Kratom is an old drug, although its recent popularity on the world stage has been helped by the opioid crisis and the claims that it can help with opioid withdrawal. Being first isolated in 1921, its chemical structure was not fully identified until 1964. However, it has been used by people in Southeast Asia for hundreds of years for its stimulant effects, as well as its supposed help with reducing opium withdrawal symptoms.
More recently it has made a comeback in Thailand, in particular, through a cocktail referred to as “4×100” which is very popular among religious youths. The name refers to its 4 ingredients: kratom leaves, cough syrup, Coke, and ice. It’s gained significant popularity among religiously observant people who choose to abstain from alcohol use.
WHAT IS KRATOM?
Kratom is typically rendered in a powdered extract which is refined from the leaves of the mitragyna speciosa tree native to Southeast Asia. It can be bought as a powder, tablet, whole leaf, or purified extract. Many people will make tea from the powder or whole leaves, or just mix the powder into a drink and drink it. The specific doses are hard to measure exactly because of the differences in kratom form as well as the particular soil conditions, refinement method, and storage conditions affecting the levels of the active ingredient mitragynine. Typically between 1 to 5 grams of raw leaves will produce moderate stimulant effects while 5 to 15 grams are said to produce opioid-like effects. The higher the dose, the greater the effect, as well as the greater the risk of serious unwanted side effects.
While clinical studies have yet to clearly define these effects, kratom does appear to show some signs of producing stimulant, sedative, anorectic (appetite reducing), and minor analgesic (pain relieving) effects. In addition, it shows signs of inhibiting inflammation, vascular permeability, and possibly enhancing immune function. These potential benefits are outweighed by the side effects which can pose very serious health risks. Also, the different types of kratom are rumored to produce varying levels and modes of intoxication.
TYPES OF KRATOM
There are several different types, or strains, of kratom which are rumored by users to produce a variety of effects. Aside from the strains, there are subcategories referred to as “veins” which come in 3 colors: red, green, and white. While there is currently minimal research done on the effects produced by different strains or veins, rumors abound as to the effects of each. These rumored effects include:
- Thai: Green and White are said to produce a euphoric high as well as act as a stimulant. Red is said to help dampen pain.
- Maeng Da: Originating in Thailand, Maeng Da will supposedly act as a stimulant while also reducing anxiety and acts as a painkiller.
- Malaysian: Reported to act as a stimulant, provide pain relief, and produce mood enhancement.
- Green Malay: Supposedly acts as a stimulant as well as assisting with concentration or focus.
- Borneo: Said to be more sedating in its effects than other strains.
- Indo: Also said to be more of a downer, this strain supposedly promotes relaxation, pain relief, and serenity.
- Bali: Reported to be a more effective pain reliever than other strains.
- Kali: Green is said to act as a stimulant with minor pain relief. White is said to produce euphoria and promote relaxation.
The medical use of kratom is a very contentious subject within the medical community. There are those who believe that kratom can offer minor therapeutic benefits, as well as those who are much more cautious as it has already resulted in deaths through overdose and it is clear that it does have a potential for abuse. Much more research is needed before a definitive and factually supported position can be taken by the medical community and government, but in the mean time, proceed with caution.
The exact way kratom works has yet to be clearly understood and research is still ongoing. What is known, however, is that there are over 40 biologically active compounds present in kratom, the most potent of which are mitragynine, its major metabolite 7-Hydroxymitragynine (7-HMG), and mitragynine pseudoindoxyl (MPI). These metabolites are the most active known compounds in kratom. The way the plant is processed can affect the balance and total quantities of these drugs in the final kratom product, be it whole leaf, powder, capsule, or tablet. Some of the different extraction and processing methods include a methanolic extract being the most active, a water-based extract close behind, and an acid extract being the least potent. Depending on the purity of the kratom and the way it was processed, the effects can be quite different.
While the potency of mitragynine is up for debate, its painkilling effects (including those of MPI & 7-HMG) are mainly due to μ-opioid receptor stimulation, regardless of their other interactions. It is known that mitragynine and its metabolites interact with several neurotransmitters and non-opioid receptors in the nervous system. Mitragynine also causes skeletal muscle relaxation through interactions at the nerve-muscle junction. In addition, MPI has known inhibitory effects on the gastrointestinal tract leading to opioid-like constipation as well as partial paralysis of male genitalia (specifically the vas deferens).
How Does Kratom Get You High
The effects of kratom are dose-dependent, which means that doing small amounts will produce stimulant-like effects while doing larger doses produces an opioid-like effect. The reason for this is not exactly clear, but the fact that different “strains” seem to have a proclivity for either stimulant or opioid type effects suggests that the particular balance of active compounds such as MPI and 7-HMG seems to play a role in the effect produced.
The way mitragynine works is very complex, in that it stimulates opioid receptors weakly but also interacts with serotonin and norepinephrine receptors. 7-HMG, while a more potent opioid receptor stimulator than mitragynine, is both present in the raw kratom plant and produced from the human body’s metabolism of mitragynine. Another interesting fact is that the painkilling effect of mitragynine is strangely more pronounced when taken orally as opposed to injected. This suggests an additional metabolite is produced during first-pass metabolism that may contribute to the painkilling effects. Strangely, injecting mitragynine straight into the brain of mice produced a similar painkilling effect as when taken orally. This also suggests that further metabolism may actually take place in the brain itself.
While there are thorough and ongoing animal studies to investigate the way kratom works, little is currently known about the exact ways kratom can produce the variety of effects observed in humans, and further research and clinical studies are needed to better understand this strange drug.
Stimulant-Like Kratom Effects
Low doses of kratom can produce stimulant-like effects such as increased energy and decreased appetite. The mechanism for this is currently unclear, but more than likely has to do with mitragynine’s effect on neurotransmitters such as serotonin, norepinephrine, and dopamine. While the overall effects are similar to other stimulants, kratom can produce secondary effects that are strangely opposite of many stimulants, such as constricted pupils as opposed to dilated pupils. Taking smaller amounts of kratom can produce effects including:
- Diaphoresis (Excessive Sweating)
- Decreased Appetite
- Elevated Mood or Euphoria
- Increased Concentration or Focus
- Increased Energy and Endurance
- Tingling in the Extremities
- Tremors or Shaking
- Increased Heart Rate and Body Temperature
Opioid-Like Kratom Effects
While it seems that mitragynine may be responsible for the stimulant like effects, 7-HMG and MPI are most likely responsible for the opioid-like effects. 7-HMG is 13 times more potent than morphine, while MPI is 20-times more potent than morphine as a painkiller. When taking medium-to-large doses of Kratom, it seems that the effects of 7-HMG and MPI become more dominant and overpower the stimulant effects of mitragynine. These two metabolites bind to the same opioid receptors in the brain as do traditional opioids, particularly the μ-opioid receptor, so the effects felt are very similar to those of classic opioid drugs. These effects can include:
- Reduced Anxiety and A Sense of Calm
- Reduction in Pain or Discomfort
- Drowsiness or “Nodding Off”
- Extreme Muscle Relaxation
- Lowered Heart Rate
- Depressed Breathing
- Delayed Orgasm (particularly in men)
Several less active compounds from kratom can lead to secondary effects through means other than opioid receptor activity. These are considered analogues of mitragynine and can include:
- Speciogynine: Contributes to skeletal muscle relaxation in a way irreversible by naloxone as well as partial gastrointestinal paralysis.
- Speciociliatine: Contributes to skeletal muscle relaxation in a way irreversible by naloxone as well as produce partial paralysis of muscles through inhibition of acetylcholine signaling.
- Paynantheine: Contributes to skeletal muscle relaxation in a way irreversible by naloxone as well as partial gastrointestinal paralysis.
Through similarly unknown means, it has been shown in rodents that chronic Kratom use can degrade working memory in mice, such as spatial orientation and cognitive behavioral function. In addition, use of high doses of kratom has been shown to produce severe liver toxicity and mild kidney toxicity in a very short time; as little as 14 days.
- European Monitoring Centre for Drugs and Drug Addiction: Kratom Drug Profile
- Bangkok Post: Kratom Leaves – Are They Really A Dangerous Drug?
- BBC World News: The Drug Addictions Devastating Thai Villages
- Pharmacognosy Research: The Evaluation of Antinociceptive Activity of Alkaloid, Methanolic, and Aqueous Extracts of Malaysian Mitragyna Speciosa Korth Leaves in Rats
- Neuroscience and Biobehavioral Reviews: From Kratom to Mitragynine and Its Derivatives – Physiological and Behavioural Effects Related to Use, Abuse, and Addiction
- Molecules: In Vitro and in Vivo Effects of Three Different Mitragyna Speciosa Korth Leaf Extracts on Phase II Drug Metabolizing Enzymes—Glutathione Transferases (GSTs)
- Journal of the American Chemical Society: Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids – Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators
- ACS Central Science: 7‑Hydroxymitragynine Is an Active Metabolite of Mitragynine and A Key Mediator of Its Analgesic Effects
- Journal of Medicinal Chemistry: Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2
- Frontiers in Psychiatry: Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom