The effects of heroin on catecholamine metabolism in man

In a study of the effects of heroin administration in nine human subjects, urinary catecholamines and metabolites were examined during an initial drug-free baseline period, a ten-day period of heroin administration and a subsequent period of methadone detoxification. All catecholamines and metabolites tended to be increased over baseline values on the first day of heroin administration. However, markedly different patterns of change emerged on subsequent days of heroin administration. Norepinephrine and normetanephrine remained increased throughout heroin administration. Epinephrine was increased during the early phase of heroin administration but returned to baseline values during the latter phase of heroin administration. After the increase on the first day of heroin administration, metanephrine decreased and substantial decrements below baseline values occurred during the latter phase of heroin administration. After increasing on the first day of heroin administration, 3-methoxy-4-hydroxy-mandelic acid (VMA) returned to approximately baseline values. During heroin administration, an increase in 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was observed in a subgroup of four of the nine subjects studied. This is in contrast to the increase in normetanephrine excretion and the decrease in metanephrine excretion that was observed in the entire group of nine subjects. It is conceivable that persistance of, or development of, tolerance might account for the failure to observe an increase in MHPG excretion in all of the subjects. It appeared as if the increase in MHPG excretion began on the day prior to the administration of heroin in the subgroup of patients with increased MHPG excretion during heroin administration, suggesting the possibility of an anticipatory or conditioned response, with the anticipation of heroin producing an increase in MHPG excretion.