Drug Effects on Mood and Behavior - Expectancy

Not Applicable

Recruiting

• Conditions: LSD
• Interventions: Drug: LSD; Drug: Placebo

• Registration Number: NCT07061886
• Lead Sponsor: University of Chicago

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).

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 Timeline

• Study First Submitted: 2025-06-06
• Study Start: 2025-06-26
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-01
• Last Update Submitted: 2025-07-01
• Study First Posted: 2025-07-11
• Last Update Posted: 2025-07-11
• Primary Completion: 2026-06-05
• Study Completion: 2026-06-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LSD (13 micrograms), Identity of substance known	LSD	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.
Placebo, Identity of substance known	Placebo	Distilled water (0.13 mL). Subjects will receive placebo, and they (but not the research assistant) will be told the identity of the drug.
LSD (13 micrograms), Identity uncertain	LSD	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.
Placebo, Identity uncertain	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Visual Analog Scale (VAS)	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).
Addiction Research Center Inventory (ARCI)	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).
Drug Effects Questionnaire (DEQ)	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.
5 Dimensions of Altered States of Consciousness (5D-ASC) scale	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.
Ultimatum Game	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 Outcome Measures

Name	Time	Method
Cardiovascular (Heart rate, blood pressure)	During in-lab session: baseline (pre-drug), and every 60 minutes post-drug from 0-4 hours	Systolic pressure (SP), diastolic pressure (DP) and heart rate (HR) will be measured using a portable digital blood pressure monitor.

Trial Locations

Locations (1)

University of Chicago; 🇺🇸 Chicago, Illinois, United States