Impairment of adrenergic-induced proopiomelanocortin-related peptide release in heroin addicts

The effects of iv stimulation with clonidine on plasma levels of β-lipotropin (β-LPH), β-endorphin (β-EP), cortisol, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) were tested in a group of 10 healthy volunteers and in 8 heroin abusers. Hormones were measured either by direct radioimmunoassay (RIA) (GH, cortisol) or after plasma extraction and Sephadex G-75 column chromatography (β-LPH and β-EP) or by immunoradiometric assay (IRMA) (ACTH). Plasma levels of GH increased in a similar fashion in the two groups. In the controls, clonidine induced release of β-LPH and β-EP after 30 min (from 8.9 ± 1.0 to 19.1 ± 4.6 fmol/ml, P < 0.01 and from 8.1 ± 0.6 to 17.9 ± 4.6, P < 0.01) and of ACTH after 60 min (from 12.1 ± 1.8 to 18.1 ± 1.8, P < 0.05) while in addicts β-EP but not β-LPH showed a significant increase (from 8.5 ± 0.7 to 19.8 ± 4.2, P < 0.05), 90 min after the injection. In heroin addicts, plasma cortisol levels decreased continuously after clonidine stimulation while in controls they showed a biphasic pattern, decreasing until the 60th min (from 135.2 ± 30.4 ng/ml to 74.0 ± 13.3, P < 0.05) and regaining basal levels 1 h later (122.0 ± 24.8, P < 0.05 vs 60th min value). These data demonstrate the existence in human beings of noradrenergic control of proopiomelanocortin (POMC)-related peptides and indicate that chronic opiate abuse greatly interferes with this control. Clonidine-induced release of plasma β-EP may be of importance with regard to its therapeutic effects in detoxification.