LSD for Mood and Behavior

(MESA-X 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: Liver disease, High blood pressure, Psychosis, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a low dose of LSD, a psychoactive substance, affects mood and behavior, particularly when participants are aware or unaware of what they are taking. Researchers are investigating the role of expectations, as many who microdose LSD believe it has positive effects. Participants will be divided into groups to receive either LSD or a placebo (a non-active substance), with some informed about their treatment and others kept uncertain. Adults who speak English, have at least a high school education, and have a BMI between 19-30 may be eligible to participate. As an Early Phase 1 trial, this research aims to understand how LSD works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

If you are currently taking any psychiatric medication, you must stop taking it at least 2 weeks before participating in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LSD is usually safe at low doses. In past studies, serious side effects were uncommon, though some participants experienced a faster heartbeat and higher blood pressure. Other possible effects include trouble sleeping and shaking. At very high doses, LSD can cause serious issues like breathing problems or high fever, but these are not expected with the low dose used in this trial. It is important to note that while the FDA has not approved LSD, researchers are studying it to better understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using LSD for mood and behavior issues because it offers a unique approach compared to standard treatments like antidepressants and mood stabilizers. Most existing treatments target neurotransmitters like serotonin over extended periods, but LSD works differently by engaging serotonin receptors in a novel way, potentially leading to faster and more profound mental shifts. While traditional options often take weeks to show effects, LSD might offer quicker mood improvements and behavioral changes. Additionally, the low-dose LSD being studied is believed to have fewer side effects than higher doses typically associated with psychedelic experiences, making it a promising option for those looking for alternative treatments.

What evidence suggests that this trial's treatments could be effective for mood and behavior?

Research has explored LSD for its potential to help with anxiety, depression, and substance use problems. Some studies suggest it might aid in anxiety and depression, but results remain uncertain. More encouraging evidence exists for its use in treating substance use disorders, as some individuals have experienced positive effects. LSD affects serotonin, a brain chemical related to mood and behavior, which might explain the changes in feelings. In this trial, participants will receive either a low dose of LSD (13 micrograms) or a placebo. However, limited information exists on the effects of low doses like the 13 micrograms used in this trial, and more research is needed to fully understand its impact. ^{2 5 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 healthy volunteers interested in how a low dose of LSD affects mood and behavior when they know or don't know what they're taking. It's not clear if you can join if you have certain health conditions, take specific medications, or have other factors that typically exclude people from clinical trials.

Inclusion Criteria

High school education or higher

BMI between 19-30 kg/m2

English Fluency

Exclusion Criteria

Severe post-traumatic stress disorder

High blood pressure (>140/90)

Current suicidal ideation or suicide attempt in past 12 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants attend a single 4-hour laboratory session to receive either a low dose of LSD or placebo, with varying levels of expectancy about the drug identity.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LSD
• Placebo

Trial Overview The study tests the effects of a small amount (13 µg) of LSD versus a placebo. Participants are split into four groups to see how knowing or not knowing whether they've taken LSD or placebo influences their experience during a single 4-hour session.

How Is the Trial Designed?

Group I: LSD (13 micrograms), Identity of substance known Experimental Treatment 1 Intervention

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.

Group II: LSD (13 micrograms), Identity uncertain Active Control 1 Intervention

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.

Group III: Placebo, Identity of substance known Placebo Group 1 Intervention

Distilled water (0.13 mL). Subjects will receive placebo, and they (but not the research assistant) will be told the identity of the drug.

Group IV: Placebo, Identity uncertain Placebo Group 1 Intervention

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.

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. 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 (52). During that time, it was also observed that LSD together with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178125002707

Review article Efficacy and Safety of LSD in the treatment ... The results suggest a possible positive effect of LSD in treating substance use disorders, although the findings for anxiety and depression remain inconclusive, ...

3. 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 ...

4. nature.com nature.com/articles/s41386-023-01574-8

The effect of lysergic acid diethylamide (LSD) on whole- ... Our results suggest that local gain is changed under LSD implicating disturbances of the E/I balance as a neural mechanism underlying LSD ...

5. mdpi.com mdpi.com/1424-8247/18/4/499

Clinical Research on Lysergic Acid Diethylamide (LSD) in ... Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030196/

Clinical Research on Lysergic Acid Diethylamide (LSD) in ... This review examines LSD's pharmacokinetics, neurobiological mechanisms, and safety considerations, including cardiovascular risks, emotional vulnerability, and ...

7. emedicine.medscape.com emedicine.medscape.com/article/1011615-overview

LSD Toxicity: Background, Pathophysiology and Etiology ... Severe LSD toxicity can lead to respiratory arrest, coma, emesis, hyperthermia, autonomic instability, and bleeding disorders.

8. mountsinai.org mountsinai.org/health-library/special-topic/substance-use-lsd

Substance use - LSD Information | Mount Sinai - New York Harmful Effects of LSD · Increased heart rate, blood pressure, breathing rate, and body temperature · Sleeplessness, loss of appetite, tremors, sweating · Mental ...