Evidence for an endorphin dysfunction in methadone addicts: lack of ACTH response to naloxone

Chronic exogenous opiate administration might be responsible for the acute and protracted abstinence syndrome by producing a prolonged decrease in the availability of endogenous opioids (endorphins). However, the hypothesis that potent exogenous opiates may have anti-endorphin effects has been difficult to test. We have been investigating this hypothesis with neuroendocrine test paradigms which have provided preliminary evidence of anti-endorphin effects for chronic methadone. Naloxone-induced ACTH response data from chronic methadone addicts offers preliminary support for the hypothesis that chronic exogenous opiate administration has anti-endorphin effects. The subjects were 7 male methadone addicts who had been addicted to greater than or equal to 40 mg of methadone and 7 male healthy opiate-naive volunteers. Naloxone failed to produce a significant increase in ACTH in methadone addicts while opiate-naive normal volunteers demonstrated a significant naloxone-induced release of ACTH. Five of the seven methadone addicts ahd no demonstrable ACTH response to naloxone. These impaired naloxone response data reported here for recently detoxified addicts suggest that chronic methadone administration comprises the functional integrity of the endorphin system. Prolonged abstinence, post-detoxification depression and other affective symptoms which contribute to relapse may result from a prolonged endorphin derangement.