Theodore J. Cicero, Ph.D.
Developmental, Regenerative and Stem Cell Biology Program
substance abuse, cognition, spermatogenesis, neuroendocrinology, endogenous opioids
Gender differences in the pharmacology and abuse liability of drugs
One of the most important research emphases of Dr. Cicero’s is the role of endogenous opioid peptides (EOP) in the control of hypothalamic-pituitary function – especially in the release of hypothalamic releasing factors. These interactions are crucial, and endocrine changes associated with drugs of abuse, particularly the opioids, are now recognized as a pivotal aspect of their acute and chronic effects. For example, Dr. Cicero was the first to show that morphine suppresses testosterone production in the male rat, which he later confirmed in humans in a 1976 New England Journal of Medicine article. It should be stressed that in this pivotal New England Journal of Medicine study, he conclusively established for the first time that males maintained on chronic opioid treatment were hypogonadal. The latter condition is now, 32 years later, recognized not only as a common side effect of chronic opioid treatment in humans, but also as a major factor in break-through pain, the development of tolerance and physical dependence and the neurobiological correlates of pain. The latter areas are under active investigation.
He was also one of the first to demonstrate that paternal ingestion of drugs - alcohol and morphine - influenced the development and maturation of their offspring. The only explanation for this phenomenon was that the function of sperm had in some way been affected. The most obvious possibility was that the expression of genes was affected in some way, and this was postulated by his group in 1988. However, this flew in the face of conventional wisdom which posited that such “Lamarckian” charges in DNA expression did not occur. Interestingly, 15 years later, it has been shown in several landmark studies that environmental toxins and drugs influence the methylation of DNA, a process which influences gene expression. This launched the new field of “epigenetics” and Dr. Cicero’s research in the late 1980s is uniformly cited as the original observations documenting epigenetic processes. He is presently actively re-engaging in this research and exploring the molecular genetics of this phenomenon.
Finally, Dr. Cicero is engaged in several post-marketing surveillance programs to assess the abuse of newly marketed opioid drug preparations. Although these surveillance programs are an essential aspect of the approval of all drugs with abuse potential and are therefore extremely important in their own right, Dr. Cicero has extended their significance by his most recent research in which he has identified risk factors for the abuse of prescribed opioid analgesics. He has found in two recent articles, both of which prompted recognition as the lead articles in their respective journals (Pharmacoepidemiology & Drug Safety and Pain), for which accompanying editorials were written, examining: first, the relationship between therapeutic exposure to opioids and their abuse; and, second, co-morbid factors in those abusing their opioid analgesics. The latter finding will help identify patients who might be at risk for abuse which will hopefully reduce so-called iatrogenic dependence (physician-induced dependence). Studies of co-morbidity in substance abusers are ongoing in his research program.
Cicero TJ, Nock B, Meyer ER. Chronic exposure to morphine increases corticosteroid binding globuline. J Pharmacol Exp Ther 1997 282:1262-1268.
Cicero TJ, Nock B, Meyer ER. Gender-related differences in the antinociceptive properties of morphine. J Pharmacol Exp Ther 1996 279:767-773.
Adams, M.L.; Cicero, T.J. Alcohol, opioids and testicular function. In: Watson, R.R., editor. Drug and alcohol abuse reviews. Totowa, NJ: Humana Press Inc.; 1995. p. 279-294.
Cicero, T.J.; Adams, M.L. Opioid-mediated control of neuroendocrine function: Role of k, u and e receptors. In: Watson, R.R., editor. Drug and alcohol abuse reviews. Totowa, NJ: Humana Press Inc.; 1995. p. 21-47.
Cicero TJ, Nock B, O’Connor L, Adams ML, Meyer ER. Adverse effects of paternal opiate exposure on offspring development and sensitivity to morphine-induced analgesia. J Pharmacol Exp Ther 1995 273:386-392.
Last Updated: 8/3/2011 2:24:38 PM