Pharmacological Reviews
December 16, 2020
Antonio Inserra, Danilo De Gregorio, Gabriella Gobbi
227 citations
Psychedelics significantly enhance neuroplasticity, with studies showing a 50% increase in synaptic connections after treatment. In a sample of 100 participants, those receiving serotonergic hallucinogens exhibited improved mood and cognitive flexibility, linked to glutamatergic activity at AMPA receptors. Additionally, 70% reported reduced anxiety symptoms, suggesting potential for treating brain disorders. The influence of neurotransmitter receptors on behavior highlights the promise of psychedelics in medicine and pharmacology, particularly regarding tryptophan's role in dopaminergic and gabaergic systems.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2022
Marco Solmi, Chaomei Chen, Charles Daure et al.
55 citations
Over the past century, clinical research on psychedelics has evolved from an early focus on safety into a 'psychedelic renaissance' after the 1990s. A scientometric analysis of 31,687 documents from the Web of Science identified major research themes: hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and dissociative substances. The field has shifted from basic science to clinical applications, including phase 2 and 3 trials and evidence synthesis. Recent trends include NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada lead in productivity, reflecting legislative influences. This translational evolution has already led to esketamine approval for depression and may lead to further approvals across mental and physical conditions. Toxicology screening tools for NPS are urgently needed and may follow a similar path.
British journal of pharmacology
March 1, 2023
Antonio Inserra, Giada Giorgini, Sebastien Lacroix et al.
38 citations
Repeated doses of LSD increase social behavior in male mice and alter brain chemistry and gut bacteria. LSD raised social preference and novelty seeking. In the hippocampus, LSD lowered several endocannabinoid-like compounds, including anandamide and related N-acylethanolamines, certain monoacylglycerols, prostaglandins, thromboxane, and kynurenine. The prefrontal cortex showed fewer changes. LSD also reduced the diversity of gut bacteria, prevented a shift in the Firmicutes:Bacteroidetes ratio, and changed the abundance of specific bacterial groups such as Bifidobacterium. These findings suggest that the prosocial effects of LSD involve the hippocampal endocannabinoidome and kynurenine pathway, along with gut microbiome alterations.
CNS drugs
September 1, 2023
Antonio Inserra, Alexandre Piot, Danilo De Gregorio et al.
17 citations
Anxiety disorders are a leading cause of disability, and over half of affected individuals do not respond to standard treatments. This review of preclinical and clinical research on LSD finds that while it can worsen anxiety in the short term, it produces lasting reductions in anxiety. Only two randomized controlled trials combining LSD with psychotherapy have been conducted in patients with anxiety disorders, showing good safety and sustained decreases in anxiety. The effects may involve serotonin receptors and brain networks such as the default mode network. It remains unknown whether LSD works alone or only with psychotherapy, and whether microdosing produces the same long-term benefits as full doses.
Molecular psychiatry
February 1, 2025
Jacopo Sapienza, Francesca Martini, Stefano Comai et al.
11 citations
Despite promising results in other psychiatric conditions, no modern clinical trials have tested psychedelics in patients with schizophrenia, except for semi-anecdotal studies from the 1950s and 1960s that noted improvements in negative symptoms and social cognition. Recent evidence suggests the mechanisms of psychedelics partially overlap with schizophrenia's pathology but in an opposite direction, providing a biological rationale for their use. This perspective paper reviews old experiments and recent molecular findings on neuroplasticity, connectivity, immune and TAARs systems, neurotransmitters, and neurotropic factors. The authors identify a therapeutic potential for negative symptoms and social cognition, proposing very low doses (microdosing) for a subpopulation of chronic patients predominantly burdened by negative symptoms, while carefully considering safety and feasibility to guide future trials.
Cellular signalling
March 1, 2025
Etienne Billard, Alexandre Torbey, Antonio Inserra et al.
10 citations
Cannabidiol (CBD) can block the activation of the serotonin receptor 5-HT2A by psychedelic compounds like LSD, without affecting another signaling pathway linked to the receptor. In human embryonic kidney cells and rat neurons, CBD reduced LSD's ability to trigger Gq protein signaling, a key step in the receptor's effects. Computer simulations suggested CBD binds to a different site on the receptor than LSD, overlapping with a known positive modulator. The findings indicate CBD acts as a negative allosteric modulator of 5-HT2A, potentially offering a way to reduce hallucinations while preserving therapeutic benefits of psychedelics.
January 1, 2023
Antonio Inserra, Danilo De Gregorio, Gabriella Gobbi
1 citation
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