Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers
This double-blind, placebo-controlled, within-subject study (n=20) found that a microdose of LSD (up to 26μg; 3x) elicited dose-dependent subjective effects during the 'peak' of the experience but not at the follow-up (48 hours).
Authors
- Harriet de Wit
- Richard Lee
- Anya Bershad
Published
Abstract
Background
Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors and with limited evidence that higher doses of LSD (100-200 μg) positively bias emotion processing. Yet, the effects of such subthreshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single, very low doses of LSD (0-26 μg) on mood and behaviour in healthy volunteers under double-blind conditions.
Methods
Healthy young adults (N = 20) attended 4 laboratory sessions during which they received 0 (placebo), 6.5, 13, or 26 μg of LSD in randomized order at 1-week intervals. During the expected peak drug effect, they completed mood questionnaires and behavioural tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.
Results
LSD produced dose-related subjective effects across the 3 doses (6.5, 13, and 26 μg). At the highest dose, the drug also increased ratings of vigour and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected.
Conclusions
Single microdoses of LSD produced orderly dose-related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13 μg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.
Research Summary of 'Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers'
Introduction
Public and anecdotal interest in microdosing lysergic acid diethylamide (LSD) has grown because users report improved mood, greater energy and enhanced cognition after taking very low doses at multi-day intervals. Earlier work has established LSD’s serotonergic pharmacology—principally partial agonism at 5-HT2A and related receptors—and controlled studies of much higher doses (100–200 mg) have shown acute changes in emotion processing and long-lasting effects on mood in some clinical contexts. However, most data on microdosing come from naturalistic surveys and open‑label reports; few double‑blind, placebo‑controlled laboratory investigations have tested the acute effects of very low doses on mood, cognition and affective processing in humans. Bershad and colleagues set out to characterise the acute subjective, behavioural and physiological effects of single very low doses of LSD in healthy young adults under double‑blind, within‑subject conditions. The primary aim was to identify threshold doses that produce detectable subjective effects and to evaluate whether these doses alter mood, cognitive performance or emotional responses to valenced stimuli—information intended to guide future studies of repeated dosing and clinical populations.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers. Biological Psychiatry, 86(10), 792-800. https://doi.org/10.1016/j.biopsych.2019.05.019
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