AGONIST EFFECTS OF METHADONE IN PATIENTS ON STABLE MAINTENANCE DOSES – TIME TO BALANCE ANECDOTE WITH EVIDENCE

Much has been written over the past four decades regarding alleged opioid agonist effects of methadone on maintenance patients. “Zombies” was a term applied early on and still heard today, along with statements that methadone “gives a buzz,” “clouds the mind,” etc. Such comments have been particularly frequent in the past few years in comparisons that are made between methadone and buprenorphine, which purportedly leaves patients “more clear-headed” and without euphoria.

As far as we know these notions are contradicted by controlled studies. Thus, a paper by Dole and Nyswanbder in 1966 (“Rehabilitation of heroin addicts after blockade with methadone,” NY State J of Med, 66(15):2011-2017) stated, “… the absence of any drug sensation at all [in stable methadone maintained subjects] was verified by tests in which the usual medication (dl-methadone) was replaced by the pharmacologically inactive isomer (d-methadone). … The patients given d-methadone in a double-blind test were unaware of the fact that the medication had been changed until they began to feel vague grippe-like sensations twenty-four to thirty-six hours later, and even then some patients did not suspect that the active medication had been omitted …”

The same year a study was published by Dole, Nyswander and Kreek (Arch Int Med 118:304-309) reporting tests for evidence of “blockade” – i.e., tolerance to the agonist effects of narcotics – when methadone-maintained patients were administered various intravenous doses of heroin or hydromorphone (dilaudid). Methadone-maintained patients experienced “little or no euphoria” even when heroin was injected “in massive doses.” This paper also noted: “An incidental finding of practical interest was the absence of euphoria or other drug effects on intravenous injection of methadone, 40 mg, into patients who were receiving daily oral doses of methadone, 40 mg or more.”

If there are studies subsequent to these that came up with contrary results, references would be most welcome. Otherwise, it would seem good to reconsider the assumptions reflected in the increasingly frequent comments about the effects of maintenance doses of methadone – in absolute terms and/or contrasted to buprenorphine..