Background We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [11C]carfentanil binding with positron emission tomography (PET).

Methods Twelve healthy male volunteers underwent [11C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a “high” dose, .5 mg/kg, or a sub-pharmacological “ultra-low” dose, 1.25 mg total dose or approximately .017 mg/kg). Reductions in [11C]carfentanil binding from baseline to post-amphetamine scans (ΔBP ND ) after the “high” and “ultra-low” amphetamine doses were assessed in 10 regions of interest.

Results [11C]carfentanil binding was reduced after the “high” but not the “ultra-low” amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior cingulate, and insula.