Kratom is one of my favorite plants and poisons. It ranks right up there with scopolamine and the Solanaceae plants it comes from. I talk about kratom in nearly every death investigation or drug talk I give – about two a year. But unlike scopolamine, it’s not the evilness of kratom that is alluring to me, rather I am drawn to it from the toxicology side of things. The history and pharmacology interests me, but the detection of it excites me. It keeps me on my toes, gives me something unusual to work on in the lab, and presents its own unique challenges. If you’ve heard of kratom before, it’s probably been framed around the words “herbal” or “natural.” If you’re a regular reader, you know that I do postmortem forensic toxicology – read: dead people. So if I’ve worked on it, it’s a pretty safe bet that it’s lethal. Sorry for the spoiler folks, I just wanted to throw that out there in the first paragraph. So if you stop reading now, and all you take away from this is “natural or legal or herbal ≠ safe,” then I’ve done my job for today. But do stick around and read the rest, it’s fun . . . and no more spoilers.

Kratom, Mitragyna speciosa, is an evergreen tree that grows in the tropical regions of southeast Asia, namely Thailand and Malaysia. In Thailand the tree is known as kratom, and in Malaysia is known as biak-biak (1). I’ll refer to it simply as kratom; it’s not nearly as fun to say as biak-biak, but it’s easier for me to type. Kratom belongs to the Rubiaceae family, a huge family of plants with over 13,000 species. Notable genera include Coffea and Cinchona, which gives us the drugs caffeine and quinine, so you know the Mitragyna genus holds something special, too.

Malaysians were first observed to use kratom as early as 1836, though they undoubtedly used it long, long before then. The locals were observed making it into a tea or by simply chewing on the leaves, delivering an opium-like effect (2). It wasn’t until 1921, however, that Ellen Field, from the Department of Medical Chemistry at the University of Edinburgh (Scotland), isolated the principle alkaloid, and named it mitragynine (3).

Early 1929 reports from the Government Laboratory of Siam (Thailand) state (4):

“According to the reports of the officials of the Revenue Department the chewing of kratom leaves is habit-forming. Addicts appear to be able to endure great fatigue and exposure to heat. The habit has not a bad reputation, like opium smoking, nor does there seem to be any progressive change in the condition of the addict or in his character. On the other hand, educated people avoid the habit.”

Endure fatigue and exposure to heat? Sign me up! I find it humorous – why I don’t know – that even in 1929 it was reported as relatively harmless, but that educated people avoided it. This is in stark contrast to cocaine, in which at first only the wealthy partook in the vice, but when the “lower” classes joined in, that’s when the prohibition started. But I digress.

Like most natural products, kratom contains many, many different chemicals – natural chemicals, there I go again. The two principle alkaloids are mitragynine and 7-hydroxymitragynine, which make up approximately 66% and 2% of kratom’s alkaloid content, respectively (5). These two alkaloids have been shown to work by way of the opioid receptors, much akin to morphine and oxycodone. It is most likely that, like morphine, they work specifically through the mu- and delta- opioid receptors. As such, they have sedating effects, as well as tolerance, addiction, opioid induced constipation, and respiratory depression. Pharmacologically, mitragynine is 4-times less potent than morphine, whereas 7-hydroxymitragynine is 10-times more potent than morphine (1). So while only making up a small percentage of kratom’s alkaloid content, 7-hydroxymitragynine packs a punch.

It is also worth mentioning that kratom appears to have stimulant properties in low doses, and was originally said to be cocaine-like (2). This reminds me of people in the Andes chewing on coca leaves to extract out cocaine, or people from Yemen or Somalia chewing on khat. In the talks I give I mention that taken like this – chewing on leaves – kratom is relatively safe, and less harmful than popping the Oxycontin prescribed by your doctor. But when “Westernized” – my catch-phrase for wretched excess – and concentrated and not taken as intended, it can lead to trouble. Fatal trouble.

An increasingly common “cocktail” made by youths in Thailand is dubbed the “4 x 100”, and sadly it’s not the track & field relay. This cocktail is made by boiling kratom leaves with Coca-Cola, cough syrup, and codeine – and sometimes other additives like alprazolam (Xanax) or anti-depressants – then served over ice in a highball glass (6). The results are often fatal as a toxicologist would suspect, as you are mixing several central nervous system depressants of unknown doses.

Here in the US, the “4 x 100” may not be popular, but kratom extracts are, in which the kratom leaves are ground, boiled, then evaporated, leaving behind the alkaloids that can than be made into a powder or dissolved further. The extracts are then sold as some factor of “X” – 8X or 20X – 8 or 20 times the alkaloid concentration of the same weight of kratom leaves. Definitely not what Nature intended. They are sold in “headshops” or online, and are legal in most states. I even have a large online distributor operating just down the highway – right next to a large Army base, imagine that – that sells kratom as “herbal blends” and “herbal remedies.” And like most of the so-called “legal highs,” kratom is not immune to catchy names.

Is kratom all bad, though? Well, if chewed like a Thai local, maybe not – though I certainly don’t recommend it. But there is also a growing number of people that believe kratom can help them deal with their opiate addiction (7). As an opiate itself, kratom is essentially acting as a “replacement therapy”, and you are just trading one opiate addiction, mitragynine, for another, usually heroin or oxycodone. This is how methadone treatment works, or buprenorphine. Does it work? It seems to for some, but again, I wouldn’t recommend it – but that’s just me.

Strangely enough, in Thailand and Malaysia, where kratom use is traditional, it has been illegal since 1943 and 1952. In the US though, where kratom is not traditional, and mostly sold as more dangerous concentrated extracts, it is completely legal. Neither kratom, nor its alkaloids are DEA controlled substances, and of this writing no state has banned kratom directly. Some states have tried to ban “synthetic drugs”, but since kratom and mitragynine are natural, these laws do not cover them. Kratom is on the DEA “watchlist,” so who knows what the future holds for it.

Despite the legality though, kratom can be lethal. So be careful, and remember, natural does not equal safe.

** UPDATE **

*** Featured image of Mitragyna speciosa by Ahmad Fuad Morad (CC BY-NC-SA 2.0) ***

References:

1. Adkins, Jessica E., Edward W. Boyer, and Christopher R. Mccurdy. “Mitragyna Speciosa, A Psychoactive Tree from Southeast Asia with Opioid Activity.” Current Topics in Medicinal Chemistry 11.9 (2011): 1165-175.

2. Jansen, Karl L.r., and Colin J. Prast. “Psychoactive Properties of Mitragynine (Kratom).” Journal of Psychoactive Drugs 20.4 (1988): 455-57.

3. Field, Ellen. “XCVIII. Mitragynine and Mitraversine, Two New Alkaloids from Species of Mitragyne.” Journal of the Chemical Society, Transactions119 (1921): 887-91.

4. “Siam. Report of the Government Laboratory.” The Analyst 54.641 (1929): 475-76.

5. Takayama, Hiromitsu. “Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna Speciosa.” Chemical & Pharmaceutical Bulletin 52.8 (2004): 916-28.

6. Chittrakarn, Somsmorn, Pimpimol Penjamras, and Niwat Keawpradub. “Quantitative Analysis of Mitragynine, Codeine, Caffeine, Chlorpheniramine and Phenylephrine in a Kratom (Mitragyna Speciosa Korth.) Cocktail Using High-performance Liquid Chromatography.” Forensic Science International 217.1-3 (2012): 81-86.

7. Boyer, Edward W., Kavita M. Babu, Grace E. Macalino, and Wilson Compton. “Self-Treatment of Opioid Withdrawal with a Dietary Supplement, Kratom.”American Journal on Addictions 16.5 (2007): 352-56.