Mood Effects of Serotonin Agonists: Depression
MESA-D
2 other identifiers
interventional
48
1 country
1
Brief Summary
This study will examine the effect of a low dose of the 5HT2A agonist LSD (26 µg), compared to placebo, on acute and protracted mood states in individuals with depression. The investigators will assess the relationship between mood-related symptoms and EEG as a neurophysiological marker.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for early_phase_1
Started Jun 2025
Shorter than P25 for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 22, 2025
CompletedStudy Start
First participant enrolled
June 9, 2025
CompletedFirst Posted
Study publicly available on registry
June 12, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
July 3, 2025
July 1, 2025
12 months
April 22, 2025
July 1, 2025
Conditions
Outcome Measures
Primary Outcomes (6)
Acute Mood Measures
Acute (Profile of Mood States scale ratings from 0-60).
Peak change (~2 hours post-drug) from pre-drug baseline
Acute Mood Measures
Acute (Visual Analog Scale questionnaires, scale ratings from 0-100).
Peak change (~2 hours post-drug) from pre-drug baseline
Delayed Mood Measures
Delayed depressed mood measures (Beck Depression Inventory \[score range: 0-63, higher scores greater symptoms severity\] and Inventory of depression and anxiety symptoms \[score range: 0-48, higher scores increased severity\])
Change from baseline (orientation) to 48-hour followup
Effort expenditure for reward (EEFRT) Behavioral Task Performance
Effort Expenditure for Reward Task
2 hours post-drug administration
Sleep Quality
Electroencephalogram (EEG) power to assess time spent in Rapid Eye Movemeent \[REM\] and slow wave sleep
Change from baseline (pre-drug) to Night 0, 1, and 2 post-drug
Sleep Quality
subjective measures of sleep function (Karolinska sleep log)
Change from baseline (pre-drug) to Night 0, 1, and 2 post-drug
Secondary Outcomes (4)
Self-reported feelings of connection using Likert scale conversation questionnaires
Collected at the end of the session, 270 minutes post-drug administration
Natural Language Processing using large language model
during 45 minute conversation, occurring 150 min after drug administration
Facial expression analysis using HUMEAI software for positive and negative affect
during 45 minute conversation, occurring 150 min after drug administration
Self-Esteem implicit association test
2 hours post drug
Study Arms (2)
placebo
PLACEBO COMPARATORdistilled water (0.26 mL)
LSD (26 micrograms)
EXPERIMENTALLSD tartrate in tasteless solution (0.26 mL)
Interventions
Eligibility Criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Chicagolead
- National Institute on Drug Abuse (NIDA)collaborator
Study Sites (1)
University of Chicago
Chicago, Illinois, 60637, United States
Related Publications (10)
Duan W, Cao D, Wang S, Cheng J. Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants. Chem Rev. 2024 Jan 10;124(1):124-163. doi: 10.1021/acs.chemrev.3c00375. Epub 2023 Nov 30.
PMID: 38033123BACKGROUNDHusain MI, Ledwos N, Fellows E, Baer J, Rosenblat JD, Blumberger DM, Mulsant BH, Castle DJ. Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action? Front Psychiatry. 2023 Feb 10;13:1076459. doi: 10.3389/fpsyt.2022.1076459. eCollection 2022.
PMID: 36844032BACKGROUNDLing S, Ceban F, Lui LMW, Lee Y, Teopiz KM, Rodrigues NB, Lipsitz O, Gill H, Subramaniapillai M, Mansur RB, Lin K, Ho R, Rosenblat JD, Castle D, McIntyre RS. Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. CNS Drugs. 2022 Jan;36(1):17-30. doi: 10.1007/s40263-021-00877-y. Epub 2021 Nov 17.
PMID: 34791625BACKGROUNDMurphy 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: 38280630BACKGROUNDWalsh CA, Gorfinkel L, Shmulewitz D, Stohl M, Hasin DS. Use of Lysergic Acid Diethylamide by Major Depression Status. JAMA Psychiatry. 2024 Jan 1;81(1):89-96. doi: 10.1001/jamapsychiatry.2023.3867.
PMID: 37819655BACKGROUNDLy C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018 Jun 12;23(11):3170-3182. doi: 10.1016/j.celrep.2018.05.022.
PMID: 29898390BACKGROUNDMoliner R, Girych M, Brunello CA, Kovaleva V, Biojone C, Enkavi G, Antenucci L, Kot EF, Goncharuk SA, Kaurinkoski K, Kuutti M, Fred SM, Elsila LV, Sakson S, Cannarozzo C, Diniz CRAF, Seiffert N, Rubiolo A, Haapaniemi H, Meshi E, Nagaeva E, Ohman T, Rog T, Kankuri E, Vilar M, Varjosalo M, Korpi ER, Permi P, Mineev KS, Saarma M, Vattulainen I, Casarotto PC, Castren E. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci. 2023 Jun;26(6):1032-1041. doi: 10.1038/s41593-023-01316-5. Epub 2023 Jun 5.
PMID: 37280397BACKGROUNDAllen N, Jeremiah A, Murphy R, Sumner R, Forsyth A, Hoeh N, Menkes DB, Evans W, Muthukumaraswamy S, Sundram F, Roop P. LSD increases sleep duration the night after microdosing. Transl Psychiatry. 2024 Apr 15;14(1):191. doi: 10.1038/s41398-024-02900-4.
PMID: 38622150BACKGROUNDHutten NRPW, Quaedflieg CWEM, Mason NL, Theunissen EL, Liechti ME, Duthaler U, Kuypers KPC, Bonnelle V, Feilding A, Ramaekers JG. Inter-individual variability in neural response to low doses of LSD. Transl Psychiatry. 2024 Jul 15;14(1):288. doi: 10.1038/s41398-024-03013-8.
PMID: 39009578BACKGROUNDBershad 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: 31331617BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hanna Molla
University of Chicago
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- OTHER
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 22, 2025
First Posted
June 12, 2025
Study Start
June 9, 2025
Primary Completion (Estimated)
June 1, 2026
Study Completion (Estimated)
June 1, 2026
Last Updated
July 3, 2025
Record last verified: 2025-07