Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial.
Robin J Murphy, Rachael Sumner, William Evans, Rhys Ponton, Sanya Ram, Kate Godfrey, Anna Forsyth, Alana Cavadino, Venkat Krishnamurthy Naga, Todd Smith, Nicholas Hoeh, David B Menkes, Suresh Muthukumaraswamy
Biological Psychiatry September 15, 2023 DOI: 10.1016/j.biopsych.2023.03.013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Healthy male volunteers |
| Intervention | Lysergic acid diethylamide (LSD) |
| Dose | 10 μg |
| Duration | 6-week intervention |
| Topics | Anxiety LSD Microdosing |
| Keywords | Cognition Psychedelics hallucinogens Entheogens Microdosing sub-perceptual dosing Mental health mood Wellbeing Emotional state Creativity |
| Citations | 69 |
| Key findings | Microdosing LSD produced transient mood-elevating effects on dose days but no lasting improvements in overall mood or cognition in healthy adult men. |
Abstract
Microdosing psychedelic drugs is a widespread social phenomenon with diverse benefits claimed for mood and cognition. Randomized controlled trials have failed to support these claims, but the laboratory-based dosing in trials conducted to date may have limited ecological validity. Healthy male volunteers were randomized into lysergic acid diethylamide (LSD) (n = 40) and placebo (n = 40) groups and received 14 doses of either 10 μg LSD or an inactive placebo every 3 days for 6 weeks. First doses were given in a supervised laboratory setting, with other doses self-administered in a naturalistic setting. Results of safety data, blinding, daily questionnaires, expectancy, and pre-/postintervention psychometrics and cognitive tasks are presented here. The most notable reported adverse event was treatment-related anxiety, which prompted the withdrawal of 4 participants from the LSD group. Daily questionnaires showed credible evidence (>99% posterior probability) of improved ratings of creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, and these effects remained when controlling for preintervention expectancy. No questionnaire or cognitive task showed a credible change between baseline and 6-week assessment time points. Microdosing LSD appears to be relatively safe in healthy adult men, notwithstanding a risk of anxiety. While microdosing elicited transient increases in scales associated with mood-elevating effects, it was not sufficient to promote enduring changes to overall mood or cognition in healthy adults. Future microdosing trials in clinical populations will require the use of active placebos to control for placebo effects and dose titration to adjust for interindividual variability in drug response.
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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Microdosing LSD (10 μg every 3 days for 6 weeks) produced transient mood-elevating effects on dose days but no lasting improvements in overall mood or cognition, with treatment-related anxiety prompting withdrawal of 4 participants from the LSD group.
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 |
| Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity. Healthy adults | 2023 | Within-subject, double-blind, placebo-controlled experiment | n = 18 |
| 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 |
Citations in the library
Cited by 28
- Expectancy Effects in Psychedelic Trials. Biological psychiatry. Cognitive neuroscience and neuroimaging May 1, 2024
- Hallucinogen use among young adults ages 19–30 in the United States: Changes from 2018 to 2021 Addiction June 7, 2023
- Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology April 1, 2024
- Microdosing Psychedelics: Current Evidence From Controlled Studies. Biological psychiatry. Cognitive neuroscience and neuroimaging May 1, 2024
- Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology June 1, 2024
and 23 more in the library
Cites 4
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2023
- Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity. Biol Psychiatry Cogn Neurosci Neuroimaging December 20, 2019
- Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study. Addict Biol February 1, 2022
- Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube Harm Reduction Journal November 28, 2019