Shortened LSD Intervention for Major Depressive Disorder

NCT07503002 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB00460674
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and clinical effectiveness of a shortened lysergic acid diethylamide (LSD) experience. This will be achieved by administering the drug risperidone 45-minutes after the administration of LSD.

Conditions

Major Depression Severe; Major Depression; Major Depression Moderate

Keywords

LSD; lysergic acid diethylamide; depression; MDD; major depression; major depressive

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery Asberg Depression Rating Scale (MADRS)

  Score range from 0 to 60. Higher scores indicate worse depression symptoms

  1 month

Study Arms (1)

LSD + Risperidone

EXPERIMENTAL

Drug: LSD + Risperidone

Interventions

LSD + Risperidone DRUG

Participants will be administered LSD followed 45-minutes later by risperidone.

LSD + Risperidone

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given written informed consent
• Meet DSM-5 criteria for MDD
• MADRS \>= 28 at screening Can read, write, and speak English fluently
• Be judged by study team clinicians to be at low risk for suicidality

You may not qualify if:

• Women who are pregnant, nursing, or not practicing an effective means of birth control
• Cardiovascular conditions: hypertension with resting blood pressure systolic \>139 or diastolic \>89, angina, heart rate \> 99, a clinically significant ECG abnormality (e.g., atrial fibrillation, QTc \> 450), TIA in the last 6 months stroke, peripheral or pulmonary vascular disease, cardiac valvulopathy
• Epilepsy
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Currently taking antipsychotics, or MAO inhibitors
• Patients taking antidepressant medications and unable to taper
• Moderate or strong CYP2D6 inhibitor antidepressants must undergo a washout period of 4 weeks or five half-lives prior to treatment
• Currently taking CYP2D6 inhibitor other than an antidepressant that will be tapered
• Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UGT1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag
• Have a seizure disorder, multiple sclerosis, history of significant head trauma, CNS tumor, movement disorders or any neurodegenerative condition
• Morbidly obese (\>100 lbs. above ideal body weight, or BMI \>=40, or BMI \>=35 with high blood pressure or diabetes)
• Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal
• Body weight \< 45 kg
• Significant acute adverse reaction (e.g., dystonia) to an antipsychotic
• Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (including substance-induced), Bipolar I or II Disorder or Major

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

Location

Related Links

• Center for Psychedelic and Consciousness Research

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Lysergic Acid Diethylamide; Risperidone

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Sandeep Nayak, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Nielsen, BA

CONTACT

917-991-0642; mnielse7@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: March 31, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)