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Completed

NCT Number: NCT07061886

Drug Effects on Mood and Behavior - Expectancy

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).

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Key information

Conditions

LSD

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

University of Chicago

Chicago, Illinois, 60637, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LSD

Drug

The serotonin 2A receptor agonist LSD

Other names: Lysergic acid diethylamide

Placebo

Drug

Distilled water (0.26 mL)

Primary outcomes

  1. 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).

  2. 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).

  3. 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.

  4. 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.

  5. 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.

Secondary outcomes

  1. 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.

  2. 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.

Sponsors and collaborators

Lead sponsor

University of Chicago

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Acronym: MESA-X

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jul 11, 2025
Registry last updated
Jul 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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