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Cortical structural differences following repeated ayahuasca use hold molecular signatures
Pablo Mallaroni1, Natasha L Mason1, Lilian Kloft1
1Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands.
Frontiers in Neuroscience
|October 23, 2023
Summary
Repeated ayahuasca use alters brain structure by changing cortical thickness and gene expression, suggesting molecular psychedelic effects scale to macro-level brain organization. This research explores neuroplasticity in long-term users.
Area of Science:
- Neuroscience
- Psychopharmacology
- Genetics
Background:
- Serotonergic psychedelics, like ayahuasca, are known to promote neural plasticity through 5-HT2A receptor agonism.
- Limited understanding exists regarding the effects of repeated psychedelic use on human neuroanatomy and large-scale brain networks.
- Previous studies suggested localized cortical thickness changes in long-term ayahuasca users.
Purpose of the Study:
- To investigate the relationship between cortical gene expression markers of psychedelic action and brain morphometric changes after repeated ayahuasca use.
- To explore how molecular mechanisms of psychedelics may influence macroscale brain organization in humans.
- To examine structural changes in brain networks associated with long-term ayahuasca consumption.
Main Methods:
- Utilized high-field 7 Tesla neuroimaging data from 24 members of an ayahuasca-using church (Santo Daime) and matched controls.
- Employed morphometric similarity network (MSN) analysis to assess brain structure.
- Examined cortical gene expression markers related to psychedelic action and neuroplasticity.
Main Results:
- Repeated ayahuasca use was linked to structural differentiation in sensorimotor areas and de-differentiation in transmodal regions.
- Cortical MSN remodeling correlated with altered 5-HT2A gene expression and other relevant receptor genes.
- These structural changes were further associated with altered expression of transcriptional factors and immediate early genes involved in psychedelic-induced neuroplasticity.
Conclusions:
- Preliminary evidence suggests that molecular mechanisms of psychedelic action can influence macroscale brain organization in vivo.
- Cortical transcriptomics may play a role in structural-functional coupling, potentially explaining behavioral differences in experienced psychedelic users.
- Further research into the neurobiological effects of repeated psychedelic use is warranted.
