Lysergic acid diethylamide (LSD) produces functional effects in rat spinal cord and brain similar to those of the serotonin (5-hydroxytryptamine) precursor 5-hydroxytryptophan, indicating that LSD stimulates central serotonin receptors. Using histochemical and biochemical techniques, LSD reduced the turnover rate of serotonin in the brain and spinal cord after inhibition of tryptophan hydroxylase. The turnover of noradrenaline, but not dopamine, was somewhat accelerated. These effects were dose- and time-dependent and were not observed with the LSD analogues 2-bromo-LSD and methysergide. The retardation of serotonin turnover by LSD may result from negative feedback mechanisms triggered by direct stimulation of central serotonin receptors.
Psilocybin, a rapid-acting antidepressant, reduces levels of the neuropeptide galanin and noradrenaline in cerebrospinal fluid, suggesting that normalization of these co-transmitters is a key pharmacodynamic effect. This finding comes from a secondary analysis of a randomized, placebo-controlled trial with multimodal biomarker measurements. The results indicate a selective effect of psilocybin on these specific neurotransmitters, offering insight into its mechanism of action in major depressive disorder.