Gabriella Gobbi

• MD, PhD
• Professor (Full) at McGill University Health Centre

Background Neuropathic pain (NP) is a chronic and debilitating condition frequently comorbid with insomnia. However, the alterations in sleep architecture under NP conditions and the mechanisms underlying both pain and sleep disturbances remain poorly understood. The reticular thalamic nucleus (RTN) plays a crucial role in non-rapid eye movement sl...

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...

Sleep, constituting approximately one‐third of the human lifespan, is a crucial physiological process essential for physical and mental well‐being. Normal sleep consists of an orderly progression through wakefulness, non‐rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referre...

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 th...

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 underpin...

Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid eye movement sleep (REMS) are lacking. This polysomnographic study in male rats showed that the first-in-class se...

Background The endocannabinoid (eCB) system and the serotonin (5-HT) are both implicated in the severity of the depression. 5-HT is synthesized from the amino acid tryptophan (Trp), which is also a precursor for kynurenine (Kyn) whose production is increased at the expense of 5-HT in depressed patients. No clinical studies have investigated the cro...

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 stat...

Purpose/Background Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT 2A , 5-HT 2C , H 1 , and D 2 as antagonists and on 5-HT 1A as partial agonists. Patients with TRD often have comorbid personality disorder (P...

Participating in scientific conferences and professional networking support productivity in research. However, there are barriers for early career scientists to benefit from these activities. In 2023, the International College of Neuropsychopharmacology (CINP) Committee for Early Careers organised the first edition of the CINP Research Fellowship f...

Mounting evidence suggests safety and tolerability of cannabis-derived and psychedelic drugs as potential novel therapeutics for psychiatric, as well as sleep and pain disorders. Evidence concerning the therapeutic efficacy of these compounds remains controversial, although some promising preliminary results are available for them in specific disor...

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 con...

Aims: Melatonin is known to inhibit platelet aggregation induced by arachidonic acid (AA). In the present study we investigated whether agomelatine (Ago), an antidepressant with agonist activity at melatonin receptor 1 (MT1) and MT2 could reduce platelets aggregation and adhesion. Main methods: Human platelets from healthy donors were used to te...

An updated third edition of this award-winning book provides a comprehensive overview of the complex associations between cannabis and mental illness. Organised into easy to navigate sections, the book has been fully revised to feature eight entirely new chapters covering important novel aspects. Marijuana and Madness incorporates new research find...

Neuropathic pain (NP) is often treated with opioids, the prolonged use of which causes tolerance to their analgesic effect and can potentially cause death by overdose. The phytocannabinoid delta-9-tetrahydrocannabinol (THC) may be an effective alternative analgesic to treat NP in morphine-tolerant subjects. Male Wistar rats developed NP after spare...

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comor...

Background and Purpose 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. Experimental Approac...

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 p...

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...

Melatonin, through its G protein‐coupled MT2 receptor, is implicated in analgesia, but the relationship between MT2 receptors and the opioid system remains elusive. In a model of rodent neuropathic pain (spared nerve injured, SNI), the selective melatonin MT2 agonist UCM924 reversed the allodynia (a pain response to a non‐noxious stimulus), and thi...

Aim: Psychedelic 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). Methods: Whole genome bisulphit...

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...

Background: Women are nearly twice as likely as men to suffer from major depressive disorder. Yet, there is a dearth of studies comparing the clinical outcomes of women and men with treatment-resistant depression (TRD) treated with similar augmentation strategies. We aimed to evaluate the effects of the augmentation strategies in women and men at...

Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-HT2A agonists lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), and their derivatives. These findings suggest a therapeutic potential of psychedelic compounds for some of the...

Purpose/background: There is a dearth of studies comparing the clinical outcomes of patients with treatment-resistant unipolar (TRD) depression and depression in bipolar disorder (BD) despite similar treatment strategies. We aimed to evaluate the effects of the pharmacological combinations (antidepressants [AD], mood stabilizers [MS], and/or antip...

Purpose/background: The link between substances of abuse, impulsivity, and violence in psychotic patients remains unclear. This study aims at unraveling whether cannabis use disorder is associated with violent and/or psychotic behavior in patients who are hospitalized in a high-security hospital. Methods/procedures: We conducted a cross-sectiona...

Background The increased degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway due to inflammation and/or activation of the hypothalamic-pituitary–adrenal (HPA) axis has been reported among the biological factors involved in the pathophysiology of major depressive disorder (MDD) and suicide. However, the interaction among these multipl...

While extensive research exists on parental loss in childhood and the related psychological interventions, little has been done in the adolescent population. Adolescence is a particular phase of life characterized by a singular psychological, emotional, neurological, and endocrinological development, paralleled by the process of self-affirmation an...

The MT2‐selective melatonin receptor ligand UCM765 (N‐(2‐((3‐methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modificat...

Introduction Autism Spectrum Disorder and Social Anxiety Disorder are mental illnesses characterized by a dysfunction in social behavior (SB); a phenomenon largely mediated by the medial prefrontal cortex (mPFC). Clinical studies have demonstrated that lysergic acid diethylamide (LSD), a partial agonist of the 5-HT 2A receptor, can promote SB. Howe...

Background: The reticular thalamus gates thalamocortical information flow via finely tuned inhibition of thalamocortical cells in the mediodorsal thalamus. Brain imaging studies in humans show that the psychedelic lysergic acid diethylamide (LSD) modulates activity and connectivity within the cortico-striato-thalamo-cortical (CSTC) circuit, alteri...

Effective pharmacotherapy for major depressive disorder remains a major challenge, as more than 30% of patients are resistant to the first line of treatment (selective serotonin reuptake inhibitors)1. Sub-anaesthetic doses of ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist2,3, provide rapid and long-lasting antidepressant effec...

Clinical studies have reported that the psychedelic lysergic acid diethylamide (LSD) enhances empathy and social behavior (SB) in humans, but its mechanism of action remains elusive. Using a multidisciplinary approach including in vivo electrophysiology, optogenetics, behavioral paradigms, and molecular biology, the effects of LSD on SB and glutama...

Mounting evidence suggests safety and efficacy of psychedelic compounds as potential novel therapeutics in psychiatry. Ketamine has been approved by the Food and Drug Administration in a new class of antidepressants, and 3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials for post-traumatic stress disorder. Psilocybin a...

A revamped interest in the study of hallucinogens has recently emerged, especially with regard to their potential application in the treatment of psychiatric disorders. In the last decade, a plethora of preclinical and clinical studies have confirmed the efficacy of ketamine in the treatment of depression. More recently, emerging evidence has point...

On June 16th, 2020, Prof. Franco Luigi Fraschini peacefully passed away in his home in Milan, Italy,surrounded by his loving wife and family. Franco Fraschini was an inspiring leader in the field of melatonin research and circadian biology. His research and teaching inspired many young scholars who are now researchers and professors in academic ins...

Background: Chronic exposure to the Δ9-tetrahydrocannabinol (THC), the main cannabis pharmacological component, during adolescence has been shown to be associated with an increased risk of depression and suicidality in humans. Aims: Little is known about the impact of the long-term effects of chronic exposure to low doses of THC in adolescent co...

Melatonin, a neurohormone that binds to two G‐protein coupled receptors MT1 and MT2, is involved in pain regulation, but the distinct role of each receptor has yet to be defined. We characterized the nociceptive responses of mice with genetic inactivation of MT1 (MT1‐/‐), or MT2 (MT2‐/‐), or both MT1/MT2 (MT1‐/‐/MT2‐/‐) receptors in the hot plate t...

Melatonin (MLT) levels fluctuate according to the external light/dark cycle in both diurnal and nocturnal mammals. We previously demonstrated that MT2 receptor knockout (MT2‐/‐) mice show a decreased non‐rapid eye sleep over 24‐hr and increased wakefulness during the inactive (light) phase. Here, we investigated the role of MT2 receptors in physiol...

The muscarinic acetylcholine receptor antagonist scopolamine elicits rapid antidepressant activity, but its underlying mechanism is not fully understood. In a chronic stress model, a single low-dose administration of scopolamine reversed depressive-like reactivity. This antidepressant-like effect was mediated via a muscarinic M1 receptor-SKC pathwa...

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We ha...

Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptors agonist are clinically used in some neuropsychiatric and/or sleep disorders. However, the selective role played by MT1 and MT2...

The pathophysiological function of the G-protein coupled melatonin MT1 and MT2 receptors has not yet been well-clarified. Recent advancements using selective MT1/ MT2 receptor ligands and MT1/MT2 receptor knockout mice have suggested that the activation of the MT1 receptors are mainly implicated in the regulation of rapid eye movement (REM) sleep,...

Importance Cannabis is the most commonly used drug of abuse by adolescents in the world. While the impact of adolescent cannabis use on the development of psychosis has been investigated in depth, little is known about the impact of cannabis use on mood and suicidality in young adulthood. Objective To provide a summary estimate of the extent to wh...

The pharmacological potential of targeting selectively melatonin MT1 or MT2 receptors has not yet been exploited in medicine. Research using selective MT1/MT2 receptor ligands and MT1/MT2 receptor knockout mice has indicated that the activation of MT2 receptors selectively increases non‐rapid eye movement (NREM) sleep whereas MT1 receptors seem mos...

Background: Antidepressants have a low rate of response paired with a delayed onset of action. Translational studies are thus seeking for novel targets for antidepressant drug development. Preclinical evidence has demonstrated that the endocannabinoid system plays an important role in mood and stress response, even if drugs targeting this system ha...

Clinical studies indicate that cannabidiol (CBD), the primary non-addictive component of cannabis that interacts with the serotonin (5-HT) 1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact in models of neuropathic pain are unknown. First, using in-vivo single unit extrac...

Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution in the pathophysiology of depressive disorders is not fully understood. We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic init...

Some evidence suggests that the cerebellum modulates affect via connectivities with mood-regulating corticolimbic structures, such as the prefrontal cortex and monoamine nuclei. In rats exposed to chronic unpredictable stress (CUS), we examined the neuro-behavioural effects of high frequency stimulation and surgical ablation/disconnection of the ce...

Objectives: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of...

Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clin...

Background: Some authors have hypothesized that Treatment-Resistant Unipolar Depression (TRD-UP) should be considered within the bipolar spectrum disorders and that hidden bipolarity may be a risk factor for TRD-UP. However, there are neither studies comparing clinical and sociodemographic data of patients with TRD-UP versus Bipolar (BP) disorders...

Depression and anxiety are psychiatric diagnoses commonly associated with low quality of life and low percentage of responsiveness by patients treated with currently available drugs. Thus, research into alternative compounds to treat these disorders is essential to guarantee a patient's remission. The last decade has witnessed a revamped interest f...

Patients with treatment-resistant unipolar depression (TRD) are treated with antidepressant combinations (ADs) or with second-generation antipsychotics plus AD (SGA+AD) augmentation; however, the clinical characteristics, the factors associated independently with response to SGA+AD, and the outcome trajectories have not yet been characterized. We p...

Early adversity can influence gene expression via epigenetic mechanisms, including DNA methylation. Peripheral tissues are essential in psychiatric epigenetics, as methylation generally cannot be assessed in the living human brain. Several magnetic resonance imaging (MRI) studies show associations of peripheral serotonin transporter gene (SLC6A4) m...

Background: The management of depressive and mixed symptoms in children and adolescents with bipolar disorder (BD) remains a matter of debate. The goal of this review is, thus, to systematically examine the impact of atypical antipsychotics (AAPs) and mood stabilisers in the treatment of bipolar depression and/or mixed states. Methods: A literat...

Background: Melatonin (5-methoxy-N-acetyltryptamine) is a hormone that has numerous physiological functions. Synthesized and released during nighttime, melatonin exerts its physiological effects in a circadian manner. Melatonin acts by binding to its different types of receptors. The purpose of this systematic review is to summarize recent findings...

Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G-protein coupled receptors, MT1 and MT2. In this review, we present the analgesic properties of MLT in preclinical and clinical studies, giving particular emphasis to the effects mediated by MT2 receptors and to recent investigations...

The psychological feelings produced by cannabis have been described as fatuous euphoria, elation, and talkativeness. However, heavy cannabis consumption can induce mood disturbances and lead to depression, especially after chronic use. Despite these clinical findings, little was known about the capacity of cannabis to modulate the transmission of s...

d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science...

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 d...

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Ag...

Aggressive behavior is one of the most challenging symptoms in psychiatry, and biological markers for aggression lack of large sample validations. Serotonin (5-HT) and other neuroactive compounds deriving from Tryptophan (Trp), including kynurenine (Kyn), have not yet been investigated in large cohorts of aggressive individuals to validate their po...

Suicide constitutes a serious medical and social problem. There are several risk factors for suicide including history of mental disorders, alcohol and substance abuse, impulsive or aggressive tendencies, family history of suicide, family history of child maltreatment, previous suicide attempts, feelings of hopelessness, cultural and religious beli...

The fatty acid amide hydrolase (FAAH) inhibitor URB597 increases anandamide, resulting in antidepressant/anxiolytic-like activity, likely via CB1 receptor-mediated modulation of serotonin (5-HT) and norepinephrine (NE) neurotransmission. However, the relative importance of the 5-HT and NE systems in these effects and on effects of URB597 on postsyn...

Objectives: About 50% of patients with unipolar depression suffer from treatment-resistant depression (TRD). Animal studies have suggested potential antidepressant properties of valproate (VPA) possibly due to its implication in epigenetic programming. Methods: Fourteen TRD patients (seven males and seven females; age 19-59) received VPA (375-10...

Objective: To determine if separation from a father is associated with short-term changes in mental health or substance use in adolescents. Methods: Every 3 months, during a 5-year period, we followed 1160 Grade 7 students participating in the Nicotine Dependence in Teens Study who were living with both parents. Participants who reported not liv...

The involvement of melatonin in mammalian brain pathophysiology has received growing interest, but information about the anatomical distribution of its two G-protein coupled receptors, MT1 and MT2 , remains elusive. In the present study, using specific antibodies, we examined the precise distribution of both melatonin receptors immunoreactivity acr...

Neuropathic pain is an important public health problem for which only a few treatments are available. Preclinical studies show that melatonin (MLT), a neurohormone acting on MT1 and MT2 receptors, has analgesic properties, likely through MT2 receptors. Here, we determined the effects of the novel selective MLT MT2 receptor partial agonist N-{2-([3-...

Melancholic depression, described also as endogenous depression, is a mood disorder with distinctive specific psychopathological features and biological homogeneity, including anhedonia, circadian variation of mood, psychomotor activation, weight loss, diurnal cortisol changes, and sleep disturbances. Although several hypotheses have been proposed,...

Background Antisocial personality disorder (ASPD) is characterised by elevated impulsive aggression and increased risk for criminal behaviour and incarceration. Deficient activity of the monoamine oxidase A (MAOA) gene is suggested to contribute to serotonergic system dysregulation strongly associated with impulsive aggression and antisocial crimin...

Direct evidence that dopamine (DA) neurotransmission varies during the 24 h of the day has been lacking. Here, we have characterized the firing activity of DA neurons located in the ventral tegmental area (VTA) using single-unit extracellular recordings in anesthetized rats kept on a standard light-dark cycle. DA neuronal firing activity was measur...