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Home Exclusive Psychopharmacology Psychedelic Drugs

Psilocybin microdosing does not reduce symptoms of depression or anxiety, according to placebo-controlled study

by Eric W. Dolan
February 7, 2022
in Mental Health, Microdosing, Psilocybin, Psychedelic Drugs
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Consuming small doses of psilocybin at regular intervals — a process known as microdosing — does not appear to improve symptoms of depression or anxiety, according to new research published in the Journal of Psychopharmacology. The placebo-controlled study casts doubt on claims that microdosing psychedelic drugs can improve mental health.

Regular doses of psilocybin — the active component in so-called “magic” mushrooms — have been shown to have profound and long-lasting effects on personality and mood. Preliminary research has indicated that microdosing psychedelic drugs is also associated with a range of psychological benefits, such as increased productivity and reduced stress. In one study, nearly 80% of individuals who microdosed with psychedelics reported improvements in their mental health.

But much of the research on microdosing has come with important limitations: namely, the lack of placebo control groups.

“The main interest in this topic stems from anecdotal reports of people who microdose and say they experience the beneficial effects. Many people do this in order to feel better, to have a more optimistic outlook on life and to cope with depression and anxiety,” said study author Michiel van Elk, an associate professor of cognitive psychology at Leiden University and supervisor of the PRiSM Lab.

“However, most research on this topic was cross-sectional in nature. This means that the research asked a group of people at a specific point in time whether they microdosed and how they were feeling. This type of research showed that microdosing was associated with better mental health.”

“But correlation does not imply causation,” van Elk explained. “It could be that the participants in those studies self-selected because they experienced the beneficial effects of microdosing. It could also be that placebo effects were at play, as people knew they were actually taking a microdose. Thus, in order to obtain more causal evidence for the effects of microdosing on emotional processing and well-being, we needed to conduct a placebo-controlled study.”

The study included a carefully screened sample of 75 participants who attended a microdosing workshop. At the end of the workshop, the participants received two bags that contained either psilocybin pills or placebo pills. The researchers instructed the participants to consume one bag of doses over the following three weeks. The participants then took a two-week break, before consuming the second bag of doses for the next three weeks.

Neither the participants nor the researchers were aware of which bag contained psilocybin and which bag contained placebo, a process known as double-blinding. Participants were also excluded from the final analysis if they consumed other psychoactive substances during the study or deviated from their microdosing schedule.

In four laboratory sessions, which took place about 1.5 hours after self-administering a dose of psilocybin or placebo, the participants completed a battery of tests that measured depression, anxiety, emotion processing, and interoceptive awareness.

Based on previous findings, the researchers had expected that psilocybin microdosing would reduce symptoms of anxiety and depression, induce a bias towards positive facial expressions, and increase interoceptive awareness. But the effects of microdosing did not differ significantly from placebo.

“We found that microdosing with psilocybin compared to a placebo did not result in reduced depression or anxiety scores,” van Elk told PsyPost. “We observed a strong generic placebo-effect though: both the placebo and the microdosing group showed a significant change in their wellbeing scores from the moment they started with the study. Thus, merely expecting that you are part of a clinical trial during which you might or might not receive a psychoactive substance already improves your wellbeing.”

The findings are in line with another placebo-controlled study, which found that small doses of LSD did not have significant effects on a test of working memory, a test of cognitive functioning, or a measure of simulated social exclusion. But it is still possible that microdosing has some positive psychological impacts. The scientific investigation into microdosing — and the use of psychedelic substances in general — is still in its infancy.

“Of course, this does not mean that microdosing is completely ineffective,” van Elk said. “We only found no objective evidence in our controlled study. But there are indeed many caveats. It could well be that the dosing we used was suboptimal and needs to be fine-tuned on an individual basis. It could also be that it takes some time for microdosing to take effect and that merely doing this for a few weeks is not enough to establish the long-term effects.”

“Another caveat is that many people in our study broke blind and they figured out what condition they were assigned to,” van Elk added. “This is a more generic problem for this type of research: the effects of psychedelics are so obvious — even at lower doses — that it is difficult to prevent people from figuring out what condition they are assigned to. If people subsequently figure out that they are in the active/experimental condition (e.g., based on subtle side-effects), this in turn can contribute again to the placebo response.”

Future studies should utilize larger sample sizes, which would make it easier to detect small effects, the researchers said.

“So in short: we found that psilocybin microdosing does not affect emotional processing and wellbeing,” van Elk said. “It could well be however that are study design was simply not sufficiently sensitive to pick up any signal that might be present in people who microdose. We need research that is more ecologically valid and that can study people in their daily lives and natural environments, rather than in a lab-based context. Smart wearables and experience-sampling techniques are important tools that can be used to this end.”

The study, “Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study“, was authored by Josephine Marschall, George Fejer, Pascal Lempe, Luisa Prochazkova, Martin Kuchar, Katerina Hajkova, and Michiel van Elk.

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