Relation of plasma morphine concentrations to severity of abrupt withdrawal in morphine-dependent monkeys

Plasma morphine levels were measured during abrupt withdrawal in four chronically dependent female monkeys. Approximately 12 hr after withdrawal, the morphine plasma concentrations were about 8 to 10 ng/ml, at which time all of the animals showed mild to moderate symptoms of opiate withdrawal. Severity of withdrawal showed a negative correlation (r = -0.93, P less than .001) with the falling phase of plasma morphine. It may be concluded that, under the conditions of this experiment, significant morphine withdrawal symptoms arose despite measurable plasma concentrations of morphine and that the relationship between plasma concentrations and withdrawal may be quantified according to a linear pharmacokinetic model for a given chronic dose (3.0 mg/kg q 6 hr) of morphine.