JUN 21, 2016 8:13 AM PDT

New Street Drug Alert: Kratom

WRITTEN BY: Cassidy Reich

There has been an increasing amount of attention on an interesting, legal drug known as kratom that purportes to help ease the difficulty of heroin withdrawal and treat chronic pain and depression. Kratom (Mitragynia speciosa korth) is a tropical tree indigenous to Southeast Asia whose leaves are chewed or dried and powdered. Recreational use of kratom is relatively new in the U.S. and Europe, but has been used in cultural ceremonies, as a stimulant for laborers, and to treat heroin addiction for many years in Southeast Asia. Thailand actually started regulating kratom in 1943 as heroin became more expensive and users adopted kratom as a cheaper alternative.

        
Kratom has a very interesting pharmacological profile because it exhibits both stimulant and opioid-like effects in a dose-dependent manner. A low dose acts as a stimulant while a higher dose acts as an opioid. A recent paper published in the Journal of the American Chemical Society showed kratom binding to human μ opioid receptors (MORs) for the first time in vitro. Opioids such as morphine, heroin, and fentanyl bind to MORs, but kratom is different in that it is less potent and has a biased response.

The kratom leaf contains over 25 different alkaloids, with the concentrations of each alkaloid varying between the different strains of kratom tree. Even with the variation, two alkaloids in particular, mitragynine and 7-hydroxymitragynine (7-HMG), are thought to cause the majority of the psychoactive effects. About 60% of the total alkaloids present in the kratom leaf extract is mitragynine, and 7-HMG accounts for about 2%. Mitragynine by itself only has about 1/100th of the binding potency of morphine at human MORs as assessed in non-neuronal cells overexpressing human MORs, but it is possible that kratom extracts contain enough of the compound to have a psychoactive effect or that the binding potency is higher in a more physiological setting. 7-HMG is 10 times more potent than mitragynine at MORs and interestingly, storage conditions can have an effect on the conversion of mitragynine to its more potent metabolite, 7-HMG. Kratom extract stored in oxidizing conditions with access to sunlight converted about half of the mitragynine to 7-HMG. Sunlight alone was able to convert about 8% of mitragynine to the more potent compound.

          
Since research on kratom is relatively new, there is no consensus of the addictive and toxic properties of kratom.  As a result of this, and because kratom is not sold for human consumption, it is in a similar legal position as synthetic cathinones (bath salts) and synthetic cannabinoids.

From a research perspective, the cocktail of alkaloids found in kratom could hold some incredibly valuable information. The Journal of the American Chemical Society paper showed that the major constituent alkaloids of kratom extract bind to and partially activate human MORs. Most importantly, mitragynine and 7-HMG bound to MORs but did not recruit β-arrestin. β-arrestin recruitment at MORs is responsible for all of the undesirable effects of classic opioids like morphine, including constipation, respiratory depression, and the development of tolerance. Researchers could exploit the biased response of the kratom alkaloid scaffold to create safer painkillers and to potentially create better treatments for opioid addiction. Considering that opioid overdose is the leading cause of accidental death in the U.S., this is imperative.  

Sources: J Am Chem Soc, New York Times, Scientific American, and Int J Legal Med

About the Author
  • Cassidy is a curious person, and her curiosity has led her to pursue a PhD in Pharmacology at the New York University Sackler Institute of Biomedical Sciences. She likes to talk about science way too much, so now she's going to try writing about it.
You May Also Like
SEP 16, 2020
Immunology
Depression, but Not Anxiety, Causes Inflammation and Metabolic Imbalances
SEP 16, 2020
Depression, but Not Anxiety, Causes Inflammation and Metabolic Imbalances
Scientists have discovered that depressed individuals show higher levels of inflammation as well as elevated fat concent ...
SEP 20, 2020
Cannabis Sciences
Can Cannabis be Used to Treat Autism?
SEP 20, 2020
Can Cannabis be Used to Treat Autism?
Currently, the consensus on whether cannabis may be used to treat autism is mixed. While some papers show signs of its p ...
SEP 21, 2020
Cannabis Sciences
Why Do We Build Tolerance to Cannabis?
SEP 21, 2020
Why Do We Build Tolerance to Cannabis?
Many notice that after regularly smoking cannabis, it takes more and more to feel its effects- if any at all. While abst ...
SEP 21, 2020
Neuroscience
Scientists Compare Structural and Functional Evolution with First Atlas of Cavefish Brains
SEP 21, 2020
Scientists Compare Structural and Functional Evolution with First Atlas of Cavefish Brains
Cavefish are fish that dwell in caves, unable to access the outside world. Often, they were separated from their closest ...
SEP 08, 2020
Neuroscience
Synchronizing Brain Waves Could Help Dyslexia Effects
SEP 08, 2020
Synchronizing Brain Waves Could Help Dyslexia Effects
New research from the University of Geneva shows that adults with dyslexia can read more fluently with a non-invasive el ...
NOV 17, 2020
Genetics & Genomics
Why Mutations in RRP7 Cause a Congenital Brain Disorder
NOV 17, 2020
Why Mutations in RRP7 Cause a Congenital Brain Disorder
A large family with some members that have a rare brain disorder has helped scientists learn more about both brain devel ...
Loading Comments...