# Chemistry and Biology of Mitragynine Alkaloids

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2022 · $593,305

## Abstract

SUMMARY
Chemistry and Biology of Mitragynine Alkaloids
!
 Mitragynine is a corynanthe-type indole alkaloid representing the major psychoactive constituent of
Mitragyna speciosa (also known as “kratom”), a plant native to Southeast Asia. The use of kratom has been
on the rise in the U.S. in the last decade, to such an extent that it attracted the attention of the Drug
Enforcement Administration (DEA). Despite the initial intent by the DEA to place two alkaloids of this plant,
mitragynine and 7-hydroxymitragynine (7OH), into Schedule I of the Control Substance Act, the DEA
eventually withdrew this action following dramatic opposition from the public. Thus, kratom remains a readily
available “opioid material” in the U.S. and most other countries worldwide. At the same time, the basic
science underlying the biological effects of kratom remains poorly understood. The proposed research
addresses an urgent need for a systematic examination of mitragynine alkaloids and builds on extensive
preliminary results generated by the PIs. We have recently reported that mitragynine is a partial mu-opioid
receptor (MOR) agonist with a G protein-biased signaling profile. In addition, we have found that mitragynine is
metabolized to 7OH, a more potent, G protein-biased MOR agonist. Furthermore, we have shown that 7OH
induces potent analgesia in mice without respiratory depression and constipation side effects, and thus,
represents an attractive atypical opioid template for further investigations. In this application, we focus on
mapping the basic science of mitragynine and its metabolite 7OH in terms of synthetic methods,
metabolism, receptor signaling and pharmacological profile,!by pursuing three integrated aims. Moreover,
we aim to explore the central hypothesis that G protein-biased MOR agonism underlies the favorable
separation of analgesia and side effects exhibited by mitragynine-type compounds. These goals will be
accomplished by an interdisciplinary team with significant experience in synthetic and computational
chemistry, opioid receptor signaling, and in vitro and in vivo pharmacology.

## Key facts

- **NIH application ID:** 10436844
- **Project number:** 5R01DA046487-05
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Susruta Majumdar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $593,305
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436844

## Citation

> US National Institutes of Health, RePORTER application 10436844, Chemistry and Biology of Mitragynine Alkaloids (5R01DA046487-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436844. Licensed CC0.

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