Pharmacological research
March 1, 2024
Sandra Ledesma-Corvi, Jordi Jornet-Plaza, Laura Gálvez-melero et al.
22 citations
Adolescent depression often requires faster-acting treatments than standard selective serotonin reuptake inhibitors, which take weeks to work. This review examines promising fast-acting options for adolescents, including non-pharmacological neuromodulation (electroconvulsive therapy and other brain stimulation) and pharmacological approaches such as ketamine, classical psychedelics, and cannabidiol. Most clinical evidence for these therapies comes from adult studies, but recent preclinical work is beginning to address sex-, age-, and dose-related differences that may affect efficacy and safety in adolescents. The authors call for more clinical studies and for designing novel treatments that are both safe and fast-acting for this age group.
Nature communications
November 20, 2025
Alaina M Jaster, Thomas M Hadlock, Belle Buzzi et al.
9 citations
A single dose of the psychedelic psilocybin reduces conditioned behavior and withdrawal caused by the opioid oxycodone in male mice but not in females. This sex-specific effect is mediated by the 5-HT2A receptor in frontal cortex pyramidal neurons that project to the nucleus accumbens. Psilocybin also alters epigenomic regulation after repeated oxycodone exposure and induces sex-specific structural plasticity in the nucleus accumbens independently of the 5-HT2A receptor. Female frontal cortex and nucleus accumbens show fewer changes at gene enhancer regions in response to psilocybin, repeated oxycodone, or their combination compared to males, with the frontal cortex displaying more pronounced sex differences at the epigenomic level.
Pharmacological reports : PR
October 1, 2024
Elena Hernández-Hernández, Sandra Ledesma-Corvi, Jordi Jornet-Plaza et al.
8 citations
A single dose of ketamine produced a fast-acting antidepressant-like effect in 14-month-old male rats, reducing immobility in the forced-swim test within 30 minutes, accompanied by increased levels of mature brain-derived neurotrophic factor (mBDNF) in the prefrontal cortex. However, repeated daily ketamine for 7 days did not sustain antidepressant-like effects and instead decreased mBDNF in the same brain region. Neither acute nor repeated ketamine altered hippocampal cell proliferation or other neurotrophic markers. The findings extend evidence for ketamine's rapid antidepressant potential to older age, but the loss of efficacy with repeated dosing and possible adverse effects in aging require further investigation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
January 1, 2025
Jordi Jornet-Plaza, Sandra Ledesma-Corvi, M Julia García-Fuster
6 citations
Ketamine, approved for treatment-resistant depression in adults, shows potential as an antidepressant for adolescents but with sex-specific dose requirements and safety concerns. In rats, a single dose of 5 mg/kg produced antidepressant-like effects in females and 10 mg/kg in males, while 7-day treatment extended efficacy to lower doses. Safety assessments revealed psychomotor sensitization in adolescent females at the antidepressant dose and addiction liability in adult males re-exposed to ketamine after adolescent treatment. These findings indicate that ketamine's antidepressant effects in adolescence are dose- and sex-dependent, but the observed safety risks warrant caution before clinical translation.