Virginia Society of Health-System Pharmacists (VSHP) Letter of Support to Classify Kratom as Schedule 1 Controlled Substance
Pharmacological studies show that the active compounds contained in Kratom, mitragynine and 7-hydroxymytragynine, are opioid agonists producing analgesic, sedative and stimulant effects. The potential for abuse of the alkaloids mitragynine and 7-hydroxymytragynine, is well documented due to the opioid and stimulant effects when ingested orally or smoked. Hallucinogenic and sedative effects are also documented at an increased dose. The National Institute for Drug Abuse reports mitragynine and 7-hydroxymytragynine are increasingly being used by the public to self-treat drug withdrawal symptoms and cravings and to manage mental health problems, despite the FDA continuously ruling that these compounds have no therapeutic use. The potential for misuse and harm to the public has been so alarming, several states have banned the sale and distribution of Kratom.
The FDA recently studied Kratom using Public Health Assessment via Structural Evaluation (PHASE) methodology, a tool designed to evaluate pharmacologic data via a 3D computer model using chemical structure. Results confirmed that mitragynine and 7-hydroxymytragynine bind strongly and activate the mu-opioid receptors. In a statement released by the FDA February 6, 2018, FDA Commissioner Dr Scott Gottlieb, MD reported “Based on the scientific information in the literature and further supported by our computational modeling and the reports of its adverse effects in humans, we feel confident in calling compounds found in Kratom, opioids.”
While research has expanded in recent years, current scientific knowledge is limited due to few human mitragynine pharmacologic studies. Gaps exist in long term use safety, efficacy, and impact on public health.
Kratom has a history of traditional use in Southeast Asia for medicinal and recreational purposes prior to gaining popularity in the United States. In 2021, the Substance Abuse and Mental Health Services Administration’s National Survey on Drug Use and Health found that an estimated 1.7 million Americans, 12 years and older, used Kratom in a 12-month time frame. A DEA Scheduling Action published in 2016 documented the use of Kratom rising among heroin users for self-treatment of withdrawal symptoms and in patients with chronic pain. This scheduling action also stated that the recreational drug market is driving increased quantities of Kratom, of uncertain purity and quality, through various points of entry into the US.
The duration and scope of Kratom abuse is increasing. Between 2014 and 2016, 55,000 kg of Kratom were encountered by law enforcement. On April 28, 2023, the FDA reported US Marshals seized 250,000 units of dietary supplements containing Kratom. Poison control center calls have also increased from 26 in 2010 to 2,312 in 2019 and the DEA has noted an increase in requests for mitragynine and 7-hydroxymytragynine analysis in human toxicology panels. Concerns for abuse and an increase in adverse effects have driven other states to issue a complete ban on Kratom and the active compounds mitragynine and 7-hydroxymytragynine, including Alabama, Arkansas, Indiana, Rhode Island, Vermont and Wisconsin. Currently, Virginia restricts the sale of Kratom to those aged 21 years and older and requires a warning label on all packages containing Kratom. In Virginia, Kratom is conveniently sold at smoke shops, gas stations, and online. Within a five-mile radius of the Virginia Board of Pharmacy, there are at least 15 smoke shops selling Kratom that were able to be easily identified.
Common adverse effects associated with mitragynine and 7-hydroxymytragynine include irritability, tachycardia, nausea, drowsiness and hypertension and serious adverse effects include seizure, coma, hallucinations, liver failure and respiratory depression. A 2019 CDC report detected 152 deaths associated with Kratom in 27 states from July 2016 to December 2017, with 91 deaths listing Kratom as the only cause. Further review of the deaths showed that 80% of the decedents had a positive history of substance abuse and 90% had no evidence they were receiving medically supervised pain management. Lack of purity and quality of Kratom products continue to be a threat to public safety, as a 2018 CDC report linked Kratom to a Salmonella outbreak that sickened 199 across 41 states. The FDA also found that laboratory testing on Kratom products yielded the heavy metals, nickel, and lead, at levels unsafe for human consumption prompting a published warning that long term use could be associated with heavy metal poisoning, including anemia, kidney damage, and increased risk for certain cancers.
Mitragynine and 7-hydroxymytragynine are associated with dependence. A 2014 study on Kratom use, conducted by surveying 293 long term, regular users, resulted in greater than 50% developing severe dependence with physical withdrawal symptoms of muscle spasms, pain, insomnia, fever, and psychological withdrawal symptoms of restlessness, anger, sadness, and nervousness. Similarly, a 2024 study found that 66.7% of patients met the DSM-5 criteria for Kratom use disorder (≥2 symptoms), with withdrawal symptoms, tolerance, using more Kratom than intended, and cravings being the most common symptoms. Various studies have also shown the presence of neonatal abstinence syndrome in infants born to mothers who used Kratom during pregnancy. While methadone and buprenorphine, the opioid in Suboxone, are available to treat some of the withdrawal effects associated with Kratom, there are no known medications to alleviate the non-opioid withdrawal symptoms.
Due to the similarities in opioid-like side effects, Kratom has been questioned as being a “gateway” drug. There is currently limited literature demonstrating this. However, a case report describes a patient with Kratom tolerance who started consuming opioids to obtain Kratom-like effects, leading to opioid dependence.
Kratom’s alkaloids, mitragynine and 7-hydroxymytragynine, are not immediate precursors of a substance already controlled under existing regulations. While the chemical composition of mitragynine and 7-hydroxymytragynine differs from opioids, the effects need to be considered in the scheduling process. Our communities are besieged by an ongoing opioid epidemic and a lot of resources and effort are being utilized to help combat this plague. The ease of Kratom’s availability in our communities help fuel the opioid-epidemic. The Virginia Society of Health System Pharmacists support the petition to make mitragynine and 7-hydroxymytragynine Schedule I substances.