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....
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...
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...
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...
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...
Abstract Background Pain conditions are major health problems resulting in physical, psychological and social impairment (1), and health care costs (2,3). Within the last decade, research has demonstrated that 5-HT2A agonists including psilocybin and LSD elicit spiritual experiences (4) and functional connectivity changes between diverse brain areas (5). Therefore, it is pertinent to...
Abstract Background Lysergic acid diethylamide (LSD), a serotonergic psychedelic, has gained renewed interest for its potential anxiolytic effects in clinical trials. However, the neurobiological mechanisms underlying these effects remain poorly understood. Aims & Objectives The goal of this study is to understand the mechanism of action of LSD in animal models by using in vivo...
Classic serotonergic psychedelics act primarily via 5-HT2A receptor agonism, yet their therapeutic effects and biological responses are heterogeneous. Biological sex remains an underexamined source of this variability because many clinical and preclinical studies have not been designed to test sex-by-treatment effects. Recent preclinical findings, together with more limited human evidence,...
BACKGROUND: Over the past decade, neuropsychopharmacology has shifted from stagnation to momentum, with first-in-class mechanisms and biomarker-enabled trials spanning psychiatry and neurology. METHODS: We narratively synthesized advances from 2013 to 2026 across central nervous system (CNS) discovery and development, including pivotal trials, regulatory actions, digital/real-world evidence,...
This Genomic Press Interview features Dr. Gabriella Gobbi, Professor of Psychiatry at McGill University, Canada Research Chair (Tier 1) in Therapeutics for Mental Health, Staff Psychiatrist at the McGill University Health Center (MUHC), and Senior Scientist, Brain Repair and Integrative Neuroscience Program at the Research Institute of the MUHC. Trained in medicine and psychiatry at the...
Psilocybin and lisuride are 5-HT2A receptor agonists, but only psilocybin elicits the head twitch response (HTR) in rodents, a behavior commonly used as a proxy for hallucinogenic activity. This study aimed to compare their effects on serotonin (5-HT) and dopamine (DA) neuronal activity, as well as related behavioral outcomes, to elucidate the mechanisms underlying their divergent effects....
Background: In recent years, there has been a resurgence of scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related effects of psilocybin and its impact on behavior remain underexplored. Aims: We aimed to evaluate the potential rewarding effects of high doses of psilocybin and its effects on rat behavior....
Abstract Background Recent years have seen renewed scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related properties and behavioral impacts of a high dose of psilocybin remain insufficiently explored. Aims & Objectives Assessing the potential rewarding properties of a high dose of psilocybin (10 mg/kg...
Abstract Background Psychedelics hold potential as therapeutics in psychological disorders. Even if they primarily act on 5-HT2A receptors, their mechanisms and effects on the brain are not well understood. Simply activating 5-HT2A receptors does not induce psychedelic effects. For example, psilocybin and lisuride both bind to 5-HT2A receptors, but only psilocybin induces hallucinogenic...
Promising clinical evidence suggests that psychedelic compounds, like lysergic acid diethylamide (LSD), have therapeutic value for treatment of psychiatric disorders. However, they often produce hallucinations and dissociative states, likely mediated by the serotonin (5-HT) receptor 5-HT2A, raising challenges regarding therapeutic scalability. Given the reported antipsychotic effects of...
Abstract Background Pain is a major health problem resulting in a high degree of suffering, physical, psychological and social impairments, and exorbitant health care costs1-2. Effective pain treatments are limited and are often accompanied by significant side effects3. Preclinical and clinical studies suggest that psychedelics, specifically psilocybin, can reset brain areas of functional...
For 3000 years, psychedelics have been used in religious contexts to enhance spiritual thinking, well-being, and a sense of community. In the last few years, a renaissance in the use of psychedelic drugs for mental disorders has occurred in Western society; consequently, a pressing scientific need to elucidate the intricate mechanisms underlying their actions has arisen. Psychedelics mainly...
Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and...
The PD-DLB psychosis complex found in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) includes hallucinations, Somatic Symptom/Functional Disorders, and delusions. These disorders exhibit similar presentation patterns and progression. Mechanisms at the root of these symptoms also share similarities with processes promoting altered states of consciousness found in Rapid Eye Movement...
Anxiety disorders (ADs) represent the sixth leading cause of disability worldwide, resulting in a significant global economic burden. Over 50% of individuals with ADs do not respond to standard therapies, making the identification of more effective anxiolytic drugs an ongoing research priority. In this work, we review the preclinical literature concerning the effects of lysergic acid...
Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7...
A scientometric analysis was realized to outline clinical research on psychedelics over the last century. Web of Science Core Collection was searched up to March 18, 2022, for publications on psychedelics. Network analyses and bibliometrics were combined, to identify research themes and trends with Bibliometrix and CiteSpace. The primary aim was to measure research trends evolution over time,...
Psychedelics have been already used by human societies for more than 3000 years, mostly in religious and healing context. The renewed interest in the potential application of psychedelic compounds as novel therapeutics has led to promising preliminary evidence of clinical benefit in some psychiatric disorders. Despite these promising results, the potential for large-scale clinical application...
AimPsychedelic compounds elicit relief from mental disorders. However, the underpinnings of therapeutic improvement remain poorly understood. Here, we investigated the effects of repeated lysergic acid diethylamide (LSD) on whole-genome DNA methylation and protein expression in the mouse prefrontal cortex (PFC).MethodsWhole genome bisulphite sequencing (WGBS) and proteomics profiling of the...
Lysergic acid diethylamide (LSD) is a serotonergic psychedelic compound receiving increasing interest due to putative anxiolytic and antidepressant properties. However, the potential neurobiological mechanisms mediating these effects remain elusive. Employing in vivo electrophysiology, microionthophoresis, behavioral paradigms and morphology assays, we assessed the impact of acute and chronic...