A new randomized controlled study of LSD microdosing has failed to find evidence that the psychedelic practice results in improvements to mood or cognition. The research has been published in the journal Addiction Biology.

Microdosing refers to the practice of consuming small amounts of a psychedelic drug at regular intervals. Preliminary research has indicated that microdosing is associated with a range of psychological benefits, such as increased productivity and reduced stress. But these studies have not utilized randomized placebo-controlled methodologies — the gold standard for proving causation.

“I saw how widespread the practice of microdosing is, and yet there are few well-controlled studies to document its apparent benefits,” said study author Harriet de Wit, a professor of psychiatry and behavioral neuroscience at the University of Chicago. “My human psychopharmacology laboratory is well suited to test effects of drugs under double-blind conditions.”

In the study, four low doses of LSD (13 or 26 μg) or placebo were administered to 56 healthy adults at 3–4 day intervals. The participants were aged 18–35 and they all reported having used a psychedelic drug at least once in their lifetime, but were not experienced with microdosing. The doses were administered under double-blind conditions, meaning that neither the participants nor the researchers knew who was receiving an active dose and who was receiving an inactive placebo.

“We removed any expectations that this was a psychedelic drug,” de Wit explained. “Because in the real world, people’s expectations can strongly influence their responses.”

After ingesting their dose, the participants completed cardiovascular assessments and hourly mood questionnaires. During the first and last sessions, the participants also completed cognitive and behavioral tasks related to emotional processing, working memory, simulated social rejection, and general cognitive performance.

Participants received their dose during five-hour laboratory sessions. They remained in a comfortable room and were given access to movies and reading materials when no activities were scheduled.

The researchers found that the higher dose of LSD (26 μg) produced a small decrease in false alarm rates for recognizing fearful emotions and a small decrease in feelings of social rejection. The higher dose of LSD also produced heightened feelings of vigor and some participants who received the higher dose reported feeling a modest “high” during the drug sessions.

But neither the lower or higher doses of LSD had a significant effect on other aspects of emotional processing, mood, working memory, or general cognitive performance. “Under these limited conditions, the effects did not differ from placebo.

But, future studies are needed to assess the effects of repeated doses under different conditions,” de Wit told PsyPost.

The participants also appeared to build a tolerance to LSD over the course of the study, with the strongest “high” reported at the first session, and the perception of a drug effect diminishing at each subsequent session.

“We can’t say necessarily that microdosing doesn’t work,” de Wit said in a news release. “All we can say is that, under these controlled circumstances, with this kind of participant, these doses, and these intervals, we didn’t see a robust effect.”

There is still much that future research needs to address. “Does microdosing have more pronounced effects in individuals with anxiety or depression, or pressing psychological problems?” de Wit said. “Would the effects be detected if different outcome measures were used, or if dosing continued for more than 2 weeks?”

The study, “Repeated low doses of LSD in healthy adults: A placebo-controlled, dose–response study“, was authored by Harriet de Wit, Hanna M. Molla, Anya Bershad, Michael Bremmer, and Royce Lee