Reward is a psychological construct that can be parsed into 3 distinct components: learning, liking and wanting. Dysfunctions in reward processing are a core feature of multiple pathologies. Psychedelics have shown promise in the treatment of multiple disorders known to have a dysfunctional reward processing. However, their impact on the reward system functional connectivity has not been accessed.

In this study, we sought to understand the effects of inhaled DMT on the mesocorticolimbic circuit by studying changes in resting-state connectivity. We hypothesized that DMT alters resting-state connectivity between reward regions.

We included a sample of 11 healthy participants (mean age SD 37±12.4 years),  with previous experience in psychedelics in a within-subject design using resting state functional connectivity, consisting of an active and a control condition. The active condition consisted of self-administered DMT, approximately 50 to 70 mg of DMT (root bark of Mimosa hostilis in freebase form), immediately before MRI acquisition. 

We found significant changes in the functional connectivity between reward areas namely, decreased connectivity between the right nucleus accumbens(NAc) and the left ventral tegmental area(VTA), increased connectivity between the right NAc and anterior cingulate cortex(ACC) and increased connectivity between the medial prefrontal cortex(mPFC) and the ACC. 

DMT causes connectivity changes in reward brain areas. These alterations are relevant to the ones found in pathologies such as substance use disorders, depression and pain. Our findings may help to understand the mechanisms behind the therapeutic potential of psychedelics in diseases with an underlying impairment in reward processing.