What the Research Cautions About Kratom’s Opioid-Like Abuse Potential
By Jyothirmai Gubili, MS, Eugenie Spiguel, MSN, ANP-BC, and Yen Nien (Jason) Hou, PharmD, Dipl OM, LAc
Kratom is a Southeast Asian tropical tree, the leaves of which have been chewed, smoked, or made as tea for their stimulant and euphoric effects. They have also been employed in traditional medicine to reduce pain and fever, to relieve diarrhea, for wound healing, and as a substitute for opium (https://doi.org/10.1016/j.neubiorev.2012.11.012). Recently, kratom supplements have become popular in the United States for alleviating pain, improving mood, lowering anxiety, and alternative opioid withdrawal treatment.
A survey of more than 8,000 users revealed that 68% take it to manage acute or chronic pain and 67% for anxiety, depression, or post-traumatic stress disorder (https://doi.org/10.1016/j.drugalcdep.2017.03.007). However, kratom use is associated with serious side effects, and has a high potential for abuse. It is banned in many countries and U.S. states.
What the Evidence Says
Kratom was shown to have muscle relaxant (https://doi.org/10.1016/j.jep.2010.03.035), anti-inflammatory (https://doi.org/10.1159/000226292), analgesic (https://www.ncbi.nlm.nih.gov/pubmed/15304982), anorectic (https://doi.org/10.1016/j.fitote.2006.04.006), and morphine-like effects (https://doi.org/10.1016/j.jep.2013.02.008) in preclinical studies, but human data are sparse.
Its stimulant effects are reported at lower doses (1–5 g), with sedative and pain-relieving activities at higher doses (5–15 g) (https://www.ncbi.nlm.nih.gov/pubmed/28072812). The effects are felt within 5–10 minutes of ingestion and may continue for 2–5 hours (https://doi.org/10.1213/xaa.0000000000000658).
The alkaloids mitragynine and 7-hydroxymitragynine are the chief psychoactive compounds (https://doi.org/10.1080/02791072.2016.1229876). Mechanistic studies showed that both compounds produce central nervous system stimulant and depressant effects (https://doi.org/10.1002/phar.1522) via monoaminergic and opioid receptors (https://doi.org/10.1007/s00414-015-1279-y). They also have opioid-like features, including affinity for opioid receptors, analgesic cross-tolerance, and competitive interaction with naloxone, a medication used to reverse opioid overdose (https://doi.org/10.1021/jm400143z). Mitragynine, by itself, can cause cognitive impairment and addiction profiles similar to those of morphine (https://doi.org/10.1111/adb.12185).
Deleterious Effects
Adverse events following kratom use include withdrawal symptoms (https://doi.org/10.1016/j.drugalcdep.2017.03.007) such as nausea, vomiting, chills, sweats, muscle spasms and pain, decreased appetite, or diarrhea; anxiety, irritability, depressed mood, hot flashes, sleeping difficulty; with symptoms more likely due to heavier use (https://doi.org/10.1016/j.drugalcdep.2014.03.017).
Several cases of addiction (https://www.ncbi.nlm.nih.gov/pubmed/27057581), overdose and withdrawal (https://doi.org/10.1002/hep.27612), liver damage (https://doi.org/10.14740/gr1204), cardiac arrest (https://doi.org/10.1136/bcr-2019-229778), cardiorespiratory arrest (https://doi.org/10.1177/1751143717712652), and cardiotoxicities (https://doi.org/10.1371/journal.pone.0115648) have also been reported, along with fatalities with kratom-containing products (https://doi.org/10.1111/1556-4029.14082) or with use of multiple drugs (https://doi.org/10.1007/s12024-018-0049-9) in which kratom was suspected to have contributed to death (https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-scientific-evidence-presence-opioid-compounds). As well, herbal mixtures containing synthetic compounds and kratom have been associated with altered behavior (https://doi.org/%2010.1016/j.forsciint.2010.10.025), hemorrhagic stroke (https://doi.org/10.1007/s13181-019-00741-y), and multiple deaths (https://www.ncbi.nlm.nih.gov/pubmed/21513619).
Given the alarming rise in use of kratom and the lack of safety data, research is urgently needed to ascertain its effects on human health.
Nursing Implications
Kratom is a controversial agent whose biological effects have yet to be well characterized. In 2018, FDA issued a public health advisory against kratom highlighting its potential for abuse (https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-scientific-evidence-presence-opioid-compounds) and recalled kratom supplements due to salmonella contamination (https://www.fda.gov/news-events/press-announcements/fda-orders-mandatory-recall-kratom-products-due-risk-salmonella). Furthermore, the Drug Enforcement Administration has placed kratom on its drugs of concern list and the National Institute of Drug Abuse labeled it as an emerging drug of abuse (https://doi.org/10.15585/mmwr.mm6529a4). However, kratom supplements continue to be widely available online and are cheaper than conventional opioid-replacement agents.
Patients with cancer are frequently concerned about opioid addiction and are often looking for substitutes to manage their pain. Nurses can educate patients as to the dangers of kratom and help direct patients seeking opioid alternatives to approved and safe therapies.