Depression and anxiety are common psychiatric diagnoses with low quality of life and poor response to current drugs, driving research into alternative compounds. Psychedelic medicine, particularly low doses of LSD and psilocybin, has shown antidepressant effects in anecdotal reports and clinical studies. These compounds modulate mood through serotonergic, dopaminergic, and glutamatergic systems; LSD interacts with 5-HT1A, 5-HT2A, D2, and NMDA receptors. Randomized clinical studies have confirmed antidepressant and anxiolytic effects in humans. This chapter reviews psychedelic pharmacology, presents clinical evidence for therapeutic potential in mood disorders, and discusses future directions.
For adults with treatment-resistant depression, taking lamotrigine alongside intravenous ketamine or intranasal esketamine does not significantly reduce the antidepressant effect of the treatments. In a historical cohort study, response and remission rates were similar whether patients were on lamotrigine or not. There was a trend toward lower dissociation scores among those taking lamotrigine, especially with IV ketamine. The study was limited by only 13 patients on lamotrigine, so the evidence is insufficient to conclude that lamotrigine attenuates the antidepressant effect, but it may reduce dissociation.