Psychedelics like LSD and psilocybin are being studied again as treatments for mental illnesses, with recent rigorous trials investigating their use for depression, terminal illness, addiction, obsessive-compulsive disorder, and post-traumatic stress disorder. Psilocybin, a serotonin 2A receptor agonist, has shown rapid and robust antidepressant effects when combined with psychological support, with benefits lasting several months to a year after one or two sessions. Australia has approved psilocybin for treatment-resistant depression. Neuroimaging studies suggest psilocybin modulates brain circuits involved in mood disorders. A clinical trial in Japan is examining ketamine and psilocybin for treatment-resistant depression.
A higher baseline ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex predicted greater improvement in depressive symptoms after ketamine treatment in adults with treatment-resistant depression. In the ketamine group, a reduction in this Glx/GABA ratio correlated with symptom improvement, but no such association appeared in the placebo group. The findings suggest that the balance between excitatory and inhibitory neurotransmission in this brain region may serve as a biomarker for predicting antidepressant response to ketamine.