Insomnia is common among people with drug-resistant depression and can undermine treatment and quality of life. In a comparison of 50 patients, those taking esketamine combined with other antidepressants had less insomnia than those taking other antidepressants alone. Longer use and higher doses of esketamine were associated with further reductions in insomnia. Esketamine produces a rapid improvement in sleep quality, offering an advantage over standard antidepressants for this population.
A single high dose of psilocybin (10 mg/kg) increased the gene expression of most noncanonical neuropeptides in the hypothalamus of male rats, while decreasing expression of neuromedin U. Psilocybin also raised expression of serotonin receptors 5-HT1A, 5-HT2A, and 5-HT2B, but not 5-HT2C. Ketamine had a more limited effect, increasing only NUCB2, GPR173, and POMC transcripts. These findings suggest psychedelics may alter neuropeptide signaling and serotonin transmission in the hypothalamus, contributing to understanding their brain actions.