Kratom and its Alkaloids
March 2017
Francisco J. Rojas, Ph.D.
In August 2016, the US Drug Enforcement Administration (DEA) announced plans to designate mitragynine and 7-hydroxymitragynine, two alkaloid compounds that naturally occur in the leaves of kratom, as a schedule 1 substances. The classification was a de facto ban on kratom (Mitragyna speciosa), a plant indigenous to Southeast Asia.
Kratom leaves and the teas brewed from then are used by people across the globe to treat chronic pain, alcohol and opioid dependence, and anxiety. A review of websites and medical literature reveal that kratom have been increasingly used for the self-management of opioid withdrawal and pain in the United States. The DEA, however, considers the plant a danger to the public health. The agency has concerns that kratom produces adverse effects including narcotic effects and that its consumption can lead to addiction. By assigning kratom and its two alkaloids to the schedule 1 category, the DEA makes them illegal to manufacture, sell or possess with intent to sell.
The kratom community appealed to the DEA to delay their decision. People who take kratom say the herb helped them overcome addiction to opiates or alcohol and treat otherwise intractable pain. Others say kratom is not more dangerous than many other herbal supplements and much less harmful than prescription opioids. In addition, some researchers familiar with kratom say kratom’s profile for both abuse potential and dependence liability is comparable to or lower than that of unscheduled substances such as caffeine, many antihistamines, antidepressants, and other substances sold directly to consumers. So people held rallies, started a “save kratom” online movement, and collected over 140,000 signatures. Citing the public outcry and a need to obtain more research, the DEA has since withdrawn its notice of intent and opened a public comment period.
The DEA decision to withdraw the intent to ban kratom is a positive development. It comes just as there is a clear need for more science on the matter. Kratom contains chemical compounds, most notably mitragynine, 7-hydroxymitragynine, paynantheine, and speciogynine, along with more than 20 other substances. These compounds have complex and potentially useful pharmacologic activities and some of them produce effects similar to opiates when ingested.
Recent studies indicate that mitragynine and 7-hydroxymitragynine bind to and partially activate human µ-opioid receptors, the same receptors fully triggered by morphine. Also, it was reported that the compound mitragynine pseudoindoxyl, generated by fermenting mitragynine, is an even more potent activator of µ-opioid receptors than mitragynine and 7-hydroxymitragynine. Mice treated with a typical painkilling dose of mitragynine pseudoindoxyl experienced little respiratory depression, a common side effect of opioids such as morphine. These are early evidence of therapeutic potential for the plant compounds and their derivatives that can be produced semisynthetically.
Placing kratom in schedule 1 would complicate scientist’s ability to study the drug in the United States. Reversing the ban makes easy for investigators to obtain kratom and its constituent compounds for conducting research and the rigorous, controlled clinical trials that are needed to assess their safety and efficacy. The work with kratom is promising; it may have beneficial effects particularly in the management of both opioid withdrawal and pain. The few available scientific data also suggests that kratom its compounds and derivatives could eventually lead to the development of non-addictive medications to powerful opiate painkillers.
References
www.deadiversion.usdoj.gov/drug_chem_info/kratom.pdf
www.painnewsnetwork.org/stories/2016/12/1/over-22000-comments-on-deas-kratom-ban
www.kpbs.org/news/2016/nov/29/kratom-healing-herb-or-dangerous-drug/
J Am Chem Soc, DIO:10.1021/jacs,6b00360
JMed Chem 2016, DIO: 10.1021/jmedchem.6b00748
c&en, 94 (36), p5, 2016
