Single dose of psilocybin relieves OCD symptoms for weeks

Psilocybin is being taken seriously in mental health research – not just for depression or anxiety, but now for obsessive-compulsive behaviors too.

A growing number of studies suggest that a single dose of this psychedelic compound might ease symptoms tied to OCD and related conditions like body dysmorphic disorder.

These disorders aren’t just frustrating habits. They involve cycles of distressing thoughts and repetitive actions that can be hard to break, even with medication or therapy.

For people who’ve tried everything and still struggle, psilocybin could offer a new kind of relief – and it may work faster than anything currently available.

Psilocybin’s impact across species

The review looked at 13 studies – four clinical trials involving people with obsessive-compulsive or body-focused disorders, and nine animal studies using lab models of compulsive behavior.

Across the board, one thing stood out: people and animals showed fewer obsessive-compulsive symptoms after being given psilocybin.

In clinical settings, some patients with long-standing OCD or body dysmorphic disorder got significant relief within a day of taking psilocybin.

Psilocybin benefits in the real world

In one study, patients saw symptom drops ranging from 23 percent to 100 percent just hours after a dose. One trial in 2024 gave a single 25-milligram dose to 12 adults with body dysmorphic disorder.

Improvements lasted up to 12 weeks – and by the end, over half met the criteria for response, and a third reached remission.

Behind this work is a team from the Florey Institute of Neuroscience and Mental Health. The researchers conducted a systematic review using strict scientific guidelines.

The goal was to determine whether psilocybin could work not just in theory, but in real-world patients and validated lab models.

What mice reveal about OCD

One part of the research focused on SAPAP3-knockout mice – a well-known model for obsessive-compulsive behaviors. These mice groom themselves so much they often get skin injuries, similar to how people with OCD might engage in harmful repetitive behaviors.

When these mice were given psilocybin, their compulsive grooming dropped – not just for a few hours, but for days or even weeks after a single dose.

One group saw reduced grooming for up to 42 days. This wasn’t just a fluke. The results were seen in different labs, using different doses and methods.

On the other hand, wild-type mice – the ones without the genetic mutation – only showed short-term changes in repetitive behavior after psilocybin.

The effects faded after a day. That contrast shows the importance of studying true disease models when testing potential treatments.

Real people are noticing benefits too

Beyond the lab and clinic, researchers also looked at a 2023 survey of 135 people who had OCD and had used psilocybin mushrooms.

Around 30 percent said their symptoms improved and stayed better for more than three months. Those who used psilocybin or LSD more than once reported stronger improvements than those who only tried it once.

Still, this kind of data comes with a grain of salt – surveys rely on self-reporting and don’t have the controls of clinical trials. But they offer valuable insight into real-world use and long-term outcomes.

Mystery behind psilocybin’s effects

Psilocybin turns into psilocin in the body, which activates serotonin receptors – especially one called 5-HT2A. This is usually linked to the “trip” people experience.

But oddly enough, the studies found that even when this receptor was blocked in animals, psilocybin still reduced compulsive behaviors.

That raises a big question: could there be a way to keep the therapeutic benefits without the hallucinogenic effects? Researchers are exploring psilocybin-like compounds that skip the intense visuals but still ease symptoms.

One of them, called 1-methylpsilocin, showed strong anti-compulsive effects in mice without triggering the classic psychedelic response.

One dose versus microdosing

Researchers also tested what happens with repeated low doses – often called microdosing. Some results were mixed.

In rats, low-dose psilocybin every other day for three weeks led to small reductions in grooming and increased certain brain proteins tied to learning and memory. But in compulsive SAPAP3-knockout mice, the same approach didn’t help.

That suggests a one-time, full-dose treatment might be more effective than frequent low doses – at least for compulsive behaviors.

Psilocybin may rewire the brain

One theory is that psilocybin helps the brain rewire itself. After taking the drug, both people and animals show signs of something called neuroplasticity – the brain’s ability to form new connections.

In mice, psilocybin increased the number of dendritic spines (tiny structures that help brain cells communicate) in brain areas tied to decision-making and behavior control.

The researchers think psilocybin might be helping normalize abnormal brain circuits seen in OCD. But they stress that more studies are needed to confirm how – and where – these changes happen.

Where the research falls short

Even with these promising results, there’s still a long way to go. Many of the clinical trials had small sample sizes – some with just nine or twelve participants. Most didn’t include a placebo group, making it hard to rule out other effects.

There’s also a lack of brain imaging data. Researchers still don’t know how psilocybin affects the brain circuits that malfunction in OCD.

One ongoing study plans to use fMRI scans to observe how psilocybin alters brain connectivity in people with OCD.

Another major gap is understanding how sex differences may affect outcomes. Researchers previously found longer-lasting effects in male mice compared to females. However, few trials have been large enough to fully explore those differences.

Next steps in OCD treatment

Psilocybin’s potential to ease compulsive behaviors in humans and animals – even after one dose – is turning heads in psychiatry.

If future trials confirm the findings, it could open the door to a new class of treatments that work faster, last longer, and don’t require daily pills.

But researchers are urging caution. They’re not calling psilocybin a cure, and they’re not recommending it for use outside controlled studies. There’s still a need for more data, more safety checks, and better understanding of how – and why – it works.

For now, it’s clear that something in psilocybin is worth paying attention to. Whether it’s the key to a new approach in treating obsessive-compulsive and related disorders remains to be seen. But the evidence so far is hard to ignore.

The full study was published in the journal Psychedelics.

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