Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers



      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.


      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.


      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.


      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.


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      Linked Article

      • The Effects of Low Doses of Lysergic Acid Diethylamide in Healthy Humans: Demystifying the Microdosing of Psychedelics
        Biological PsychiatryVol. 86Issue 10
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          Research on the effects of psychedelics in healthy volunteers and clinical populations has seen a revival in the last decade. More recently, a practice called “psychedelic microdosing” has gained public attention, with several books and magazine and newspaper articles published on this topic within the last few years. In contrast to the pharmacological meaning of “microdosing”—administering <100 μg/1% of the pharmacologically active dose to assess the pharmacokinetics of a substance to optimize drug development and selection—microdosing psychedelics implies the use of low doses of hallucinogenic substances, primarily lysergic acid diethylamide (LSD), to increase work performance, enhance creativity, or boost energy levels.
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