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  • Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor [Elektronski vir]
    Preller, Katrin H. ...
    Background:Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor ... contributions to its neurobiological effects remain unknown. Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over study (ClinicalTrials.gov, NCT02451072) during which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 mg po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps. Findings: LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans. Conclusion: Together, these results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD's mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics. Funding: Swiss National Science Foundation (SNSF, P2ZHP1_161626, KHP), the Swiss Neuromatrix Foundation (2015 - 0103, FXV), the Usona Institute (2015 - 2056, FXV), the NIH (R01MH112746, JDM; DP5OD012109, AA; R01MH108590, AA), the NIAA ( P50AA012870-16, AA & JHK), the NARSAD Independent Investigator Grant (AA), the Yale CTSA grant (UL1TR000142 Pilot Award, AA), and the Slovenian Research Agency (ARRS J7-6829 & ARRS J7-8275, GR).
    Vir: eLife [Elektronski vir]. - ISSN 2050-084X (Vol. 7, e35082, 2018, str. 1-31)
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2018
    Jezik - angleški
    COBISS.SI-ID - 66393186