Long-lasting effects of early barbiturates on central nervous system and behavior

Forty years of prescribing barbiturates to pregnant women and infants, and thirty years of animal research have shown that barbiturates affect the developing central nervous system (CNS) and behavior. This paper compiles and reviews animal and selected human literature in this research area. Early barbiturate exposure in animals reduces brain weight with related changes in brain biochemistry and neuromorphology. Significant changes may be found in surviving adult offspring. Evidence of CNS and behavioral damage in human beings due to early barbiturate exposure is not clearcut, however, confounded by the conditions for which the drugs are prescribed. In animals, early drug exposure significantly reduces levels of hormones, vitamins, and other biologically active macromolecules via (long-lasting) induction of hepatic metabolizing enzymes. Whether or not in humans treated with barbiturates, hormone levels remain within the normal range (by-feed-back regulation) and, also, if vitamin deficiencies can be simply corrected by supplements is still being debated. Early barbiturates administered to animals is associated with long-lasting disturbances in activity, learning performance, sexual behavior, and reproductive function, but not in a simple dose-exposure related manner. Animal studies show that long-lasting functional tolerance to drugs develops following early barbiturate exposure. Although infants become "passively addicted" following in utero exposure, there is as yet no data on subsequent development of human adult tolerance. Drug related damage must, in any case, be weighed against therapeutic benefits of drug administration and the results of failure to treat.