Kratom

Kratom (Mitragyna speciosa), also known as ketum or kratum, is derived from the leaves of the Southeast Asian tree Mitragyna speciose. The leaves have been chewed for decades for its ability to fight fatigue. The tree shares the same plant family of Rubiaceae with coffee (1, 2).

Similar to the various types of ginseng that differ in their active components, the alkaloid content between the kratom plants of different geographical origin differs as well.

Kratom grows wildly and abundantly in the tropical forests where the mix of humidity, rainfall and sunlight is ideal for the growth of multiple strains. Indonesia, Thailand, and Bali are among the world's biggest exporters of kratom. Most variants of kratom are cultivated in one of these areas and denoted as such; other common types of kratom are known by location or origin and include Borneo and Malaysia.

Also Known As

Mitragyna speciosa, ketum, kratum

Quick Navigation

History of Kratom

Traditionally, kratom leaves are chewed or consumed in a capsulated form with the intent of overcoming fatigue and staying mentally focused, very similar to how many people use caffeine and nicotine. Reports suggest that this stimulant effect is only part of the equation, with higher doses being more associated with sedative and pain-relieving effects (3). While many manual laborers use the leaf for improved performance, many others have turned to kratom to avoid pain, to transition away from traditional opiates, and even as a tool to overcome withdrawal and addiction (1).

Kratom reemerged as an opium alternative in the early 20^th century, due to rising opiate costs. In place of opium or to ease the pain of withdrawal from such substances, kratom became a natural choice. (3, 4).

Benefits of Kratom

The main benefit of kratom is as a painkiller for those with acute and chronic pain. Kratom operates by behaving similarly with opioid receptors as morphine even though it is not an opiate itself [5]. This can be used in isolation for people with chronic back or joint paint, but is also useful for those who currently use opiates (whether prescribed or not) and desire being free from the drug without the withdrawal symptoms.

Kratom is thus used in some retreat centers (as well as recreationally) in order to treat withdrawal symptoms from opiate addiction [6]. Anecdotal reports suggest that the plant is calming and can have anxiety-reducing effects.

According to anecdotes and most case studies, a main benefit of kratom is the “kratom high”. People who experience this kratom high feel that it is a legal way to become intoxicated similar to opiates.

The main benefits, reducing addiction to alcohol and opiates as well as managing chronic pain, are not well researched and may come at a relatively high cost. Much of the existing research focuses on side effects and problems rather than the benefits. This may be a function of the government’s desire to reduce the usage, but is nevertheless worth noting.

How Does Kratom work for Pain?

Kratom’s leaves contain alkaloids that interact with opioid receptors throughout the body and brain in ways similar to actual opiates. There are over 40 different alkaloids in kratom, but only two of these are psychoactive. These alkaloids can stimulate opiate effects more potently than true opiates, which carries an increased risk of addiction and dependence on Kratom itself (5, 6, 7).

The three primary types of opioid receptors in the body are μ (Mu), δ (Delta), and K (Kappa), which have different actions depending on whether an agonist or antagonist stimulates them (agents that increase or inhibit activity, respectively) (12).

Kratom’s specific alkaloids mitragynine and 7-hydroxymitragynine (7-HMG) interact with the Mu and Kappa opioid receptors. In-vitro research suggests that Kratom’s primary alkaloid mitragynine is roughly 13 times more potent than morphine, and 7-hydroxymitragynine is considerably more potent than mitragynine (1). The alkaloid concentrations can vary depending on the strain; the Borneo variant is considered more sedative, for example, due to its heavy concentration of 7-hydroxymitragynine.

Mu Opioid Receptor Interactions

Mu receptors are primarily responsible for many of the pain-relieving benefits of opiates. When endogenous ligands such as endorphins and exogenous substances like morphine dock onto Mu receptors, they function as agonists by increasing the activity of these receptors. As a result, it has potent pain-relieving benefits. This is, of course, a primary reason that opiates are often prescribed for pain relief (13).

Unfortunately, stimulation of the Mu opioid receptor is a primary cause of dependence, tolerance, and ultimately addiction. With traditional Mu receptor agonists like morphine or heroin, stimulation of these receptors results in the up-regulation of proteins known as β-arrestins (15, 16).

Research suggests that while kratom’s alkaloids do indeed stimulate these Mu receptors, they do so in the absence of interacting with β-arrestins (16). Kratom acts only as a partial agonist of the Mu opioid receptor, displaying lower affinity than traditional opiates. This means that despite the potential for potent effect, these alkaloids function differently than traditional opioids like morphine (18).

Kratom’s potential for lessening opioid withdrawal and addiction is due to the interaction with the Mu receptor, similar to methadone (an effective treatment for heroin abuse) which also interacts with the Mu receptor. Since methadone interacts with Mu receptors, it eliminates the need to occupy those receptors with heroin, thus reducing the potential for withdrawal (19, 20).

Since kratom stimulates Mu receptors, it can provide similar pain-relieving effects while avoiding many of the other potential side effects associated with traditional opiate use.

Kappa Opioid Receptor Interactions

Kappa receptors, on the other hand, play a much different role by inhibiting neuropeptides like dynorphin. Dynorphin causes immense feelings of discomfort and pain. For instance, dynorphin levels rise in response to drug use, but also other stressful stimuli. As a result of activating or agonizing this receptor, one can expect to have feelings of discomfort, pain, and even traditional withdrawal symptoms associated with ceasing opioid use (14).

Stimulation of these receptors with the neurotransmitter dynorphin creates feelings of distress, discomfort, and even depression. Unsurprisingly, this interaction increases as a result of drug abuse and withdrawal (21).

Some research does suggest that kratom’s alkaloids act via inhibiting the kappa opioid receptor. This means that the alkaloids of kratom dock onto the kappa receptor, thus blocking the reception and action of dynorphin. This is theoretically the reason that many people use kratom for alleviating symptoms of withdrawal (14, 21).

Side Effects of Kratom

According to an import alert by the United States DFA, side effects of kratom can include nervousness, anxiety, agitation, hallucinations, constipation, nausea, and respiratory depression [9]. Again, evidence from the government requires a grain of salt, but it is telling that there are far more side effects than proven benefits.

The side effects of kratom can be potentially hazardous and uncomfortable for some. Others have severe kratom side effects from overusing the drug. While certainly biased given the state of Wisconsin’s recent banning of kratom, a State Medical Society publication in Wisconsin noted that a 37-year old woman suffered “severe opioid-like withdrawal syndrome” from using kratom. The review continued to argue against the use of kratom and the toxicity studies against the drug [7].

Indeed, within the western world toxicity is a rare and manageable problem, but includes death in some instances. Within the Brain Research Bulletin, a survey of the literature showed Southeast Asian cultures using kratom have none of these toxicity issues as the west [8].

Toxicity & Serious Side Effects of Kratom

There are a few cases where individuals using kratom have experienced tremor, seizures, and in some rare cases, death.

However, it’s important to distinguish that many of these cases include other substances as well, which raises concern over unknown interactions of kratom with pharmaceuticals of any sort. This is alarming because the National Institute on Drug Abuse suggests that more than 30 percent of opioid-related are a result of interactions with benzodiazepines (27, 28).

In one case, a young individual with a history of heroin use was found unresponsive. Blood analysis indicates that high levels of the primary kratom alkaloid mitragynine were found. However, this report also revealed levels of cold medications and benzodiazepines (27).

In a second report, a gentleman aged 64 years was found having a seizure after drinking kratom-infused tea and then also experienced a second seizure upon arriving at the hospital. It was, however, revealed that this individual was not only using kratom but also traditional opiates like oxycodone as well as antidepressants (29).

In a third case, a patient using kratom to manage opiate withdrawal experienced a seizure when mixing kratom with modafinil, a pharmaceutical often prescribed for treating narcolepsy (30, 31).

Clearly, our collective general understanding of drug interactions with kratom use is severely lacking. In more than one case we see extremely adverse effects when kratom is mixed with often-prescribed drugs.

According to the US Department of Health and Human Services, the number of reported exposure calls made to poison centers as a result of kratom use has increased exponentially over the past decade, rising from only a few calls in 2011 to more than 250 kratom-related calls in 2015 (8).

However, the lack of experimental human evidence does inhibit us from making firm conclusions here. Because there is no data with respect to how long-term use of kratom influences the body, it’s difficult to know if the increase in exposure reports is due to kratom being toxic or if there is simply an increase in the volume of usage.

If we compare the track record for a common over the counter pain-reliever such as Tylenol, for instance, the general consensus is that Tylenol is regarded as a safe substance for most cases. However, of the reported 60 million daily American users of Tylenol, this popular drug sends roughly 30-50 thousand people to the emergency room each year (9, 10, 11).

Amazingly, however, those 30-50 thousand cases represent less than 1% of all Tylenol users, and because of this reality, we consider the drug to be safe. Regarding kratom, however, it's difficult to say if the rise in exposure calls is simply because of an increasing number of users, like Tylenol, or because kratom alone is toxic.

The lack of primary research means that almost all conclusions about kratom are due to anecdotal reports, case studies, and surveys provided to regular users.

Addictive Potential

Kratom's ability to stimulate opioid receptors and alleviate withdrawal symptoms has led many to this seemingly miracle supplement. However, with almost no human data and some evidence to suggest a potential for addiction and dependence, a dangerous precedent has been set with widespread use despite an extremely limited breadth of knowledge on both safety and effectiveness. You will notice that any kratom you can purchase will be marketed as “not for human consumption”.

Considering that kratom alkaloids have a lower affinity for opioid receptors, the risk of addiction is indeed markedly lower than that of true opiates. However, if stimulating opioid receptors is considered to be a primary cause of dependence, it becomes clear that kratom does indeed have addictive potential (1).

Case reports confirm the addictive potential of kratom. One survey study conducted in 1975 with persistent kratom users suggests that despite beginning use with roughly three leaves of kratom per day, many had increased consumption to 10-20 or even 30 leaves of kratom daily, suggesting tolerance and dependence (24, 25).

Many Asian countries where kratom use is prominent have taken steps to ban the use of the popular substance. In addition to being indicative of the power of kratom, this ban has also generated practices often seen with other illicit drugs, in an attempt to increase potency.

In Thailand, where kratom use is illegal, an emergence of kratom users mixing the popular leaf with other substances like cough syrup and soda to increase potency has increased. Interactions with Kratom have not been studied (1, 23).

Unfortunately, reports on kratom users do suggest addictive tendencies for users. For many of these individuals, what once started as a therapeutic venture turned into escalating dosages and the manifestation of intense, opiate-like withdrawal symptoms upon attempting to cease use (5, 6, 7)

Kratom Strains and Conversion Chart

In order to buy kratom online, you need to be able to understand the different strains. If you have plans to use kratom for your own purposes, use this comparison chart to help guide you through the process.

How and Where to Buy Kratom

Kratom is difficult to find because of the legal status. For safety purposes, it is best if you purchase kratom on the internet. There are dozens of vendors online and many of them are reliable according to the reviews and anecdotes from people in online communities.

One method you might want to utilize is searching through Reddit kratom, which has plenty of evidence on how to buy kratom and where to buy kratom.

We currently recommend Coastline Kratom, which is headquartered in the United States (North Carolina) and has a customer service phone number if you need. If you are interested in purchasing Kratom from Coastline Kratom, you can do so here.

Legal Status of Kratom

Currently, kratom is not a scheduled substance, but it’s definitely on the FDA and DEA’s radars. Many different states and countries have gone so far as to ban the use and sale of the popular supplement, which is alarming (4, 26)

States that have limited or restricted kratom sales:

Arkansas
Alabama
Illinois (age restricted)
Rhode Island
Tennessee
Indiana
Wisconsin
Vermont

Note: there is more pending legislation at the time of this article.

International countries that limited, restrict, or prohibit kratom sale:

Australia
Burma
Denmark
Finland
Israel
Lithuania
Malaysia
Miramar
Poland
Romania
South Africa
South Korea
Sweden
Thailand
Vietnam
United Kingdom

In the United States, kratom is typically marketed as some sort of herbal product not for human consumption; in some cases, it is marketed as tea or simply an herbal powder.

The availability of kratom presents an issue for many individuals hoping to use it to avoid withdrawal or even end addiction to potent opiates like heroin. For instance, if a heroin user successfully transitions to kratom use alone, but kratom becomes illegal, is there a solution here?

This uncertainty regarding legal status presents a potentially dangerous cycle of users ingesting kratom to cease opiate use, only to relapse once kratom becomes illegal. The potential for changes in legal status should be strongly considered before using kratom to transition from other addictive drugs.

Selected Community Experiences

The community anecdotes and experiences are polarizing. There are many people who claim the effects were so powerful it saved their lives (from alcohol or opiate abuse). These people are often associated with the legal battle to maintain kratom’s legal status.

Other people have significant withdrawal symptoms and claim much suffering as a result. Thus, there is a heavy individualistic component to kratom consumption.

Case Report #1

In one case report, we see that kratom does indeed provide many of the pain-relieving effects often claimed, but also results in addiction, similarly to how one might become addicted to other substances.

In this case study, a middle-aged woman was experiencing pain from fibromyalgia. In an attempt to avoid classical opiates, she began using kratom successfully for pain relief.

As reported, however, short-term use turned into long-term use, sourcing higher potency kratom, escalating doses, and classic withdrawal symptoms upon attempting to cease using.

This case report suggests that regular use of kratom can lead to tolerance, addiction, and withdrawal upon attempting to abolish use (5, 7).

Case Report #2

In another case report, a young woman experienced severe acute withdrawal symptoms after avoiding the use of kratom for a single day.

In this case, a young female began taking kratom in small doses to improve endurance and reduce fatigue, as many kratom users do. However, this also led to her using higher doses of kratom in the evening, undoubtedly to induce its traditional opiate effects.

In this case, the subject was eventually consuming close to 40 grams of kratom, daily, which is roughly six times the standard dose of 5 grams.

However, upon losing her employment and access to kratom, she was forced to cease consumption, which ultimately led to a trip to the emergency room as a result of experiencing withdrawal symptoms including anxiety, body pain, extreme body temperature, and tachycardia (7).

Case Report #3

In a similar light, another case report exists where a middle-aged man with a history of alcohol dependence began using kratom regularly to reduce feelings of anxiety. Because the user was under the impression that kratom was effective, safe, and reportedly non-addictive, they began using kratom regularly.

After three years of regular use, the user was admitted to a detoxification center, in an attempt to end this long-withstanding habit of consuming upwards of 40 grams of kratom daily. In this case, the user experienced intense withdrawal symptoms, lasting upwards of four days, which included immense anxiety, chills, nausea, and overall pain.

Interestingly in this report, the user described their withdrawal experience as more difficult than ceasing alcohol use. The user also mentioned they began regularly attending narcotics anonymous, a therapeutic group setting to aid addicts in their attempts at recovery to overcome their cravings for kratom (6).

Some Thoughts on Kratom

I have never used kratom, but a friend spoke with me about his experience recently. He told me that it doesn’t really effect him much except as a relaxing agent to allow him to complete his professional work more easily.

It isn’t stimulatory for him, but it allows him to get out of his own way with anxiety, stress, or tension and just get the work done that he desires.

While I am not privy to the reasoning and debate, I imagine there is a reason the drug is being made illegal in regions of the United States. I remain skeptical about the U.S. FDA and DEA, but I suspect there is some valid concern if the states are starting to go after this drug.

Mansal Denton, Nootropedia Contributor

References--Parentheses

Hassan, Z., Muzaimi, M., Navaratnam, V., Yusoff, N. H., Suhaimi, F. W., Vadivelu, R., … & Jayabalan, N. (2013). From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction. Neuroscience & Biobehavioral Reviews, 37(2), 138-151.
Gibbons, S., & Arunotayanun, W. (2013). Natural Product (Fungal and Herbal) Novel Psychoactive Substances. In Novel Psychoactive Substances(pp. 345-362). Academic Press.
Warner, M. L., Kaufman, N. C., & Grundmann, O. (2016). The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. International journal of legal medicine, 130(1), 127-138.
Tanguay P (2011) Kratom in Thailand: decriminalisation and community control? Series on Legislative Reform of Drug Policies No. 13, Transnational Institute. https://www.tni.org/files/download/ kratom-briefing-dlr13.pdf. Accessed 24 Apr 2019
Galbis-Reig, D. (2016). A case report of kratom addiction and withdrawal. Wmj, 115(1), 49-52.
McWhirter, L., & Morris, S. (2010). A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence. European addiction research, 16(4), 229-231.
Stanciu, C. N., Gnanasegaram, S. A., Ahmed, S., & Penders, T. (2019). Kratom Withdrawal: A Systematic Review with Case Series. Journal of psychoactive drugs, 51(1), 12-18.
Anwar, M., Law, R., & Schier, J. (2016). Notes from the field: kratom (Mitragyna speciosa) exposures reported to poison centers—United States, 2010–2015. MMWR Morb Mortal Wkly Rep, 65(29), 748-749.
Yoon, E., Babar, A., Choudhary, M., Kutner, M., & Pyrsopoulos, N. (2016). Acetaminophen-induced hepatotoxicity: a comprehensive update. Journal of clinical and translational hepatology, 4(2), 131.
Nourjah, P., Ahmad, S. R., Karwoski, C., & Willy, M. (2006). Estimates of acetaminophen (paracetomal)‐associated overdoses in the United States. Pharmacoepidemiology and drug safety, 15(6), 398-405.
Budnitz, D. S., Lovegrove, M. C., & Crosby, A. E. (2011). Emergency department visits for overdoses of acetaminophen-containing products. American journal of preventive medicine, 40(6), 585-592.
Mansour, A., Khachaturian, H., Lewis, M. E., Akil, H., & Watson, S. J. (1988). Anatomy of CNS opioid receptors. Trends in neurosciences, 11(7), 308-314.
Pasternak, G., & Pan, Y. X. (2011). Mu opioid receptors in pain management. Acta Anaesthesiologica Taiwanica, 49(1), 21-25.
López, J. L. V., Schild, L., Günther, T., Schulz, S., Neurath, H., & Becker, A. (2017). The effects of kratom on restraint–stress-induced analgesia and its mechanisms of action. Journal of ethnopharmacology, 205, 178-185.
Yusoff, N. H., Mansor, S. M., Müller, C. P., & Hassan, Z. (2017). Opioid receptors mediate the acquisition, but not the expression of mitragynine-induced conditioned place preference in rats. Behavioural brain research, 332, 1-6.
Ma, L., & Pei, G. (2007). β-arrestin signaling and regulation of transcription. Journal of cell science, 120(2), 213-218.
Porter-Stransky, K. A., & Weinshenker, D. (2017). Arresting the development of addiction: the role of β-Arrestin 2 in drug abuse. Journal of Pharmacology and Experimental Therapeutics, 361(3), 341-348.
Havemann-Reinecke, U. (2011). P01-50-Kratom and alcohol dependence: Clinical symptoms, withdrawal treatment and pharmacological mechanisms-A case report. European Psychiatry, 26, 50.
Marsch, L. A. (1998). The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta‐analysis. Addiction, 93(4), 515-532.
Anderson, I. B., & Kearney, T. E. (2000). Medicine Cabinet: Use of methadone. Western Journal of Medicine, 172(1), 43.
Lalanne, L., Ayranci, G., Kieffer, B. L., & Lutz, P. E. (2014). The kappa opioid receptor: from addiction to depression, and back. Frontiers in psychiatry, 5, 170.
Prozialeck, W. C., Jivan, J. K., & Andurkar, S. V. (2012). Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. The Journal of the American Osteopathic Association, 112(12), 792-799.
Kratom (Mitragyna speciosa) drug profile. European Monitoring Centre for Drugs and Drug Addiction, January, 2015. http://www.emcdda.europa.eu/publications/drug-profiles/kratom. Accessed 24 Apr 2019
Suwanlert, S. (1975). A study of kratom eaters in Thailand. Bulletin on narcotics.
White, C. M. (2018). Pharmacologic and clinical assessment of kratom. The Bulletin of the American Society of Hospital Pharmacists, 75(5), 261-267.
Kratom. (n.d.). Retrieved from https://www.dea.gov/factsheets/kratom
Neerman, M. F., Frost, R. E., & Deking, J. (2013). A drug fatality involving Kratom. Journal of forensic sciences, 58, S278-S279.
National Institute on Drug Abuse. (2018, March 15). Benzodiazepines and Opioids. Retrieved May 9, 2019, from https://www.drugabuse.gov/drugs-abuse/opioids/benzodiazepines-opioids
Nelsen, J. L., Lapoint, J., Hodgman, M. J., & Aldous, K. M. (2010). Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure. Journal of medical toxicology, 6(4), 424-426.
Boyer, E. W., Babu, K. M., Adkins, J. E., McCurdy, C. R., & Halpern, J. H. (2008). Self‐treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction, 103(6), 1048-1050.
Modafinil Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing. (n.d.). Retrieved May 9, 2019, from https://www.webmd.com/drugs/2/drug-16962/modafinil-oral/details