Acute mood-elevating properties of microdosed LSD in healthy volunteers: a home-administered randomised controlled trial

Background

Microdosing psychedelic drugs is a widespread social phenomenon with diverse claimed benefits to mood and cognition. Randomised controlled trials have failed to support these claims, but the laboratory-based dosing in trials to date may have limited ecological validity.

Methods

Healthy male volunteers were randomised 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 three days for six 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-/post-intervention psychometrics and cognitive tasks are presented here.

Results

The most notable reported adverse event was treatment-related anxiety, prompting the withdrawal of four 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 relative to non-dose days, which persisted when controlling for pre-intervention expectancy. No questionnaire or cognitive task showed a credible change between baseline and six-week assessment time-points.

Conclusions

Microdosing LSD in healthy adult males appears relatively safe, notwithstanding a risk of anxiety. While microdosing elicited transient increases in scales associated with mood effects, in healthy adults this was not sufficient to promote enduring changes to overall mood or cognition. Future microdosing trials in clinical populations will require active placebos to control placebo effects and dose titration to adjust for inter-individual variability in drug response.