A recent clinical trial in Sweden found that a single oral dose of psilocybin reduced depressive symptoms within 48 hours in participants suffering from moderate to severe depression. Participants also reported improvements that persisted for more than three months.

The study, carried out at the Northern Stockholm Psychiatric Clinic and published in JAMA Network, is the first randomized, double-blind trial of psilocybin for depression in Sweden. Researchers at Karolinska Institutet followed 35 participants for 12 months, making this one of the more rigorous long-term, placebo-controlled studies of psilocybin therapy for major depressive disorder.

Most antidepressants take anywhere from two to six weeks before patients begin to notice any change, and even then, about two out of three people don’t fully recover after their first round of treatment. If psilocybin’s fast-acting effect holds up in larger studies, it could provide doctors with a much-needed alternative method for treating depression.

Psilocybin vs. Placebo

All 35 participants suffered from recurrent moderate to severe major depressive disorder. Researchers randomly assigned 17 people to receive a 25 mg oral dose of psilocybin and 18 others to receive an active placebo. The placebo was niacin, a vitamin known to cause temporary flushing and tingling sensations to help mimic the experience of taking a drug.

Everyone in the study also participated in five psychotherapy sessions spread over 17 days. This included a session to prepare participants before taking the drug, the dosing session itself, and three follow-up sessions to help process their reported experiences. On the day of treatment, participants wore eyeshades and listened to music for several hours, with clinical staff nearby to monitor their safety.

Clinicians who did not know which treatment participants received used the Montgomery-Åsberg Depression Rating Scale (MADRS), a 0 to 60-point assessment, to measure depressive symptoms at days 8, 15, 42, and 365 after the initial dose.

Clinically Significant Results

By day 8, people who received the psilocybin dose had an average drop in MADRS score of 7.27 points compared with the placebo group. Researchers say that a difference of this size is statistically significant. This difference continued through day 15 and day 42. By the end of the first year, researchers no longer observed a clear difference between the groups.

Participants’ self-assessments began to show improvement even sooner. Using a self-report version of the MADRS, the group that received the psilocybin dose reported significant improvement starting on the second day; the difference in self-reported assessments between groups persisted until about day 102.

At six weeks, remission rates (defined as a MADRS score below 10) were at 53% in the psilocybin group and 6% in the niacin group. By the end of the year, both groups had similar outcomes, as the placebo group showed gradual improvement over time.

“Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important,” said lead author Hampus Yngwe, a consultant psychiatrist and PhD student at Karolinska Institutet’s Department of Clinical Neuroscience.

The Psychedelic Caveat

The psychedelic effects of psilocybin made it difficult to keep participants unaware of which treatment they received. After the first year, 94% of those in the psilocybin group and all in the niacin group correctly identified which dose they received.

This is important to note because a person’s expectations can shape how they report their symptoms. The researchers pointed out this limitation and said the effect size might partly be due to participants believing they had received the real drug. Clinician ratings, which were also unaware of the administered doses, showed a similar, though smaller, benefit for the psilocybin group compared to self-reports, which supports this concern.

“We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” Yngwe said.

What Comes Next

Most reported side effects were mild and brief. Headache, anxiety, and hallucinations were the most common adverse effects reported in the psilocybin group. However, two participants experienced severe anxiety that required medical attention in the weeks after dosing. The researchers say this finding highlights the need for careful patient selection and follow-up in future studies.

“It is important to emphasize that the treatment is not risk-free and that some patients may need extra support,” said senior author Johan Lundberg, professor at Karolinska Institutet’s Department of Clinical Neuroscience.

The research team plans to analyze PET scans and biological samples collected before and after dosing to see whether psilocybin changes synaptic density in the brain. This could help explain how the drug produces its rapid antidepressant effect and whether repeated dosing might extend this benefit.

While these results are encouraging, the study only included 35 people at one clinic, which makes it hard to draw broad conclusions about long-term effects. Larger and more diverse studies will be needed before psilocybin therapy could become a standard treatment.

Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.

A new study shows that one psychedelic experience doesn’t just alter how a person feels; it may also change the brain itself. Researchers at UC San Francisco and Imperial College London found that a single 25 mg dose of psilocybin produces signs of likely anatomical changes in the brain that persist for at least a month after the experience.

Published in Nature Communications, the study was conducted in healthy adults with no prior psychedelic use. These results may help explain why psilocybin-assisted therapy is being explored as a treatment for depression, anxiety, and addiction.

The researchers identified a key mechanism behind these changes. Instead of focusing on a single brain region, they identified brain entropy as a key factor linking the experience to later outcomes.

What the Brain Looks Like on Psilocybin

Brain entropy refers to the diversity of neural activity happening at any given moment. A low-entropy brain tends to fall into predictable, repetitive patterns. A high-entropy brain is processing a richer, more varied stream of information. Within 60 minutes of taking the 25 mg dose, EEG recordings showed a sharp spike in entropy.

This increase in entropy persisted longer than the drug’s immediate effects. People who experienced the biggest jumps in entropy also reported more psychological insight the next day, saying they felt a deeper sense of emotional self-awareness. These insights coincided with improvements in well-being that lasted for at least two to four weeks.

“Psychedelic means ‘psyche-revealing,’ or making the psyche visible,” said senior author Robin Carhart-Harris, PhD, the Ralph Metzner Distinguished Professor of Neurology at UCSF. “Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health.”

How the Study Was Designed

The study included 28 healthy adults with no mental health diagnoses. The experiment had two phases. First, each person received a very low 1 mg dose of psilocybin, which acted as a placebo. Researchers then tracked their brain activity and structure using EEG, MRI, and diffusion tensor imaging over the next few weeks.

One month later, those same participants received the 25 mg dose. The researchers then repeated the same series of brain scans and assessments.

Diffusion tensor imaging (DTI), a technique that measures water movement along neural pathways, showed that participants’ brain connections were more structurally intact a month after the high dose. This finding is the opposite of what typically happens with aging, which tends to weaken these connections. The most noticeable changes were in pathways linking the front and middle parts of the brain, areas involved in self-reflection, emotional regulation, and decision-making.

The Trip Is the Treatment

All but one participant described the 25 mg experience as the most unusual state of consciousness they had ever experienced. The other person ranked it among their top five. A month later, the group also performed better on a test of cognitive flexibility, which measures how well a person can adapt their thinking to new information.

Author Taylor Lyons, PhD, a research associate at Imperial College London, pointed to this chain of effects as the study’s most significant takeaway.

“Psilocybin seems to loosen up stereotyped patterns of brain activity and give people the ability to revise entrenched patterns of thought,” Lyons said. “The fact that these changes track with insight and improved well-being is especially exciting.”

These results could guide future research. If brain entropy during the experience predicts how well the treatment works, scientists might be able to use it to calibrate dosage in real time. This could help ensure patients get enough to support insight and recovery, without so much that it causes excessive stimulation.

What Comes Next

Carhart-Harris noted that the therapeutic promise of psilocybin has been recognized for years. This study now provides new details about the biological mechanisms that may underlie its effects.

“We already knew psilocybin could be helpful for treating mental illness,” Carhart-Harris said. “But now we have a much better understanding of how.”

Microdosing is typically associated with psychedelics, specifically small, sub-perceptual doses of psilocybin or LSD that some people use to improve focus, mood, or anxiety. However, a new national survey upends this common association.

A research team at the University of California, San Diego, found that cannabis is the most widely microdosed substance in the United States. An estimated 24 million adults reported having microdosed cannabis at some point, nearly double the number who reported microdosing psilocybin or LSD. The study, published in the American Journal of Preventive Medicine, is among the first to examine national patterns of microdosing across multiple substances.

“Microdosing is often discussed in the context of psychedelics like psilocybin or LSD, but what surprised us most was that cannabis microdosing was almost twice as common,” said Kevin Yang, MD, a resident physician in the Department of Psychiatry at UC San Diego School of Medicine and first author of the study. “That suggests conversations about microdosing may be overlooking a large group of people who are using small amounts of cannabis in similar ways.”

Survey Results

The team surveyed 1,525 adults across the U.S. in late 2023 using a probability-based panel designed to reflect the U.S. population to understand these trends nationally. They asked people whether they had ever intentionally taken very small amounts—roughly one-fifth to one-twentieth of a usual recreational dose—of substances like cannabis, psilocybin, LSD, or MDMA. The idea behind microdosing is to avoid the strong psychoactive effects while still hoping for subtle benefits.

About 9.4% of adults said they had microdosed cannabis at some point, compared to 5.3% for psilocybin, 4.8% for LSD, and 2.2% for MDMA. While fewer people reported currently microdosing, cannabis still led the way, with 3.3% of adults saying they use it in this way now.

People’s reasons for microdosing varied depending on the substance. Most cannabis microdosers said they were looking for medical benefits, like easing anxiety, depression, or chronic pain. On the other hand, those who microdosed psychedelics or MDMA tended to be after a gentler version of the recreational effects, rather than using them for health reasons.

Mental Health and Policy Patterns

The study found that people who rated their mental health as poor were more likely to report microdosing any substance. About 21% of adults with poor mental health said they had microdosed cannabis, compared to about 8% of those who described their health as excellent.

It is not yet clear whether people are microdosing as a way to cope with mental health challenges or for other reasons. Since the study was cross-sectional, capturing data at a single point in time, the researchers could not determine whether microdosing influences mental health or if people with mental health concerns are simply more drawn to the practice.

The study also found that people microdosed psychedelics more often in places that have decriminalized possession. This suggests that changes in policy may influence both access to these substances and people’s willingness to report using them.

The Evidence Gap

Although many people report microdosing, the researchers note that scientific evidence of its effects remains limited. Researchers have conducted few placebo-controlled trials, and those studies have produced inconsistent results so far. Most people who microdose do not test their substances, which raises concerns about contamination and dosing mistakes, especially with unregulated psychedelics.

Senior author Eric Leas, PhD, MPH, an assistant professor at the UC San Diego Herbert Wertheim School of Public Health, pointed to a gap between public enthusiasm and clinical evidence. “There’s a lot of anecdotal enthusiasm around microdosing, especially for mental health,” Leas said. “But we still need rigorous studies to determine whether these perceived benefits are real, who might benefit and what the potential risks could be.”

These findings come at a time when cannabis legalization and psychedelic policy reforms are changing laws across the United States. As these changes continue, the researchers emphasize that understanding how and why people microdose will become increasingly important.

Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.