Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study

This is the fourth publication on the administration of a microdose of LSD (5, 10, or 20µg). The double-blind, placebo-controlled study (n=24) found enhanced attention, slower information processing, more positive mood, and increased anxiety and confusion. Again, the results are small and ambiguous.

Abstract of Mood and cognition after administration of low LSD doses in healthy volunteers

“There is a popular interest in microdosing with psychedelics such as LSD. This practice of using one-tenth of a full psychedelic dose according to a specific dosing schedule, anecdotally enhances mood and performance. Nonetheless, controlled research on the efficacy of microdosing is scarce. The main objective of the present dose-finding study was to determine the minimal dose of LSD needed to affect mood and cognition. A placebo-controlled within-subject study including 24 healthy participants, was conducted to assess the acute effects of three LSD doses (5, 10, and 20 mcg) on measures of cognition, mood, and subjective experience, up until 6 h after administration. Cognition and subjective experience were assessed using the Psychomotor Vigilance Task, Digit Symbol Substitution Test, Cognitive Control Task, Profile of Mood States, and 5-Dimensional Altered States of Consciousness rating scale. LSD showed positive effects in the majority of observations by increasing positive mood (20 mcg), friendliness (5, 20 mcg), arousal (5 mcg), and decreasing attentional lapses (5, 20 mcg). Negative effects manifested as an increase in confusion (20 mcg) and anxiety (5, 20 mcg). Psychedelic-induced changes in waking consciousness were also present (10, 20 mcg). Overall, the present study demonstrated selective, beneficial effects of low doses of LSD on mood and cognition in the majority of observations. The minimal LSD dose at which subjective and performance effects are notable is 5 mcg and the most apparent effects were visible after 20 mcg.”

Authors: Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder, Eef L. Theunissen, Friederike Holze, Matthias E. Liechti, Amanda Feilding, Johannes G. Ramaekers & Kim P. C. Kuypers

Notes

This paper uses the same participants as Holze et al. (2020), Hutten et al. (2020), and Ramaekers et al. (2020). The other studies respectively looked at pharmacodynamics and felt effect (only really at 20 µg), blood plasma levels (ambiguous results), and increased pain tolerance.

This study is quite similar to Yanakieva et al. (2019), which found only small effects on mood (more vigour, lower rating of positive images).

The study is supported in part by the Beckley Foundation.

It was (lazily) reported on in Futurism (October 2020).

Although the conclusions presented in the abstract are valid. Please do consult Figure 1 in the paper to see how small and relatively ‘random’ these results are (i.e. noise). Also:

“Binomial tests indicated that the proportion of observations containing fewer attentional lapses after administration of 5 and 20 mcg LSD was respectively 76% ( p < 0.01) and 74% ( p < 0.01), while this was 38% ( p = 0.19) after 10 mcg LS.” (this is represented in the top-left bar graph in figure 1)

The same can be said of Table 3, which displays mood and cognition scores that move only ever so slightly.

Summary of Mood and cognition after administration of low LSD doses in healthy volunteers