Psychedelics

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This laboratory is motivated in exploring the powers of psychedelic compounds on physiological functions, neural circuitry, and psychological disorders. Compounds include lysergic acid diethylamide (LSD), psilocbyin, N,N-dimethyltryptamine (DMT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). These compounds have potent effects on the brain, yet we still understand little about their mechanisms of action. Increasing our understanding of their actions on the brain will allow us to explore potential applications of these drug in the clinical setting but also help us learn more about how the brain functions in pathological states such as schizophrenia and psychosis. In our lab, we are assessing the effects of these drugs at the behavioral, brain circuit, neuronal, and subcellular levels.

Learn more about the field and our current research in our two reviews

Psychedelic Publications

Richardson, B., Inserra, A., Pileggi, M., Prud'Homme, T., Bruno, V., Wan-Yan-Chan, D., Shareghi-Ghahreman, I., Nasini, S., Strand, T., Leyton, M., Sonenberg, N., De Gregorio, D., Sprouse, J., Bambico, F. R., & Gobbi, G. (2025). Differential effects of psilocybin and lisuride on serotonin and dopamine neuronal activity and behavior. Progress in neuro-psychopharmacology & biological psychiatry, 111522. Advance online publication.
Bruno, V., López-Canul, M., Richardson, B., Camarini, R., Marcourakis, T., & Gobbi, G. (2025). High dose of psilocybin induces acute behavioral changes without inducing conditioned place preference in Sprague-Dawley rats. Journal of psychopharmacology (Oxford, England), 2698811251368361. Advance online publication.

Gobbi G. (2024). CCNP Innovations in Neuropsychopharmacology Award: The psychopharmacology of psychedelics: where the brain meets spirituality. Journal of psychiatry & neuroscience : JPN, 49(5), E301–E318.

Inserra, A., Piot, A., De Gregorio, D., & Gobbi, G. (2023). Lysergic Acid Diethylamide (LSD) for the Treatment of Anxiety Disorders: Preclinical and Clinical Evidence. CNS drugs, 37(9), 733–754.

Onofrj, M., Russo, M., Delli Pizzi, S., De Gregorio, D., Inserra, A., Gobbi, G., & Sensi, S. L. (2023). The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics. Translational psychiatry, 13(1), 384.

Inserra, A., Giorgini, G., Lacroix, S., Bertazzo, A., Choo, J., Markopolous, A., Grant, E., Abolghasemi, A., De Gregorio, D., Flamand, N., Rogers, G., Comai, S., Silvestri, C., Gobbi, G., & Di Marzo, V. (2023). Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome. British journal of pharmacology, 180(6), 721–739.

De Gregorio, D., Inserra, A., Enns, J. P., Markopoulos, A., Pileggi, M., El Rahimy, Y., Lopez-Canul, M., Comai, S., & Gobbi, G. (2022). Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(6), 1188–1198.

Aguilar-Valles, A., De Gregorio, D., Matta-Camacho, E., Eslamizade, M. J., Khlaifia, A., Skaleka, A., Lopez-Canul, M., Torres-Berrio, A., Bermudez, S., Rurak, G. M., Simard, S., Salmaso, N., Gobbi, G., Lacaille, J. C., & Sonenberg, N. (2021). Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature, 590(7845), 315–319.

De Gregorio, D., Popic, J., Enns, J. P., Inserra, A., Skalecka, A., Markopoulos, A., Posa, L., Lopez-Canul, M., Qianzi, H., Lafferty, C. K., Britt, J. P., Comai, S., Aguilar-Valles, A., Sonenberg, N., & Gobbi, G. (2021). Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission. Proceedings of the National Academy of Sciences of the United States of America, 118(5), e2020705118.

De Gregorio, D., Enns, J. P., Nuñez, N. A., Posa, L., & Gobbi, G. (2018). d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Progress in brain research, 242, 69–96.

De Gregorio, D., Posa, L., Ochoa-Sanchez, R., McLaughlin, R., Maione, S., Comai, S., & Gobbi, G. (2016). The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors. Pharmacological research, 113(Pt A), 81–91.

Melatonin

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This laboratory is a major contributor to scientific advancement in our understanding of melatonin and its receptors. It is now well know that the neurohormone melatonin affects mood, anxiety and sleep. But which of its receptors, such as MT1 and MT2, mediate these functions is still obscure (see more in ). We have recently characterized the role of the MT2 receptor in the and . We are also investigating the role of novel selective MT1 receptor agonists in the treatment of depression, sleep disorders, and chronic pain (see in ).

Melatonin

López-Canul, M., He, Q., Sasson, T., Ettaoussi, M., Gregorio, D., Ochoa-Sanchez, R., Catoire, H., Posa, L., Rouleau, G., Beaulieu, J. M., Comai, S., & Gobbi, G. (2024). Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT1 Receptors Located in the Locus Ceruleus Norepinephrine Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 44(29), e0914232024.

Posa, L., De Gregorio, D., Lopez-Canul, M., He, Q., Darcq, E., Rullo, L., Pearl-Dowler, L., Luongo, L., Candeletti, S., Romualdi, P., Kieffer, B. L., & Gobbi, G. (2022). Supraspinal melatonin MT2 receptor agonism alleviates pain via a neural circuit that recruits mu opioid receptors. Journal of pineal research, 73(4), e12825.

Posa, L., Lopez-Canul, M., Rullo, L., De Gregorio, D., Dominguez-Lopez, S., Kaba Aboud, M., Caputi, F. F., Candeletti, S., Romualdi, P., & Gobbi, G. (2020). Nociceptive responses in melatonin MT2 receptor knockout mice compared to MT1 and double MT1 /MT2 receptor knockout mice. Journal of pineal research, 69(3), e12671.

Comai, S., Lopez-Canul, M., De Gregorio, D., Posner, A., Ettaoussi, M., Guarnieri, F. C., & Gobbi, G. (2019). Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives. Pharmacological research, 144, 343–356.

Gobbi, G., & Comai, S. (2019). Sleep well. Untangling the role of melatonin MT1 and MT2 receptors in sleep. Journal of pineal research, 66(3), e12544.

Gobbi, G., & Comai, S. (2019). Differential Function of Melatonin MT1 and MT2 Receptors in REM and NREM Sleep. Frontiers in endocrinology, 10, 87.

Posa, L., De Gregorio, D., Gobbi, G., & Comai, S. (2018). Targeting Melatonin MT2 Receptors: A Novel Pharmacological Avenue for Inflammatory and Neuropathic Pain. Current medicinal chemistry, 25(32), 3866–3882.

Comai S, Posa L, Ochoa-Sanchez R, Spadoni G, Gobbi G. (2017). Neuropsychopharmacological properties of novel melatonin MT1 receptor ligands. European Neuropsychopharmacology, 27(4), S569.

Gobbi G, Lopez-Canul M, Ochoa-Sanchez R, Comai S. (2017). Anxiolytic, hypnotic and analgesic properties of melatonin MT2 receptor partial agonists. European Neuropsychopharmacology. 27(4), S569-S570.

López-Canul, M., Comai, S., Domínguez-López, S., Granados-Soto, V., & Gobbi, G. (2015). Antinociceptive properties of selective MT(2) melatonin receptor partial agonists. European journal of pharmacology, 764, 424–432.

Lopez-Canul, M., Palazzo, E., Dominguez-Lopez, S., Luongo, L., Lacoste, B., Comai, S., Angeloni, D., Fraschini, F., Boccella, S., Spadoni, G., Bedini, A., Tarzia, G., Maione, S., Granados-Soto, V., & Gobbi, G. (2015). Selective melatonin MT2 receptor ligands relieve neuropathic pain through modulation of brainstem descending antinociceptive pathways. Pain, 156(2), 305–317.

Comai, S., Ochoa-Sanchez, R., Dominguez-Lopez, S., Bambico, F. R., & Gobbi, G. (2015). Melancholic-Like behaviors and circadian neurobiological abnormalities in melatonin MT1 receptor knockout mice. The international journal of neuropsychopharmacology, 18(3), pyu075.

Ochoa-Sanchez, R., Comai, S., Spadoni, G., Bedini, A., Tarzia, G., & Gobbi, G. (2014). Melatonin, selective and non-selective MT1/MT2 receptors agonists: differential effects on the 24-h vigilance states. Neuroscience letters, 561, 156–161.

Comai, S., & Gobbi, G. (2014). Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology. Journal of psychiatry & neuroscience : JPN, 39(1), 6–21.

Comai, S., Ochoa-Sanchez, R., & Gobbi, G. (2013). Sleep-wake characterization of double MT₁/MT₂ receptor knockout mice and comparison with MT₁ and MT₂ receptor knockout mice. Behavioural brain research, 243, 231–238.

Ochoa-Sanchez, R., Rainer, Q., Comai, S., Spadoni, G., Bedini, A., Rivara, S., Fraschini, F., Mor, M., Tarzia, G., & Gobbi, G. (2012). Anxiolytic effects of the melatonin MT(2) receptor partial agonist UCM765: comparison with melatonin and diazepam. Progress in neuro-psychopharmacology & biological psychiatry, 39(2), 318–325.

Domínguez-López, S., Mahar, I., Bambico, F. R., Labonté, B., Ochoa-Sánchez, R., Leyton, M., & Gobbi, G. (2012). Short-term effects of melatonin and pinealectomy on serotonergic neuronal activity across the light-dark cycle. Journal of psychopharmacology (Oxford, England), 26(6), 830–844.

Ochoa-Sanchez, R., Comai, S., Lacoste, B., Bambico, F. R., Dominguez-Lopez, S., Spadoni, G., Rivara, S., Bedini, A., Angeloni, D., Fraschini, F., Mor, M., Tarzia, G., Descarries, L., & Gobbi, G. (2011). Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(50), 18439–18452.

Rivara, S., Vacondio, F., Fioni, A., Silva, C., Carmi, C., Mor, M., Lucini, V., Pannacci, M., Caronno, A., Scaglione, F., Gobbi, G., Spadoni, G., Bedini, A., Orlando, P., Lucarini, S., & Tarzia, G. (2009). N-(Anilinoethyl)amides: design and synthesis of metabolically stable, selective melatonin receptor ligands. ChemMedChem, 4(10), 1746–1755.

Neuropathic Pain

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Neuropathic pain is a complex pathology that often occurs co-morbid with diseases and injuries, including physical traumas, diabetes, HIV, multiple sclerosis, and more. Full relief from this pain is exceedingly rare for these patients and current available treatments (tricyclic antidepressants, SSRIs, anticonvulsants, and lidocaine) only achieve partial relief from symptoms. Neuropathic pain also accompanies psychiatric comorbidities such as insomnia, depression, and anxiety. There is a massive clinical need to better understand the central and peripheral mechanisms that create this pain in order to create more treatment options. We are exploring alternative treatments for this type of pain, including cannabis derivatives (THC and ) and .

Cannabis

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Does cannabis have an effect on mood? We have demonstrated that cannabis at low doses has antidepressant-like effects in animal models and increases the firing activity of serotonin, a neurotransmitter implicated in mood regulation. At higher doses, cannabis decreases this activity. This process is mediated primarily by the prefrontal cortex. We have also shown that the CB1 antagonist rimonabant decreases serotonin activity (see more in , see also ).

More recently, Dr. Gobbi and colleagues have also replicated these data in humans, showing through a meta-analysis that the consumption of cannabis in adolescence increases the risk of depression and suicidal behavior in young adulthood (see article in ).

Does the enhancement of the endocannabinoid system induce antidepressant-like effects? The enhancement of anandamide (an endogenous cannabinoid), through the blockage of its degrading enzyme FAAH, induces an antidepressant-like effect. The FAAH inhibitors may thus potentially represent a novel target to treat mood disorders (see more in ).

Cannabis Publications

De Gregorio, D., Dean Conway, J., Canul, M. L., Posa, L., Bambico, F. R., & Gobbi, G. (2020). Effects of chronic exposure to low doses of Δ9- tetrahydrocannabinol in adolescence and adulthood on serotonin/norepinephrine neurotransmission and emotional behaviors. The international journal of neuropsychopharmacology, 23(11), 751–761. Advance online publication.

Gobbi, G., Atkin, T., Zytynski, T., Wang, S., Askari, S., Boruff, J., Ware, M., Marmorstein, N., Cipriani, A., Dendukuri, N., & Mayo, N. (2019). Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood: A Systematic Review and Meta-analysis. JAMA psychiatry, 76(4), 426–434.

De Gregorio, D., McLaughlin, R. J., Posa, L., Ochoa-Sanchez, R., Enns, J., Lopez-Canul, M., Aboud, M., Maione, S., Comai, S., & Gobbi, G. (2019). Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain, 160(1), 136–150.

Bambico, F. R., Hattan, P. R., Garant, J. P., & Gobbi, G. (2012). Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission. Progress in neuro-psychopharmacology & biological psychiatry, 38(1), 88–96.

Bambico, F. R., Cassano, T., Dominguez-Lopez, S., Katz, N., Walker, C. D., Piomelli, D., & Gobbi, G. (2010). Genetic deletion of fatty acid amide hydrolase alters emotional behavior and serotonergic transmission in the dorsal raphe, prefrontal cortex, and hippocampus. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35(10), 2083–2100.

Bambico, F. R., Nguyen, N. T., Katz, N., & Gobbi, G. (2010). Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission. Neurobiology of disease, 37(3), 641–655.

Hill, M. N., Hillard, C. J., Bambico, F. R., Patel, S., Gorzalka, B. B., & Gobbi, G. (2009). The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends in pharmacological sciences, 30(9), 484–493.

Bambico, F. R., Duranti, A., Tontini, A., Tarzia, G., & Gobbi, G. (2009). Endocannabinoids in the treatment of mood disorders: evidence from animal models. Current pharmaceutical design, 15(14), 1623–1646.

Bambico, F. R., & Gobbi, G. (2008). The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert opinion on therapeutic targets, 12(11), 1347–1366.

Di Marzo, V., Gobbi, G., & Szallasi, A. (2008). Brain TRPV1: a depressing TR(i)P down memory lane?. Trends in pharmacological sciences, 29(12), 594–600.

Gobbi, G., Bambico, F. R., Mangieri, R., Bortolato, M., Campolongo, P., Solinas, M., Cassano, T., Morgese, M. G., Debonnel, G., Duranti, A., Tontini, A., Tarzia, G., Mor, M., Trezza, V., Goldberg, S. R., Cuomo, V., & Piomelli, D. (2005). Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proceedings of the National Academy of Sciences of the United States of America, 102(51), 18620–18625.

Mood disorders

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Major depression is a mental illness characterized by sadness, lack of pleasure, fatigue, anxiety, sleep, worthlessness, despair, and cognitive impairments. Patients with depression have a high suicide risk. Depression is a major cause of morbidity worldwide, with a lifetime prevalence from 3%-17%. Investigating psychiatric conditions in animal models is challenging, yet critically necessary if we are to understand the disease etiologies and explore new pharmacological therapies. We use different protocols to induce depressive-like and anxiety-like phenotypes in rodents and measure their resultant phenotypes using well-validated behavioral paradigms. Additionally, we are able to corroborate our behavior findings with physiological mechanisms, elucidated through techniques such as in vivo electrophysiology, EEG/ECoG, protein analysis, and dendritic spine analysis. From these models, we are able to test the efficacy of novel treatments for these conditions.

Mood Disorder Publications

Aguilar-Valles, A., Haji, N., De Gregorio, D., Matta-Camacho, E., Eslamizade, M. J., Popic, J., Sharma, V., Cao, R., Rummel, C., Tanti, A., Wiebe, S., Nuñez, N., Comai, S., Nadon, R., Luheshi, G., Mechawar, N., Turecki, G., Lacaille, J. C., Gobbi, G., & Sonenberg, N. (2018). Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E. Nature communications, 9(1), 2459.

Bambico, F. R., Comai, S., Diwan, M., Hasan, S. M. N., Conway, J. D., Darvish-Ghane, S., Hamani, C., Gobbi, G., & Nobrega, J. N. (2018). High frequency stimulation of the anterior vermis modulates behavioural response to chronic stress: involvement of the prefrontal cortex and dorsal raphe?. Neurobiology of disease, 116, 166–178.

Bambico, F. R., Lacoste, B., Hattan, P. R., & Gobbi, G. (2015). Father absence in the monogamous california mouse impairs social behavior and modifies dopamine and glutamate synapses in the medial prefrontal cortex. Cerebral cortex (New York, N.Y. : 1991), 25(5), 1163–1175.

Treatment-Resistant Depression

In recent years, at the ɬ﷬ Health Center, she has developed a registry for patients with treatment-resistant depression, including unipolar and bipolar depression. This Registry is unique in Canada allowing to follow the clinical therapeutic trajectories of people with severe depression. See in . See also .

Clinical Studies

Moderie, C., Nuñez, N., Fielding, A., Comai, S., & Gobbi, G. (2022). Sex Differences in Responses to Antidepressant Augmentations in Treatment-Resistant Depression. The international journal of neuropsychopharmacology, 25(6), 479–488.

Moderie, C., Nuñez, N., Comai, S., Saint-Laurent, M., Fielding, A., Low, N., & Gobbi, G. (2022). Distinct Effects of Antidepressants in Association With Mood Stabilizers and/or Antipsychotics in Unipolar and Bipolar Depression. Journal of clinical psychopharmacology, 42(2), 118–124.

Comai, S., Bertazzo, A., Vachon, J., Daigle, M., Toupin, J., Côté, G., & Gobbi, G. (2019). Trace elements among a sample of prisoners with mental and personality disorders and aggression: correlation with impulsivity and ADHD indices. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 51, 123–129.

Messaoud, A., Mensi, R., Douki, W., Neffati, F., Najjar, M. F., Gobbi, G., Valtorta, F., Gaha, L., & Comai, S. (2019). Reduced peripheral availability of tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 20(9), 703–711.

Nuñez, N. A., Comai, S., Dumitrescu, E., Ghabrash, M. F., Tabaka, J., Saint-Laurent, M., Vida, S., Kolivakis, T., Fielding, A., Low, N., Cervantes, P., Booij, L., & Gobbi, G. (2018). Psychopathological and sociodemographic features in treatment-resistant unipolar depression versus bipolar depression: a comparative study. BMC psychiatry, 18(1), 68.

Gobbi, G., Ghabrash, M. F., Nuñez, N., Tabaka, J., Di Sante, J., Saint-Laurent, M., Vida, S., Kolivakis, T., Low, N., Cervantes, P., Booij, L., & Comai, S. (2018). Antidepressant combination versus antidepressants plus second-generation antipsychotic augmentation in treatment-resistant unipolar depression. International clinical psychopharmacology, 33(1), 34–43.

Ismaylova, E., Di Sante, J., Szyf, M., Nemoda, Z., Yu, W. J., Pomares, F. B., Turecki, G., Gobbi, G., Vitaro, F., Tremblay, R. E., & Booij, L. (2017). Serotonin transporter gene promoter methylation in peripheral cells in healthy adults: Neural correlates and tissue specificity. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 27(10), 1032–1041.

Nuñez, N. A., & Gobbi, G. (2017). Lurasidone and Mood Stabilizers in Treatment-Resistant Unipolar Depression: A Case Report Study. Journal of clinical psychopharmacology, 37(2), 263–264.

Ghabrash, M. F., Comai, S., Tabaka, J., Saint-Laurent, M., Booij, L., & Gobbi, G. (2016). Valproate augmentation in a subgroup of patients with treatment-resistant unipolar depression. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 17(2), 165–170.

Blier, P., Gobbi, G., Turcotte, J. E., de Montigny, C., Boucher, N., Hébert, C., & Debonnel, G. (2009). Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 19(7), 457–465.

Gobbi, G., Gaudreau, P. O., & Leblanc, N. (2006). Efficacy of topiramate, valproate, and their combination on aggression/agitation behavior in patients with psychosis. Journal of clinical psychopharmacology, 26(5), 467–473.

Other

Other fields of research we have examined in the past include the , (and), the role of in depression and anxiety, effects of , the impact of , and impacts of .