Effects of LSD on Neuroplasticity in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Lysergic Acid Diethylamide

• Registration Number: NCT05177419
• Lead Sponsor: University of Fribourg

Brief Summary

Neuroplasticity is the brain's ability to reorganize itself and adapt in response to changing environmental conditions or pathological stimuli. LSD is a potent psychedelic drug which has been able to rapidly stimulate neuroplasticity in animal studies. Various authors have speculated that changes in neuroplasticity may contribute to LSD's long-term effects, but there is still little direct evidence that LSD or other psychedelics enhance neuroplasticity in humans. The goal of this study is to investigate the effects of LSD on several measures of neuroplasticity in healthy human subjects.

Detailed Description

Neuroplasticity is the brain's ability to reorganize itself and adapt in response to changing environmental conditions or pathological stimuli. Its dysregulation may play a role in the etiology of depression and anxiety disorders, and it is also essential for recovery from neural injury and stroke.

LSD is a potent psychedelic drug and a member of the psychoplastogen family of small molecules, which are able to rapidly stimulate neuroplasticity in cortical neurons following a single dose. Previous research suggests that changes in neuroplasticity may contribute to LSD's long-term effects, which include increases in subjective well-being and life satisfaction, reduced anxiety, and increased openness to experience. Additionally, there is some evidence that LSD and other psychedelics could be viable clinical treatments for depression, anxiety, and addictive disorders, and that changes in neuroplasticity may underlie this clinical potential. However, there is still little direct evidence that LSD or other psychoplastogens enhance cortical plasticity in humans.

The goal of this study is to investigate the effects of LSD on several measures of neuroplasticity in healthy human subjects, as well as other abilities and traits thought to be related to neuroplasticity. Determining whether LSD enhances cortical plasticity, how long this may last, where in the brain it occurs, and what it means for cognition and emotion is essential for understanding LSD's long-term effects, including but not limited to its clinical potential.

Study Timeline

• Study First Submitted: 2021-12-15
• Study First Submitted QC: 2021-12-15
• Study First Posted: 2022-01-04
• Study Start: 2022-05-02
• Primary Completion: 2025-03-12
• Study Completion: 2025-03-12
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Aged 21-55
2. Body mass index 18-29
3. Right-handed as assessed by the Edinburgh Handedness Inventory (score > 60)
4. Fluent understanding of German
5. Willingness to adhere to study protocol
6. Willingness to refrain from taking illicit psychoactive substances for the duration of the study
7. Willingness to refrain from consuming alcohol for 24 hours before each study appointment.
8. Willingness to not operate a motor vehicle or other heavy machinery 48 hours after each substance administration.
9. Women of childbearing potential must be willing to use effective birth control during the study (e.g. birth control pill; condoms must be combined with a second reliable method).
10. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests will be repeated before each treatment day and must remain negative.
11. A friend or relative must be available to accompany the participant home following LSD appointments.

Exclusion Criteria

1. Severe chronic or acute medical condition
2. History of any seizure disorder, stroke, or cardiovascular illness
3. History of severe head trauma resulting in loss of consciousness
4. Personal or family history (first-degree relative) of psychotic disorders
5. Current or previous major neurological or psychiatric disorder within the last 3 years (e.g. major depression, anorexia, substance use disorder),
6. History of medically relevant suicide attempts
7. Current use of psychoactive medications
8. Lifetime use of hallucinogens, dissociatives, or entheogens more than 10 times, or any time within the previous three months
9. Regular (daily or near-daily) use of cannabis, alcohol, nicotine, or illicit substances
10. Pregnant or nursing women
11. Presence of any implanted, metal or electronic devices (e.g. pacemaker)
12. Recent or current participation in another clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High-dose LSD	Lysergic Acid Diethylamide	High dose of lysergic acid diethylamide
Low-dose LSD	Lysergic Acid Diethylamide	Low dose of lysergic acid diethylamide

Primary Outcome Measures

Name	Time	Method
Change in motor evoked potential amplitude after paired associative stimulation (PAS)	Baseline, 8 hours post-treatment, 1 day post-treatment, 1 week post-treatment	Assessment of capacity for neuroplastic changes in the motor cortex

Secondary Outcome Measures

Name	Time	Method
Motor learning ability	1 day post-treatment	Speed and accuracy on a motor learning task
Change in auditory event-related potential (ERP) amplitude after tetanic stimulation	Baseline, 8 hours post-treatment, 1 day post-treatment, 1 week post-treatment	Assessment of capacity for neuroplastic changes in the auditory cortex
Plasma and serum levels of brain-derived neurotrophic factor (BDNF)	Baseline, 8 hours post-treatment, 1 day post-treatment, 1 week post-treatment	Marker of neuroplasticity

Trial Locations

Locations (1)

University of Fribourg; 🇨🇭 Fribourg, FR, Switzerland