Data and publications

Relmada Therapeutics, Inc.

Data, congress presentations,
and publications

  • Published articles
  • Congress presentations
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  • No indication of abuse or withdrawal potential with esmethadone (REL-1017): results from two phase 3 randomized placebo-controlled trials in patients with major depressive disorder

  • 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

  • The novel uncompetitive NMDA receptor antagonist esmethadone has no meaningful abuse potential in recreational drug users

  • REL-1017 (esmethadone) as adjunctive treatment in patients with major depressive disorder: a phase 2 randomized double-blind trial

  • Subanalysis of subjective cognitive measures from a phase 2, double-blind, randomized trial of REL-1017 in patients with major depressive disorder

  • Esmethadone‐HCl (REL‐1017): a promising rapid antidepressant

  • The serotonin receptor agonist psilocybin as a novel therapeutic approach for NAFLD: preclinical studies

  • Behavioral effects of a 14-day repeated treatment with psilocybin at a low non-psychedelic dose: a preliminary study in C57BL/6J mice

  • Efficacy of esmethadone (REL-1017) in patients With major depressive disorder and antidepressant tolerance (antidepressant tachyphylaxis)

  • No indication of abuse potential and absence of withdrawal from esmethadone (REL-1017) in patients with major depressive disorder

  • Efficacy and safety of esmethadone (REL-1017) in patients with major depressive disorder and inadequate response to standard antidepressants: a phase 3 randomized controlled trial

  • No indication of abuse potential and absence of withdrawal signs and symptoms from esmethadone (REL-1017): results from a phase 3 randomized controlled trial in patients with major depressive disorder

  • Esmethadone (REL-1017) compares with NMDA receptor antagonists in FLIPR-calcium assay

  • REL-1017 (esmethadone hydrochloride), a potential rapid-acting antidepressant has no meaningful opioid abuse potential in non-clinical and clinical abuse potential studies

  • REL-1017 (esmethadone) may rapidly reduce dissociative symptoms in adults with major depressive disorder unresponsive to standard antidepressants: a report of 2 cases

  • No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

  • REL-1017 (esmethadone hydrochloride) demonstrates neither toxic effects on maternal health nor teratogenic effects in pregnant rats

  • REL-1017 (esmethadone) increases circulating BDNF levels in healthy subjects of a phase 1 clinical study

  • Characterization of the safety and pharmacokinetic profile of d-methadone, a novel N-methyl-D-aspartate receptor antagonist in healthy, opioid-naive subjects: results of two phase 1 studies

  • No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

  • Drug–drug interaction studies of esmethadone (REL‐1017) involving CYP3A4‐ and CYP2D6‐mediated metabolism

  • Pharmacological comparative characterization of REL-1017 (esmethadone-HC1) and other NMDAR channel blockers in human heterodimeric N-Methyl-D-Aspartate receptors

  • The N-Methyl-D-Aspartate receptor blocker REL-1017 (esmethadone) reduces calcium influx induced by glutamate, quinolinic acid and gentamicin

  • REL-1017 (esmethadone hydrochloride) a novel uncompetitive NMDAR antagonist with a preference for NR1-NR2D subtypes shows rapid, robust and sustained rapid antidepressant effects as adjunctive treatment for Major Depressive Disorder

  • No meaningful opioid abuse liability of REL-1017 (esmethadone; d-methadone), a rapid-acting antidepressant in clinical development: a human abuse potential study

  • REL-1017 (esmethadone, d-methadone) does not cause reinforcing effect, physical dependence and withdrawal signs in Sprague Dawley rats

  • REL-1017 (esmethadone), a novel NMDAR blocker for the treatment of MDD is not neurotoxic in Sprague-Dawley rats

  • Esmethadone (REL-1017) blocks NMDA receptors and reduces Ca2+ entry in presence of quinolinic acid and gentamicin

  • REL-1017 (esmethadone) showed no reinforcing properties compared to oxycodone in a rat self-administration study

  • The N-methyl-D-aspartate receptor antagonist d-methadone acutely improves depressive-like behavior in the forced swim test performance of rats

  • N-methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects

  • REL-1017 (esmethadone) demonstrates no physical dependence and no withdrawal effects in a rat study

  • No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

  • No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

  • Case report: REL-1017 reduces abnormal Clinician Administered Dissociative States Scale scores in patients with major depressive disorder

  • A Phase 2a double-blind randomized trial of REL-1017 (esmethadone) in patients with major depressive disorder: Analysis of subscales from the Symptoms of Depression Questionnaire

  • Effect of REL-1017 (esmethadone) on cholesterol, triglycerides, PCSK9 and hs-CRP in patients with major depressive disorder

  • Effect of percentage of life-years from the start of major depressive disorder on the therapeutic response to REL-1017

  • Esmethadone (REL-1017) reduces glutamate-induced currents in NMDA receptors with the GluN2D subunit

  • Esmethadone (REL-1017) reduces NMDA receptor currents in a concentration dependent manner

  • Esmethadone (REL-1017) shows slower onset kinetics compared to ketamine in manual patch clamp studies

  • Esmethadone (REL-1017) restores NMDA receptor 1 subunit expression in an in vitro model of glutamatergic excitotoxicity

  • Esmethadone (REL-1017) and other uncompetitive NMDAR channel blockers may improve mood disorders via modulation of synaptic kinase-mediated signaling

Congress presentations

No indication of abuse or withdrawal potential with esmethadone (REL-1017): results from two phase 3 randomized placebo-controlled trials in patients with major depressive disorder

Shram M, Pappagallo M, Henningfield J, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Bushnell D, Guidetti C, O’Gorman C, Folli F, Traversa S, Inturrisi CE, Manfredi PL

ACNP 2023

Congress presentations

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

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

ACNP 2023

Published articles

The novel uncompetitive NMDA receptor antagonist esmethadone has no meaningful abuse potential in recreational drug users

Shram M, Henningfield J, Apseloff G, Gorodetzky C, Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Mattarei A, Guidetti C, Comai S, O'Gorman C, Traversa S, Inturrisi C, Manfredi P, Pappagallo M

Transl Psychiatry 13, 192 (2023)

Published articles

REL-1017 (esmethadone) as adjunctive treatment in patients with major depressive disorder: a phase 2 randomized double-blind trial

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 G, Gilbert A, Mehta H, Kearney M, Mattarei A, Gentilucci M, Folli F, Traversa S, Inturrisi C, Manfredi P

Am J Psychiatry. 2022 Feb;179(2):122-131.

Published articles

Subanalysis of subjective cognitive measures from a phase 2, double-blind, randomized trial of REL-1017 in patients with major depressive disorder

Guidetti C, Serra G, Pani L, Pappagallo M, Maglio G, De Martin S, Mattarei A, Folli F, Manfredi P, Fava M

Prim Care Companion CNS Disord. 2023;25(1):22m03267.

Published articles

Esmethadone‐HCl (REL‐1017): a promising rapid antidepressant

Fava M, Stahl S, De Martin S, Mattarei A, Bettini E, Comai S, Alimonti A, Bifari F, Pani L, Folli F, Guidetti C, Furlan A, Sgrignani J, Locatelli P, Cavalli A, O’Gorman C, Traversa S, Inturrisi C, Pappagallo M, Manfredi P

Eur Arch Psychiatry Clin Neurosci. 2023.

Congress presentations

The serotonin receptor agonist psilocybin as a novel therapeutic approach for NAFLD: preclinical studies

De Martin S, Gabbia D, Colognesi M, Zanotto I, Sayaf K, Comai S, Mattarei A, Banzato M, Folli F, Centofanti L, Traversa S, Pappagallo M, Manfredi PL

American Association For The Study Of Liver Diseases (AASLD)

Congress presentations

Behavioral effects of a 14-day repeated treatment with psilocybin at a low non-psychedelic dose: a preliminary study in C57BL/6J mice

Nasini S, Colognesi M, Tidei S, De Martin S, Banzato M, Mattarei A, Folli F, Pappagallo M, Manfredi PL, Comai S

European College of Neuropsychopharmacology (ECNP) 2023

Congress presentations

Efficacy of esmethadone (REL-1017) in patients With major depressive disorder and antidepressant tolerance (antidepressant tachyphylaxis)

Fava M, Stahl S, Pani L, De Martin S, Guidetti C, Alimonti A, Comai S, Mattarei A, Folli F, Bushnell D, O’Gorman C, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M

European College of Neuropsychopharmacology (ECNP) 2023

Congress presentations

No indication of abuse potential and absence of withdrawal from esmethadone (REL-1017) in patients with major depressive disorder

Shram M, Pappagallo M, Henningfield J, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Bushnell D, Guidetti C, O’Gorman C, Folli F, Traversa S, Inturrisi CE, Manfredi PL

European College of Neuropsychopharmacology (ECNP) 2023

Congress presentations

Efficacy and safety of esmethadone (REL-1017) in patients with major depressive disorder and inadequate response to standard antidepressants: a phase 3 randomized controlled trial

Fava M , Stahl SM , Pani L , Bushnell D, O’Gorman C, De Martin S, Guidetti C, Mattarei A, Comai S , Folli F, Traversa S , Inturrisi CE , Manfredi PL, Pappagallo M

American Society of Clinical Psychopharmacology (ASCP) 2023

Congress presentations

No indication of abuse potential and absence of withdrawal signs and symptoms from esmethadone (REL-1017): results from a phase 3 randomized controlled trial in patients with major depressive disorder

Shram M , Henningfield J , Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Bushnell D, Guidetti C, O’Gorman C, Folli F, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M

American Society of Clinical Psychopharmacology (ASCP) 2023

Congress presentations

Esmethadone (REL-1017) compares with NMDA receptor antagonists in FLIPR-calcium assay

Bettini E, De Martin S, Inturrisi C, Mattarei A, Pappagallo M, Stahl S, Traversa S, Manfredi P

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S294.

Congress presentations

REL-1017 (esmethadone hydrochloride), a potential rapid-acting antidepressant has no meaningful opioid abuse potential in non-clinical and clinical abuse potential studies

Shram M, Henningfield J, Apseloff G, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi CE, Manfredi P, & Pappagallo M.

The College of Problems of Drug Dependence (CPDD) 2022.

Published articles

REL-1017 (esmethadone) may rapidly reduce dissociative symptoms in adults with major depressive disorder unresponsive to standard antidepressants: a report of 2 cases

Guidetti C, Serra G, Pani L, Pappagallo M, Maglio G, Trasolini M, De Martin S, Mattarei A, Bifari G, Folli F, Manfredi P, Fava M

Journal of Clinical Psychopharmacology. 2022;10.1097/JCP.0000000000001583.

Congress presentations

No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

Shram M, Henningfield J, Apseloff G, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi CE, Manfredi P, & Pappagallo M.

American Society of Clinical Psychopharmacology (ASCP) 2022.

Congress presentations

REL-1017 (esmethadone hydrochloride) demonstrates neither toxic effects on maternal health nor teratogenic effects in pregnant rats

Bifari F, Pappagallo M, Folli F, Manfredi M

Society of Biological Psychiatry (SOBP) Annual Meeting 2022.

Published articles

REL-1017 (esmethadone) increases circulating BDNF levels in healthy subjects of a phase 1 clinical study

De Martin S, Gabbia D, Folli F, Bifari F, Fiorina P, Ferri N, Stahl S, Inturrisi C, Pappagallo M, Traversa S, Manfredi P

Frontiers in Pharmacology. 2021;12:973-978.

Published articles

Characterization of the safety and pharmacokinetic profile of d-methadone, a novel N-methyl-D-aspartate receptor antagonist in healthy, opioid-naive subjects: results of two phase 1 studies

Bernstein G, Davis K, Mills C, Wang L, McDonnell M, Oldenhof J, Inturrisi C, Manfredi P, Vitolo O

Journal of Clinical Psychopharmacology. 2019;39(3):226-237.

Congress presentations

No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

Shram M, Henningfield J, Apseloff G, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi C, Manfredi P, Pappagallo M

Ketamine 2022.

Published articles

Drug–drug interaction studies of esmethadone (REL‐1017) involving CYP3A4‐ and CYP2D6‐mediated metabolism

Ferri N, De Martin S, Stuart J, Traversa S, Folli F, Pappagallo M, O’Gorman C, Guidetti C, Mattarei A, Inturrisi C, Manfredi P

Drugs in R&D. Nov 27 2023. Epub ahead of print. PMID: 38010591

Published articles

Pharmacological comparative characterization of REL-1017 (esmethadone-HC1) and other NMDAR channel blockers in human heterodimeric N-Methyl-D-Aspartate receptors

Bettini E, Stahl S, De Martin S, Mattarei A, Sgrignani J, Carignani C, Nola S, Locatelli P, Pappagallo M, Inturrisi C, Bifari F, Cavalli A, Alimonti A, Pani L, Fava M, Traversa S, Folli F, Manfredi P

Pharmaceuticals 2022;15(8):997.

Published articles

The N-Methyl-D-Aspartate receptor blocker REL-1017 (esmethadone) reduces calcium influx induced by glutamate, quinolinic acid and gentamicin

Bettini E, De Martin S, Mattarei A, Pappagallo M, Stahl S, Bifari F, Inturrisi C, Folli F, Traversa S, Manfredi P

Pharmaceuticals. 2022;15 (7), 882.

Congress presentations

REL-1017 (esmethadone hydrochloride) a novel uncompetitive NMDAR antagonist with a preference for NR1-NR2D subtypes shows rapid, robust and sustained rapid antidepressant effects as adjunctive treatment for Major Depressive Disorder

Pappagallo M & Manfredi P

Ketamine 2022.

Congress presentations

No meaningful opioid abuse liability of REL-1017 (esmethadone; d-methadone), a rapid-acting antidepressant in clinical development: a human abuse potential study

Henningfield J, Apseloff G, Gorodetzky C, Pappagallo M, Shram M, De Martin S, Fant R, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi C, Manfredi P

American College of Neuropsychopharmacology (ACNP) 60th Annual Meeting 2021.

Neuropsychopharmacol. 46, 218-368, P315 (2021).

Published articles

REL-1017 (esmethadone, d-methadone) does not cause reinforcing effect, physical dependence and withdrawal signs in Sprague Dawley rats

Henningfield J, Gauvin D, Bifari F, Fant R, Shram M, Buchhalter A, Ashworth J, Lanier R, Pappagallo M, Inturrisi C, Folli F, Traversa S, Manfredi P

Scientific Reports. 2022;12,11389.

Published articles

REL-1017 (esmethadone), a novel NMDAR blocker for the treatment of MDD is not neurotoxic in Sprague-Dawley rats

Bifari F, Pappagallo M, Bleavins M, Traversa S, Folli F, Manfredi P

Frontiers in Pharmacology. 2022. 13:863959.

Congress presentations

Esmethadone (REL-1017) blocks NMDA receptors and reduces Ca2+ entry in presence of quinolinic acid and gentamicin

Bettini E, De Martin S, Inturrisi C, Mattarei A, Pappagallo M, Stahl S, Traversa S, Manfredi P

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S198.

Congress presentations

REL-1017 (esmethadone) showed no reinforcing properties compared to oxycodone in a rat self-administration study

Henningfield J, Gauvin D, Bifari F, Fant R, Buchhalter A, Ashworth J, Lanier R, Caron J, Pappagallo M, Folli F, Manfredi P

The College on Problems of Drug Dependence (CPDD) Annual Meeting 2021.

Published articles

The N-methyl-D-aspartate receptor antagonist d-methadone acutely improves depressive-like behavior in the forced swim test performance of rats

Hanania T, Manfredi P, Inturrisi C, Vitolo O

Exp Clin Psychopharmacol. 2020;28(2):196-201.

Published articles

N-methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects

Fogaça M, Fukumoto K, Franklin T, Liu R, Duman C, Vitolo O, Duman R

Neuropsychopharmacology. 2019;44(13):2230-2238.

Congress presentations

REL-1017 (esmethadone) demonstrates no physical dependence and no withdrawal effects in a rat study

Gauvin D, Henningfield J, Bifari F, Fant R, Buchhalter A, Ashworth J, Lanier R, Caron J, Pappagallo M, Folli F, Manfredi P

The College on Problems of Drug Dependence (CPDD) Annual Meeting 2021.

Congress presentations

No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

Shram M, Henningfield J, Apseloff G, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi CE, Manfredi P, & Pappagallo M.

American Society of Clinical Psychopharmacology (ASCP) 2022.

Congress presentations

No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

Shram M, Henningfield J, Apseloff G, Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi C, Manfredi P, Pappagallo M

Ketamine 2022.

Congress presentations

Case report: REL-1017 reduces abnormal Clinician Administered Dissociative States Scale scores in patients with major depressive disorder

Guidetti C, Pani L, Fava M, Pappagallo M, Serra G, De Martin S, Folli F, Manfredi P

Neuroscience Education Institute (NEI) 2021.

CNS Spectrums, Volume 27, Issue 2, April 2022, pp. 236.

Congress presentations

A Phase 2a double-blind randomized trial of REL-1017 (esmethadone) in patients with major depressive disorder: Analysis of subscales from the Symptoms of Depression Questionnaire

Guidetti C, Fava M, Pani L, Pappagallo M, Serra G, De Martin S, Mattarei A, Folli F, Manfredi P

Neuroscience Education Institute (NEI) 2021.

CNS Spectrums, Volume 27, Issue 2, April 2022, pp. 235.

Congress presentations

Effect of REL-1017 (esmethadone) on cholesterol, triglycerides, PCSK9 and hs-CRP in patients with major depressive disorder

Ferri N, Pappagallo M, Patel S, Folli F, De Martin S, Lupo MG, Traversa S, Manfredi PL

Neuroscience Education Institute (NEI) 2021.

CNS Spectrums, Volume 27, Issue 2, April 2022, pp. 246 – 247.

Congress presentations

Effect of percentage of life-years from the start of major depressive disorder on the therapeutic response to REL-1017

Fava M, Pani L, De Martin S, Pappagallo M, Manfredi P

American Psychiatric Association (APA) Annual Meeting 2021.

Congress presentations

Esmethadone (REL-1017) reduces glutamate-induced currents in NMDA receptors with the GluN2D subunit

Bettini E, Nola S, De Martin S, Inturrisi C, Mattarei A, Pappagallo M, Stahl S, Traversa S, Manfredi P

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S198-S199.

Congress presentations

Esmethadone (REL-1017) reduces NMDA receptor currents in a concentration dependent manner

Bettini E, Carignani C, De Martin S, Inturrisi C, Mattarei A, Pappagallo M, Stahl S, Traversa S, Manfredi P

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Congress presentations

Esmethadone (REL-1017) shows slower onset kinetics compared to ketamine in manual patch clamp studies

Bettini E, Carignani C, De Martin S, Inturrisi C, Mattarei A, Pappagallo M, Stahl S, Traversa S, Manfredi P

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S294-S295.

Congress presentations

Esmethadone (REL-1017) restores NMDA receptor 1 subunit expression in an in vitro model of glutamatergic excitotoxicity

De Martin S, Colognesi M, Inturrisi C, Mattarei A, Bettini E, Pappagallo M, Folli F, Stahl S, Traversa S, Manfredi P

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S383-S384.

Published articles

Esmethadone (REL-1017) and other uncompetitive NMDAR channel blockers may improve mood disorders via modulation of synaptic kinase-mediated signaling

Stahl S, De Martin S, Mattarei A, Bettini E, Pani L, Guidetti C, Folli F, de Somer M, Traversa S, Inturrisi C, Pappagallo M, Gentilucci M, Alimonti A, Fava M, and Manfredi P

Int. J. Mol. Sci. 2022; 23(20), 12196.

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