Should You Choose Psilocybin Over Antidepressants?

The UK has a large mental health problem. In some places, 20% of the population are being prescribed antidepressants. 

At the same time, a small study out of Johns Hopkins Medicine is reporting incredible success with psilocybin-assisted therapy for treating depression. 

A recent follow up study found just two doses of psilocybin combined with a handful of psychotherapy sessions can produce significant antidepressant effects that last at least a year.  

Although the sample group had only 27 participants, 75% of them responded favourably to the treatment, while 58% were considered to be in remission.

Results like these suggest psilocybin could revolutionise psychiatry, as current treatments don’t work for many (particularly over the long-term) and often come with undesirable side effects. 

Having said that, research is in its infancy and, as all careful researchers like to point out, more research on larger samples are needed before psilocybin can be considered for widespread medical use. 

But what if you can’t wait until then? What if you’re suffering today and you feel you may need some chemical help? Should you choose psilocybin over antidepressants? 

Let’s break it down…

What is psilocybin?

Psilocybin is the compound in certain mushrooms that makes them “magic” due to its potent mind-altering effects. 

It’s been consumed by humans in the form of mushrooms for thousands of years in various cultures around the world, particularly in ceremonial situations for spiritual and religious reasons. 

It was first isolated in 1959 by the Swiss chemist Albert Hofmann, who also discovered LSD.

In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also include possible adverse reactions such as nausea and panic attacks.

In recent years, a number of studies have now shown psilocybin to have powerful antidepressant effects. 

How does psilocybin work for depression?

It is not known exactly how psilocybin exerts its antidepressant effects. However, we do that it binds to serotonin receptors in the brain as it’s structurally very similar to the neurotransmitter.

Psilocybin also 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’. Most studies 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. 

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. 

The most recent research has found two doses of psilocybin plus therapy to be effective in the treatment of Major Depressive Disorder (MDD) for up to one year after being administered. 

Is psilocybin safe?

While it only included 27 participants, this recent follow up study states: 

“There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study.”

This is generally the case with most psilocybin studies. 

But what about the stories of people having bad trips, losing their minds and jumping from windows believing they can fly? Well, they are just that – stories.  

Yes, it’s true that consuming psilocybin can lead to distressing and challenging experiences. However, in a medical setting, supervised by experienced facilitators and therapists, and with adequate preparation, so-called “bad trips” are very manageable and there is little risk to the patient. 

In fact, difficult experiences on psilocybin are often necessary and beneficial. 

Overall, the most commonly reported side effects of psilocybin are short-term anxiety, headache and nausea. Long-term issues and risk of addiction or abuse are unheard of. 

What are antidepressants?

Antidepressants are a range of medications that target neurotransmitters in the brain to treat a wide number of mental disorders, including but not limited to depression, anxiety and PTSD.

They come in several forms, including:

  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclics (TCAs)

Antidepressants have been in use since the 1950s and are based on the theory that depleted levels of neurotransmitters (particularly serotonin, norepinephrine, dopamine) is the cause of depression. 

How do antidepressants work for depression?

Neurotransmitters are the chemical messengers that transport information around your brain from one neuron to another.

In depression and many other mental disorders, there’s often a disruption to how these chemical messengers work. In some cases, there is not enough of a certain neurotransmitter, while in others the neurotransmitters don’t activate receptors as well as they should. 

Antidepressants affect how neurotransmitters function in order to rectify dysregulation. They generally do this by slowing down the reuptake of neurotransmitters, which essentially makes more available in the brain. 

This can often help brains to work better while reducing symptoms. However, they don’t work for everyone and often come with severe side effects. 

Are antidepressants safe?

The brain is an infinitely complex network that is constantly changing. The idea that depression can be fixed by increasing concentrations of certain neurotransmitters is too simplistic. 

Each neurotransmitter has a lot of different jobs. So while increasing neurotransmitters might have the desired effect of alleviating depression or improving one’s thought process, it can also have unwanted effects.

The potential side effects of antidepressants are many and range from mild to life-threatening. On top of that, antidepressants are known to become less effective over time and getting off of them can see withdrawal symptoms and a rebound of symptoms. 

A 2016 paper published in the Patient Preference and Adherence looked at side effects of taking antidepressants long-term.

While those questioned in the study did report less depression and an overall better quality of life, many reported unwanted side effects.The most common were:

  • Sexual problems (72%), including the inability to reach orgasm (65%)
  • Weight gain (65%)
  • Feeling emotionally numb (65%)
  • Not feeling like themselves (54%)
  • Reduced positive feelings (46%)
  • Feeling as if they’re addicted (43%)
  • Caring less about other people (36%)
  • Feeling suicidal (36%)

About 74% of people also mentioned withdrawal symptoms and said they needed support when coming off of antidepressants.


Psilocybin-assisted therapy is a revolutionary new treatment for depression. Exactly how it works is not well understood, but the mushroom-derived compound certainly has a unique ability to allow one to analyse and let go of old thinking patterns while having a strong safety profile.   

Antidepressants, on the other hand, are based on a simplistic model of depression – in that it’s merely an imbalance of chemicals in the brain. While antidepressants are useful, especially in the short term, they do not treat the underlying cause of depression and they come with a host of negative side effects over the long-term. 

Roland Griffiths, Ph.D., founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research, says it best:

“Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression. 

“Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments.”

Read: Where To Buy The Best Magic Mushroom Grow Kits In The UK

Read: 5 Species Of Magic Mushroom That Grow Wild In The UK

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