In studies of patients having maintenance treatment for heroin addiction (stabilized with methadone hydrochloride in high doses of 80 to 120 mg daily), we found minimal side effects and no toxic effects. These studies have included a prospective study of the first consecutive 214 patients admitted to methadone treatment and reevaluation of the 129 patients of this group still in treatment after three or more years. In addition, we studied 1,435 methadone maintenance patients retrospectively and performed special studies on a smaller group. Abnormalities in liver function and serum protein tests, which were found in 57% and 49% of patients at admission, persisted without significant change during treatment. Increased sweating was reported by 48% and persistent constipation by 17% of patients after methadone treatment for three or more years.
Kreek MJ. Medical Safety and Side Effects of Methadone in Tolerant Individuals. JAMA. 1973;223(6):665-668. doi:10.1001/jama.1973.03220060039009