“…The side effects observed during the first 6 months of methadone treatment are those which could be anticipated from earlier studies of the effects of morphine or any pure opioid agonist in humans, including initially drowsiness, nausea, vomiting, and more persistently, sleep disorders, primarily insomnia, difficulty in urination, and when the dose of methadone is increased too rapidly, even edema of the lower extremities probably due to inappropriate secretion of antidiuretic hormone; also significant constipation and increased sweating occur (DOBBS 1971;KREEK 1972KREEK , 1973aKREEK ,b, 1978aKREEK , 1983bYAFFE et al 1973). Neuroendocrine abnormalities of the hypothalamic-pituitaryadrenal axis have been documented during cycles of subacute and chronic opiate addiction, including menstrual irregularities in heroin addicted females and sexual dysfunction in both men and women.…”