Sex and opioid maintenance dose influence response to naloxone in opioid-dependent humans: A retrospective analysis

Pooled self-report and physiological data from 32 male and 15 female methadone or levo-α-acetyl methadol (LAAM) maintained volunteers were retrospectively analyzed for individual differences in response to naloxone (0.15 mg/70 kg, IM) and placebo at 20 and 40 min post-injection. Males and females were each divided by the median split methadone maintenance dose (MMD, in mg/kg body weight) into high and low MMD groups and MMD was used as a factor in the analyses, along with sex, drug, and time post-drug. Females in the low, but not high, MMD group showed naloxone-induced increases in ratings on the Antagonist and Mixed-Action sub-scales of the Adjective Rating Scale, and the Lysergic acid diethyl amine (LSD) sub-scale of the Addiction Research Center Inventory at 20 min post-injection. Males in the high MMD group showed significant naloxone-induced increases in scores of these measures at both post-injection time-points. In addition, low MMD subjects showed more short-lived naloxone-induced increases on Visual Analogue Scale (VAS) Bad and Any drug effects ratings than high MMD subjects. These results suggest that those on a lower MMD, especially women, experience a more intense, but short-lived, response to naloxone, whereas those on a higher MMD experience a more modest, but longer-lasting effect.