Title & Introduction

  • Paper Title: Dissociable Effects of LSD and MDMA on Striato-Cortical Connectivity in Healthy Subjects
  • Published In: bioRxiv (Preprint)
  • Publish Date: February 8, 2025
  • Authors: Natalie Ertl, Imran Ashraf, Lisa Azizi, Leor Roseman, David Erritzoe, David J Nutt, Robin L Carhart-Harris, Matthew B Wall
  • Objective: To investigate how LSD and MDMA differentially affect striatal connectivity and its implications for psychiatric medicine.
  • Importance: Understanding the distinct neurobiological effects of LSD and MDMA can help inform their therapeutic use in treating psychiatric conditions such as PTSD and addiction.

Summary & Takeaways

Key Takeaway: LSD and MDMA differentially modulate striato-cortical connectivity, with LSD increasing connectivity to sensory and cognitive regions, while MDMA reduces amygdala-limbic striatal connectivity, suggesting potential implications for therapy.

Practical Application: These findings provide insight into how each drug may support therapeutic interventions, with LSD potentially enhancing cognitive flexibility and MDMA facilitating emotional processing in PTSD treatment.

Key Background Information

  • Context: Both LSD and MDMA have been studied for their potential therapeutic effects, but their distinct impacts on brain connectivity remain unclear.
  • Hypothesis: LSD and MDMA will produce distinct changes in striatal connectivity that align with their known behavioral and subjective effects.

Methodology

  • Study Design: Double-blind, placebo-controlled, within-subject crossover study.
  • Participants: 16 participants for LSD study; 22 for MDMA study.
  • Intervention/Exposure: LSD (75µg IV) or MDMA (100mg oral) versus placebo.
  • Controls: Placebo-controlled design.
  • Duration: Two separate sessions for each drug, spaced apart by at least two weeks.

Key Findings

Primary Outcomes:

  • LSD increased connectivity between the associative striatum and sensory/cognitive regions (visual cortex, frontal cortex, and sensorimotor cortex).
  • MDMA reduced connectivity between the limbic striatum and the amygdala.
  • Neither LSD nor MDMA significantly altered within-network striatal connectivity.

Secondary Outcomes:

  • LSD increased sensorimotor striatal connectivity with the parahippocampus, suggesting effects on memory and perception.
  • MDMA increased limbic striatum connectivity with the sensorimotor cortex, reflecting its effects on emotional processing.
  • MDMA reduced connectivity with the cerebellum, potentially affecting motor control.

Interpretation & Implications

  • Conclusion: LSD primarily enhances sensory and cognitive integration, while MDMA facilitates emotional regulation by reducing amygdala connectivity.
  • Implications: These findings support LSD’s potential role in enhancing cognitive flexibility for addiction treatment, while MDMA’s ability to dampen amygdala activity may contribute to its efficacy in PTSD therapy.
  • Limitations: Small sample sizes and head-motion artifacts may limit generalizability; further studies with larger cohorts are needed.

Researchers & Publication

  • Researchers: Natalie Ertl, Imran Ashraf, Lisa Azizi, Leor Roseman, David Erritzoe, David J Nutt, Robin L Carhart-Harris, Matthew B Wall
  • Publication Name: bioRxiv (Preprint)
  • Study URL: https://doi.org/10.1101/2025.02.07.637042
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