LSD-Perceptual-Choice-Study (LUCY)

• ClinicalTrials.gov Identifier: NCT05976698
• Recruitment Status: Recruiting
• First Posted: August 4, 2023
• Last Update Posted: February 21, 2024
• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: University of Basel; University Psychiatric Clinics Basel
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
LSD Reaction	Drug: LSD 10 μg; Drug: LSD 20 μg; Drug: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized, double-blinded, cross-over study
• Masking: Double (Participant, Investigator)
• Masking Description: double-blinded
• Primary Purpose: Basic Science
• Official Title: Effects of LSD on Perceptual Decision-making in Healthy Subjects
• Actual Study Start Date: February 20, 2024
• Estimated Primary Completion Date: September 2024
• Estimated Study Completion Date: September 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in changepoint task [ Time Frame: three times (once on each of the three test days; interval between test days at least 7 days) ]

   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.

2. Change in history bias task [ Time Frame: three times (once on each of the three test days; interval between test days at least 7 days) ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Philipp Sterzer, Prof. Dr.; +41 61 325 81 55; philipp.sterzer@upk.ch

Contact: Lucca Jaeckel; +41 61 325 81 51; lucca.jaeckel@unibas.ch

Locations

Switzerland

University Psychiatric Clinics Basel; Recruiting

Basel, Switzerland, 4002

Contact: Philipp Sterzer, Prof.Dr. +41 61 325 81 55 philipp.sterzer@upk.ch

Contact: Lucca Jaeckel +41 61 325 8151 Lucca.Jaeckel@unibas.ch

Principal Investigator: Philipp Sterzer, Prof. Dr.

Sponsors and Collaborators

University Hospital, Basel, Switzerland

University of Basel

University Psychiatric Clinics Basel

Investigators

• Principal Investigator: Philipp Sterzer, Prof. Dr.; University Psychiatric Clinics Basel

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT05976698
• Other Study ID Numbers: 2023-00763, pk23Sterzer
• First Posted: August 4, 2023
• Last Update Posted: February 21, 2024
• Last Verified: February 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Basel, Switzerland:

neural and behavioral indicators; serotonergic system; perceptual decision-making

Additional relevant MeSH terms:

Lysergic Acid Diethylamide; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Receptor Agonists