Summary: New controlled research finds no clear evidence that LSD microdosing improves mood or cognitive performance.
Source: University of Chicago
Advocates of LSD microdosing—regularly taking very small amounts of the psychedelic—often report improved mood, focus and creativity. A new University of Chicago study, however, found no reliable benefits to mood or cognitive function when low doses of LSD were given under controlled laboratory conditions.
Harriet de Wit, Ph.D., Professor of Psychiatry and Behavioral Neuroscience at the University of Chicago, cautions that the study does not definitively rule out any potential benefits of microdosing. Rather, it demonstrates that under the specific conditions tested—dose levels, timing, participant characteristics and setting—microdoses produced negligible improvements. Importantly, the research also confirms that these low-dose regimens were well tolerated and did not produce measurable safety concerns.
“These substances are already being used widely, and rigorous scientific evaluation is essential,” de Wit said. “We need controlled studies to determine whether the claimed benefits hold up, to confirm safety, and to separate pharmacological effects from expectations.”
Published on February 1 in Addiction Biology, the study builds on de Wit’s long-running program of carefully controlled psychopharmacology research. It also received support from the Institute of Translational Medicine, a Chicago-based collaboration focused on accelerating therapeutic discovery and development.
The trial tested repeated low doses of LSD administered every three to four days. Participants were randomly assigned to one of three groups: 13 micrograms of LSD, 26 micrograms of LSD, or placebo. For context, typical recreational doses that cause full psychedelic experiences are usually around 100–200 micrograms—far higher than the microdoses used here.
Researchers selected LSD for the study because it is the most commonly reported psychedelic in microdosing practice. Sessions took place in a supervised lab setting where participants attended four five-hour dosing visits and one drug-free follow-up, each separated by 3–4 days. To reduce expectancy effects, participants were not told the class of drug being tested or that the study focused on microdosing.
“We deliberately removed cues that might signal ‘this is a psychedelic,’” de Wit explained. “Expectations can strongly influence how people report their experience, and that can confound efforts to measure any real pharmacological benefit.”
During dosing sessions and at follow-up, participants completed standardized cognitive tests, emotional processing tasks, and mood assessments. At the higher microdose (26 μg) some participants reported modest subjective effects—slight feelings of a drug effect or mild stimulant-like sensations—but these were short-lived and diminished with repeated dosing.
Across objective measures, repeated low doses of LSD did not improve mood scores, enhance psychomotor performance, or produce consistent changes in emotional task outcomes either during dosing sessions or at the drug-free follow-up. The researchers concluded that, in healthy volunteers and under the controlled conditions studied, microdosing produced negligible cognitive or mood benefits.
De Wit said the results were somewhat surprising given the large number of anecdotal reports supporting microdosing. From a neurobiological perspective, there were plausible reasons to expect mood effects, since LSD acts at serotonin receptors targeted by many antidepressant drugs. Still, this controlled trial did not find evidence of robust therapeutic effects.
“We can’t claim microdosing never works,” de Wit emphasized. “What we can say is that, with these doses, intervals, participants, and in this laboratory setting, we did not observe a reliable benefit. Outside the lab, strong expectations about improvement could contribute to perceived effects or interact with any pharmacological action.”
Safety was a clear finding: repeated low doses of LSD produced no measurable adverse effects on heart rate, blood pressure, cognitive impairment or other vital signs. Prior human and animal research also suggests LSD is not overtly toxic even at higher doses. Notably, participants showed signs of tolerance across sessions—the subjective peak effect was strongest at the first dosing visit and decreased thereafter—suggesting the drug does not accumulate over repeated short-interval administrations.
Conducting the study posed logistical and regulatory challenges. Because LSD is heavily regulated, the laboratory obtained approvals from the DEA, FDA and an Institutional Review Board. The multiple five-hour visits required of volunteers also made recruitment demanding.
De Wit underscored the public health importance of controlled research on practices that are becoming commercialized. “Companies are marketing products and making claims about psychedelics and related compounds,” she said. “There’s limited empirical evidence to back up many of those claims, so systematic testing is essential.”
About this psychopharmacology research news
Author: Ilima Loomis
Source: University of Chicago
Contact: Ilima Loomis – University of Chicago
Image: The image is in the public domain
Original Research: Closed access.
“Repeated low doses of LSD in healthy adults: A placebo‐controlled, dose–response study” by Harriet de Wit et al. Addiction Biology
Abstract
Repeated low doses of LSD in healthy adults: A placebo‐controlled, dose–response study
Interest in psychedelic therapies has renewed attention to unsupervised microdosing practices. Many users report that very low doses of LSD, taken at 3–4 day intervals, boost mood and cognition, yet few controlled studies have evaluated these claims. In a double-blind, placebo-controlled study, researchers tested four repeated low doses of LSD tartrate (13 or 26 μg) or placebo in healthy adults, administered every 3–4 days, assessing mood, cognitive performance and emotional processing.
Participants were randomized to placebo (N=18), 13 μg LSD (N=19) or 26 μg LSD (N=19). They attended four five-hour drug-administration sessions separated by 3–4 days, followed by a drug-free follow-up session several days later. The 26 μg dose produced modest subjective sensations, including increased reports of feeling a drug effect and some stimulant-like and LSD-like sensations, but no meaningful improvements in mood or performance on psychomotor and most emotional tasks were observed. No residual effects appeared at the drug-free follow-up.
The study concludes that, in this controlled setting with a limited number of administrations, repeated low doses of LSD are safe but produce negligible changes in mood or cognition in healthy volunteers.