Recent evidence has shown that a single maintenance dose of
heroin attenuates psychophysiological stress responses in
heroin-dependent patients, probably reflecting the effectiveness of
heroin-assisted
therapies for the treatment of severe
heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22
heroin-dependent and
heroin-maintained outpatients from the Centre of
Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after
heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by
hormone releases and subjective ratings. Relative to placebo,
heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after
heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in
heroin-dependent patients transiently normalizes after acute
heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in
heroin-dependent patients and to quantify the efficacy of maintenance treatments in
drug addiction.