OPEN Foundation

R. Lee

Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity.

Abstract

BACKGROUND:
The practice of “microdosing,” or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment.
METHODS:
The present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed.
RESULTS:
LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength.
CONCLUSIONS:
These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug’s purported antidepressant effect.

Bershad, A. K., Preller, K. H., Lee, R., Keedy, S., Wren-Jarvis, J., Bremmer, M. P., & de Wit, H. (2019). Preliminary report on the effects of a low dose of LSD on resting state amygdalar functional connectivity. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging., https://doi.org/10.1016/j.bpsc.2019.12.007
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Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers

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 sub-threshold 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 – 26μg) on mood and behavior in healthy volunteers under double-blind conditions.
Methods
Healthy young adults (N=20) attended four laboratory sessions during which they received placebo, 6.5μg, 13μg, or 26μg LSD in randomized order at one-week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.
Results
LSD produced dose-related subjective effects across the three doses (6.5μg, 13μg, or 26μg). At the highest dose the drug also increased ratings of “vigor” 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 13μg 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.
Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry., https://doi.org/10.1016/j.biopsych.2019.05.019
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Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

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 behavior 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 expected peak drug effect, they completed mood questionnaires and behavioral 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 vigor 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.

Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry., 10.1016/j.biopsych.2019.05.019
Link to full text