Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity.
James Glazer, Conor H. Murray, Robin Nusslock, Royce Lee, Harriet de Wit
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2023 DOI: 10.1038/s41386-022-01479-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subject, double-blind, placebo-controlled experiment Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Healthy adults |
| Intervention | LSD |
| Dose | 13 μg, 26 μg |
| Duration | Three sessions (single doses per session) |
| Topics | Microdosing LSD |
| Keywords | Psychedelics Brain research Reward systems |
| Citations | 52 |
| Key findings | Single low doses of LSD (13 μg and 26 μg) increased reward-related event-related potential components (RewP, FB-P3, LPP) compared to placebo, indicating enhanced hedonic, motivational, and affective processing of reward feedback. |
Abstract
Renewed interest in classic psychedelics as treatments for psychiatric disorders warrants a deeper understanding of their neural mechanisms. Single, high doses of psychedelic drugs have shown promise in treating depressive disorders, perhaps by reversing deficits in reward processing in the brain. In addition, there are anecdotal reports that repeated ingestion of low doses of LSD, or "microdosing", improve mood, cognition, and feelings of wellbeing. However, the effects of low doses of classic psychedelics on reward processing have not been studied. The current study examined the effects of two single, low doses of LSD compared to placebo on measures of reward processing. Eighteen healthy adults completed three sessions in which they received placebo (LSD-0), 13 μg LSD (LSD-13) and 26 μg LSD (LSD-26) in a within-subject, double-blind design. Neural activity was recorded while participants completed the electrophysiological monetary incentive delay task. Event-related potentials were measured during feedback processing (Reward-Positivity: RewP, Feedback-P3: FB-P3, and Late-Positive Potential: LPP). Compared to placebo, LSD-13 increased RewP and LPP amplitudes for reward (vs. neutral) feedback, and LSD-13 and LSD-26 increased FB-P3 amplitudes for positive (vs. negative) feedback. These effects were unassociated with most subjective measures of drug effects. Thus, single, low doses of LSD (vs. placebo) increased three reward-related ERP components reflecting increased hedonic (RewP), motivational (FB-P3), and affective processing of feedback (LPP). These results constitute the first evidence that low doses of LSD increase reward-related brain activity in humans. These findings may have important implications for the treatment of depressive disorders.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Single low doses of LSD (13 μg and 26 μg) increased reward-related event-related potential components compared to placebo, indicating enhanced hedonic, motivational, and affective processing of reward feedback.
Synthesized
Comparable studies
Other randomized controlled trials on LSD and microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity. Healthy young adults, 18 to 35 years old | 2019 | Randomized controlled trial | n = 20 |
| Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Healthy male volunteers | 2023 | Randomized controlled trial | n = 80 |
| Greater subjective effects of a low dose of LSD in participants with depressed mood. Adults with mild depressed mood (scoring high or low on the Beck Depression-II inventory) | 2024 | Randomized controlled trial | n = 39 |
| Inter-individual variability in neural response to low doses of LSD. Healthy participants | 2024 | Randomized controlled trial | n = 53 |
| LSD increases sleep duration the night after microdosing. Healthy adult male volunteers | 2024 | Randomized controlled trial | n = 80 |