In his frequently hilarious and always engaging 2006 travelogue, Getting Stoned with Savages: A Trip Through the Islands of Fiji and Vanuatu, memoirist J. Maarten Troost describes his multi-year sojourn in a culture that kicks back after a long day’s spear fishing in the Pacific island sun with a rather unique herbal beverage. Think of it in the same way as Monday night football with beer and the guys in a local bar. A modern day anthropologist/adventurer, writer Troost details how ‘getting profoundly stoned each night is a venerable tradition’ in a sunset gathering in which ‘the most wretchedly foul-tasting beverage ever concocted’ is consumed by men in a sacrosanct ceremonial area known as a nakamal.(1) The herbal infusion in question – the semi-digested pabulum of root fiber and human saliva – is created by the efforts of prepubescent boys who chew and spit Piper methysticum, a shrub from the pepper family, into a wad of coconut fiber before squeezing out the solids and diluting the remains with water. Served in a coconut shell, the beverage – known to us as kava – is best enjoyed rapidly while focusing upon a particularly spectacular sunset. Or anything that would distract the drinker from the origins of the beverage, one imagines…

Currently the subject of a contentious review, kratom has been recently classified as an opioid and is therefore subject to Schedule 1 drug provisions.

Returning stateside, it’s easy to imagine Troost’s relief at finding kava available in a range of potencies and in sterile caplet form at many health stores and vitamin/supplement vendors. And that sort of relief is something that users of a similar botanical, kratom, hope to soon find if the Food and Drug Administration (FDA) can reverse its decision on the extract. Currently the subject of a contentious review, kratom has been recently classified as an opioid and is therefore subject to Schedule 1 drug provisions. But controversy rages around this classification with opponents emphasizing the plant’s use in aiding those who are dealing with opioid addiction and withdrawal.

Confused? So were we. At least initially…

The current administration has set the exploding ‘opioid crisis’ firmly within its regulatory cross-hairs, promising to ‘spend the money’ and ‘commit to fighting the drug epidemic and helping get treatment for those in need.’(2) In 2016 alone, opioid abuse took the lives of more than 64,000 people earning it the moniker ‘the epidemic of epidemics.’ And it is not a secret that opioid addiction results not only in an increased number of deaths among specific geographical and socio-economic demographics, but also in steeply increased costs to the healthcare system as a whole. In addition to the number of tragic deaths each year, the instances of drug-induced infections such as endocarditis has nearly doubled, and the cost of treating opioid patients has mushroomed to more than $15 billion. If that figure seems intimidating, it should. But it’s actually only one part of the problem. According to White House sources, the cost of treating the opioid crisis is more in the region of $45 billion although, writing for an article in Vox, Ella Nilsen notes that ‘experts say that’s just a quarter of what’s needed. If you take into account the costs of treating the diseases associated with addiction like hepatitis C and bacterial endocarditis, the number is closer to $186 billion over a decade.’(3)

But what if there was another tool in the arsenal against opioid addiction? According to advocates for kratom, there just could be.

…kratom is a plant within the coffee family, or Rubiacaea.

Lying ‘at the intersection of the debate between natural product and drug abuse,’ according to Alyson L. Wooten writing in Lexology, kratom is a plant within the coffee family, or Rubiacaea.(4) With sedative effects at high doses and stimulant effects as low ones, the plant also offers analgesic and anti-diarrheal effects. Anecdotally, it has also been said to be useful in managing restless leg syndrome, arthritis, and fibromyalgia. And  significantly, it is also purported to be useful in combatting opioid addiction. How? It’s time to delve deeper…

With a long lineage amongst indigenous peoples of its native tropical southest Asia where it is considered a safe and effective herbal supplement, kratom – or Mitragyna speciosa to give it its botanical name – contains two very interesting compounds: mitragynine and 7-hydroxymitragynine. A psychoactive component, 7-hydroxymitragynine is a terpenoid indole alkaloid, a substance that gives a derived product a signature aroma. Terpenoids such as cannabinoids, for instance, give cannabis its signature scent while curcuminoids, found in turmeric, render the powder that characteristic yellow-orange hue. And it is also an intercellular signal molecule – a chemical that facilitates communication between cells in order for them to understand their microenvironment in develop, to perform tissue repair, and to maintain immune responses.

…ingesting 7-hydroxymitragynine through kratom mimics the effect of opioid ingestion.

So apart from containing psychoactive compounds, how does kratom actually provide pain relief? Let’s take a look at the bio-chemistry involved…Both mitragynine and 7-hydroxymitragynine are known exogenous agonists for multiple receptors within the human body. Binding to opioid receptors, for instance, they stimulate the receptor to behave as if an opioid were present thereby inducing the same biological response. In short: ingesting 7-hydroxymitragynine through kratom mimics the effect of opioid ingestion but, as an agonist, is even more potent than morphine.(5) So switching to kratom from an opioid narcotic – whether one that is prescribed legally or otherwise –allows the user access to a safer substitute which can be more easily reduced over time without the dangers associated with actual opioid withdrawals.

As we’ve seen in other articles about supplements and nutraceuticals, compliance with the U. S. Food and Drug Administration’s (FDA) mandates regarding branding is critically important in terms of the ways in which a product is positioned within the market. Indeed, it has impacts even upon the legality of the product’s manufacture and retail. In order to be classed as intended for human consumption, any drug, supplement, or indeed food product must be labeled within compliance of FDA guidelines. And those guidelines are comparatively broad in scope. The Federal Food, Drug, and Cosmetic Act of 1938, for instance, establishes a definition of labeling to include any data affixed to the product and any written materials within the product wrapper or anything accompanying the product. Although clearly not foreseen by the framers of the act, this definition is now sufficiently expansive as to include information posted on a company’s website or ‘Likes’ generated via a social media post or update. And, as the law stands, even a ‘customer posting a testimonial on a manufacturer’s website about the benefit she got from consuming the product, if it is “liked” by the manufacturer, would count as “labeling” and could lead to a mislabeling charge.’(6)

So is the workaround simply to mark the product as ‘not for human consumption,’ or NFHC?

In kratom’s case, certain vendors have adopted exactly this stance, retailing the product in semi-anonymous, generic packaging without any detail on sourcing, usage, or contra-indications. Indeed, one of our in-house researchers obtained imagery of a bottle of kratom without product labels and a partial dosage data: ‘600mg/cap;100% kratom.’ The only other information on the product read: ‘This product is sold as a bulk botanical without directions or claims.’ And this lack of pharmacological detail is not only confined to information disseminated by the manufacturer, but also by the retailer. According to an article by the Botanical Education Alliance, retailers should be especially cautious about selling a product such as kratom when it is labeled as NFHC given that additional information contained a descriptor on how to steep the product for tea and how to smoke it in a pipe. Even shelf placement is an area of scrutiny – woe betide the retailer, for instance, who stocks their kratom teas adjacent to the stacks of Tazo or Tetley.

“Today, we notified a company making claims for a compound in kratom that its product is an unapproved new drug and an adulterated dietary supplement.”

Of course there are outliers, companies who defy FDA guidelines and make overt claims that kratom products are indeed dietary supplements. Industrial Chemicals LLC, makers of Mitrasafe, was one such company that incurred the wrath of the organization and, famously, was very rapidly closed down. In a statement excerpted online at Forbes.com, FDA Commissioner Scott Gottlieb is quoted as saying “Today, we notified a company making claims for a compound in kratom that its product is an unapproved new drug and an adulterated dietary supplement. The company is claiming that its product is a ‘natural substitute for opium,’ that it has ‘morphine-like effects,’ and that it can help relieve pain along with a litany of other ailments. Just as troubling, this company promotes kratom as effective in ‘curing addiction’ and treating ‘withdrawal symptoms.’ These unlawful practices not only mislead consumers, but can also prevent people suffering from addiction from seeking effective treatments. These claims are unproven and dangerous given the scientific evidence supporting kratom’s potential for abuse, addiction and serious health consequences, including death.”(7)

Especially galling to the FDA is not only the positioning of the product as a ‘new drug’ but the fact of its potential adulteration. In other words, contamination.

The FDA’s actions come hot on the heels of the Center for Disease Control and Prevention’s (CDC) warning in February that a multi-state outbreak of Salmonella was possibly linked with kratom products. As of March 1^st 2018, more than fifty cases of salmonella poisoning have been identified by the CDC across 27 states with patients ranging in age from 67 down to just 6 years old. Sixty percent of the affected were male and forty-five percent of patients were hospitalized. To date, no fatalities have occurred but the CDC is erring on the side of abundant caution by advising against consuming kratom in any form.(8)

…with most of the raw product coming from China or Thailand, this could represent an ideal opportunity for the creation of a stronger net of manufacturing guidelines and protocols.

It is especially troubling that no common brand or specific product has been identified as the source of the outbreak. But this puzzle could also offer an unexpected silver lining: with most of the raw product coming from China or Thailand, this could represent an ideal opportunity for the creation of a stronger net of manufacturing guidelines and protocols. Whilst it’s true that the FDA and CDC are recommending against the use of kratom in any form for any purpose, it is also the case that a market does already exist for these products. At least if they are guaranteed to be contamination-free. So the adoption of current Good Manufacturing Practices (cGMP) could make the difference for any manufacturer wishing to persuade the regulatory authorities of the U. S. that a course correction needs to be made. cGMPs ensure that environments are controlled and maintained to a certain standard of hygiene, that cross-contamination is prevented, that operators are fully trained and educated in procedures and processes, that correct records are kept, potentially defective products are quickly identified, and that – in the worst case scenario – recalls are issued swiftly and without delay.

Unlike the nascent cannabis products industry, there does not seem to be an interest on the part of kratom manufacturers to adopt cleanroom technology in ensuring the purity of their products.

At this point in time, the adoption of cGMP, Hazard Analysis and Critical Control Points (HACCP) protocols, and 3^rd party testing for dietary supplements such as kratom would all be voluntary on the part of players on a field in which product efficacy may not legally be claimed. Unlike the nascent cannabis products industry, there does not seem to be an interest on the part of kratom manufacturers to adopt cleanroom technology in ensuring the purity of their products. And given the official reluctance to permit the distribution of any kratom-related supplements, it is understandable that companies are slow to adopt such new technologies. But, it is worth noting that the argument has been made that the first major vendor to opt in to voluntary sanction, to 3^rd-party testing, and to transparency of protocols when it comes to its manufacturing processes and its hazard control and prevention will be the one that wins the (relative) favor of our governmental oversight bodies and the hearts of the supplement-hungry public.

And according to the National Center for Complementary and Integrative Health, in the United States we spend almost $13 billion (or a mean expenditure of $368 per person) out of pocket on natural product supplements such as vitamins and other nutraceuticals per year. That’s a significant market into which to gain access. And that doesn’t even begin to factor in those new customers seeking relief from the exploding opioid crisis. Perhaps it is indeed time to move beyond simply declaring a public health emergency and, in the carefully-scripted words of our president, to actually ‘spend the money.’

Love them or loathe them, we’re interested in your view of dietary supplements. Do you take them? Do you worry about their purity and safety? Please let us know in the comments!

Update: Kicking Back with Kratom – and Salmonella?

Reference:

1. Troost, J. Maarten, 2006, Getting Stoned with Savages: A Trip Through the Islands of Fiji and Vanuatu, p. 56
2. https://www.vox.com/policy-and-politics/2018/1/23/16909984/trump-opioid-epidemic-2017
3. https://www.vox.com/2018/3/6/16453530/america-opioid-crisis-epidemic-bacterial-endocarditis-hepatitis-c
4. https://www.lexology.com/library/detail.aspx?g=da4d6076-2d60-4ee2-b996-1a193cdcdaf1&utm_source=lexology+daily+newsfeed&utm_medium=html+email+-+body+-+general+section&utm_campaign=lexology+subscriber+daily+feed&utm_content=lexology+daily+newsfeed+2018-02-15&utm_term
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550469/pdf/13181_2010_Article_79.pdf
6. https://www.botanical-education.org/big-kratom-question-not-human-consumption-human-consumption/
7. https://www.forbes.com/sites/davidkroll/2018/02/27/fda-warns-against-launch-of-kratom-extract-mitrasafe-cites-misleading-regulatory-and-drug-claims/#6e6c8a1b2d5a
8. https://www.cdc.gov/salmonella/kratom-02-18/index.html