Drug Effects on Mood and Behavior - Expectancy

NCT07061886 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: IRB25-06585R01DA002812-35
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

LSD

Keywords

Healthy Adults

Outcome Measures

Primary Outcomes (5)

• Visual Analog Scale (VAS)

  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)

  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)

  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

  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

  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 Outcomes (2)

• Cardiovascular (Heart rate; beats per minute)

  During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours

• Cardiovascular (blood pressure; mmHg)

  During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours

Study Arms (4)

LSD (13 micrograms), Identity of substance known

EXPERIMENTAL

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

LSD (13 micrograms), Identity uncertain

ACTIVE COMPARATOR

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

Placebo, Identity of substance known

PLACEBO COMPARATOR

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

Placebo, Identity uncertain

PLACEBO COMPARATOR

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

Interventions

LSD DRUG

The serotonin 2A receptor agonist LSD

Also known as: Lysergic acid diethylamide

LSD (13 micrograms), Identity of substance known; LSD (13 micrograms), Identity uncertain

Placebo DRUG

Distilled water (0.26 mL)

Placebo, Identity of substance known; Placebo, Identity uncertain

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Related Publications (18)

• Aron, A., Melinat, E., Aron, E. N., Vallone, R. D., & Bator, R. J. (1997). The Experimental Generation of Interpersonal Closeness: A Procedure and Some Preliminary Findings. Personality and Social Psychology Bulletin, 23(4), 363-377. https://doi.org/10.1177/0146167297234003

  BACKGROUND

• Beck, A. T., Steer, R. A., & Brown, G. (1996). Beck Depression Inventory-II (BDI-II). In APA PsycTests

  BACKGROUND

• Bershad AK, Schepers ST, Bremmer MP, Lee R, de Wit H. Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers. Biol Psychiatry. 2019 Nov 15;86(10):792-800. doi: 10.1016/j.biopsych.2019.05.019. Epub 2019 Jun 3.

  PMID: 31331617 BACKGROUND

• de Wit H, Molla HM, Bershad A, Bremmer M, Lee R. Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study. Addict Biol. 2022 Mar;27(2):e13143. doi: 10.1111/adb.13143. Epub 2022 Feb 1.

  PMID: 35106880 BACKGROUND

• Dittrich A. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry. 1998 Jul;31 Suppl 2:80-4. doi: 10.1055/s-2007-979351.

  PMID: 9754838 BACKGROUND

• Fadiman, J and Gruber, J (2025) Microdosing for Health, Healing, and Enhanced Performance, St Martins Group

  BACKGROUND

• Fischman MW, Foltin RW. Utility of subjective-effects measurements in assessing abuse liability of drugs in humans. Br J Addict. 1991 Dec;86(12):1563-70. doi: 10.1111/j.1360-0443.1991.tb01749.x.

  PMID: 1786488 BACKGROUND

• Güth, W, RSchmittberger, B Schwarze (1982) An experimental analysis of ultimatum bargaining. Journal of Economic Behavior & Organization, Volume 3, 367-388

  BACKGROUND

• Hammami MM, Al-Gaai EA, Alvi S, Hammami MB. Interaction between drug and placebo effects: a cross-over balanced placebo design trial. Trials. 2010 Nov 19;11:110. doi: 10.1186/1745-6215-11-110.

  PMID: 21092089 BACKGROUND

• Lyvers MF, Maltzman I. The balanced placebo design: effects of alcohol and beverage instructions cannot be independently assessed. Int J Addict. 1991 Sep;26(9):963-72. doi: 10.3109/10826089109058933.

  PMID: 1743824 BACKGROUND

• Martin WR, Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971 Mar-Apr;12(2):245-58. doi: 10.1002/cpt1971122part1245. No abstract available.

  PMID: 5554941 BACKGROUND

• McNair, D., Lorr, M., Droppleman, L., (1971). POMS, Profile of Mood States. E. a. I. T. Services.

  BACKGROUND

• Metrik J, Kahler CW, Reynolds B, McGeary JE, Monti PM, Haney M, de Wit H, Rohsenow DJ. Balanced placebo design with marijuana: pharmacological and expectancy effects on impulsivity and risk taking. Psychopharmacology (Berl). 2012 Oct;223(4):489-99. doi: 10.1007/s00213-012-2740-y. Epub 2012 May 16.

  PMID: 22588253 BACKGROUND

• Molla H, Lee R, Tare I, de Wit H. Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacology. 2024 Apr;49(5):774-781. doi: 10.1038/s41386-023-01772-4. Epub 2023 Dec 2.

  PMID: 38042914 BACKGROUND

• Murphy RJ, Muthukumaraswamy S, de Wit H. Microdosing Psychedelics: Current Evidence From Controlled Studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May;9(5):500-511. doi: 10.1016/j.bpsc.2024.01.002. Epub 2024 Jan 26.

  PMID: 38280630 BACKGROUND

• Palmer AM, Brandon TH. Nicotine or expectancies? Using the balanced-placebo design to test immediate outcomes of vaping. Addict Behav. 2019 Oct;97:90-96. doi: 10.1016/j.addbeh.2019.04.026. Epub 2019 Apr 26.

  PMID: 31174168 BACKGROUND

• Skopp G, Potsch L, Mattern R, Aderjan R. Short-term stability of lysergic acid diethylamide (LSD), N-desmethyl-LSD, and 2-oxo-3-hydroxy-LSD in urine, assessed by liquid chromatography-tandem mass spectrometry. Clin Chem. 2002 Sep;48(9):1615-8. No abstract available.

  PMID: 12194952 BACKGROUND

• Szigeti B, Heifets BD. Expectancy Effects in Psychedelic Trials. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May;9(5):512-521. doi: 10.1016/j.bpsc.2024.02.004. Epub 2024 Feb 20.

  PMID: 38387698 BACKGROUND

Related Links

• Bershad et al., 2019
• Dittrich, 1998
• Hammami et al., 2010
• Metrik et al., 2012
• Molla et al., 2024
• Murphy et al., 2024
• Palmer et al., 2019
• Szigeti \& Heifets, 2024

MeSH Terms

Interventions

Lysergic Acid Diethylamide

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hanna Molla

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hanna Molla

CONTACT

7737023560; hmolla@uchicago.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: July 11, 2025
• Study Start: June 26, 2025
• Primary Completion (Estimated): June 5, 2026
• Study Completion (Estimated): June 5, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)