# Development of a Safer and More Effective Ibogaine Analog for the Treatment of Opioid Use Disorder

> **NIH NIH UG3** · GILGAMESH PHARMACEUTICALS INC · 2024 · $2,747,151

## Abstract

SUMMARY
Opioid use disorder (OUD) contributes to disability, loss of work, and over 100,000 overdose deaths per year
in the U.S., emphasizing the critical need for novel medications for OUD treatment. Ibogaine, a
psychoactive alkaloid from the Tabernanthe iboga shrub, has shown promise in interrupting opioid
dependence, reducing withdrawal symptoms, and increasing abstinence rates, even after a single
treatment. However, ibogaine's cardiotoxicity and neurotoxicity pose significant barriers to its development
as a drug. To leverage ibogaine’s potential as an OUD therapeutic and address the risks to patient safety,
we have developed a new class of synthetic iboga alkaloids, named “oxa-iboga”. These compounds show no
pro-arrhythmic potential, no neurotoxic effects, and enhanced efficacy in OUD-relevant preclinical behavioral
assays compared to ibogaine. We propose to advance one of these compounds, GM-3009, into clinical
studies by advancing GMP-manufacturing and formulation of GM-3009, completing IND-enabling toxicity
studies, and determining the expected therapeutic exposures of GM-3009 and target engagement via
translational biomarkers. These studies will complete the UG3 portion of this grant. If successful, the
proposal will advance to the UH3 portion, which will conduct first-in-human trials, including safety and
tolerability studies in healthy volunteers (a single ascending dose study, SAD) and a safety study with
exploratory measures of efficacy in OUD patients undergoing opioid withdrawal. The endpoint of the entire
project is generation of clinical safety and preliminary efficacy data to support subsequent Phase 2 efficacy
studies in OUD. The development of GM-3009 builds on decades of research on ibogaine and has the potential
to deliver an innovative OUD therapy with rapid and long-term mitigation of acute and protracted withdrawal
symptoms and cravings, which lead to non-medical opioid use.

## Key facts

- **NIH application ID:** 10835278
- **Project number:** 1UG3DA060053-01
- **Recipient organization:** GILGAMESH PHARMACEUTICALS INC
- **Principal Investigator:** GERARD JOSEPH MAREK
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,747,151
- **Award type:** 1
- **Project period:** 2024-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835278

## Citation

> US National Institutes of Health, RePORTER application 10835278, Development of a Safer and More Effective Ibogaine Analog for the Treatment of Opioid Use Disorder (1UG3DA060053-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10835278. Licensed CC0.

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