LSD for Depression

(MESA-D Trial)

Overseen By Hanna Molla

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Chicago

Must not be taking: Psychiatric medications

Disqualifiers: Psychosis, Substance use, Pregnancy, others

Compensation: Varies

Number of Visits: 3

Duration: 1 day

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the impact of a low dose of LSD, a psychedelic drug, on mood in people with depression. Researchers aim to determine if LSD can improve mood and how it interacts with brain activity, measured through EEG, which records brain waves. Participants will receive either a low dose of LSD or a placebo to compare effects. Individuals dealing with depression who meet specific health criteria, such as having a BMI between 19-30 and not currently taking psychiatric medications, may qualify for this trial. As an Early Phase 1 trial, this research seeks to understand how LSD works in people, offering participants a chance to contribute to groundbreaking knowledge.

Will I have to stop taking my current medications?

Yes, if you are currently taking any psychiatric medication, you must stop taking it for at least 2 weeks before joining the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that small amounts of LSD might be safe for people with depression. In studies, participants who took low doses of LSD reported feeling less depressed, suggesting that LSD could improve mood.

Importantly, these studies did not find any serious side effects at low doses, and participants tolerated the treatment well. However, caution is necessary because LSD is not yet approved for treating depression.

For those considering joining a trial, early studies primarily focus on assessing safety, closely monitoring for any side effects. Always consult your healthcare provider if you have questions about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for depression, which typically include SSRIs, SNRIs, and therapy, LSD offers a novel approach by potentially influencing serotonin receptors in new and unique ways. Researchers are excited about LSD because it might rapidly alter mood and perception, offering quicker relief of depressive symptoms compared to traditional antidepressants, which often take weeks to show effects. Additionally, LSD's potential to foster introspective and transformative experiences could complement therapeutic interventions, providing a holistic benefit that current medications can't offer.

What evidence suggests that LSD might be an effective treatment for depression?

Research has shown that higher doses of LSD can significantly reduce symptoms of depression. This trial will evaluate the effects of a specific dose of LSD (26 micrograms) compared to a placebo. Studies also suggest that LSD has helped with other mental health issues, such as anxiety and addiction, with some positive results. However, many of these studies are older and did not follow today's research standards. While scientists are still determining exactly how LSD works in the brain, they know it affects serotonin receptors, which help control mood. ^{2 4 6 7 8}

Who Is on the Research Team?

Hanna Molla

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for individuals with depression, including major depressive disorder. Participants should be interested in exploring the mood effects of a serotonin agonist. Specific eligibility details are not provided, so general health requirements and consent to EEG monitoring may apply.

Inclusion Criteria

English fluency

High school education or higher

BMI between 19-30 kg/m2

Exclusion Criteria

Personal or first-degree relative with history of psychosis

Current suicidal ideation or suicide attempt in past 12 months

Individuals with a medical condition contraindicating study participation as determined by the study physician (e.g., liver disease, abnormal EKG, liver or cardiovascular disease)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single low dose of LSD (26 µg) or placebo, followed by assessments of mood and neurophysiological changes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for mood changes and neurophysiological effects, including EEG and sleep quality assessments

48 hours

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• LSD

Trial Overview The study tests the impact of a low dose of LSD (26 µg), which stimulates serotonin receptors, against a placebo on mood changes in depressed individuals. Mood symptoms will be correlated with brain activity measured by EEG.

How Is the Trial Designed?

Group I: LSD (26 micrograms) Experimental Treatment 1 Intervention

LSD tartrate in tasteless solution (0.26 mL)

Group II: placebo Placebo Group 1 Intervention

distilled water (0.26 mL)

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025001527

Efficacy and safety of low- versus high-dose-LSD-assisted ... Results showed that patients receiving higher doses of LSD experienced greater reductions in depression scores, suggesting potential therapeutic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37819655/

Use of Lysergic Acid Diethylamide by Major Depression ... This study suggests that, from 2008 to 2019, there was a disproportionate increase in the prevalence of past-year LSD use among US adults ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6985449/

Therapeutic Use of LSD in Psychiatry: A Systematic Review of ... LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary ...

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2810623

Use of Lysergic Acid Diethylamide by Major Depression ... This study suggests that, from 2008 to 2019, there was a disproportionate increase in the prevalence of past-year LSD use among US adults with past-year ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03866252

LSD Therapy for Persons Suffering From Major Depression This study will evaluate the potential benefits of LSD-assisted psychotherapy in patients suffering from Major Depressive Disorder.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10568444/

Use of Lysergic Acid Diethylamide by Major Depression Status This study suggests that, from 2008 to 2019, there was a disproportionate increase in the prevalence of past-year LSD use among US adults with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40482648/

Efficacy and safety of low- versus high-dose-LSD-assisted ... This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder.

8. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(22)01553-0/fulltext

Lysergic Acid Diethylamide–Assisted Therapy in Patients ... LSD produced long-lasting and notable reductions in anxiety and comorbid depression symptoms up to 16 weeks.