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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-002633-42 | EudraCT Number |
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The investigators wish to quantify the relation between administered dose of lysergic acid diethylamide (LSD), plasma LSD levels, and occupancy at the serotonin 2A receptor (5-HT2AR) using [11C]CIMBI-36 positron emission tomography.
Healthy participants will be administered one of a single dose of lysergic acid diethylamide (LSD) between 25 and 200 micrograms equivalent freebase. They will receive [11C]CIMBI-36 positron emission tomography (PET) scans at baseline and twice following LSD administration during peak and declining drug effects. PET scans will be acquired in a simultaneous PET/Magnetic Resonance Imaging (MRI) scanner which will also collect functional brain imaging data. Venous blood samples will be repeatedly drawn during acute drug effects for quantification of plasma LSD levels. Participants will also repeatedly rate their subjective drug intensity on a scale from 0 to 10 during acute drug effects. Together these data will inform the dose-binding relation of LSD at the serotonin (5-HT) 2A receptor, the primary site of action. This data will also inform the relation between 5-HT2A receptor binding by LSD and the induced subjective effects, as well as the effects on functional brain activity as measured with functional MRI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LSD dose-ranging group | Experimental | All participants will receive between 25 and 200 micrograms of lysergic acid diethylamide equivalent as freebase, single blinded with respect to dose. Simultaneous PET/MR imaging will be performed during acute drug effects. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lysergic Acid Diethylamide Tartrate | Drug | D-Lysergic Acid Diethylamide (LSD) D-tartrate as oral drinking solution (water / ethanol 20% m/m) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma LSD - serotonin 2A receptor (5-HT2AR) occupancy relation | Occupancy will be estimated by comparing non-displaceable binding potential (BPND) values using baseline and intervention rescans as calculated using a simplified reference tissue model (SRTM). Occupancy values will be compared to plasma lysergic acid diethylamide (LSD) levels. | Within 24 hours following drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Subjective drug intensity - 5-HT2AR occupancy relation | Occupancy will be calculated as described above. Subjective drug intensity is collected during positron emission tomography (PET) scans by asking participants. | Within 24 hours following drug administration |
| fMRI network disintegration - 5-HT2AR occupancy relation |
| Measure | Description | Time Frame |
|---|---|---|
| Hysteresis effect of 5-HT2AR binding | Estimated dose-occupancy curves derived from the first PET scan and second PET scan will be calculated separately to evaluate whether there are differences in estimated plasma level-occupancy relation at different timepoints following LSD administration which may indicate a hysteresis effect due to peripheral LSD metabolism without unbinding of LSD from the 5-HT2A receptor. |
Inclusion Criteria:
• Healthy individual between 18-75 years old
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gitte M Knudsen, DMsc, MD | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neurobiology Research Unit, Rigshospitalet | Copenhagen | 2100 | Denmark |
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| Label | URL |
|---|---|
| Lab study homepage | View source |
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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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Each participant will be given one of 25, 50, 75, 100, 125, 150, 175 or 200 micrograms of lysergic acid diethylamide (LSD) equivalent as freebase.
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Participants will be blinded with respect to dose only.
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functional magnetic resonance imaging (fMRI) data will be used to estimate functional-network connectivity using a standard functional brain atlas. Then the relation between decreases in functional network connectivity and 5-HT2AR occupancy will be estimated. |
| Within 24 hours following drug administration |
| fMRI brain entropy - 5-HT2AR occupancy relation | fMRI brain entropy will be estimated by the shannon entropy of dynamic conditional correlation of within and between network connectivity as well as the lempel-ziv complexity of concatenated binarised blood-oxygen level dependent (BOLD) signals across regions. The relation between each of these measures with 5-HT2AR occupancy will be estimated. | Within 24 hours following drug administration |
| Cerebral perfusion - 5-HT2AR occupancy relation | Cerebral perfusion will be estimated using arterial spin labelling. The relation between this measure and 5-HT2AR occupancy will be estimated. | Within 24 hours following drug administration |
| Administered LSD dose - 5-HT2AR occupancy relation | Administered dose (25 to 200 mcg) will be compared with peak LSD occupancy to determine what doses produce maximal occupancy at the 5-HT2AR. | Within 24 hours following drug administration |
| Within 24 hours following drug administration |
| D006571 |
| Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |