# Real-world momentary assessment of kratom use and laboratory-based observed cessation accompanied by product assays: Toward an interdisciplinary characterization of kratom use and pharmacology

> **NIH NIH R00** · JOHNS HOPKINS UNIVERSITY · 2024 · $248,999

## Abstract

Project Summary/Abstract
Mitragyna speciosa (kratom) is a plant indigenous to Southeast Asia with over 40 bioactive alkaloids, two of
which, mitragynine (MG) and 7-hydroxymitragynine (HMG), act at mu opioid receptors (MORs). Use of kratom
and kratom products increased in the US contemporaneous a critical change-point in the opioid crisis (when
painkiller prescribing became more conservative), with many US adults initiating kratom use for putatively
therapeutic indications, such as mitigation of withdrawal from prescribed or nonprescribed opioids, and as a
self-treatment for symptoms of pain, fatigue, or psychiatric or substance use disorders (SUDs). The number of
US users in the past few years is likely >10 million—and increasing. Yet we have little understanding of the
balance of, or determinants of, beneficial or adverse effects of kratom either proximal to use (e.g., sedation,
nausea, analgesia) or over time (e.g., symptoms of SUD). Preclinical work shows that MG and HMG act as
partial biased at MORs but also have non-opioid mechanisms of action and that these and other alkaloids may
have therapeutic potential for the treatment of pain and SUDs with less risk than traditional opioids. This
converges with self-report data, where there is remarkably consistent therapeutic benefit attributed to kratom
with minor-moderate side effects and fewer indicators of abuse potential than might be expected from a
substance that, for some, reportedly substitutes for opioids. Yet this work is limited to cross-sectional surveys,
case reports, and social-media analyses, which may suffer from self-selection and recall bias and sheer lack of
information. Many large surveys of regular users are outdated, given rapid expansion of kratom products, and
diverge from findings in smaller samples, particularly with respect to prevalence of kratom addiction and
withdrawal. Given kratom’s complex pharmacology and novelty (in the US), and the accompanying near-
vacuum in policy and in clinical recommendations, more work is needed to understand its risks and potential
benefits. So, too, is scientific consilience in developing a systematic line of kratom research. The aims of this
K99/R00 work towards both. For the K99, we aim to, using a sample of kratom-using US adults: (1) conduct
momentary assessment of individual instances of kratom product use in daily life; (2) determine associations of
momentary responses with directly assayed content of samples of participants’ kratom products; (3) evaluate
relationships among kratom effects (including withdrawal-like effects), the kratom products used, and alkaloid
concentrations in biospecimens; (4) explore narrative accounts of kratom use. For the R00, I will (5)
systematically evaluate effects of kratom discontinuation. Collectively, these studies will be a bridge to
randomized interventional studies to be proposed in an R01. These studies also begin the interdisciplinary and
interinstitutional collaboration I believe is needed i...

## Key facts

- **NIH application ID:** 10876533
- **Project number:** 4R00DA055571-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** KIRSTEN SMITH
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,999
- **Award type:** 4N
- **Project period:** 2024-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876533

## Citation

> US National Institutes of Health, RePORTER application 10876533, Real-world momentary assessment of kratom use and laboratory-based observed cessation accompanied by product assays: Toward an interdisciplinary characterization of kratom use and pharmacology (4R00DA055571-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10876533. Licensed CC0.

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