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Twelve-month treatment of heroin addicts with methadone or buprenorphine normalized plasma cortisol levels, and controlled withdrawal symptoms as well as craving. During treatment, the time course of plasma cortisol levels and craving was not strictly correlated: heroin craving was more elevated at 12 than at 3 months. The results suggest a correlation between hypercortisolism, withdrawal symptoms and heroin use and suppose a more complex role for craving and its components in drug-taking behaviour. The main goal of the pharmacological treatment of opioid-dependence should be addressed at the normalization of hypothalamic-pituitary-adrenocortical (HPA) axis more than at the control of craving.

1. Lymphocyte subsets and neutrophil function were studied in chronic psychiatric patients on long-term multiple drug therapy, and the correlation with disease and drug treatments was also investigated. 2. Patients showed decreased CD4+ percentage, CD4+/CD8+ ratio, B lymphocyte percentage, increased absolute and percentage NK, and impaired neutrophil chemotaxis, phagocytosis, and oxidative metabolism. Correlations were found between: patient status and lower CD4+ percentage, CD4+/CD8+ ratio, neutrophil chemotaxis, phagocytosis, and oxidative metabolism; schizophrenia and higher absolute and percentage NK, and neutrophil random migration; benzodiazepines and higher CD8+ absolute number and lower NBT reduction frequency; carbamazepine and higher NK percentage, neutrophil chemotaxis, phagocytosis, stimulated O2-production, and lower microbicidal activity. 3. The present study provides direct evidence for the existence of immunologic abnormalities in a population of chronic psychiatric patients on long-term drug therapy. Although a possible role by other factors could not be excluded, such abnormalities are strongly associated with chronic administration of benzodiazepines and carbamazepine. Further investigations are warranted to confirm these findings and disclose the possible mechanism(s) involved.