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Research on Kratom

Kratom is under research for a range of uses, including in psychiatry thanks to possible antidepressant and antipsychotic properties, and treatment for acute and chronic pain, opioid use disorder, and various mental health conditions, including depression and anxiety. Scientists are also hoping to develop novel drugs based on kratom’s molecular structure that might treat alcohol use disorder, opioid use disorder, and pain more effectively.

A 2010 report in the International Journal on Drug Policy surveyed 136 active kratom users in Malaysia, The kratom users reported that it was readily available, affordable, and that even with prolonged use kratom had no serious side effects, but the researchers stopped with the survey. In other words, they did not test potential risks or health effects.

However, a 2014 survey of 293 regular kratom users published in Drug and Alcohol Dependence found that over half of the kratom users developed severe problems with dependence and kratom withdrawal symptoms including anger, sleep disruption, muscle spasms, and tension.

A 2016 study conducted on mice and published in the Journal of Medicinal Chemistry found that unlike other pain-relieving drugs such as morphine, kratom may not slow breathing as much. As respiratory depression is a leading cause of death during opioid overdoses, the researchers suggest that analogs may be part of a novel class of pain relievers, warranting further research.

A 2017 study in the Journal of Drug and Alcohol Dependence surveyed 10,000 current kratom users in the US in October of 2016. The researchers found that the main population of US kratom users were 31 to 50 years old with incomes of at least $35,000. They mainly used kratom for mood swings, pain, and opioid-related withdrawal symptoms, and 40 percent of respondents discussed their kratom use with their healthcare provider or other health care professionals. For both beneficial and negative symptoms there was a possible dose-dependent effect, and a low incidence of kratom-related toxicity requiring treatment of 0.65 percent.

Research into the potential for abuse of kratom from 2018 found that there was no documented threat to public health that would warrant emergency Schedule I status for kratom products, and such classification within the Controlled Substances Act itself carries risks of creating new and serious public health issues. The researchers also concluded that to ensure safe and appropriate use of kratom, appropriate FDA regulation would be vital.

Another Journal of Drug and Alcohol Dependence study, this time from 2018, conducted a systematic, comprehensive review of all studies of mental health and kratom use from 1960 to July 2017—for them, the present. They found that kratom has high potential as a harm reduction tool, particularly for people addicted to opioids. The researchers also found that kratom relieves anxiety and enhances mood among many users. Finally, they concluded that relative to those of opioids, kratom’s withdrawal symptoms appear to be mild, and that these symptoms are the lion’s share of kratom’s negative mental health effects, although abstinence can be difficult and withdrawal is highly uncomfortable for some users.

A 2018 study in Pharmacology presented a more complete pharmacological profile than we’d seen to date on this plant and its active ingredients. The researchers confirm that kratom leaves contain alkaloids which bind with opioid receptors, which explains the opiate-like effects of the plant. However, the 7-hydroxy- and mitragynine do not facilitate β-arrestin binding with the mu-opioid receptor, and for various reasons kratom and its alkaloids do not cause the kind of significant respiratory depression that makes opioids so dangerous. The researchers found that kratom is used as mood enhancer, as an analgesic, and to treat symptoms of opioid withdrawal. Finally, the team confirms the dose-dependent effects of kratom, with low doses of kratom causing stimulant effects and high doses causing analgesic effects.

However, a 2019 study in Pharmacotherapy reviewed kratom exposures reported by poison centers to the National Poison Data System and records from a county medical examiner’s office in the State of New York to identify deaths associated with kratom and determine toxicities associated with kratom use. They identified a total of 2,312 reported kratom exposures, with 935 cases involving only kratom reported. Most common reported effects were less serious, but serious effects were also reported, including withdrawal (6.1 percent), seizures (6.1 percent), and hallucinations (4.8%).

Contrary to other findings, this team reports respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%), but they also report only four deaths where kratom was listed as a contributing factor or cause. This leads us to conclude that their numbers do in fact include polysubstance and adulteration cases, bringing their findings, if not their conclusions that kratom poses a public health threat, into line with other results. However, it is a very useful compilation of a wide range of potential side effects that could be related to kratom.

An article from authors engaged in various aspects of kratom research, also from 2019, concluded that both animal and human studies “strongly suggest” that mitragynine, the main constituent alkaloid of kratom, and the plant itself, may manage symptoms of opioid withdrawal and alleviate pain. There are real concerns about how safe and high-quality imported kratom products are, but only more research and regulation can resolve them. Classification of kratom and the Mitragyna alkaloids as Schedule I controlled substances would only make these issues worse.

Results from a 2019 analysis of a 2017 online survey of 2,867 current users and 157 former users of kratom reported that kratom users often use the substance to treat conditions in place of opioids, including to treat pain and reduce existing opioid use. Users report high efficacy and a low incidence of adverse reactions to kratom, especially compared to opioids. The researchers conclude kratom may offer an alternative to opioids for some and suggest further study.

A 2020 National Institutes of Health study found opioid-like effects from kratom and suggested it may have a role to play in fighting the opioid epidemic.

A 2020 study in Drug and Alcohol Dependence reported on a cross-sectional, anonymous online survey that was conducted of 2,798 kratom users in 2017, almost entirely located in the US. The researchers concluded that middle-aged white Americans are the most frequent users of kratom, and that these users are treating symptoms of anxiety, pain, depression, and opioid withdrawal. Most are not using kratom as a recreational drug. Serious kratom-related adverse effects and SUD were rare despite regular use, which was typical. The team concludes that in light of the present opioid epidemic, additional research on kratom pharmacology and epidemiology is imperative.

A 2020 short report in Addiction endeavored to describe past-year prevalence of kratom use and characterize kratom users by using results from the Cross-sectional Survey of Non-medical Use of Prescription Drugs (NMURx) Program from parts of 2018 and 2019 and estimating behavior proportions. They estimated the past-year prevalence of kratom use in the US at 0.8 percent, and found that kratom users tended to have more serious substance abuse profiles than users of cannabis, alcohol or cigarettes, or non-users.

However, a response from January 2021, also in Addiction, calls the 2020 short report’s characterization misleading and argues they may be misinterpreted to support the notion that kratom use increases the risk of abusing other drugs, or to infer a cause-effect relationship between substance-use disorders and kratom use—neither of which exist. The authors argue that the current weight of evidence shows that kratom use tempers more problematic use of other more dangerous substances, and that its risks are substantially lower than those other drugs.

Finally, a 2020 study in Nature presented chemical profiles of 53 commercial kratom products to better assess their safety and efficacy in treating pain. The study demonstrates that kratom alkaloids have unique binding and functional profiles, suggesting probable pain management benefits. However, the team also found that all three tested kratom alkaloids inhibit select cytochrome P450 enzymes, suggesting a potential risk from polysubstance consumption when kratom is consumed with drugs metabolized by these enzymes. The researchers point out that further studies are needed.

A January 2021 study in Cellular and Molecular Biology tested claims of kratom’s effectiveness against opioid dependence and withdrawal by evaluating the ability of chronically administered kratom in several forms to induce hyperalgesia and produce physical dependence. The team tested a blended extract of kratom alkaloids and the individual alkaloids mitragynine (MG) and its analog mitragynine pseudoindoxyl (MP), in morphine-dependent mice. They suggest “some clinical value,” finding that all three ameliorated precipitated withdrawal and produced significantly less physical dependence in morphine-dependent mice.

A March 2021 study in Substance Abuse Treatment, Prevention, and Policy assessed the quality of available information on 51 eligible kratom websites in Canada. They found that overall mostly poor quality consumer health information was available online, with 78 percent of vendors getting 2 or less out of 5 as their score. They conclude that better information for consumers could improve health outcomes in Canada.

A study in the September 2021 Journal of Drug and Alcohol Dependence analyzed user-generated social media Reddit posts from 42 subreddits between June 2019–July 2020 to gain a more nuanced view into kratom use patterns and determine if descriptive, independent accounts mostly line up with prior findings from surveys of US kratom users. Results validated many prior survey findings and supported continued investigation. For example: kratom was often used as an opioid substitute or to self-treat opioid withdrawal; polydrug use with kratom was common; users perceive kratom as both lifesaving and potentially addictive and describe symptoms of kratom dependence and withdrawal in detail; and most kratom users are patients with pragmatic goals, not recreational users.

The bottom line here is that the latest research into kratom reveals that, although much more work remains, it is a much less risky substance than anything it replaces. Using safely-sourced kratom wisely is a low-risk activity for most people.

Author

  • Ed Markey

    Ed Markey is a former special education teacher turned psychedelics enthusiast. His goal is to help shine a light on the emerging potential of psychedelics to help improve people's lives--focusing especially on writing in-depth pieces, research based, to help educate those interested in how psilocybin, MDMA, ketamine, and more can potentially help improve mental health (when taken in conjunction with medical supervision, in states where it is legal to do so).