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
P-C Wu, T-P Su, C-T Li et al.
Abstract Background While ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), response heterogeneity necessitates robust biomarkers to optimize clinical decision-making. Aims & Objectives To validate a machine-learning (ML) framework for predicting ketamine antidepressant response from pre-treatment multimodal neuroimaging features across independent...
The International Journal of Neuropsychopharmacology
September 9, 2026
B Richardson, J O'Byrne, V Bruno et al.
Abstract Background Psychedelics induce altered states of consciousness (AOC) with profound perceptual, cognitive, and emotional shifts, often linked to positive therapeutic outcomes. Although serotonergic psychedelics such as psilocybin, LSD, and 5-MeO-DMT share receptor targets, they differ in behavioral and neural effects. How these compounds alter cortical dynamics relative to other...
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
Sota Tomiyama, K Yonezawa, K Kusudo et al.
Abstract Background Cognitive dysfunction is associated with impaired psychosocial functioning in patients with major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) exhibit more pronounced cognitive dysfunction than those with non-resistant MDD, underscoring the need for effective therapeutic strategies. Psilocybin has emerged as a promising treatment for...
The International Journal of Neuropsychopharmacology
September 9, 2026
Y-H Chan, H-M Chang
Abstract Background Esketamine, the S-enantiomer of ketamine, is an NMDA receptor antagonist approved for treatment-resistant depression (TRD). Although regulated clinical trials suggest a low risk of misuse, concerns remain that esketamine exposure may facilitate transition to ketamine dependence, particularly in East Asia where illicit ketamine is widely available. Aims & Objectives To...
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
Claudio Agnorelli, Joseph Peill, Danielle Kurtin et al.
Abstract Background Clinical studies have shown that ketamine and classic psychedelics can produce robust and rapid antidepressant effects after a single or a few administrations. However, the neurobiological mechanisms driving these long-lasting changes remain unclear. A leading framework proposes that both drug classes induce sustained increases in neuroplasticity, potentially reshaping...
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
J Ramaekers
Abstract Background Short-acting psychedelics such as 5-MeO-DMT and DMT may induce rapid relief of depressive symptoms after brief but intense psychedelic experiences. Aims & Objectives This presentation examines their clinical pharmacology and therapeutic potential in depression. Method Review of clinical data. Results Both compounds primarily target serotonergic receptors, notably 5-HT1A and...
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
Z Wang, W Chen, C Hu et al.
Abstract Background Within the rapidly expanding field of psychedelic research, psilocybin, along with its active metabolite psilocin, has emerged as a highly promising candidate in the search for innovative treatments for neuropsychiatric disorders. In this context, preclinical research using animal disease models has produced somewhat inconsistent results when employing standard tests to...
The International Journal of Neuropsychopharmacology
September 9, 2026
Z-J Zhang
Abstract Background While nitrous oxide (N2O) abuse has been a growing international public health issue, there is a dearth of effective intervention strategies. Our previous study has demonstrasted that addictive properties of N2O are associated with its regulation of D1 receptor and BDNF pathway in the ventral tegmental area-nucleus accumbens. Aims & Objectives This study aimed to investigate...
The International Journal of Neuropsychopharmacology
September 9, 2026
Rei Yokoyama, M Matsumi, S Asano et al.
Abstract Background The execution of prosocial behaviors requires the ability to accurately understand and infer others’ affective states. Impairments in prosocial functioning have been shown to be associated with the pathology of several psychiatric disorders. In particular, individuals with depression exhibit reduced cognitive and affective responses to others’ emotions. These impairments may...
The International Journal of Neuropsychopharmacology
September 9, 2026
M Saje, Jurij Bon, Aleš Oblak
Abstract Background Esketamine is a NMDA receptor antagonist that has been approved as treatment for treatment-resistant depression (TRD). Unlike serotoninergic therapies requiring weeks for effect, intranasal esketamine modulates glutamate neurotransmission, often yielding symptom relief within hours and significant response rates within one month [1]. This rapid action is particularly...
The International Journal of Neuropsychopharmacology
September 9, 2026
V Bruno, Martha López-canul, B Richardson et al.
Abstract Background Psilocybin has shown therapeutic potential for several neuropsychiatric disorders; however, concerns remain regarding its abuse liability and long-term neurobiological effects following repeated use. While acute psychedelic administration is generally considered to have low addictive potential, the consequences of repeated exposure on reward processing, withdrawal-related...
The International Journal of Neuropsychopharmacology
September 9, 2026
B Richardson, S Socolow, Martha López-canul et al.
Abstract Background Recent clinical trials show that 5-MeO-DMT produces rapid antidepressant effects, yet the receptor mechanisms underlying these outcomes remain incompletely defined. Although 5-MeO-DMT is a high-affinity agonist at multiple serotonergic receptors, the relative contribution of 5-HT1A and 5-HT2A receptor signaling to its antidepressant-like actions has not been causally...
The International Journal of Neuropsychopharmacology
September 9, 2026
G Goodwin
Abstract Background There are no approved medications for treating anorexia nervosa (AN) despite having the highest mortality rate of all psychiatric conditions. Talk therapies have limited efficacy, with relapse rates as high as 52% and poor long-term outcomes. Aims & Objectives This study evaluated the effects and safety of COMP360 psilocybin, a novel treatment, in individuals with anorexia...
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
Friederike Holze, F Müller, Peter Gasser et al.
Abstract Background Anxiety disorders are a major health burden and current treatment options yield unsatisfactory results. Psychedelics, such as lysergic acid diethylamide (LSD) that act via agonism on serotonin 2A receptors, have recently been shown to be effective in the treatment of anxiety symptoms. Aims & Objectives Here, we determine the relationship between the acute experience and...
The International Journal of Neuropsychopharmacology
September 9, 2026
J Vieira-Andrade, I Marques, M Brito
Abstract Background Serotonin 2A receptor (5-HT2AR) agonists play a crucial role in multiple cognitive processes, namely executive functions, learning and memory. Owing partly to this, psychedelics such as lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline and ayahuasca might be valuable adjuvants in improving memory deficits and language impairment. Thanks to...
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
Katarzyna Henke‐Ciążyńska, Daniel Pankowski, Bartosz Helfer
Abstract Background Systematic reviews with meta-analyses (SR-MAs) of psychedelic-assisted psychotherapy (PAP) guide clinical and policy decisions. Their trustworthiness depends, in part, on how consistently different SR-MAs assess risk of bias (RoB) in the same underlying randomized controlled trials (RCTs), and how transparently those judgments are justified. Aims & Objectives To summarise...
The International Journal of Neuropsychopharmacology
September 9, 2026
C Zarate
Abstract Background Ketamine produces rapid antidepressant and anti-anhedonic effects in treatment-resistant depression, but response is heterogeneous and mechanisms at the circuit level remain incompletely defined. Convergent imaging work implicates anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and reward-related networks as key loci for ketamine’s therapeutic and...
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...