Biological psychiatry
September 15, 2023
Robin J Murphy, Rachael Sumner, William Evans et al.
69 citations
Microdosing LSD (10 μg every three days for six weeks) in healthy adult men produced transient improvements in creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, even after controlling for preintervention expectancy. However, no enduring changes in overall mood or cognition were observed between baseline and six-week assessments. The most notable adverse event was treatment-related anxiety, which led four participants in the LSD group to withdraw. Microdosing appears relatively safe in this population but does not support claims of lasting mood or cognitive benefits.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Robin J Murphy, Suresh Muthukumaraswamy, Harriet de Wit
31 citations
Taking regular low doses of psychedelic drugs (microdosing) has drawn attention for potential psychotherapeutic effects, but controlled studies have lagged. A review of 14 rigorous double-blind placebo-controlled studies using investigator-supplied lysergic acid diethylamide (LSD) at 5-20 micrograms found that acute microdoses dose-dependently altered blood pressure, sleep, neural connectivity, social cognition, mood, and perception of pain and time. Perceptible drug effects occurred at 10-20 micrograms but not 5 micrograms. No serious adverse effects were reported. Repeated doses did not alter mood or cognition on any measures. Low doses of LSD appear safe and produce acute behavioral and neural effects in healthy adults, warranting further study in patient samples and with other psychedelics.
BMC neuroscience
February 5, 2024
Robin J Murphy, Kate Godfrey, Alexander D Shaw et al.
16 citations
Microdosing psychedelics is claimed to improve cognition, but clinical evidence is limited. In a placebo-controlled trial, 80 healthy adult males took 10 µg of LSD or placebo every third day for six weeks. A visual long-term potentiation (LTP) EEG paradigm measured neural plasticity indirectly. Standard event-related potential (ERP) analyses of N1b and P2 components showed no evidence of changes in LTP from LSD, either acutely or after six weeks. However, dynamic causal modeling of the ERP timecourse using a thalamocortical model revealed changes in laminar connectivity in primary visual cortex, including acute changes to self-gain and inhibitory input parameters and differences in excitatory connectivity from layer 2/3 to layer 5 between...
Trials
August 24, 2024
Dimitri Daldegan-Bueno, Carina Joy Donegan, Anna Forsyth et al.
14 citations
A phase 2b randomized controlled trial will test whether repeated low doses of LSD (4 to 20 micrograms, taken twice weekly for 8 weeks at home) reduce depressive symptoms in people with major depressive disorder, compared to an active placebo. The trial is triple-blind and includes measures of mood, personality, sleep, brain activity, blood biomarkers, and safety. This is the first controlled trial to test microdosed LSD in patients' natural environment. Results will help determine whether psychedelic microdosing is a viable additional treatment for depression and guide future research.
Psychopharmacology
February 1, 2025
Robin J Murphy, Rachael L Sumner, Kate Godfrey et al.
9 citations
A randomized controlled trial gave 80 healthy adult males 10 µg doses of LSD or placebo every third day for six weeks and tested creativity with the Alternate Uses Test, Remote Associates Task, Consensual Assessment Technique, and an Everyday Problem-Solving Questionnaire. No drug effect was found on any creativity measure at the first dose or after six weeks, despite participants reporting feeling more creative on dose days. Baseline vocabulary skill significantly influenced scores on two tests. The null findings may reflect that laboratory testing misses naturalistic creative differences, available tests do not capture the facets of creativity anecdotally affected, or reported enhancements are placebo effects.
Journal of psychopharmacology (Oxford, England)
April 18, 2025
James D Morse, Soo Hee Jeong, Robin J Murphy et al.
3 citations
After a 10 µg sublingual dose of LSD, the drug's concentration in the blood peaks at about 0.20 µg/L after 1.5 hours and has an elimination half-life of roughly 3 hours. A one-compartment model best describes how the body processes the drug. The small increases in heart rate and perceived drug effect (less than 15% above baseline) limited the ability to model those effects. Two participants who withdrew due to anxiety had intermediate-to-weak CYP2D6 enzyme activity, and several CYP genotypes appeared to influence LSD concentration. No evidence of changes in peripheral BDNF levels was found. The findings provide a pharmacokinetic model and assay useful for future clinical studies, but larger samples are needed to assess CYP genotypes as response biomarkers.