For over 30 years, empirical studies have demonstrated expression of chemically authentic morphine by diverse
animal tissues and organs systems. De novo biosynthesis of endogenous morphine by animal cells displays striking similarities
to the multi-enzyme mediated biosynthetic pathway previously characterized in great biochemical and molecular
detail in opium poppy (Papaver somniferum). The committed enzyme step within this pathway involves an asymmetric
Pictet-Spengler condensation of dopamine (DA) and 3,4 dihydroxyphenylacetaldehyde (DOPAL), the oxidation product
of L- 3,4-dihydroxyphenylalanine (L-DOPA), to form the essential intermediate precursor tetrahydropapaveroline (THP).
We have hypothesized that endogenous morphine is synthesized within peripheral sites via conversion of THP in a regulated
biosynthetic pathway, or conversely, THP may be directly transported into the CNS and converted to endogenous
morphine within a similar biosynthetic pathway. The fundamental chemical relationship of the prototype catecholamine
DA and its immediate precursor L-DOPA to endogenous morphine expression indicates a novel reciprocally interactive
mechanism that links catecholamine and “morphinergic” pathways in the activation and inhibition of key physiological
responses, including higher order neural integration. Dysregulation of interactive DAergic and “morphinergic” signaling
pathways within CNS foci may contribute to the etiological factors driving co-morbid behavioral syndromes in major psychiatric
disorders. Our short review is designed to provide insights on comorbidity and self-medication in schizophrenia
from a novel perspective involving endogenous morphine signaling mechanisms.
Keywords: Schizophrenia, comorbidity, self-medication, endogenous morphine, dopamine, catecholamines, L-DOPA, tetrahydropapaveroline (THP), CNS, De novo biosynthesis.
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