Dissociable effects of LSD and MDMA on striato-cortical connectivity in healthy subjects

LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region central to reward and motivation—communicates with other areas. In a resting-state fMRI study, neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connectivity between the limbic striatum and the amygdala, while LSD increased connectivity between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, suggesting the drugs reduce the brain's usual network segregation, which may help explain their therapeutic potential for conditions like addiction, mood disorders, and PTSD.

Study at a glance

Abstract

Abstract Introduction Lysergic acid diethylamide (LSD) and 3,4-Methylenedioxymethamphetamine (MDMA) are widely used psychoactive drugs and their potential use in psychiatric medicine is currently generating interest. The mechanism by which these drugs may assist recovery in addiction, mood disorders and post-traumatic stress disorder (PTSD) is still not well understood. Most investigations of the effects of these drugs on brain activity have focussed on cortical resting-state networks, however the striatum is a key reward and motivation hub of the brain and aberrant striatal processing may be part of the pathophysiology of these disorders. Consequently, we investigated striatal connectivity following acute MDMA and LSD administration. Method Resting-state fMRI (rs-fMRI) data were acquired, and seed-voxel functional connectivity analyses were used with the striatum subdivided into three seed regions: 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 seed regions. However, striatal connectivity with other brain regions was significantly altered with both 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 previous findings that psychedelics reduce network modularity or between-network segregation and increase connectivity across standard networks.