Progress in Neuro-Psychopharmacology and Biological Psychiatry
June 28, 2022
Antonio Inserra, Antonella Campanale, David Cheishvili et al.
39 citations
Repeated administration of lysergic acid diethylamide (LSD) to mice over seven days altered DNA methylation at 635 sites and changed the expression of 178 proteins in the prefrontal cortex. The affected genes and proteins are involved in nervous system development, axon guidance, synaptic plasticity, and cell viability. Four specific genes—Coro7, Pef1, Rps24, and Abhd6—showed both increased methylation and increased transcription. These results suggest that LSD modifies epigenetic and protein-expression pathways related to neuroplasticity, which may underlie its therapeutic effects in mental disorders.
Translational Psychiatry
September 4, 2024
Antonio Inserra, Antonella Campanale, Tamim Rezai et al.
24 citations
Rapid-acting antidepressants, such as dissociative anesthetics, psychedelics, and empathogens, may improve psychiatric disorders by modulating neuroplasticity, neurotransmission, and immunity. Preliminary evidence suggests these drugs are accompanied by epigenetic changes—including alterations in DNA methylation, histone modifications, and non-coding RNA regulation—in stress-responsive brain regions, similar to those seen with conventional antidepressants. Whether these epigenetic changes causally contribute to therapeutic effects, are a consequence, or are unrelated remains unknown. Candidate mechanisms involve neuronal activity, serotonin and TRKB signaling, and direct interaction with chromatin. Causation, cell type-specificity, and mechanisms are largely unconfirmed.
Progress in neuro-psychopharmacology & biological psychiatry
August 30, 2024
Antonella Campanale, Antonio Inserra, Stefano Comai
18 citations
The kynurenine pathway (KP) plays a crucial role in the altered gut-brain axis balance in severe mental illness (SMI), including depression, bipolar disorder, and schizophrenia, as well as in cardiometabolic comorbidities. Serotonergic psychedelics may hold therapeutic potential by modulating the KP, either directly through influencing rate-limiting enzymes and tryptophan levels, or indirectly via effects on the gut microbiome, metabolism, and immune system. Preliminary evidence suggests psychedelics improve outcomes in preclinical models of obesity, metabolic syndrome, and vascular inflammation. However, the mechanisms and outcomes remain largely unknown, and concerns about side effects in specific SMI cohorts require further investigation.
Elsevier eBooks
January 1, 2026
Antonio Inserra, Jared VanderZwaag, Antonella Campanale et al.
Microglia, the brain's immune cells, play a crucial role in neuroinflammation linked to cognitive decline. In a study involving 200 participants, those with higher levels of specific alkaloids showed a 30% reduction in neurodegeneration markers. The findings highlight how psychedelics could enhance neuroprotection by modulating histone activity and nicotinic acetylcholine receptors. This intersection of neuroscience and psychology suggests that epigenetics may offer new avenues for addressing neuroinflammation and improving cognitive health, paving the way for innovative drug studies in treating age-related disorders.
Frontiers in neuroscience
January 1, 2025
Antonio Inserra, Colin J Murray, Antonella Campanale et al.
Rapid-acting antidepressants, such as ketamine and serotonergic psychedelics, may affect myelin homeostasis. A systematic review of 41 studies (12 in humans, 21 in animals, 7 in vitro, and 1 computational) found that these drugs modulate myelination in a dose- and exposure-dependent manner: therapeutic doses generally promote myelin integrity and oligodendrocyte maturation, while high or repeated doses, or neonatal exposure, can disrupt myelin structure, impair oligodendrocyte viability, and produce cognitive, affective, and neurotoxic side effects. Myelin regulation may be a component of antidepressant action, but further research is needed to clarify mechanisms and implications for therapy.