Differences in - and -Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects
Neuropsychopharmacology (2008) 33, 653–665


Blockade of brain -opioid receptor (-OR) and -opioid receptor (-OR) was investigated in recently abstinent alcohol-dependent subjects (N=21) maintained on naltrexone.

Naltrexone inhibition of [¹¹C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean+SD% inhibition=94.9+4.9%). Naltrexone only partially inhibited the [¹¹C]MeNTI K_i and there was more variability across subjects (mean+SD% inhibition=21.1+14.49%).

Peak serum levels of naltrexone were positively correlated with % inhibition of -OR K_i in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of -OR BP. Peak levels of 6--naltrexol were not significantly correlated with % inhibition of -OR BP or -OR K_i.

Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the -OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of -OR and greater variability in -OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone.

Further investigations on the relationship between individual differences in -OR blockade by naltrexone and clinical outcomes should be explored.

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