Psilocybin Therapy Produces Long-Lasting Antidepressant Effects, 4 Times More Effective Than Pills

Just two sessions of psilocybin-assisted therapy can produce significant and lasting antidepressant effects, a new clinical study finds. 

In fact, psilocybin therapy proved to be approximately two-and-a-half times more effective than psychotherapy on its own, and more than four times more effective than commonly-prescribed antidepressant drugs. 

These exciting results add to the growing evidence that psilocybin – the hallucinogenic compound found in ‘magic’ mushrooms – offers a profoundly effective treatment for depression and other mental health conditions.   

The promising research into psychedelic-assisted therapy, characterised by these latest findings, may well represent the beginning of a major paradigm shift in mental health treatment.

The study

While the new randomised study was quite small and didn’t include a traditional control group, a very large and statistically significant effect was found. What’s more, published in Jama Psychiatry, the results are the first peer-reviewed published data showing the efficacy of psilocybin therapy on MDD.

Analysing a group of 24 volunteers with major depressive disorder (MDD), psilocybin-assisted therapy was found to be twice as effective as psychotherapy by itself, and over four times more effective as common antidepressant drugs.  

Subjects were given a total of two psilocybin-assisted therapy sessions spaced two weeks apart, along with a number of psychotherapy sessions both before and after the psilocybin sessions.

During the sessions, psilocybin was administered in pill form (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) while participants laid out on a sofa in a living room-like space. In the room were two facilitators who encouraged participants to focus their attention inward and stay with any experience that arose. 

To enhance inward reflection, music was played and participants were instructed to wear blindfolds and headphones. The playlist used, which can be found here, includes Vivaldi and Bach. 


Four weeks into the trial, 71 percent of subjects displayed more than a 50% reduction in depressive symptoms. A month later, the average depression score for the group fell dramatically from 23 to 8, with more than half of subjects considered to be in clinical remission.

The trial showed that psilocybin-assisted therapy produced “large, rapid, and sustained antidepressant effects.” It proved to be approximately two-and-a-half times more effective than psychotherapy on its own, and more than four times more effective than commonly-prescribed antidepressant drugs. 


The study authors also note how well the psilocybin was tolerated by the subjects, with only “non-serious adverse effects” reported in the cases of mild-to-moderate headaches and challenging emotions. 

They suggested this makes psilocybin therapy preferable than widely prescribed antidepressant medications that have much worse side-effects, such as suicidal ideation, decrease in sex drive, and weight gain.

“The effectiveness of psilocybin therapy after a single or only a few administrations represents another substantial advantage over commonly used antidepressants that require daily administration,” the study states. 

Previous research

This isn’t the first trial to highlight psilocybin’s potential to treat depression. This 2016 trial found high-doses of psilocybin (with no therapy) in terminal cancer patients decreased depression and anxiety. Even after six months, 80 percent were still experiencing benefits. 

Earlier that year, a trial published in The Lancet found lasting benefits after two doses of psilocybin among patients with treatment-resistant depression. 

It is not known exactly how psilocybin exerts its antidepressant effects. However, we do that it binds to serotonin receptors in the brain, reduces activity in the amygdala – the part of the brain that deals with emotional responses, stress, and fear – and reduces activity in the “default mode network”, which is thought to be a collection of brain regions and neurotransmitters that construct the self and controls perception. 

At high doses, many describe the loss of self or ‘ego death’. 

Many studies, including this latest one, have found that mystical experiences are not only common with psilocybin, but they are predictive of positive outcomes. In other words, it seems to work better if you have a mystical, meaningful or spiritual experience. 


The United States’ Food and Drug Advisory (FDA) has twice designated psilocybin a “breakthrough therapy” in a bid to speed up research on it. Many more trials are underway in the US as a result of this and we should have lots of results published next year. 

In the last few days, Oregon became the first US state to legalise psilocybin therapy. It’s set to be available for those with PTSD, addiction and also depression.

In the UK, psilocybin has Schedule 1 status, meaning it is very difficult (and expensive) for researchers to study it. Despite this, the UK has produced a number of important studies on psilocybin. 


It’s still early in the third psychedelic revolution. Research is producing promising findings but more is needed – including larger samples and placebo control groups. 

However, it does look like psilocybin-assisted therapy offers a cheap, simple, safe and highly effective treatment for depression. And considering how common depression is becoming, it’s needed more than ever. 

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2 Comments on “Psilocybin Therapy Produces Long-Lasting Antidepressant Effects, 4 Times More Effective Than Pills”

  1. Hey, those red mushrooms are amanita muscaria, which does not contain any psilocybe (but which do have their own effects, just not the same as ‘magic’ mushrooms)

  2. I strongly second the comment above. The mushroom pictured contains muscimol and ibotenic acid these hallucinogens will give you a terrifying experience almost without fail and have no place in psilocbyn therapy. You should change the photos with your otherwise excellent piece.

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