Opioid receptor

Are there therapeutic applications for Kratom?

Answer: Yes, but much more research has yet to be done.

Kratom is a plant (Mitragyna speciosa) indigenous to Southeast Asia, mainly in countries such as Indonesia, Malaysia, and Thailand. Kratom is traditionally consumed by chewing the leaves, or can be steeped as a tea as an herbal medicine. Kratom is in the same family as the coffee plant.

Effects of kratom

Historically, kratom has been used for a variety of reasons. Primarily, it is used by day laborers in Southeast Asia while working in strenuous conditions. The analgesic and stimulant effects of the drug both led to their widespread use, allowing workers to be more productive.

The drug was also used in the 1800s and early 1900s as a way to help opium addicts stop using the drug (A botanical, phytochemical and ethnomedicinal review of the genus Mitragyna korth: implications for products sold as kratom.) Because kratom acts at a similar population of receptors as opium, they are able to decrease the severity of the withdrawal symptoms. Additionally, kratom produces much less dangerous side effects than opium. In this way, kratom has been used as a harm reduction tool.

The compounds found in kratom may function as anxiolytics, and therefore help in treating anxiety. 

Kratom has also been used to treat other, non nervous system conditions, including diarrhea. Opioid receptor activation is known to result in decreased gut motility, which can be helpful to reduce bowel output. Also, the increase in sympathetic nervous system activity from kratom, the "fight or flight" response, reduces bowel movement.

Pharmacology of kratom

As a plant, kratom contains several chemicals that are capable of influencing cellular activity. Many of these compounds are alkaloids.

One of the main compounds of interest with potential psychoactive properties is mitragynine. As a natural compound, mitragynine has strong action at several different receptor systems. For example, it likely binds to alpha adrenergic receptors, which are also activated by the endogenous neurotransmitter norepinephrine, released during sympathetic nervous system activation ("fight or flight"). This could be the source of kratom's stimulant effect.

Mitragynine also binds to and activates one class of opioid receptors, particularly acting as a partial agonist at the mu and delta opioid receptors. (Opioid receptors and legal highs: Salvia divinorum and Kratom) These receptors are also activated strongly by opioid drugs, such as morphine. Some users of kratom, when taken at a high dose, report a painkilling analgesic effect, which is likely mediated through these opioid receptors.

After being ingested, mitragynine can be metabolized by the liver enzyme cytochrome P450, CYP3A4 (Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom)). This particular cytochrome P450 is one of the most important ones in the body, since it is responsible for breaking down several different chemicals, ranging from SSRIs, opioids, benzodiazepines, calcium channel blockers, and some sex hormones.

The main metabolite of mitragynine, 7-hydroxymitragynine, has strong activity at the mu opioid receptors. There is debate in the field about how much 7-hydroxymitragynine is found in preparations of the plant, but studies report that it is about 2 orders of magnitude smaller (one hundred times less) than the amount of mitragynine (The medicinal chemistry and neuropharmacology of kratom: a preliminary discussion of a promising medicinal plant and analysis of its potential for abuse.)