LSD-Perceptual-Choice-Study (LUCY)

Effects of LSD on Perceptual Decision-making in Healthy Subjects

The aim of the study is to characterize the effects of low doses of LSD (d-lysergic acid diethylamide) on behavioral and neural indicators of feedback and feedforward signaling in perceptual decision-making.

Study Overview

• Status: Completed
• Conditions: LSD Reaction
• Intervention / Treatment: Drug: LSD 10 μg; Drug: LSD 20 μg; Drug: Placebo

Detailed Description

The study team will subject healthy participants to multiple perceptual decision-making tasks after the administration of low doses of LSD (d-lysergic acid diethylamide) as a pharmacological challenge. The investigators want to illuminate the behavioral and neural effects of psychedelics on prior beliefs and evidence processing. Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Subjects will be under continuous supervision until approximately 4.5h after substance administration. The participants are asked to perform the following cognitive tasks alongside EEG measurement after administration of either LSD or placebo: Changepoint task, history bias task, surround suppression task, auditory steady-state response paradigm, motor localizer task.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4002
    • University Psychiatric Clinics Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willingness to adhere to the study protocol and sign the consent form
• ≥ 18 and ≤ 65 years of age at Screening
• Body mass index 18-29
• Fluent understanding of German
• Normal or corrected-to-normal vision
• Willingness to not operate a traffic vehicle or heavy machinery 24 hours after substance administration
• Willingness to refrain from taking illicit psychoactive substances, including cannabis, for the duration of the study
• Willingness to not consume more than one alcoholic standard drink the night before the study sessions and not consume alcohol for 24 h after each study session
• Willingness to abstain from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
• Willingness to use effective birth-control throughout the study duration
• Adequate task performance in the decision-making tasks during a practice session in the screening visit

Exclusion Criteria:

• Recent (<30 days) or current participation in another clinical trial
• Women that are pregnant, nursing, or planning to become pregnant during the study period
• Current use of contraindicated/psychoactive medications or illicit drugs
• Lifetime use of classical psychedelics more than 20 times, or any time within the previous two months
• Consumption of >5 cigarettes per day or >20 alcoholic standard drinks per week
• Severe chronic or acute medical condition
• Hypertension (>140/90 mmHg) or hypotension (<85mmHg systolic)
• Current or lifetime major mental health disorder
• Personal or family (first-degree) history of a primary psychotic disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention order: 10 μg LSD - 20 μg LSD - Placebo; Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Order of drug administration will be 10 μg LSD - 20 μg LSD - Placebo. Vials will contain either 10μg (Active) or 0 μg LSD (Placebo). Thus, participants will be administered two vials on each study visit. 1. visit: active+placebo; 2. visit: active+active, 3. visit: placebo+placebo.	Drug: LSD 10 μg; 0.5 h after the start of each study session the participants will be administered 10 μg LSD per os in the form of vials containing 1ml 20% EtOH (ethanol).; Drug: LSD 20 μg; 0.5 h after the start of each study session the participants will be administered 20 μg LSD per os in the form of vials containing 1ml 20% EtOH.; Drug: Placebo; 0.5 h after the start of each study session the participants will be administered placebo per os in the form of vials containing 1ml 20% EtOH.
Experimental: Intervention order: 10 μg LSD - Placebo - 20 μg LSD; Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Order of drug administration will be 10 μg LSD - Placebo - 20 μg LSD. Vials will contain either 10μg (Active) or 0 μg LSD (Placebo). Thus, participants will be administered two vials on each study visit. 1. visit: active+placebo; 2. visit: placebo+placebo, 3. visit: active+active.	Drug: LSD 10 μg; 0.5 h after the start of each study session the participants will be administered 10 μg LSD per os in the form of vials containing 1ml 20% EtOH (ethanol).; Drug: LSD 20 μg; 0.5 h after the start of each study session the participants will be administered 20 μg LSD per os in the form of vials containing 1ml 20% EtOH.; Drug: Placebo; 0.5 h after the start of each study session the participants will be administered placebo per os in the form of vials containing 1ml 20% EtOH.
Experimental: Intervention order: 20 μg LSD - 10 μg LSD - Placebo; Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Order of drug administration will be 20 μg LSD - 10 μg LSD - Placebo. Vials will contain either 10μg (Active) or 0 μg LSD (Placebo). Thus, participants will be administered two vials on each study visit. 1. visit: active+active; 2. visit: active+placebo, 3. visit: placebo+placebo.	Drug: LSD 10 μg; 0.5 h after the start of each study session the participants will be administered 10 μg LSD per os in the form of vials containing 1ml 20% EtOH (ethanol).; Drug: LSD 20 μg; 0.5 h after the start of each study session the participants will be administered 20 μg LSD per os in the form of vials containing 1ml 20% EtOH.; Drug: Placebo; 0.5 h after the start of each study session the participants will be administered placebo per os in the form of vials containing 1ml 20% EtOH.
Experimental: Intervention order: 20 μg LSD - placebo - 10 μg LSD; Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Order of drug administration will be 20 μg LSD -placebo - 10 μg LSD. Vials will contain either 10μg (Active) or 0 μg LSD (Placebo). Thus, participants will be administered two vials on each study visit. 1. visit: active+active; 2. visit: placebo+placebo, 3. visit: active+placebo.	Drug: LSD 10 μg; 0.5 h after the start of each study session the participants will be administered 10 μg LSD per os in the form of vials containing 1ml 20% EtOH (ethanol).; Drug: LSD 20 μg; 0.5 h after the start of each study session the participants will be administered 20 μg LSD per os in the form of vials containing 1ml 20% EtOH.; Drug: Placebo; 0.5 h after the start of each study session the participants will be administered placebo per os in the form of vials containing 1ml 20% EtOH.
Experimental: Intervention order: placebo - 10 μg LSD - 20 μg LSD; Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Order of drug administration will be placebo - 10 μg LSD - 20 μg LSD. Vials will contain either 10μg (Active) or 0 μg LSD (Placebo). Thus, participants will be administered two vials on each study visit. 1. visit: placebo+placebo; 2. visit: active+placebo, 3. visit: active+active.	Drug: LSD 10 μg; 0.5 h after the start of each study session the participants will be administered 10 μg LSD per os in the form of vials containing 1ml 20% EtOH (ethanol).; Drug: LSD 20 μg; 0.5 h after the start of each study session the participants will be administered 20 μg LSD per os in the form of vials containing 1ml 20% EtOH.; Drug: Placebo; 0.5 h after the start of each study session the participants will be administered placebo per os in the form of vials containing 1ml 20% EtOH.
Experimental: Intervention order: placebo - 20 μg LSD - 10 μg LSD; Each subject will participate in 3 x 5 h study sessions separated by at least 7 days. Order of drug administration will be placebo - 20 μg LSD - 10 μg LSD. Vials will contain either 10μg (Active) or 0 μg LSD (Placebo). Thus, participants will be administered two vials on each study visit. 1. visit: placebo+placebo; 2. visit: active+active, 3. visit: active+placebo.	Drug: LSD 10 μg; 0.5 h after the start of each study session the participants will be administered 10 μg LSD per os in the form of vials containing 1ml 20% EtOH (ethanol).; Drug: LSD 20 μg; 0.5 h after the start of each study session the participants will be administered 20 μg LSD per os in the form of vials containing 1ml 20% EtOH.; Drug: Placebo; 0.5 h after the start of each study session the participants will be administered placebo per os in the form of vials containing 1ml 20% EtOH.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in changepoint task	Using the changepoint task, it is examined how explicit expectations about upcoming stimuli are derived from the perceptual history and how they influence the perceptual decision in a volatile environment. The study team utilizes an established computerized task and analysis pipeline including a behavioral modeling strategy based on Bayesian inference. The task requires participants to view a train of stimuli consisting of checkerboards presented on a half-circle gradient either more on the right or more on the left side of a fixation cross. Each checkerboard represents information about whether stimuli are currently more likely to appear on the right or left side of the screen. The participants have to indicate by button press, whether they believe the right or the left side is active. Task difficulty is fixed.	three times (once on each of the three test days; interval between test days at least 7 days)
Change in history bias task	With the history bias task, the study team investigates how implicit expectations about upcoming stimuli are derived from perceptual history and how they bias perceptual discrimination. In each trial, two circular gratings will be presented concurrently on the left and right sides of a fixation cross. After complete stimulus presentation, the participants indicate by button press which of the two gratings they believe had the stronger contrast in the trial (left vs. right). Task difficulty will be adjusted individually using an online quest staircase procedure, such that participants will always perform at their 75% accuracy level.	three times (once on each of the three test days; interval between test days at least 7 days)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: University of Basel; University Psychiatric Clinics Basel
• Investigators: Principal Investigator: Philipp Sterzer, Prof. Dr., University Psychiatric Clinics Basel

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2024
• Primary Completion (Actual): February 25, 2025
• Study Completion (Actual): February 25, 2025

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: serotonergic system; neural and behavioral indicators; perceptual decision-making
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Ergot Alkaloids; Ergolines; Lysergic Acid; Lysergic Acid Diethylamide
• Other Study ID Numbers: 2023-00763, pk23Sterzer

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No