In a therapeutic trial, rapid increases and abrupt discontinuation of the serotonin precursor 5-hydroxytryptophan (5 HTP) produced striking behavioral effects in a group of phenothiazine-resistant chronic schizophrenic patients. These effects were greatly diminished by gradual changes in 5HTP dosages.
It is speculated that tolerance and dependence developed to 5HTP administration in these patients and perhaps to serotonin itself. It is further speculated that rapid changes, even from normal serotonin concentration, might be responsible for many of the behavioral effects seen when the metabolism of serotonin is altered.
Wyatt RJ, Kaplan J, Vaughan T. Tolerance and Dependence to Serotonin: A Speculation. Arch Gen Psychiatry. 1973;29(5):597–599. doi:10.1001/archpsyc.1973.04200050011002
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