International Journal of Molecular Sciences
February 15, 2023
Martina di Bartolomeo, Tibor Stark, Serena di Martino et al.
23 citations
Rats exposed to the toxin methylazoxymethanol acetate (MAM) before birth or to THC shortly after birth showed adult behaviors resembling schizophrenia, such as social withdrawal and memory problems, along with increased expression of cannabinoid and dopamine receptor genes in the prefrontal cortex linked to DNA methylation changes. Giving THC during adolescence impaired social behavior in otherwise healthy rats but did not worsen the schizophrenia-like traits in rats already exposed to THC after birth. In rats exposed to MAM before birth, adolescent THC paradoxically reversed their memory deficit by altering dopamine receptor gene expression. The effects of adolescent THC exposure appear to depend on individual differences in dopamine signaling.
Psychiatry Research
August 18, 2025
Ilenia Rosa, L. Padula, Francesco Semeraro et al.
2 citations
Treatment-resistant depression (TRD) challenges standard approaches, prompting a shift toward non-monoaminergic interventions like neuromodulation and glutamatergic agents. This narrative review examines the endocannabinoid system (ECS) as a potential common pathway for these treatments. Evidence indicates that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) increase endocannabinoids anandamide and 2-arachidonoylglycerol, correlating with clinical improvement. Ketamine and esketamine modulate CB1 receptors, while psilocybin restores 2-AG and enhances CB1 expression in mood-related brain regions. These findings suggest ECS modulation may unify diverse antidepressant mechanisms in TRD, offering a promising target for novel therapies.
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.