Translational Psychiatry
June 24, 2026
Mauro Pettorruso, Giacomo D’andrea, Antonio Inserra et al.
Emerging clinical and preclinical evidence suggests that the therapeutic benefits of psychedelics for depression and anxiety may be separable from their consciousness-altering effects. Psychedelics produce profound brain changes, including suppression of the default mode network, leading to intense subjective experiences such as ego dissolution. These effects require extensive preparation and integration, exclude individuals with certain psychiatric vulnerabilities, and raise scalability concerns. Pharmacological strategies like serotonin 2A receptor antagonism and development of biased psychedelic analogues might retain therapeutic efficacy without psychedelic experiences. Preclinical data indicate that downstream molecular and network-level mechanisms could mediate therapeutic effects independently of subjective states. Confirming this dissociation could enable more scalable, accessible treatments for broader psychiatric populations.
Clinical Neuropsychopharmacology and Addiction
April 17, 2026
Antonio Inserra, Francesca Zoratto, Mauro Pettorruso et al.
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Psychopharmacology
April 14, 2026
Guilherme Lodetti, Antonio Inserra, Henrique Redivo et al.
A single exposure to ayahuasca reversed behavioral and biochemical changes caused by 14 days of unpredictable chronic stress in adult zebrafish. Stressed fish showed impaired sociability, anxiety-like behavior, hyperactivity, elevated whole-body cortisol, and reduced whole-brain BDNF. Ayahuasca restored sociability, reduced anxiety-like behavior and hyperactivity, normalized cortisol levels, and increased BDNF. These findings suggest ayahuasca can reverse stress-induced behavioral and neuroendocrine alterations, supporting further clinical studies for chronic stress.
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.
The International Journal of Neuropsychopharmacology
February 1, 2025
Martha Lopez Canul, Vivienne Nguyen, Antonio Inserra et al.
Acute administration of psilocybin reduced mechanical allodynia in a rat model of neuropathic pain but had no effect on acute thermal pain in mice. In the neuropathic pain model, psilocybin at 3 mg/kg and 10 mg/kg significantly increased mechanical withdrawal thresholds at 0.5, 1, and 2 hours after administration compared to vehicle, with no difference between the two doses. In the hot plate test, psilocybin did not raise the thermal withdrawal threshold. These preliminary findings suggest psilocybin's pain-reducing action may specifically target neuropathic pain rather than generalized acute nociception, indicating potential for treating neuropathic pain.
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.