title: Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects.
abstract: Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (P<0.05, family-wise error). Notably, there was a significant negative correlation between LSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (P<0.05). These data suggest that acute administration of LSD modulates the engagement of brain regions that mediate emotional processing.
authors.affiliation: Department of Psychiatry, Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Mueller
authors.affiliation: Department of Psychiatry, Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Lenz
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: P C
authors.initials: PC
authors.lastname: Dolder
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Harder
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Schmid
authors.affiliation: Department of Psychiatry, Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland.
authors.forename: U E
authors.initials: UE
authors.lastname: Lang
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: M E
authors.initials: ME
authors.lastname: Liechti
authors.affiliation: Department of Psychiatry, Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Borgwardt
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects*; D001364:Awareness / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005239:Fear / Q000502:physiology / Q000523:psychology*; D005260:Female; D006213:Hallucinogens / Q000009:adverse effects* / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010465:Perception / Q000187:drug effects; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects
chemical_list: D006213:Hallucinogens; D008238:Lysergic Acid Diethylamide