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 1964¹. 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 attenuating opium withdrawal. 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 in the area. 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 based on their beliefs¹²³.
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 swallow it. The specific doses are hard to measure exactly because of the differences in Kratom form as well as the particular soil conditions, refinement method¹, 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 opiod 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 however by the side effects which can pose very serious health risks¹. 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 is 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 producing a serenity and act 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 applications¹, as well as those who are much more cautious as it has already killed many people through overdose¹ and it is apparent 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 you should proceed with caution.
The mechanism of action that produces the effect Kratom has on the mind and body 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 Kratom¹, the most potent of which is Mitragynine and its major metabolite 7-Hydroxymitragynine (7-HMG)¹ as well as a more minor metabolite Mitragynine Pseudoindoxyl (MPI)¹. The 2 major metabolites Mitragynine and 7-HMG are the most active drugs known in Kratom so far. The way the plant is processed can effect 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 potent¹. Depending on the purity of the Kratom you have and the way it was processed, the effects can be quite different. Also, the amount of Kratom that you do can change the effects with low doses producing stimulant like effects while higher doses producing Opioid like effects.
While the potency of Mitragynine is up for debate, its painkilling effects (including those of MPI & 7-HMG)¹ are mainly due to μ-Opioid receptor stimulation, regardless of their other interactions¹². It is known that Mitragynine and its metabolites interact with several neurotransmitters and non-Opioid receptors in the nervous system¹. Mitragynine also causes skeletal muscle relaxation through interactions at the nerve-muscle junction¹². In addition, MPI has known inhibitory effects on the gastrointestinal tract¹ leading to Opioid like constipation as well as partial paralysis of male genitalia (specifically the Vas Deferens)¹.
How Does Kratom Get You High
As mentioned, the effects of Kratom are dose dependent. This means that doing small amounts will produce stimulant like effects, while doing larger doses produces effects more like Opioid painkillers. 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 (in particular Mitragynine and 7-HMG) seems to play a role in the effect produced.
The compound Mitragynine is very interesting in that it produces both a neurotransmitter cascade as well as weak μ-Opioid receptor stimulation¹. 7-HMG, while a more potent painkiller than Mitragynine, is both present in the raw Kratom plant and produced from the human bodies 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 and which may contribute to the painkilling effects. Strangely, injecting Mitragynine straight into the brain of mice produced a similar painkilling effect as when taken orally¹. This also suggests that further metabolism may actually take place in the brain itself¹.
Very little is currently known about the exact way(s) 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 Mitragynines effect on neurotransmitters such as serotonin, norepinephrine, and dopamine¹. Similar to other stimulants in effect, some of the observable symptoms are strangely opposite of many stimulants such as pupillary contraction as opposed to dilation. Having effects resembling those of both Cocaine and Methamphetamine, it seems that Mitragynine produces these effects by a similar means of promoting secretion of norepinephrine and dopamine in particular. While not nearly as potent as either Cocaine or Meth, the fact that it produces effects in a similar manner to these two drugs suggests that it may produce related long term changes in the structure or signalling pathway in the brain. Taking low doses of Kratom typically results in effects such as¹:
- Diaphoresis (Excessive Sweating)
- Decreased Appetite
- Elevated Mood or Euphoria
- Increased Concentration or Focus
- Increased Energy and Endurance
- Tingling or Tremors in the Extremities
- Increased Heart Rate and Body Temperature
Opioid Like Kratom Effects
As mentioned, there are a variety of psychoactive compounds present in Kratom. While it seems that Mitragynine may be responsible for the stimulant like effects, 7-HMG is most likely the culprit for the Opioid like effects. Since 7-HMG is 13 times more potent than Morphine as an Opioid receptor activator, it is an extremely potent painkiller. When taking medium to large doses of Kratom, it seems that the effects of 7-HMG become more dominant and overpower the stimulant effects of Mitragynine. 7-HMG binds to the same Opioid receptors in the brain as other Opioids, particularly the μ-Opioid receptor, so the effects felt are very similar to those of many Opioids. These effects can include:
- Sense of Calmness or Serenity
- Reduction in Pain or Discomfort
- Drowsiness or “Nodding Off”
- Extreme Muscle Relaxation
- Lowered Heart Rate
- Depressed Breathing
- Delayed Orgasm (particularly in Males)
Several less active compounds from Kratom can lead to secondary effects through means other than Opioid receptor activity. These are considered analogues of Mitragynine. Some of these include:
- Speciogynine¹: Skeletal muscle relaxation in a way irreversible by Naloxone as well as promote constipation.
- Speciociliatine¹: Skeletal muscle relaxation in a way irreversible by Naloxone as well as produce partial paralysis of muscles through inhibition of Acetylcholine secretion.
- Paynantheine¹: Skeletal muscle relaxation in a way irreversible by Naloxone as well as promote constipation.
Through similarly unknown means, it has been shown in rodents that chronic Kratom use can degrade working memory, such as spatial orientation and cognitive behavioral function¹. 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 days¹².