The International Journal of Neuropsychopharmacology
September 9, 2026
Todd M Solomon, Robert Barrow, Daniel R Karlin et al.
Abstract Background Effective and well-tolerated pharmacotherapies for generalized anxiety disorder (GAD), which is one of the most common psychiatric disorders, are needed. Aims & Objectives To determine the dose-response relationship of MM120 (lysergide D-tartrate) in adults with moderate to severe GAD. Method This phase 2b, multicenter, randomized, double-blind, placebo-controlled study...
The International Journal of Neuropsychopharmacology
September 9, 2026
D McCulloch
Abstract Background LSD has recently entered phase 3 clinical trials for anxiety and depressive disorders, yet understanding of its mechanisms of action in the human brain remains incomplete. The serotonin 2A receptor (5-HT2AR) is the critical target for psychedelic effects, but no investigations to date have evaluated the relation between target engagement and systems-level brain function....
The International Journal of Neuropsychopharmacology
September 9, 2026
Noemi Nicosia, Jessica Mingardi, G Terribile et al.
Abstract Background Chronic stress is a key risk factor for major depressive disorder (MDD), one of the leading causes of disability worldwide1. Despite available pharmacological therapies, treatment-resistant depression (TRD) remains a clinical challenge. Hallucinogens such as ketamine and serotonergic psychedelics including psilocybin and lysergic acid diethylamide (LSD)2 show rapid...
The International Journal of Neuropsychopharmacology
September 9, 2026
Omer A. Syed, Fahad Alam, Peter Giacobbe
Abstract Background Major depressive disorder (MDD) is a debilitating medical condition that places a significant psychological, social, and financial burden on the individuals and families of those affected. However, a third of individuals with MDD do not respond to standard treatments – diagnosed with treatment-resistant depression (TRD). Repeated dosing of intravenous (IV) ketamine has...
The International Journal of Neuropsychopharmacology
September 9, 2026
Mario F Juruena
Abstract Background Ketamine has rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD), but optimal implementation, route selection, and longer-term maintenance strategies remain areas of active clinical development. At the Maudsley Advanced Treatment Service (MATS), ketamine and esketamine are delivered within a specialist governance framework, using multiple...
The International Journal of Neuropsychopharmacology
September 9, 2026
Mostafa El Mansari, Naomichi Okamoto, Pierre Blier
Abstract Background Low-dose racemic ketamine enhances the firing rate and burst activity of rat norepinephrine neurons in the locus coeruleus, as well as the population activity of dopamine neurons in the ventral tegmental area [El Iskandrani et al, 2015]. These brainstem monoamine nuclei densely innervate the prefrontal cortex (PFC), whereas clinical studies have shown a facilitation of...
The International Journal of Neuropsychopharmacology
September 9, 2026
S Socolow, B Richardson, Sofia Nasini et al.
Abstract Background Major depression (MD) is a prevalent and debilitating disorder, characterized by anhedonia, persistent low mood, and learned helplessness, affecting up to 21% of adults over a lifetime. Chronic stress is a major environmental contributor to MD, and preclinical models of chronic mild stress (CMS) allow investigation of its behavioral and neurobiological consequences....
The International Journal of Neuropsychopharmacology
September 9, 2026
Romain Hacquet, P Pantiya, G Gotti et al.
Abstract Background Psychedelics such as psilocybin have demonstrated rapid and sustained antidepressant effects in humans, particularly when administered in carefully designed therapeutic environments (Borkel et al., 2024; Carhart-Harris et al., 2021). DMT and 5-MeO-DMT, distinguished by their brief duration of psychedelic effects, have also shown encouraging preliminary outcomes in depressive...
The International Journal of Neuropsychopharmacology
September 9, 2026
A Solomon, Y Domany
Abstract Background A critical gap exists in understanding the biological mechanism linking ketamine’s rapid anti-suicidal effects to the Interpersonal Theory of Suicide (IPTS). While the "Kinetic Mismatch" between acute relief and delayed synaptogenesis is well-known, current models overlook how ketamine modulates “Thwarted Belongingness” (a core IPTS pillar) and the attachment anxiety that...
The International Journal of Neuropsychopharmacology
September 9, 2026
Gabriella Gobbi
Abstract Background While the monoaminergic hypothesis has long dominated the treatment of mood disorders, its limitations have prompted the exploration of alternative mechanisms. Early work by Skolnick et al. (1996) demonstrated that chronic antidepressant treatment induces adaptive changes in N-methyl-D-aspartate (NMDA) receptors, suggesting glutamatergic signaling as a convergent pathway in...