The use of topical ophthalmic naloxone to detect physiological opioid depen
dence was tested in two double-blind, placebo-controlled trials a week apar
t. The subject group consisted of opioid-dependent patients on methadone ma
intenance treatment. The control group consisted of medical student volunte
ers, For trial 1, two drops of naloxone hydrochloride (1 mg/ml) were instil
led in one eye of both subjects and controls, while two drops of an inert s
aline solution were instilled into the opposite eye. For trial 2 the proced
ure was repeated. However, on this occasion all controls were administered
a single subcutaneous injection of morphine sulphate, Pupil diameter follow
ing administration of naloxone was measured by photographs taken at 0, 60 a
nd 90 minutes. Complete data for both days were obtained from 15 controls a
nd 13 subjects. A significant difference was found between mean changes in
pupil/iris ratio for the control group compared with the opioid group for b
oth trials. However, discriminant analysis revealed that the test is likely
to produce significant numbers of false positive and false negative result
s. in addition, the test precipitated an opiate withdrawal syndrome in many
subjects, and bilateral mydriasis was evident in trial 2, The naloxone eye
-drop test does not appear to be a useful tool in determining the presence
of neuroadaptation to opioids.