Endogenous Hallucinogens in Cerebrospinal Fluid

The search for an endogenous psychotogen as a biochemical cause or biochemical indicator of schizophrenia was stimulated in 1952 when Harley-Mason, Osmond, and Smythies suggested that abnormal transmethylation of an endogenous amine could possibly produce a psychotomimetic compound.11 Much of the research activity in the years that followed focused on methylated metabolites of tryptamine, such as dimethyltryptamine (DMT) and O-methylbufotenin (OMB), as putative endogenous psychotogens. These compounds are strongly hallucinogenic, and biochemical evidence has been presented to show that precursors and enzymes required for their synthesis are found in mammalian brain in vivo.9,12 Many studies did, in fact, provide evidence for the presence of these compounds in urine and blood, but the significance of these findings with respect to the etiology of schizophrenia has been criticized on the grounds that the assays were not sufficiently specific or sensitive. More recent studies using sophisticated mass spectrometric analyses have confirmed earlier positive results on the presence of DMT in blood and urine and have provided more accurate quantification.10,15 However, direct correlations between the concentration of these hallucinogens in blood and psychiatric illness have not yet been described.