Drug Effects on Mood and Behavior - Expectancy (MESA-X)

April 28, 2026 updated by: University of Chicago
This study will examine the effects of a single low dose of the 5HT2A agonist LSD (Lysergic Acid Diethylamide) (13 µg) or placebo in individuals who are or are not explicitly told what drug they will receive. Although it is known that expectancies strongly influence subjective responses to most drugs, no studies have examined expectancies on response to a very low dose of LSD. This is especially important in the context of 'microdosing' of drugs. People who practice microdosing typically do so with strong expectations of positive effects, making it difficult to determine whether there is a pharmacological effect. To minimize expectancies in the laboratory, participants are usually not told exactly what drug they will receive (i.e., double-blind), but given a range of possibilities. In the present study, the study team will test half the subjects under single-blind conditions, where the participants (but not the research assistant) will know exactly what they are receiving. Other subjects will receive the usual instructions. Healthy volunteers will receive either a marginally detectable dose of LSD (13 micrograms) or placebo, under conditions where they i) know for sure what drug they are receiving or ii) where the identity of the drug is uncertain. Four groups of subjects (N=12 each) will attend single 4-hour laboratory session. The study team will examine subjective and behavioral responses to the drug in each of four conditions (Known-Drug; Known-Placebo; Uncertain-Drug; Uncertain-Placebo).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Expectancies are known to influence responses to psychoactive drugs. The study team and others have shown previously, using a balanced placebo design, that expectancies influence responses to alcohol, nicotine, caffeine, stimulant drugs, and cannabinoids. In these studies subjects are randomly assigned to one of four conditions: Expect the drug and get the drug; Expect the drug and get placebo; Expect placebo and get the drug; Expect placebo and get placebo. This allows researchers to separate pharmacological effects from expectancy effects.

Recently there has been much discussion about the role of expectancies specifically in responses to psychedelic drugs. Expectancies are especially important in the use of very low doses, referred to as 'microdoses'. These doses are typically at or below the threshold of detectability, but users take them with strong prior beliefs that the drugs improve mood and cognition. The beneficial effects have been difficult to demonstrate under laboratory conditions, perhaps because in the laboratory the drugs are administered without the explicit expectation of benefits, and the administration of the drugs is to some extent blinded. The present study is designed to separate the pharmacological effects of a low dose of LSD from effects that are influenced by expectancies.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago
        • Contact:
        • Principal Investigator:
          • Harriet de Wit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • English Fluency
  • High school education or higher
  • BMI between 19-30 kg/m2

Exclusion Criteria:

  • Individuals with a medical condition contraindicating study participation as determined by the study physician (e.g., liver disease, abnormal EKG, liver or cardiovascular disease)
  • High blood pressure (>140/90)
  • Current suicidal ideation or suicide attempt in past 12 months
  • Past year severe substance use disorder
  • Personal or first-degree relative with history of psychosis
  • Currently taking any psychiatric medication (for conventional antidepressants must be off for ≥ 2 weeks)
  • Active panic disorder
  • Severe obsessive-compulsive disorder
  • Severe post-traumatic stress disorder
  • Women who are pregnant or planning to become pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LSD (13 micrograms), Identity of substance known
LSD tartrate in tasteless solution (0.13 mL). Subjects will receive LSD, and they (but not the research assistant) will be told the identity of the drug.
Drug: LSD
The serotonin 2A receptor agonist LSD
Other Names:
  • Lysergic acid diethylamide
Active Comparator: LSD (13 micrograms), Identity uncertain
LSD tartrate in tasteless solution (0.13 mL). Subjects will be told they might receive a stimulant, sedative, low dose of hallucinogen, or placebo, and will receive LSD.
Drug: LSD
The serotonin 2A receptor agonist LSD
Other Names:
  • Lysergic acid diethylamide
Placebo Comparator: Placebo, Identity of substance known
Distilled water (0.13 mL). Subjects will receive placebo, and they (but not the research assistant) will be told the identity of the drug.
Drug: Placebo
Distilled water (0.26 mL)
Placebo Comparator: Placebo, Identity uncertain
Distilled water (0.13 mL). Subjects will be told they might receive a stimulant, sedative, low dose of hallucinogen, or placebo, and will receive placebo.
Drug: Placebo
Distilled water (0.26 mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual Analog Scale (VAS)
Time Frame: During in-lab session: Pre-drug, and every 60 minutes post-drug from 0-4 hours
Momentary states will be assessed using VAS to measure ratings of 'depressed', 'anxious', 'motivated', and 'energetic', on a scale of 0 (Not at all) to 100 (Very much).
During in-lab session: Pre-drug, and every 60 minutes post-drug from 0-4 hours
Addiction Research Center Inventory (ARCI)
Time Frame: During in-lab session: Pre-drug, and every 60 minutes post-drug from 0-4 hours
The ARCI is a 53-item true or false questionnaire that assess effects of specific drug classes. It includes scales measuring: amphetamine (A); benzedrine group (BG; energy and intellectual efficiency); morphine-benzedrine group (MBG; euphoric effects); LSD (hallucinogen-like effects); pentobarbital-chlorpromazine-alcohol group (PCAG; sedative effects); and marijuana (M).
During in-lab session: Pre-drug, and every 60 minutes post-drug from 0-4 hours
Drug Effects Questionnaire (DEQ)
Time Frame: During in-lab session: Pre-drug, and every 60 minutes post-drug from 0-4 hours
The DEQ measures overall drug effects. It consists of questions on a visual analog scale about the subjective effects of drugs. Subjects are asked to rate the extent they feel a drug effect, whether they like or dislike the drug effect, and if given a choice would they want to take more of the drug. Scores range from 0-100.
During in-lab session: Pre-drug, and every 60 minutes post-drug from 0-4 hours
5 Dimensions of Altered States of Consciousness (5D-ASC) scale
Time Frame: End of session (4 hours post-drug)
The 5D-ASC assesses altered states of consciousness in five domains, and is sensitive to LSD administration (Schmid et al. 2014). Scores range from 0-100.
End of session (4 hours post-drug)
Ultimatum Game
Time Frame: During in lab session: 1.5 hours post-drug
In this task, participants play the role of responder in a series of single-shot computer interactions. They engage in 60 trials in which they interact with different computer-simulated proposers. On each trial they are allocated $10 to split between themselves and the participant. Participants will receive 60 different monetary offers ranging from fair (50:50 splits) to increasingly unfair (10:90 splits), presented in random order. For each offer, participants must decide whether to accept the offer, in which case both players receive the proposed amounts, or reject the offer, in which case both players receive nothing. This task will measure how the drug affects perception of fairness, and decision-making in social contexts. The task takes approximately a 30 minutes to complete.
During in lab session: 1.5 hours post-drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular (Heart rate; beats per minute)
Time Frame: During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours
heart rate (HR) will be measured using a portable digital blood pressure monitor.
During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours
Cardiovascular (blood pressure; mmHg)
Time Frame: During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours
Systolic pressure (SP), and diastolic pressure (DP) will be measured using a portable digital blood pressure monitor.
During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Hanna Molla, University of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 26, 2025

Primary Completion (Estimated)

June 5, 2026

Study Completion (Estimated)

June 5, 2026

Study Registration Dates

First Submitted

June 6, 2025

First Submitted That Met QC Criteria

July 1, 2025

First Posted (Actual)

July 11, 2025

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB25-0658
  • 5R01DA002812-35 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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