Relmada Study Overview

If you’re struggling with depression even while on medication, learn about a research study for an add-on investigational drug that may offer relief

The Relmada Studies are evaluating an oral investigational drug to see if it may safely and effectively reduce symptoms of depression. The investigational drug is believed to work differently than most currently approved antidepressant drugs.

If your prescription antidepressants aren’t relieving your symptoms and you’re currently experiencing an episode of depression *, this research study may be an option for you

The Relight clinical research program is testing an investigational medication for people living with Major Depressive Disorder (MDD).

(*) Major depression includes symptoms of depressed mood or loss of interest, most of the time for at least 2 weeks, that interfere with daily activities. https://www.nimh.nih.gov/health/topics/depression

You will take the investigational drug in addition to your current antidepressants

Taking an additional antidepressant is a common treatment option for people who still experience depression symptoms after a full course of treatment with a single medication.

The study lasts up to 9 weeks including a 4-week treatment period and includes 7 visits to the study site. If you meet the criteria for the study and decide to participate, you will have a 1 in 2 (50%) chance of receiving the active investigational drug and a 1 in 2 (50%) chance of receiving a placebo (an inactive material that looks like the investigational drug but does not contain any active investigational drug).

How do I qualify?

In order to participate you must:

Be 18 to 65 years old
Be diagnosed with depression
Currently be experiencing an episode of depression that’s lasted at least 8 weeks
Be taking prescription antidepressants

Why participate?

If you qualify and decide to participate, you will receive:

The investigational drug and all study-related care at no cost
Close monitoring by an experienced study doctor and staff
The opportunity to advance medical knowledge about depression

See if you qualify

What is a research study?

A research study, also known as a clinical trial, is a scientific study that evaluates the safety and effectiveness of an investigational drug. A research study may show that the investigational drug is better than, as good as, or worse than the standard treatment or inactive placebo (looks like the investigational drug but contains no active ingredient). Qualified doctors, nurses, and other medical professionals are responsible for conducting the study.

It is only through the completion of research studies that investigational drugs can be evaluated and, if proven safe and effective, approved for a particular use. Different regulatory bodies in different countries will provide this approval after a thorough review. Prescription medications in use today were first proven safe and effective during research studies.

About the study drug

The active ingredient in REL-1017 is esmethadone. REL-1017 interacts with a family of brain receptors called N-methyl-D-aspartate (NMDA) receptors, which are unique and distinct from other brain receptors ^1,2. The active ingredient in REL-1017 tablets is esmethadone. Esmethadone is also sometimes referred to as dextro-methadone or d-methadone. Opioid effects, such as addiction and withdrawal, have not been seen with esmethadone.

One of the purposes of Phase 3 clinical trials is to evaluate the potential for adverse events. In Phase 1, Phase 2 and similar Phase 3 studies REL-1017 was found to be overall well tolerated ^3,4,5. A recently completed dedicated study called the Human Abuse Potential (HAP) study showed that REL-1017 does not have addictive potential ⁶.

Bettini E, Stahl SM, De Martin S, et al. Pharmacological Comparative Characterization of REL-1017 (Esmethadone-HCl) and Other NMDAR Channel Blockers in Human Heterodimeric N-Methyl-D-Aspartate Receptors. Pharmaceuticals (Basel). 2022;15(8):997. Published 2022 Aug 13. doi:10.3390/ph15080997

Mathews DC, Henter ID, Zarate CA. Targeting the glutamatergic system to treat major depressive disorder: rationale and progress to date. Drugs. 2012;72(10):1313-1333

Bernstein G. et al. Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects. J Clin Psychopharmacol. 2019;39: 226-237

Fava M, Stahl S, Pani L, De Martin S, Pappagallo M, Guidetti C, Alimonti A, Bettini E, Mangano RM, Wessel T, de Somer M, Caron J, Vitolo OV, DiGuglielmo GR, Gilbert A, Mehta H, Kearney M, Mattarei A, Gentilucci M, Folli F, Traversa S, Inturrisi CE, Manfredi PL. REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial. Am J Psychiatry. 2022 Feb;179(2):122-131.

Fava M, Stahl S, Pani L, De Martin S, O'Gorman C, Guidetti C, Gorodetzky C, Vocci F, Sapienza F, Kosten T, Alimonti A,Comai S, Mattarei A, Folli F, Bushnell D, Kroeger C, Champasa P, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M. Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Placebo-Controlled Trial. American College of Neuropsychopharmacology (ACNP); Tampa FL 2023.

Shram MJ, Henningfield JE, Apseloff G, et al. The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users. Transl Psychiatry. 2023;13(1):192. Published 2023 Jun 7. doi:10.1038/s41398-023-02473-8