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.
Is Kratom Safe? | Kratom Withdrawal and Addiction Guide
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.
How Does Kratom Get You High
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 method of extraction does have some impact on the efficacy of these compounds with a methanolic extract being the most active, a water based extract close behind, and an acid extract being the least potent¹. The way these compounds produce the variety of effects reported are not totally clear, and the different compounds have varying potency, ranging from 13 times¹ more potent than Morphine (for 7-HMG), to being a much weaker (for Mitragynine) μ-Opioid partial agonist and δ & κ competitive antagonist¹.
While the potency of Mitragynine is up for debate, its analgesic effects (including MPI & 7-HMG) are mainly due to μ-Opioid receptor (partial or full) agonist action, regardless of their other interactions¹². It is known that Mitragynine and its derivatives interact with several other non-Opioid receptors in the nervous system¹. Mitragynine also inhibits skeletal muscle contraction via nerve signal blockade through modulation of Ca2+ (Calcium Ion) channels in nerve cells at the neuro-muscular junction¹². In addition, MPI has known inhibitory effects on the gastrointestinal tract¹ leading to an Opioid like semi paralysis of GI peristalsis as well as partial paralysis of male genitalia (specifically the Vas Deferens)¹.
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 descending serotonergic, noradrenergic, and dopaminergic pathways¹. Similar to Cocaine in effect, some of the observable symptoms are strangely opposite of Cocaine, such as pupillary contraction as opposed to dilation. The results of low doses of Kratom often include motor excitement, giddiness, loss of coordination, and possibly tremors in the extremities¹.
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: Produces inhibition of skeletal muscle contraction in a Naloxone-insensitive manner as well as contribute inhibition of GI peristalsis via muscarine receptor inhibition.
- Speciociliatine¹: Produces inhibition of skeletal muscle contraction in a Naloxone-insensitive manner as well as reduce Acetylcholine release from nerves through means other than Opioid receptor agonist action.
- Paynantheine¹: Produces inhibition of skeletal muscle contraction in a Naloxone-insensitive manner as well as contribute inhibition of GI peristalsis via muscarine receptor inhibition.
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.