019. Available at: https://kratom.com/en/trending/a-leaf-of-faith-documentary-official-trailer/13-01-2019. Accessed December 6, 2019.
17. SAMHSA: Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2018 National Survey on Drug Use and Health. August 2019. Available at: http://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHNationalFindingsReport2018/NSDUHNationalFindingsReport2018.pdf. Accessed December 6, 2019.
18. Post S, Spiller HA, Chounthrirath T, Smith GA. Kratom exposures reported to United States poison control centers: 2011-2017.Clin Toxicol (Phila). 2019;57(10):847-854.
19. Rao N, Spiller HA, Hodges NL, et al. An Increase in Dietary Supplement Exposures Reported to US Poison Control Centers. J Med Toxicol.2017;13(3):227-237.
20. Pinney Associates. Assessment of Kratom under the CSA Eight Factors and Scheduling Recommendation. November 28, 2016: pp 75-126. Available at: https://d3n8a8pro7vhmx.cloudfront.net/americankratomassociation/pages/21/attachments/original/1485630505/Henningfield_Eight_Factor_Analysis.pdf?1485630505. Accessed December 6, 2019.
21. American Kratom Association. AKA Good Manufacturing Practice (GMP) Standards Program. AKA Web site. https://www.americankratom.org/abou-aka/akagmpprogram.html. Accessed December 6, 2019.

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Saul Marcus, ND, is a 2009 graduate of the University of Bridgeport College of Naturopathic Medicine (UBCNM), and is licensed in the state of CT. He has a private practice in New York City. His website is saulmarcusnd.com.