International Journal of Neuropsychopharmacology
September 9, 2026
G 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...
International Journal of Neuropsychopharmacology
September 9, 2026
R Freire, C Chaves, M Cabo et al.
Abstract Background Anxiety disorders are among the most prevalent psychiatric disorders worldwide, causing significant impacts on physical and emotional health and substantial functional impairment. Not only individuals with anxiety disorders have severe and debilitating anxiety symptoms; patients with PTSD, OCD and mood disorders often present with anxiety. The term classic psychedelics...
International Journal of Neuropsychopharmacology
September 9, 2026
S Socolow, B Richardson, S 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....
International Journal of Neuropsychopharmacology
September 9, 2026
S 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...
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...
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...
International Journal of Neuropsychopharmacology
September 9, 2026
O Mallon
Abstract Background Opioid Use Disorder (OUD) is associated with substantial morbidity and mortality, with relapse remaining common despite the availability of opioid agonist and antagonist pharmacotherapies. Scotland continues to experience a disproportionate burden of drug-related deaths relative to other parts of the United Kingdom and Europe, reflecting the ongoing clinical and public...
International Journal of Neuropsychopharmacology
September 9, 2026
M El Mansari, N Okamoto, P 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...
International Journal of Neuropsychopharmacology
September 9, 2026
R 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...
International Journal of Neuropsychopharmacology
September 9, 2026
M Saje, J Bon, A 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...
International Journal of Neuropsychopharmacology
September 9, 2026
K Henke-Ciążyńska, D Pankowski, B 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...
International Journal of Neuropsychopharmacology
September 9, 2026
F Holze, F Müller, P 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...
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...
International Journal of Neuropsychopharmacology
September 9, 2026
C Agnorelli, J Peill, D 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...
International Journal of Neuropsychopharmacology
September 9, 2026
T Solomon, R Barrow, D 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...
International Journal of Neuropsychopharmacology
September 9, 2026
N Nicosia, J 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...
International Journal of Neuropsychopharmacology
September 9, 2026
B Richardson, S Socolow, M Lopez-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...
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...
International Journal of Neuropsychopharmacology
September 9, 2026
J Keeler, H Himmerich, J Treasure et al.
Abstract Background Approximately a third of people with anorexia nervosa (AN) develop a severe and enduring form of the illness, which is often accompanied by depression. This can be a key barrier to recovery. Anti-depressant medications are less effective in treating depression in patients with acute AN, thus new pharmacological treatment options are needed. Ketamine is currently used for...
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...
International Journal of Neuropsychopharmacology
September 9, 2026
M Di Forti, I Austin-Zimmerman, E Spinazzola et al.
Abstract Background Epidemiological data have consistently shown an association between heavy cannabis use and increased risk of psychotic disorders. Nevertheless, not all cannabis users develop the illness. Evidence from other substance of abuse such as Alcohol suggest how genetic differences in enzymes involved in its metabolism influence individual response to the drug. No studies to data...
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....
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...
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...
International Journal of Neuropsychopharmacology
September 9, 2026
R 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...