Brief introduction

Danilo De Gregorio obtained a Pharm.D degree from the University of Naples “Federico II”, Italy, followed by a Ph.D. in Pharmacological Science and Experimental Medicine from the University of Campania “Vanvitelli”, Naples, Italy. He trained as a postdoctoral fellow at the Department of Psychiatry, McGill University, Montreal (QC), Canada under the supervisions of Prof. Gabriella Gobbi and Prof.  Nahum Sonenberg. In March 2021, he relocated back to Italy where he has been appointed Assistant Professor of Pharmacology at the Vita-Salute San Raffaele University and Project Leader of the Neuropsychopharmacology Unit of the San Raffaele Scientific Institute.  By combining cutting-edge in vivo behavioral and electrophysiological techniques in animal models, Danilo has made contributions to the understanding of the psychopharmacology of psychoactive compounds including hallucinogens and cannabinoids and their role in mental disorders.  His work has been published in relevant scientific journals (including Nature, PNAS, Nature Communications). He has received numerous awards for his work including grants from the Canadian Institute of Health Research (CIHR), the Fonds pour la recherche en Santé du Québec. Since March 2024, he holds the position of Associate Professor in Pharmacology at the Vita-Salute San Raffaele University. Currently, his research is supported by the Zardi Gori Foundation and by the Ministry of University and Research (2023).

Research activity

Psychoactive drugs alter brain function, influencing thoughts, actions, and emotions. Each drug carries unique risks, but they share the ability to induce addiction and exacerbate mental illness symptoms. Low doses of selectedpsychoactive compounds, such as hallucinogens, have been suggested to be useful to treat distinct mental disorders. Using a combination of behavioral assays and electrophysiology in rodents, our goal is to comprehend how these drugs affect behavior in healthy subjects as well as in psychiatric diseases. Particularly, our team is interested on the exploration of the effects of hallucinogenic compounds such as LSD (lysergic acid diethylamide) and ketamine in the treatment of psychiatric disorders. Nowadays, hallucinogens represent a growing area of interest in neuroscience research since these studies are foundational for understanding potential therapeutic mechanisms and for preclinical validation before human trials. LSD affects neurotransmitter systems associated with mood and cognition, which are often dysregulated in psychiatric disorders. In rodent models, LSD promotes sociability (De Gregorio et al., 2021, PNAS) and reduce anxiety-like behaviors (De Gregorio et al., 2002, Neuropsychopharmacology). These effects are thought to be mediated through the serotonin 5-HT2A receptor, a common target of many psychedelics. Our lab is currently investigating the potential use of LSD to reduce alcohol consumption. Ketamine, on the other hand, is not traditionally classified as a hallucinogen but rather as a dissociative anesthetic. It has gained significant attention for its rapid-acting antidepressant effects in both clinical and preclinical settings. In rodent models, ketamine has been demonstrated to quickly alleviate symptoms of depression and has been observed to promote synaptic remodeling, particularly in the prefrontal cortex and hippocampus. The antidepressant effects of ketamine are primarily attributed to its action on the NMDA receptor, a type of glutamate receptor, which leads to the activation of mammalian target of rapamycin (mTOR) signaling pathway (Aguilar-Valles, De Gregorio et al., Nature). These studies help clarify the neurobiological mechanisms through which these drugs exert their effects, such as alterations in neuroplasticity, neurotransmitter modulation, and changes in network connectivity. This ongoing research is critical, given the complexity of psychiatric illnesses and the limitations of current treatments.

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