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The aim of the present study is to assess the neuronal correlates of alterations in waking consciousness pharmacologically induced by a 5-hydroxytryptamine (HT)2A receptor agonist in healthy subjects using functional magnetic resonance imaging (fMRI).
Functional neuroimaging may be useful in the diagnosis and characterization of early schizophrenia. However, little is known about how the subjectively experienced alterations in consciousness and perception are related with objective neuroimaging measures. The present study explores the association of subjective alterations and objective imaging findings and will inform us on the neuronal correlates of psychotic states and whether subjective alterations in perception translate into neuronal activation patterns that can be objectively measured in a brain scanner. Therefore, alterations in consciousness will be assessed in 20 healthy subjects using a random order 2-period (normal and altered state of consciousness) cross-over design. Alterations in consciousness will be induced by the hallucinogenic 5-hydroxytryptamine (HT)2A receptor agonist (5-HT2A) receptor agonist lysergic acid diethylamide (LSD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo, LSD | Other | Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two treatment conditions in the same subject. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LSD | Drug | 100ug per os, single dose |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| fMRI brain activity | Associations between fMRI activity (resting state, amygdala-BOLD response to fear and frontoparietal connectivity during working memory processing) and alterations in waking consciousness pharmacologically induced by LSD | 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Physiological effects (Association of alterations in consciousness and autonomic nervous system reactions (blood pressure, heart rate, pupil size) | Association of alterations in consciousness and autonomic nervous system reactions (blood pressure, heart rate, pupil size) | 24 hours |
| Plasma hormone levels (Associations of alterations in consciousness with plasma hormone levels) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD, MAS | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital | Basel | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28375205 | Derived | Mueller F, Lenz C, Dolder PC, Harder S, Schmid Y, Lang UE, Liechti ME, Borgwardt S. Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects. Transl Psychiatry. 2017 Apr 4;7(4):e1084. doi: 10.1038/tp.2017.54. | |
| 28197931 | Derived | Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects. Clin Pharmacokinet. 2017 Oct;56(10):1219-1230. doi: 10.1007/s40262-017-0513-9. |
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| ID | Term |
|---|---|
| D006212 | Hallucinations |
| ID | Term |
|---|---|
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D008238 | Lysergic Acid Diethylamide |
| ID | Term |
|---|---|
| D008237 | Lysergic Acid |
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
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| Placebo | Drug | Capsules containing mannitol looking identical to LSD |
|
Associations of alterations in consciousness with plasma hormone levels |
| 24 hours |
| 27714429 | Derived | Liechti ME, Dolder PC, Schmid Y. Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology (Berl). 2017 May;234(9-10):1499-1510. doi: 10.1007/s00213-016-4453-0. Epub 2016 Oct 7. |
| 27249781 | Derived | Dolder PC, Schmid Y, Muller F, Borgwardt S, Liechti ME. LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality. Neuropsychopharmacology. 2016 Oct;41(11):2638-46. doi: 10.1038/npp.2016.82. Epub 2016 Jun 1. |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |