Major Depression ModeratePhase 1SLIMNCT07503002
Shortened LSD Intervention for Major Depressive Disorder
A Phase 1 study testing LSD and Risperidone in people with Major Depression Moderate and Major Depression Severe, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Major Depression Moderate, Major Depression Severe, Major Depression
- What is being tested?
- LSD and Risperidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 1 Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Depression with psychotic features
- Have a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or Bipolar I Disorder.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Johns Hopkins Center for Psychedelic and Consciousness Research
Baltimore, Maryland, 21224
Matthew Nielsen, BA, 917-991-0642, mnielse7@jh.edu
Sandeep Nayak, MD
About this study
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.
Read the detailed description
This study will administer open-label oral LSD hemi-L-tartrate 250 µg followed 45 minutes later by oral risperidone 1 mg to 10 participants with Major Depressive Disorder (MDD) for a pilot investigation into the effects of abbreviated LSD on depression. Participants will be monitored for 10.5 hours and assessed for subjective effects and discharge readiness at several time points following the dose. The main aim of this study is to test whether risperidone can be used to abbreviate the subjective effects of LSD, and whether this abbreviated LSD experience will have any potential therapeutic benefit in patients with MDD.
- Being tested
- LSD, Risperidone
- Keywords
- LSD, lysergic acid diethylamide, depression, MDD, major depression, major depressive
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LSDDrug
Participants will be administered LSD followed 45-minutes later by risperidone.
RisperidoneDrug
Participants will be administered LSD followed 45-minutes later by risperidone.
| Study group | Role | What they receive |
|---|---|---|
| LSD + Risperidone | Experimental | Not described Receives: Drug: LSD; Drug: Risperidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery Asberg Depression Rating Scale (MADRS)
Score range from 0 to 60. Higher scores indicate worse depression symptoms
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depression ModerateStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sandeep Nayak, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07503002
- Sponsor's protocol ID
- IRB00460674
- Acronym
- SLIM
- Status last verified
- Sep 2026
- First submitted
- 25 Mar 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No