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.

A team of Canadian researchers studying the possible anxiety-reducing effects of psilocybin, the psychoactive ingredient in so-called magic mushrooms, has revealed that the chemical compound makes an innately aggressive species of fish less aggressive and lazier compared to undrugged fish without reducing its overall social activities.

The research team behind the discovery said future research will be needed to confirm their findings, explore how the active ingredient in magic mushrooms alters neural signaling, identify the active serotonin pathways involved in these behavioral changes, and determine why certain behaviors are altered by exposure while others appear to remain unaffected.

Testing Magic Mushrooms to Evaluate Changes in Fish Aggressiveness

According to a statement announcing the research, over 200 mushroom species contain the active compound psilocybin. The majority of these species belong to the genus Psilocybe, including the well-known magic mushrooms popularized in the counterculture era for their psychoactive properties.

When this substance is ingested by mammals, it can bind to serotonin receptors that are involved in the regulation of behavior and emotions. Notably, these chemically induced changes can affect aggression, appetite, and overall mood. However, the researchers note, the effect of psilocybin on animals “remains largely undescribed.”

Since conducting experiments on human subjects poses significant challenges and limitations, the researchers examined whether these behavioral and mood changes also occur in fish. This led the team to choose the amphibious mangrove rivulus (Kryptolebias marmoratus), which they described as “innately aggressive,” especially when paired with another fish.

“Their aggressive behaviors are straightforward, and subtle changes can easily be detected,” the team explained. “Therefore, this model ensures all observed effects are caused by psilocybin treatment rather than genetic differences between fish.”

‘Dosed’ Fish Appear to Selectively Reduce Energetically Costly Behaviors

After selecting three genetically distinct laboratory-bred lines of mangrove rivulus, they exposed one to psilocybin, whereas the second line served as  “stimulus fish,” intended to trigger behaviors in the ‘drugged’ fish. The team said that the third selected line was used to “quantify whole-body concentrations and absorption of psilocybin” rather than for behavioral evaluation.

During the experiment’s first phase, fish from the first group were placed in a tank already containing the second line of ‘stimulus’ fish. Critically, the two groups were separated by an opaque cover placed over a fiberglass mesh barrier. The researchers said this arrangement allowed the fish to see and smell each other but prevented direct contact.

During this five-minute adjustment period, the team measured behavior to establish a baseline. When the five minutes expired, the barrier was removed, and the interaction between the two fish groups was closely monitored for signs of behavioral or mood changes.

Twenty-four hours after the first phase was completed, the team placed the fish from the first ‘focal’ group in a water tank containing dissolved psilocybin. The fish remained in the psilocybin-enriched tank for 20 minutes to ensure sufficient saturation, then were returned to the tank with the stimulus fish from the previous day’s experiments. Like before, the fish remained separated for five minutes by the opaque mesh barrier before it was removed.

Once again, the team monitored interactions between the two groups to determine whether the ‘drugged’ fish exhibited any behavioral changes. They also looked for potential clues to the fish’s mood. This included measuring the time the fish spent moving and their aggression levels, such as the frequency of swimming ‘bursts’ toward other fish.

According to the researchers, when they compared the fish in the first group’s activities before and after exposure to psilocybin, several changes were observed. Among the most prevalent was an overall reduction in activity after exposure to magic mushrooms’ key ingredient.

“Dosed fish (spent) less time moving than control fish when paired with a conspecific,” they explained, “and performed fewer swimming bursts compared to specimens that hadn’t received psilocybin treatment.”

The study’s senior author, Dr. Suzie Currie, a biologist at The University of British Columbia, defined swimming bursts as “high‑energy attack behaviors that represent an escalation of aggression towards the stimulus fish” but stop short of making physical contact.

“Other types of aggressive behaviors, like head‑on displays, are more about communication and social assessment and require very little energy,” Dr. Currie explained.

The study’s first author, Dayna Forsyth, a research associate and former MSc student at Acadia University in Nova Scotia, said the calming effect of psilocybin observed during their experiments appeared to “selectively reduce energetically costly, escalated behaviors” while other social display behaviors that require less energy remained largely unchanged.

“This suggests that this compound can selectively dampen escalated social conflict rather than shutting down behavior altogether,” Forsyth added.

Reducing Escalated Aggression Without Suppressing Social Interaction

When discussing the implications of their findings, Forsyth said their findings show that an acute, low dose of the active ingredient from magic mushrooms “significantly reduces activity and aggressive attack behavior during social interactions in adult mangrove rivulus fish.” The research added that the observed change was particularly significant, as the selected fish is a “naturally highly aggressive” species.

“These findings provide the first evidence that psilocybin can selectively reduce escalated aggression in a vertebrate model without suppressing social interaction,” added Currie.

When discussing the potential long-term impacts of their findings, the team said their work can provide “robust results” that can, in theory, ultimately be translated to humans. They also noted that their work could “help inform therapeutic research” by helping scientists further clarify which aspects of social behavior are most sensitive to psilocybin exposure.

Although the results were statistically significant, the researchers caution that their study faced several limitations that should be explored by future efforts. For example, they did not test any potential clinical treatments. They also noted that their findings “cannot be directly extrapolated” to humans exposed to psilocybin.

“The study also focused on single doses and short periods of exposure, and didn’t examine long-term effects, repeated dosing, or adaptation over time,” they added.

The team noted that future studies will be needed to determine whether the social changes observed after magic mushroom ingestion are sustained or transitory.

“Future studies can build on this work to explore how psilocybin alters neural signaling, which serotonin pathways are involved, and why some aspects of social behavior are affected while others are not,” Currie said, adding that “these are questions that are difficult or impossible to answer directly in humans.”

The study “The magic of mushrooms: Psilocybin influences behaviour in the mangrove rivulus fish, Kryptolebias marmoratus” was published in Frontiers in Behavioral Science.

Christopher Plain is a Science Fiction and Fantasy novelist and Head Science Writer at The Debrief. Follow and connect with him on X, learn about his books at plainfiction.com, or email him directly at christopher@thedebrief.org.