Harmine Safety Study

Overseen By Leah Israel

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: James Murrough

Must not be taking: Psychotropics, Antidepressants, Benzodiazepines, others

Disqualifiers: Cancer, Stroke, Seizures, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safe dosage of a substance called harmine. Researchers are testing harmine in various doses to determine the highest amount that does not cause serious side effects. Eligible participants should be healthy, aged 18 to 55, with a BMI (a measure of body fat based on height and weight) between 19 and 30. The study excludes individuals with major health issues or those taking certain medications that affect the brain or heart. Participants will take harmine in the form of Harmine Hydrochloride Capsules. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial does not allow medications that affect the central nervous system or cardiovascular system, as well as some over-the-counter drugs and herbal remedies. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that harmine is likely to be safe for humans?

Research shows that harmine hydrochloride is still under investigation for safety in humans. Clear information from past studies about its tolerability remains unavailable. This trial is in the early stages, known as Phase 1, where scientists begin assessing harmine's safety. Researchers aim to find the right dose that people can handle without excessive side effects. Participants might experience some reactions as scientists determine the safest way to use harmine. Since it's in Phase 1, limited safety data is available for humans so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about harmine because it offers a novel approach to treatment with its unique mechanism of action. Unlike many standard treatments that target symptoms directly, harmine works by interacting with specific pathways in the brain that may influence mood and cognition. This could potentially lead to faster and more effective outcomes for conditions related to these pathways. Additionally, harmine's active ingredient is derived from natural sources, offering a fresh alternative to synthetic pharmaceuticals.

What evidence suggests that harmine might be an effective treatment?

Research shows that harmine has potential benefits in several areas. Studies have found that harmine can slow cancer cell growth and prevent their spread by blocking the process that allows cancer cells to change and move. Other research suggests that harmine can reduce heart muscle enlargement, potentially aiding heart problems. While these findings are promising, they primarily come from lab and animal studies. More research is needed to understand harmine's effectiveness in humans. Participants in this trial will receive one of seven possible doses of harmine to further investigate its effects. ^{6 7 8 9 10}

Who Is on the Research Team?

James Murrough, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Inclusion Criteria

Your body mass index (BMI) falls between 19 and 30.

Women must not be breastfeeding

Women of childbearing potential and men must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator

Exclusion Criteria

Children under the age of 18 and adults over the age of 55 due to concerns regarding neurodevelopmental and neurocognitive effects, respectively

Presence or history of psychiatric disorder as diagnosed by Mini Neuropsychiatric Interview (MINI)

Urine toxicology positive for illicit drugs or dis-allowed concomitant medications as per study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of harmine in a dose escalation design

1 day

1 visit (in-person)

Monitoring

Participants are monitored for adverse events and dose limiting toxicities for 24 hours post-dosing

24 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Harmine Hydrochloride Capsules

How Is the Trial Designed?

Group I: Harmine Dose Experimental Treatment 1 Intervention

There will be a total of seven possible doses that include 100 mg, 200 mg, 300 mg, 500 mg, 700 mg, 900 mg and 1200 mg. Each study subject will receive a single oral dose of harmine in this single ascending dose design.

Who Is Running the Clinical Trial?

James Murrough

Lead Sponsor

Trials

9

Recruited

250+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

An international study found that 70% of adverse drug events in humans were predicted by animal studies, indicating a good correlation between animal and human toxicity assessments.

While animal studies effectively identified many toxic effects, certain severe adverse events, like immuno-allergies, were not detected, highlighting the need for improved predictive tools in drug safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Are non-clinical studies predictive of adverse events in humans?]. Claude, N.[2019]

Between 2010 and 2016, 164 safety advisories regarding cardiac-related adverse events were issued by regulators in Australia, Canada, the UK, and the US, highlighting the prevalence of risks associated with 61 different drugs, primarily involving cardiac arrhythmias and coronary artery disorders.

While monitoring patients was the most common recommendation in these advisories, only 41.2% provided detailed guidance on how to conduct this monitoring, indicating a need for more consistent and comprehensive information for healthcare professionals and consumers regarding rare but serious medication harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. Hooimeyer, A., Bhasale, A., Perry, L., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11549898/

A Phase 1 single ascending dose study of pure oral harmine ... In this study, no vomiting and no psychedelic effects were observed, although a close look at the data reveals that a mild blissful state did ...

2. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1382142/full

Research progress on the antitumor effects of harmine Recent mechanistic studies have shown that harmine can inhibit cancer cell proliferation and metastasis through epithelial-to-mesenchymal transition.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8724320/

Harmine is an effective therapeutic small molecule for the ... We found that harmine significantly alleviated cardiac hypertrophy in a blood pressure-independent manner in vivo. We further established a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05526430?term=HARMINE&rank=1&tab=results

NCT05526430 | Study of Harmine in Healthy Subjects In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0344033820303265

The impact of Harmine hydrochloride on growth, apoptosis ... The MTT results in this study have showed that HH had inhibitory effects on AGS, SGC7901, and HGC-27 cell lines, and the cell activity gradually weakened ...

6. tcichemicals.com tcichemicals.com/BE/en/sds/H0002_EU_6N.pdf

SAFETY DATA SHEET Skin and body protection: Impervious protective clothing. Protective boots, if the situation requires. H0002. Harmine Hydrochloride. Page 2 of 5 ...

7. file.medchemexpress.com file.medchemexpress.com/batch_PDF/HY-N0737/Harmine-hydrochloride-SDS-MedChemExpress.pdf

Harmine hydrochloride-SDS-MedChemExpress Harmine (hydrochloride). Catalog No. : HY-N0737 ... Safety Data ... No data available. Oxidizing properties. No data available. 9.2 Other safety information.

8. chemicalbook.com chemicalbook.com/msds/harmine-hydrochloride.htm

HARMINE HYDROCHLORIDE - Safety Data Sheet Avoid dust formation. Avoid breathing mist, gas or vapours.Avoid contacting with skin and eye. Use personal protective equipment.Wear chemical impermeable ...

9. datasheets.scbt.com datasheets.scbt.com/sc-295136.pdf

Harmine hydrochloride SWALLOWED ! Accidental ingestion of the material may be harmful; animal experiments indicate that ingestion of less than 150 gram may be fatal or.

10. abmole.com abmole.com/literature/harmine-hydrochloride-msds.html?srsltid=AfmBOop5zR8KOLLOlqW0NSpwPg6_xfJU4nwhZnAbUYHY-8lyokPNmlj6

Material Safety Data Sheet of Harmine-hydrochloride Material Safety Data Sheet of Harmine-hydrochloride contains identification of substance and details of the supplier of the safety data sheet.