Introduction  

3,4-Methylenedioxymethamphetamine (MDMA) and Lysergic acid diethylamide (LSD) are widely used recreational drugs, and more recently their use in psychiatric medicine is also becoming more widely accepted. The mechanism by which these medicines may work to assist recovery in illness such as addiction and post-traumatic stress disorder (PTSD) is still not completely understood. The striatum is the key reward hub of the brain and aberrant striatal processing may be part of the pathophysiology of some of these disorders. Consequently, we investigated alterations in striatal connectivity with acute MDMA and LSD administration. 

Method 

Resting-state fMRI (rs-fMRI) data was acquired, and seed-voxel analysis was used. The striatum was subdivided into three seed regions based on a previous functional/connectivity parcellation: the associative, limbic, and sensorimotor striatum. Within-network connectivity was measured using group mean network maps and whole-brain connectivity (seed-to-voxel) was also examined.  

Results 

Neither MDMA nor LSD significantly changed within-network connectivity of any of the three striatal seeds. However, striatal connectivity with other brain regions was significantly altered with MDMA and LSD. Most notably, MDMA reduced connectivity between the limbic striatum and the amygdala. While LSD increased connectivity between the associative striatum and the frontal, sensorimotor, and visual cortices.  

Conclusion  

Changes in connectivity were mostly observed outside the standard striatal networks, consistent with the theory that psychedelics reduce modularity and increase between-network connectivity. Hyperactivation of the amygdala is often observed in PTSD so MDMA induced reductions in connectivity with the amygdala may be beneficial to the disorder. Increased fronto-striatal connectivity may also be beneficial for decision making in addiction disorders.