Neurodevelopmental disorders (NDDs) comprise a heterogeneous group of conditions arising from altered brain development and leading to impairments in social, cognitive, emotional, and motor domains. Clinical manifestations are highly variable in severity and symptom profile, reflecting the complex and multifactorial etiology of NDDs. Available treatments are limited to early behavioral...
Perioperative depressive symptoms (PDSs) are common among patients who undergo major surgery and can lead to worse clinical outcomes. Esketamine has been reported to alleviate PDSs in patients undergoing certain types of surgery. However, there is a lack of evidence from large-scale, multisurgery studies to support its therapeutic effects in individuals with preexisting moderate-to-severe PDSs....
Pharmacological ResearchDecember 29, 2025Martina Colognesi, Daniela Gabbia, Anna Signor et al.3 citations
The therapeutic potential of low, non-psychedelic doses of psilocybin, a fungal tryptamine alkaloid, was investigated in metabolic disorders including obesity, type 2 diabetes mellitus (T2DM), and liver steatosis. Mice fed a high-fat/high-fructose diet received chronic treatment with psilocybin (0.05 mg/kg) for 12 weeks. Body weight, liver histology, insulin sensitivity, and skeletal muscle...
Pharmacological ResearchNovember 22, 2025Zhuo-Ning Zhang, Xin-Yu Hao, Chen Cai et al.5 citations
This randomized, double-blind, parallel-group trial evaluated the efficacy of a single intravenous dose of esketamine (0.3mg/kg) administered at anesthesia induction in reducing postoperative depression and anxiety among patients undergoing cardiac valve surgery. A total of 142 patients from three centers were randomly assigned to receive esketamine or saline. The primary outcomes were the...
Treatment-resistant depression (TRD) represents a major clinical challenge. Affecting about 30 % of major depressive disorder (MDD) patients, effective treatments for TRD are urgently needed. While depression research and antidepressant (AD) development have long centred on monoaminergic targets, research over the past 35 years has increasingly explored glutamatergic mechanisms. Here we present...
Pharmacological ResearchJuly 31, 2025C. Pisanu, R. Carvalho Silva, Mattia Meattini et al.6 citations
Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However,...
People with eating disorders experience high rates of psychiatric comorbidities, including anxiety disorders such as generalised anxiety disorder, social anxiety disorder and specific phobias. Anxiety can influence the prognosis of an eating disorder, by worsening symptoms, and acting as a barrier to treatment. Therefore, targeting treatment efforts towards anxiety may improve eating disorder...
Chronic pain is a debilitating disease with current treatments lacking efficacy and safety, therefore discovery of new treatments is crucial. Initial studies suggest that psychedelics may be feasible for targeting pain, however clinical and preclinical controlled studies are necessary to further investigate that possibility. In this study we assessed the effects of two classical psychedelics...
Δ9-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, acts in the brain primarily via cannabinoid CB1 receptors. These receptors are implicated in several forms of synaptic plasticity - depolarization-induced suppression of excitation (DSE), metabotropic suppression of excitation (MSE), long term depression (LTD) and activation-dependent desensitization. Cultured...
Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls,...
Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain...
The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here,...
There is an urgent need for novel fast-acting antidepressants for adolescent treatment-resistant depression and/or suicidal risk, since the selective serotonin reuptake inhibitors that are clinically approved for that age (i.e., fluoxetine or escitalopram) take weeks to work. In this context, one of the main research lines of our group is to characterize at the preclinical level novel...
Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical...
Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic...
Ibogaine is a powerful psychoactive substance that not only alters perception, mood and affect, but also stops addictive behaviors. Ibogaine has a very long history of ethnobotanical use in low doses to combat fatigue, hunger and thirst and, in high doses as a sacrament in African ritual contexts. In the 1960's, American and European self-help groups provided public testimonials that a single...
OBJECTIVE Cannabis sativa is a recreational drug commonly consumed in Europe and is getting popularity for both recreational and therapeutic use. In some individuals, the use of cannabis leads to psychotic disorders. This systematic review summarizes the current evidence linking genetic polymorphisms and inter-individual susceptibility to psychosis induced by cannabis. METHOD Studies published...
We have here assessed, using Δ9-tetrahydrocannabinol (Δ9-THC) for comparison, the effect of Δ9-tetrahydrocannabinolic acid (Δ9-THCA) and of Δ9-tetrahydrocannabivarin (Δ9-THCV) that is mediated by human versions of CB1, CB2, and CB1-CB2 receptor functional units, expressed in a heterologous system. Binding to the CB1 and CB2 receptors was addressed in living cells by means of a homogeneous...
The recent shift in socio-political debates and growing liberalization of Cannabis use across the globe has raised concern regarding its impact on vulnerable populations such as adolescents. Concurrent with declining perception of Cannabis harms, more adolescents are using it daily in several countries and consuming marijuana strains with high content of psychotropic delta...
Perinatal exposure to Δ9-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) and the dopamine D2 receptor (Drd2) in perinatal...
Graphical abstract Figure. No Caption available. Abstract The 3,4‐methylenedioxymethamphetamine (MDMA) is a popular recreational drug, which ultimately leads to serotonergic (5‐HT) neurotoxicity and psychiatric disorders. Previous in vitro studies have consistently demonstrated that MDMA provokes autophagic activation, as well as damage of 5‐HT axons and nerve fibers. So far, whether autophagy,...
The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) and CBD are the major pharmacologically active...
Pharmacological ResearchDecember 2016Francesca Felicia Caputi, Martina Palmisano, Lucia Carboni et al.
The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been shown to produce neurotoxic damage and long-lasting changes in several brain areas. In addition to the involvement of serotoninergic and dopaminergic systems, little information exists about the contribution of nociceptin/orphaninFQ (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by MDMA....
d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT1 and 5-HT2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity,...
Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly...