Kratom: The Fine Line Between Supplement and Substance Use

Written by Hayley Davidson, PharmD; Amanda M. Morrill, PharmD, BCPS;

Jessica Putney, PharmD, BCPP

Introduction

In many states, kratom is so accessible as a supplement that it is sold at smoke shops,  gas stations, or online supplement marketplaces. Often advertised for treatment of pain, low energy, opioid use disorder (OUD), and mood improvement, kratom is regularly utilized by patients without the guidance of a health care provider.(1) Pharmacists are trained extensively to screen and provide education on the risks of supplements and drugs with high misuse potential.  Given the estimated use by 1.7 million Americans, it’s time for pharmacists to add kratom to that list.

What is Kratom?

Kratom (Mitragyna speciosa) is a tree from Southeast Asia.(2,3) For over 300 years, people in this region have chewed the raw leaves, smoked them, or boiled them in water to make teas. Today, in the United States, leaves are typically processed into powders, capsules and extracts. Kratom contains approximately forty psychoactive compounds, including a diverse combination of alkaloids, of which mitragynine is the most common. Both mitragynine and 7-hydroxymitragynine target mu-opioid receptors, with 7-hydroxymitragynine being the more potent, and up to thirteen times more potent than morphine.(3,4) Other alkaloids interact with serotonin and adrenergic receptors, which may contribute to additional pharmacologic effects.(5) Lower doses are reported to produce more stimulant-like effects, whereas higher doses exert opioid-like effects.(4)  Though more dose studies are needed, less than 5 grams may be considered a lower dose. This duality may make kratom particularly appealing to patients.

Legal Challenges and Confusion for Patients and Providers  

Kratom’s complicated legal history further muddies its use. Ten years ago, the Drug Enforcement Administration attempted to classify mitragynine and 7-hydroxymitragynine as Schedule I controlled substances, but was unsuccessful due to lobbying groups and opposition in Congress.(3) The Food and Drug Administration (FDA) states that products containing kratom are adulterated and not appropriate for use as a dietary supplement. It advises that the public should not use kratom due to risk of serious side effects, and  issued numerous recalls for kratom products after reports of salmonella contamination.(1,3) Despite federal concerns, state laws vary.(1,6) As of early 2026, six states have banned kratom and several more have proposed bans and local restrictions, while nineteen states have legalized it after passing a Kratom Consumer Protection Act.(6) This patchwork of laws can be confusing for both patients and providers.

Clinical Effects, Safety Concerns and Dependence

Evidence supporting kratom’s clinical efficacy is limited and low quality for indications such as anxiety, cough, depression, fatigue, and acute and chronic pain.(3) For pain and OUD or withdrawal, there are no large, high-quality randomized controlled trials demonstrating efficacy.(5) Observational studies of patients in Malaysia who chronically used opioids suggest that kratom may decrease withdrawal symptoms and pain, but the design and small sample size limit generalizability. At this time, there is not enough evidence to recommend kratom over FDA-approved modalities.

Pharmacokinetic studies indicate that mitragynine and other kratom alkaloids may inhibit both CYP3A4 and CYP2D6, raising concern for clinically significant drug interactions.5)  Reported serious adverse effects include psychosis, sinus tachycardia, rhabdomyolysis, hepatoxicity, and seizures, the last which appears dose-dependent in some reports.(3,5)

Between 2016 and 2017, 152 deaths were linked to kratom, although only seven involved kratom as the sole substance detected on toxicology reports.(7)  Some users co-ingest kratom with other substances to enhance effects, which may increase toxicity.(5)  Given kratom’s mu-opioid receptor activity, it is not surprising that naloxone has been used to reverse toxicity in case reports. Human data on dependence potential are limited, but longer duration of use and higher doses are thought to increase risk.(5) Case reports describe withdrawal symptoms including anxiety, insomnia, depressed mood, restlessness, and fatigue.

How Pharmacists Can Approach the Conversation

Many patients use kratom for self-treatment of pain and OUD because it is relatively inexpensive and perceived as “natural”. An approach of nonjudgmental assessment and motivational interviewing, rather than confrontation, is essential. Education should emphasize that there are no FDA-approved indications for kratom, largely due to limited evidence of benefit, and significant safety concerns. Underrecognized risks of kratom include its potential for dependence and the risk of product adulteration or variable potency.  Advise patients that regular use can lead to tolerance, dependence, and withdrawal, particularly at higher daily doses or with chronic use. Pharmacists can offer evidence-based alternatives, including FDA-approved medications for OUD, multimodal pain strategies, and mental health treatment. For patients using or considering use, pharmacists should provide naloxone and education on overdose recognition and drug interactions. Given kratom’s dependence potential, a harm-reduction framework, consistent with approaches recommended by treatment experts for opioid and other substance use disorders, may be more clinically appropriate than a purely abstinence-based approach.

Conflict of Interest Statement: The authors have nothing to disclose.

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1. FDA and Kratom. U.S. Food and Drug Administration website.  https://www.fda.gov/news-events/public-health-focus/fda-and-kratom. Accessed March 31, 2026.  

2. Singh D, Narayanan S, Müller CP, et al. Motives for using kratom (Mitragyna speciosa Korth.) among regular users in Malaysia. J Ethnopharmacol. 2019;233:34-40. doi: 10.1016/j.jep.2018.12.038.

3. Kratom. In: Natural Medicine [database]. Somerville, MA: Therapeutic Research Center; 2026 [Updated August 15, 2025; Accessed February 12, 2026].  https://naturalmedicines.therapeuticresearch.com/Data/ProMonographs/Kratom

4. Hossain R, Sultana A, Nuinoon M, et al. A critical review of the neuropharmacological effects of kratom: an insight from the functional array of identified natural compounds. Molecules. 2023;28(21):7372. doi: 10.3390/molecules28217372.

5. McCurdy CR, Sharma A, Smith KE et al. An update on the clinical pharmacology of kratom: uses, abuse potential and future considerations. Expert Rev Clin Pharmacol. 2024;17(2):131–142. doi:10.1080/17512433.2024.2305798.

6. Kratom state legality and legislation. American Kratom Association. https://www.americankratom.org/aka-in-your-state. Accessed March 30, 2026.  

7. Olsen EO, O’Donnell J, Mattson CL, et al. Notes from the field: unintentional drug overdose deaths with kratom detected—27 states, July 2016-December 2017. MMWR Morb Mortal Wkly Rep. 2019; 68:326-327. doi: 10.15585/mmwr.mm6814a2.

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Hayley Davidson, PharmD

PGY1 Pharmacy Resident

Veterans Affairs Medical Center

Manchester, NH

Amanda M. Morrill, PharmD, BCPS

Professor of Pharmacy Practice

Massachusetts College of Pharmacy and Health Sciences School of Pharmacy - Worcester/Manchester

Clinical Pharmacist Practitioner

Primary Care/Tobacco Use Treatment

Veterans Affairs Medical Center

Manchester, NH

Jessica Putney, PharmD, BCPP

PGY1 Pharmacy Residency Program Director

Clinical Pharmacist Practitioner - Mental Health

Veterans Affairs Medical Center

Manchester, NH