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.
Trials
April 23, 2021
Robin J Murphy, Rachael Sumner, William Evans et al.
23 citations
A proposed study will test whether regular low doses of LSD, known as microdosing, produce the cognitive and emotional benefits reported anecdotally. Eighty healthy men will receive either a placebo or 10 micrograms of LSD every third day for six weeks. The study will measure personality, creativity, mood, cognition, brain plasticity, and brain imaging at baseline and after the protocol, with additional acute measures after the first dose. Daily functioning will be tracked via questionnaires and a wearable device. The goal is to rigorously evaluate microdosing claims using objective measures, with potential future applications for treating depression, addiction, and other conditions.
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...
Translational Psychiatry
April 15, 2024
Nathan Allen, Aron Jeremiah, Robin J Murphy et al.
15 citations
Microdosing LSD (10 µg every third day for six weeks) increased sleep duration in healthy adult male volunteers. On nights after dosing, the LSD group slept an extra 24.3 minutes per night compared to placebo, with no change in sleep on dosing days. Sleep stage proportions and physical activity remained unchanged. The findings indicate that microdosing LSD modifies physiological sleep requirements, and the objective changes are unlikely to be a placebo effect.
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 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.
Progress in Neuro-psychopharmacology and Biological Psychiatry
February 18, 2026
Dimitri Henriques Daldegan-Bueno, C Donegan, Rachael Sumner et al.
1 citation
Taking very low doses of LSD (8 micrograms) repeatedly over a short period may temporarily improve mood in people with depression, though the effect needs confirmation in controlled experiments. The drug's behavior in the body was measured in this group, and no evidence of tolerance or increased sensitivity appeared, even when the dose was gradually increased.
Journal of Humanistic Psychology
November 10, 2025
Robin J Murphy, Mia Wardlaw, Thomas A. Smith et al.
After a six-week double-blind placebo-controlled trial of 10 µg of lysergic acid diethylamide taken every third day, healthy male participants reported changes in emotions, mood, social life, mindfulness, cognition, work, creativity, and physiological effects. Openness to experience and bidirectionality of effects were overarching themes. Some reported changes have potential clinical relevance for mood disorders, and reports of changes in anxiety suggest careful patient and dose selection. Participants' experiences with set and setting, uncertainty from placebo control, and perceived bidirectionality of effects inform psychedelic clinical trial design.
The International Journal of Neuropsychopharmacology
August 1, 2025
C Donegan, D Daldagen-Bueno, Robin J Murphy et al.
In an open label trial, 17 people with major depressive disorder took 15 doses of LSD at home and one in a clinic over 8 weeks. Afterward, participants reported increased connectedness to self, others, and nature; greater motivation for activities; improved mood; and better coping with negative situations. Some experienced side effects or no change in symptoms. The findings suggest that microdosing LSD may create a positive feedback loop where improved mood, behavioral activation, and connectedness reinforce each other, and that adding a titration protocol and encouraging psychologically beneficial activities could enhance benefits and reduce side effects.