This placebo-controlled, randomized, naturalistic study (n=80) of repeated microdoses of LSD (10μg, 14x, 6w) finds improved ratings, on dosing days, on creativity, connectedness, energy, and other wellness ratings. Though these transient changes were found, no enduring changes to mood and cognition were observed.

Abstract of Acute mood-elevating properties of microdosed LSD in healthy volunteers

“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.“

Authors: Robin J. Murphy, Rachael Sumner, William Evans, Rhys Ponton, Sanya Ram, Kate Godfrey, Anna Forsyth, Alana Cavadino, Venkat Krishmamuthy, Todd Smith, Nicholas R. Hoeh, David B. Menkes & Suresh Muthukumaraswamy

Summary of Acute mood-elevating properties of microdosed LSD in healthy volunteers

Microdosing psychedelic drugs is now a prevalent community phenomenon. Retrospective surveys of community microdosers have reported a wide range of benefits to mood and cognition. Still, RCTs conducted in laboratory environments have only detected minor acute effects and no durational effects of repeated doses. The current RCT uses repeated self-administered microdoses of LSD over a six-week period to address the lack of ecological validity and employing treatment regimens that are too brief in RCTs conducted in artificial laboratory environments.

Healthy male volunteers were randomly assigned to receive 14 doses of 10 g LSD base (in distilled water) or inactive placebo (water only) every 3 days for 6 weeks. Self-recorded videos verified dose compliance submitted every dosing day. Pre-/postintervention questionnaires, cognitive tasks, and expectancy questionnaires were administered at Baseline, Treatment, and Final visits. Results of creativity, brain plasticity and connectivity, blood-based biomarkers, and qualitative interviews will be presented elsewhere.

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Find this paper

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

https://doi.org/10.1016/j.biopsych.2023.03.013

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Study details

Compounds studied
LSD

Topics studied
Microdosing

Study characteristics
Original Placebo-Controlled Double-Blind Randomized

Participants
80 Humans

Institutes

Institutes associated with this publication

MindBio Therapeutics
MindBio Therapeutics is conducting clinical research exploring the effects of microdosing psychedelic medicines to treat a range of medical conditions such as depression, anxiety, PTSD, panic disorder, chronic pain and opioid addiction.

Compound Details

The psychedelics given at which dose and how many times

LSD 10 μg | 14x

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
This randomized controlled trial (n=80) investigated the effects of microdosed LSD (10µg; 14x) on neural plasticity using a visual long-term potentiation (LTP) EEG paradigm. Participants received either LSD or placebo and completed the visual LTP paradigm both acutely and after six weeks of repeated microdosing. While event-related potential (ERP) analyses didn't show changes in visually induced LTP, dynamic causal modelling revealed alterations in laminar connectivity in the primary visual cortex, suggesting a more sensitive approach to assessing neural plasticity compared to traditional peak analysis methods.

LSD increases sleep duration the night after microdosing
This Phase I RCT (n=80) examined the effects of microdosing LSD (10μcg; 14x; 6w) on sleep in healthy adult male volunteers, with doses self-administered every third day and sleep monitored through a commercially available sleep/activity tracker. The results showed that participants in the LSD group slept an extra 24.3 minutes per night on the night after microdosing compared to the placebo group, with no changes in sleep stages or physical activity.

Linked Clinical Trial

A randomised, double-blind, placebo-controlled trial to study the effects of repeated microdoses of lysergic acid diethylamide (LSD) on creativity and brain activity in healthy adult males
This randomized, double-blind, placebo-controlled trial (n=80) will study the effects of repeated microdoses of lysergic acid diethylamide (LSD) on creativity and brain activity in healthy adult males. Participants will receive either 10 µg of LSD or a placebo, dissolved in water in 1 ml oral syringes, taken once every three days for a total of 14 doses over a 41-day regimen.