# Preclinical assessment of kratom as an intervention for opioid use disorder

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2020 · $252,725

## Abstract

ABSTRACT
Opioid use disorder (OUD) is a major epidemic in the US. Drug craving and relapse are major challenges in
treating OUD as abstinent drug users remain at risk of relapse even after extended drug-free periods, and well
after the acute physical withdrawal symptoms have subsided. Once abstinent, long-lasting negative affective
symptoms contribute to increased drug craving, and following exposure to drug-associated cues or stress, an
increased risk of relapse which further intensifies over abstinence. New treatments are critically needed to reduce
craving and prevent relapse for OUD as current approaches result in ~50% relapse. One promising anti-relapse
intervention is kratom, Mitragyna speciosa, a medicinal herb used for centuries in Southeast Asia and more
recently in the US, as a self-treatment for pain, depression and anxiety, and opioid withdrawal, craving, and
relapse. There are an estimated 3 to 5 million users of kratom in the US, and despite a high prevalence of kratom
use as a self-treatment for OUD, its efficacy has yet to be established in humans or animal models. While kratom
itself has not yet been examined in the context of addiction, there have been a few studies conducted with
alkaloid-rich extracts of kratom and several with mitragynine (MG), its most abundant alkaloid. Findings
demonstrate that while both compounds induce positive reinforcing effects, their abuse liability is relatively low.
Importantly, as with reports in humans, in animals, kratom (extract) and MG reduce opioid withdrawal symptoms,
and these effects are believed to occur via agonistic effects at mu-opioid receptors (MOR). However, unlike
classical opioids, MG does not recruit β-arrestin signaling, and thus the beneficial effects associated with MOR
activation (analgesic, anxiolytic, and antidepressant effects) can be obtained with less risk of dangerous side
effects (i.e. respiratory depression). Together, these data provide compelling support for the overall
objective of this R21 application: to determine in a rat model the potential utility of kratom as an anti-
relapse intervention. To do so, we will first determine the composition of commercially-purchased kratom
powder with respect to MG as well as 7-hydroxymitragynine (7-HMG), a structurally-related alkaloid that also
has agonistic effects at MORs (Aim 1). Although less research has been conducted with 7-HMG since it
constitutes significantly less of kratom's total alkaloid content (approximately 2% versus 66% for MG), it has a
higher affinity and potency for MORs as compared to MG. Next, using characterized samples, we will determine
the efficacy of kratom at reducing relapse vulnerability in response to two of the most common triggers of craving
in humans, drug-associated cues (Aim 2) and stress (Aim 3). Effects will be determined in both males and
females and correlational analyses will be conducted to determine how the composition of kratom, and
specifically, levels of MG and 7-HMG, impacts its...

## Key facts

- **NIH application ID:** 9998431
- **Project number:** 1R21DA049992-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Wendy Jean Lynch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,725
- **Award type:** 1
- **Project period:** 2020-03-04 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998431

## Citation

> US National Institutes of Health, RePORTER application 9998431, Preclinical assessment of kratom as an intervention for opioid use disorder (1R21DA049992-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9998431. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*