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09/27/16

The Secret of Kratom

36473493 - tablet with the chemical formula of kratom (mitragyna speciosa) mitragynine. drugs and narcotics

© Vitally Vodolazskyy | 123rf.com

So you’ve never heard of kratom? A CDC study of kratom exposures reported to poison centers showed a tenfold increase from 26 in 2010 to 263 in 2015. If kratom becomes more widely known and used, those figures will be increasing. The CDC published a report on kratom on June 29, 2016, citing its potential as an “emerging drug of abuse.” The cited NIDA document, “Drug Facts: Kratom,” does not refer to it as an emerging drug of abuse as claimed, but it does say, “Like other opioid drugs, kratom may cause dependence.” The CDC report itself suggested it was an emerging public health threat.

Kratom use appears to be increasing in the United States, and the reported medical outcomes and health effects suggest an emerging public health threat. Members of the public and health care providers should be aware that the use of kratom can lead to severe adverse effects, especially when consumed in combination with alcohol or other drugs.

Kratom is a tropical tree-like plant native to Thailand, Malaysia, Myanmar and other countries in Southeast Asia. It has a long history of use as a stimulant in low doses. Kratom is often brewed as a tea, but it can also be smoked or swallowed in capsules. Southeast Asian laborers and farmers chew the leaves for energy to work harder and to relieve muscle strains. It has been used as a substitute for opium when opium is not available. And it’s used to manage opioid withdrawal symptoms. Long-term kratom use has produced anorexia, weight loss, insomnia, skin darkening, dry mouth frequent urination and constipation.

The DEA included kratom on its Drugs of Concern list and recently announced its intention classify kratom and two of its psychoactive chemicals temporarily as a Schedule I controlled substances. “The two chemicals are called mitragynine and 7-hydroxymitragynine. By banning the active chemicals, the DEA is making sure that both the plant and any synthetic versions of it are included in the new regulation.” STAT reported the DEA is authorized to temporarily place substances in Schedule I for up to two years when it believes they are a potential public health threat. If their studies demonstrate there is a threat, the ban will remain. If not, it will revert to being legal.

Like marijuana, it contains multiple alkaloids, but mitragynine and 7-hydroxymitragynine are the primary active one in the plant. At lower doses, it produces stimulant effects. Users report increased alertness, physical energy, talkativeness and sociable behavior. At higher doses, opiate effects, including sedation and euphoria occur. “Effects occur within 5 to 10 minutes of ingestion and last 2 to 5 hours.” The DEA announcement described the following health risks from kratom in some detail.

Several deaths associated with kratom have been reported, often when it is mixed with other substances. There are also reports of drug-induced liver damage, psychosis, seizures, weight loss, insomnia, tachycardia, vomiting, poor concentration and hallucinations. Fifteen of the reported deaths occurred between 2014 and 2016. There was a cluster of nine deaths reported in Sweden from a kratom product called “krypton.” See “Krypton Can Kill You.”

The CDC kratom study said 24.5% of the reports on adverse events were for minor complications; 41.7% required some treatment and were considered to be moderate complications. There were major complications—meaning life-threatening signs or symptoms, with some residual disability—for 7.4% of the kratom exposures. The adverse effects included: tachycardia [abnormally rapid heart beat] in 25% of the reported cases, agitation or irritability in 23.8%, drowsiness in 19.4%, nausea in 14.7% and hypertension in 11.7%.

A recent article in the International Journal of Legal Medicine by Warner, Kaufman and Grundmann reported the death of a young adult who had mixed kratom with prescribed medications—Prozac and Lamictal. Another article, “A Drug Fatality Involving Kratom,” noted a 17-year-old male with a history of heroin abuse and chronic back pain who died from a “possible Kratom toxicity.” He had mixed kratom, benzodiazepines and over-the-counter cold medications (containing DXM?).

In “Pharmacology of Kratom,” Prozialeck et al. found there was an increasing level of kratom use, especially among college students. They also noted a large number of online vendors and general information websites for kratom. An Internet search they did with Google had more than 2 million hits in February of 2012. When I repeated the search in August of 2016, I had over 6.36 million hits. Prozialeck et al. said their search of websites indicated kratom was being used for pain management as well as a recreational drug.

Kratom is regulated as an herbal product in the U.S. and is currently considered a legal substance, despite the CDC concern for its abuse potential. Along with the DEA declaration that there isn’t a legitimate medical use for kratom, this meant: “it cannot legally be advertised as a remedy for any medical reason.”

Pharmacologically, the mitragynine in kratom activates the μ, δ, and κ opioid receptors. Its main activity is on the μ receptor, the one that produces the analgesic and euphoric effects with opioids; and of course results in physical dependency. Despite kratom’s reputation as a “legal opioid,” there have been few scientific studies that addressed its psychoactive properties. Most of the available information is in anecdotal reports, like those on the website, Erowid.

Erowid has a plethora of Kratom reports categorized in groups such as: First Times, Combinations, Preparation/Recipes, Difficult Experiences, Health Problems, Addiction & Habituation, Mystical Experiences and Medical Use. A nondrinking male reported it caused liver toxicity in “Killing My Liver.” A more serious reaction resulted in a hospital stay for a drug–induced hepatic injury in “”Almost Destroyed My Liver.” Then there was a disturbing report under Addiction & Habituation called “This Thing Is a Secret.”

A man with a history of drug and alcohol addiction hadn’t used any “hard stuff” like heroin, alcohol, amphetamines or cocaine in five years. He was active in Alcoholic Anonymous. Then in January of 2005, he decided to order some kratom on a whim from an online vendor. When it kicked in, it had a “Definite opiate effect.” Nine months later, when he wrote his report for Erowid, he said he was using it daily. If he forgets to place his order in time, he’ll have to go a day without it. It was just like the withdrawals from his hydrocodone/Ambien habit.

His wife doesn’t know. No one knows, except the people he orders kratom from. He said he felt guilty spending family money of the stuff, but not guilty enough to stop. “Maybe I’ll quit some time, but for now, things are maintaining. It’s better than shooting heroin or oxycontin or any stuff like that…”

 Naturally, I don’t go around blabbing to my AA associates about how I am using this plant every day. They are some of the best people I have ever met and cherish their friendship. We have a saying in AA, ‘your secrets keep you sick.’ This Kratom thing is a secret.

Prozialeck et al. reported that as kratom use has expanded to Europe and the U.S., there have been increasing reports of individuals becoming physically dependent or addicted to kratom. Most of the published studies, like this one by McWhirter and Morris were case reports. They described a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. His withdrawal symptoms were consistent with mild opioid withdrawal: anxiety, restlessness, tremors, sweating and cravings.

Evidence suggests that kratom is being used extensively for both medical and nonmedical purposes. Recent studies have shown that kratom contains a variety of active compounds that produce major pharmacologic effects at opioid and other receptors. Kratom and kratom-derived drugs may potentially be used for the management of pain, opioid withdrawal symptoms, and other clinical problems. At the same time, serious questions remain regarding the potential toxic effects and the abuse and addiction potential of kratom. This issue is further confounded by the lack of quality control and standardization in the production and sale of kratom products. The possibilities of kratom products being adulterated or interacting with other drugs are also serious concerns. Until these issues are resolved, it would not be appropriate for physicians to recommend kratom for the treatment of patients. Nevertheless, physicians need to be aware that patients may use kratom or kratom-based products on their own. Further studies to clarify the efficacy, safety, and addiction potential of kratom are needed.

Regulating kratom presents issues similar to what we are now facing with marijuana. Both plants contain dozens of compounds with some potential medical use. Both are currently not viewed by the U.S. government as having any medical use.  Where marijuana’s classification as a Scheduled I controlled substance makes scientific research into its potential medical uses difficult, the limited use and knowledge of kratom contributes to it being understudied. Each also has one or two dominant psychoactive ingredients.

There is also a lack of quality control with both. The strength of THC or CBD in marijuana and mitragynine or 7-hydroxymitragynine in kratom can vary widely. Products containing these herbal substances cannot be guaranteed to carry similar doses of the active ingredients. And they are likely to have contaminants, such as pesticides, if grown commercially. The limited, scientifically reliable knowledge of their medical usefulness, and the lack of regulation with regard to that knowledge, results in a wide variety of anecdotal claims similar to past the age of patent medicines.

What is to be done? Federal funding of research into kratom’s potential medical uses needs to occur. The two-year temporary classification as Schedule I can be extended another year if more time is needed while the studies of it medical uses are completed. A permanent classification of kratom as a Schedule I Controlled substance seems inadvisable. Remember that hasn’t worked very well with marijuana. Future classification as a controlled substance seems reasonable, given its activation of the μ, δ, and κ opioid receptors. But let’s base it upon reliable scientific information.